2019

  • Hutfilz, A;Burri, C;Theisen-Kunde, D;Meier, C and Brinkmann, R: Ex vivo investigation of different μs laser pulse durations for selective retina therapy. no. 11079, SPIE, 2019
    BibTeX Link
    @book{Hutfilz 2019,
       author = {Hutfilz, A;Burri, C;Theisen-Kunde, D;Meier, C and Brinkmann, R},
       title = {Ex vivo investigation of different μs laser pulse durations for selective retina therapy},
       publisher = {SPIE},
       volume = {11079},
    Keywords = {selective retina therapy, SRT, retinal pigment epithelium, eye model, ED-values, intensity modulation factor, IMF},
       series = {European Conferences on Biomedical Optics},
       url = {https://doi.org/10.1117/12.2526948},
       year = {2019},
       type = {Book}
    }
    
  • Bliedtner,K; Seifert, E and Brinkmann,R: Dosimetry for microsecond selective laser trabeculoplasty. in Proc. SPIE 11079, Medical Laser Applications and Laser-Tissue Interactions IX, no. 11079, 2019
    BibTeX Link
    @inproceedings{Bliedtner2019,
       author = {Bliedtner,K; Seifert, E and Brinkmann,R},
       title = {Dosimetry for microsecond selective laser trabeculoplasty},
       volume = {11079},
       DOI = {10.1117/12.2526987},
       year = {2019},
    keywords = {Ophthalmology, ophthalmic optics and devices, selective laser trabeculoplasty, micro bubble detection},
    booktitle =    {Proc. SPIE 11079, Medical Laser Applications
    and Laser-Tissue Interactions IX},
       type = {Conference proceedings}
    }
    
  • Detrez, N;Miura, Y;Seifert, E;Theisen-Kunde, D and Brinkmann, R: Heating and optoacoustic temperature determination of cell cultures. in Proc. SPIE 11079, Medical Laser Applications and Laser-Tissue Interactions IX, no. 11079, SPIE, 2019
    BibTeX Link
    @inproceedings{Detrez2019,
       author = {Detrez, N;Miura, Y;Seifert, E;Theisen-Kunde, D and Brinkmann, R},
       title = {Heating and optoacoustic temperature determination of cell cultures},
       publisher = {SPIE},
       volume = {11079},
       series = {European Conferences on Biomedical Optics},
    booktitle =    {Proc. SPIE 11079, Medical Laser Applications
    and Laser-Tissue Interactions IX},
       url = {https://doi.org/10.1117/12.2527024},
    keywords = {Laser, Noninvasive thermometry, hyperthermia, temperature measurement, photoacoustics}, optoacoustics,
       year = {2019},
       type = {Conference Proceeding}
    }
    
  • Burri, C;Hutfilz, A;Grimm, L;Arnold, P;Ebneter, A;Brinkmann, R;Theisen-Kunde, D;Považay, B and Meier, C: Optical coherence tomography controlled selective retina therapy with a novel microsecond laser. no. 11079, SPIE, 2019
    BibTeX Link
    @book{Burri2019,
       author = {Burri, C;Hutfilz, A;Grimm, L;Arnold, P;Ebneter, A;Brinkmann, R;Theisen-Kunde, D;Považay, B and Meier, C},
       title = {Optical coherence tomography controlled selective retina therapy with a novel microsecond laser},
       publisher = {SPIE},
       volume = {11079},
    keywords = {Selective retina therapy, Retinal pigment epithelium, (170.0170) Medical optics and biotechnology, (170.4500) Optical coherence tomography, (170.4460) Ophthalmic optics and devices, instrumentation, (170.4470) Ophthalmology},
       series = {European Conferences on Biomedical Optics},
       url = {https://doi.org/10.1117/12.2526720},
       year = {2019},
       type = {Book}
    }
    
  • Abbas, H. S.;Kren, C.;Danicke, V.;Herzog, C. and Brinkmann, R.: Toward feedback temperature control for retinal laser treatment. no. 11079, SPIE, 2019
    BibTeX Link
    @book{Abbas  2019,
       author = {Abbas, H. S.;Kren, C.;Danicke, V.;Herzog, C. and Brinkmann, R.},
       title = {Toward feedback temperature control for retinal laser treatment},
       publisher = {SPIE},
       volume = {11079},
    keywords = {Retina, Laser, Temperature, Optoacoustics, Photocoagulation, System identification, Automatic control},
       series = {European Conferences on Biomedical Optics},
       url = {https://doi.org/10.1117/12.2527169},
       year = {2019},
       type = {Book}
    }
    
  • Strenge,P; Lange,B; Grill, C; Draxinger, W; Danicke, V; Theisen-Kunde, D; Bonsanto, M; Huber, R and Brinkmann R: Ex vivo and in vivo imaging of human brain tissue with different OCT systems. in Proc. SPIE 11078, Optical Coherence Imaging Techniques and Imaging in Scattering Media III, 110781C, no. 11078, 2019
    BibTeX Link
    @proceeding{Strenge2019,
    author = {Strenge,P; Lange,B; Grill, C; Draxinger, W; Danicke, V; Theisen-Kunde, D; Bonsanto, M; Huber, R and Brinkmann R},
    title = {Ex vivo and in vivo imaging of human brain tissue with different OCT systems},
    volume = {11078},
    year = {2019},
    
    URL = {https://doi.org/10.1117/12.2526932},
    keywords = {AG-Huber_OCT},
    booktitle =    {Proc. SPIE 11078, Optical Coherence Imaging Techniques and Imaging in Scattering Media III, 110781C},
    eprint = {}
    }
    
  • Richert, E;Bartsch, S;Hillenkamp, J;Treumer, F;Tode, J;von der Burchard, C;Brinkmann, R;Klettner, A K and Roider, J: Einfluss der Selektiven Retinatherapie (SRT) auf inflammatorische Zellmediatoren des subretinalen Raums. Klin Monatsbl Augenheilkd(EFirst), 2019
    BibTeX Link
    @article{Brinkmann2019-4,
       author = {Richert, E;Bartsch, S;Hillenkamp, J;Treumer, F;Tode, J;von der Burchard, C;Brinkmann, R;Klettner, A K and Roider, J},
       title = {Einfluss der Selektiven Retinatherapie (SRT) auf inflammatorische Zellmediatoren des subretinalen Raums},
       journal = {Klin Monatsbl Augenheilkd}{(EFirst)},
    URL = { https://doi.org/10.1055/a-0838-5633}
       ISSN = {0023-2165},
       Year = {2019},
       type = {Journal Article}
    }
    
  • Miura, Y;Seifert, E;Rehra, J;Kern, K;Theisen-Kunde, D;Denton, M and Brinkmann, R: Real-time optoacoustic temperature determination on cell cultures during heat exposure: a feasibility study. Int J Hyperth, pp. 1-7, 2019
    BibTeX Link
    @article{Miura2019/4,
       author = {Miura, Y;Seifert, E;Rehra, J;Kern, K;Theisen-Kunde, D;Denton, M and Brinkmann, R},
       title = {Real-time optoacoustic temperature determination on cell cultures during heat exposure: a feasibility study},
       journal = {Int J Hyperth},
       pages = {1-7},
       ISSN = {0265-6736},
      
       url = {https://doi.org/10.1080/02656736.2019.1590653},
       year = {2019},
       type = {Journal Article}
    }
    
  • Kolb, J P;Weng, D;Hakert, H;Eibl, M;Draxinger, W;Meyer, T;Gottschall, T;Brinkmann, R;Birngruber, R;Popp, J;Limpert, J;Karpf, S and Huber, R: Virtual HE histology by fiber-based picosecond two-photon microscopy. in Multiphoton Microscopy in the Biomedical Sciences XIX Proc. SPIE,10882, pp. 108822F, International Society for Optics and Photonics, 2019
    BibTeX Link
    @inproceedings{Kolb2019/2,
       author = {Kolb, J P;Weng, D;Hakert, H;Eibl, M;Draxinger, W;Meyer, T;Gottschall, T;Brinkmann, R;Birngruber, R;Popp, J;Limpert, J;Karpf, S and Huber, R},
       title = {Virtual HE histology by fiber-based picosecond two-photon microscopy},
       booktitle = {Multiphoton Microscopy in the Biomedical Sciences XIX} {Proc. SPIE,10882},
       editor = {Ammasi Periasamy; Peter T. C. So; Karsten König},
       publisher = { International Society for Optics and Photonics},
       year = {2019},
       pages = {108822F},
    keywords = {AG-Huber_NL},
       
    doi = {10.1117/12.2507866},
       type = {Conference Proceedings}
    }
    
  • Miura, Y;Lewke, B;Hutfilz, A and Brinkmann, R: Change in fluorescence lifetime of retinal pigment epithelium under oxidative stress. Nippon Ganka Gakkai Zasshi 123 (2), pp. 105-114, 2019
    BibTeX Link
    @article{Miura2019/3,
       
       author = {Miura, Y;Lewke, B;Hutfilz, A and Brinkmann, R},
       title = {Change in fluorescence lifetime of retinal pigment epithelium under oxidative stress},
       journal = {Nippon Ganka Gakkai Zasshi } {123 (2)},
      
       pages = {105-114},
       url = {http://journal.nichigan.or.jp/Disp?style=abst&vol=123&year=2019&mag=0&number=2&start=105},
       year = {2019},
       type = {Journal Article}
    }
    
    
  • Rudolf, M; Curcio, C A; Schlözer-Schrehardt, U; Sefat, A M M; Tura, A; Aherrahrou, Z; Brinkmann, M; Grisanti, S; Miura, Y and Ranjbar, M: Apolipoprotein A-I mimetic peptide L-4F removes Bruch`s membrane lipids in aged nonhuman primates. Invest Ophthalmol Vis Sci, pp. 461-472, 2019
    BibTeX Link
    @article{Miura2019-2,
       author = {Rudolf, M; Curcio, C A; Schlözer-Schrehardt, U; Sefat, A M M; Tura, A; Aherrahrou, Z; Brinkmann, M; Grisanti, S;  Miura, Y and Ranjbar, M},
       title = {Apolipoprotein A-I mimetic peptide L-4F removes Bruch's membrane lipids in aged nonhuman primates},
       journal = {Invest Ophthalmol Vis Sci},
       pages = {461-472},
      
       url = {https://www.ncbi.nlm.nih.gov/pubmed/30707219},
       year = {2019},
       type = {Journal Article}
    }
    

2018

  • Herzog C;Thompson O; Schmarbeck B; Siebert M and Brinkmann, R: Temperature-controlled laser therapy of the retina via robust adaptive Ɦ∞-control. at-Automatisierungstechnik 66 (12), pp. 1051-1063, De Gruyter, 2018
    BibTeX Link
       @book{Brinkmann2018/2,
       author = {Herzog, C;Thompson, O; Schmarbeck, B; Siebert, M and Brinkmann, R},
       title = {Temperature-controlled laser therapy of the retina via robust adaptive Ɦ∞-control},
       publisher = {De Gruyter},
       
       journal = {at-Automatisierungstechnik} {66 (12)},
       pages = {1051-1063},   
       year = {2018},
       type = {Book}
      URL = {https://doi.org/10.1515/auto-2018-0066},
       
      
    keywords = {Laser therapy; robust control; parameter estimation; photoacoustics; real-time temperature determination},
       abstract = {Recent studies demonstrate therapeutic benefits in retinal laser therapy even for non-visible effects of the irradiation. However, in practice, ophthalmologists often rely on the visual inspection of irradiation sites to manually set the laser power for subsequent ones. Since absorption properties vary strongly between sites, this procedure can lead to under- or over-treatment. To achieve safe automatic retinal laser therapy, this article proposes a robust control scheme based on photoacoustic feedback of the retinal temperature increase. The control scheme is further extended to adapt to real-time parameter estimates and associated bounds on the uncertainty of each irradiation site. Both approaches are successfully validated in ex vivo experiments on pigs’ eyes, achieving consistent irradiation durations of 55 ms despite the uncertainty in absorption properties.}
    }
    
  • Seifert, E; Tode, J; Pielen, A; Theisen-Kunde, D; Framme, C; Roider, J; Miura, Y; Birngruber, R and Brinkmann, R: Selective retina therapy: toward an optically controlled automatic dosing. J Biomed Opt 23(11), pp. 1-12, 2018
    BibTeX Link
    @article{seifert2018,
       author = {Seifert, E; Tode, J; Pielen, A; Theisen-Kunde, D; Framme, C; Roider, J; Miura, Y; Birngruber, R and Brinkmann, R},
       title = {Selective retina therapy: toward an optically controlled automatic dosing},
       journal = {J Biomed Opt} {23(11)},
       
       pages = {1-12},
       ISSN = {1560-2281 (Electronic)
    1083-3668 (Linking)},
       DOI = {10.1117/1.JBO.23.11.115002},   
    keywords = {algorithm, lasers in medicine, ophthalmology, retinal pigment epithelium, selective retina therapy, selectivity}
       year = {2018},
       type = {Journal Article}
    }
    
  • Tode, J; Richert, E; Koinzer, S; Klettner, A; von der Burchard, C; Brinkmann, R; Lucius, R and Roider, J: Thermal Stimulation of the Retina Reduces Bruch`s Membrane Thickness in Age Related Macular Degeneration Mouse Models. Transl Vis Sci Technol 7(3), pp. 2, 2018
    BibTeX Link
    @article{Tode2018,
       author = {Tode, J; Richert, E; Koinzer, S; Klettner, A; von der Burchard, C; Brinkmann, R; Lucius, R and Roider, J},
       title = {Thermal Stimulation of the Retina Reduces Bruch's Membrane Thickness in Age Related Macular Degeneration Mouse Models},
       journal = {Transl Vis Sci Technol} {7(3)},
      
       pages = {2},
       ISSN = {2164-2591 (Print)
    2164-2591 (Linking)}, 
       url = {https://www.ncbi.nlm.nih.gov/pubmed/29736323},
       year = {2018},
       type = {Journal Article}
    }
    
  • Richert, E; Koinzer, S; Tode, J;Schlott, K; Brinkmann, R; Hillenkamp, J; Klettner, A and Roider, J: Release of Different Cell Mediators During Retinal Pigment Epithelium Regeneration Following Selective Retina Therapy. Invest Ophthal Vis Scie 59(3), pp. 1323-1331, 2018
    BibTeX Link
    @article{Richert2018,
       author = {Richert, E; Koinzer, S; Tode, J;Schlott, K; Brinkmann, R; Hillenkamp, J; Klettner, A and Roider, J},
       title = {Release of Different Cell Mediators During Retinal Pigment Epithelium Regeneration Following Selective Retina Therapy},
       journal = {Invest Ophthal Vis Scie} {59(3)},
       
       pages = {1323-1331},
       ISSN = {1552-5783},
       DOI = {10.1167/iovs.17-23163},
       
       year = {2018},
       type = {Journal Article}
    }
    
  • Kern, K; Mertineit, C L; Brinkmann, R and Miura, Y: Expression of heat shock protein 70 and cell death kinetics after different thermal impacts on cultured retinal pigment epithelial cells. Exp Eye Res 170, pp. 117-126, 2018
    BibTeX Link
    @article{Miura2018,
       author = {Kern, K; Mertineit, C L; Brinkmann, R and Miura, Y},
       title = {Expression of heat shock protein 70 and cell death kinetics after different thermal impacts on cultured retinal pigment epithelial cells},
       journal = {Exp Eye Res} {170},
      
       pages = {117-126},
       ISSN = {1096-0007 (Electronic)
    0014-4835 (Linking)},
       DOI = {10.1016/j.exer.2018.02.013},
       year = {2018},
       type = {Journal Article}
    }
    
  • Richert, E; Koinzer, S; Tode, J; Schlott, K; Brinkmann, R; Hillenkamp, J; Klettner, A and Roider, J: Release of Different Cell Mediators During Retinal Pigment Epithelium Regeneration Following Selective Retina Therapy. Investigative Ophthalmology & Visual Science 59(3), pp. 1323-1331, 2018
    BibTeX Link
    @article{Brinkmann2018,
       author = {Richert, E; Koinzer, S; Tode, J; Schlott, K; Brinkmann, R; Hillenkamp, J; Klettner, A and Roider, J},
       title = {Release of Different Cell Mediators During Retinal Pigment Epithelium Regeneration Following Selective Retina Therapy},
       journal = {Investigative Ophthalmology & Visual Science} {59(3)},
       
       pages = {1323-1331},
       ISSN = {1552-5783},
      
       url = {http://dx.doi.org/10.1167/iovs.17-23163},
       year = {2018},
       type = {Journal Article}
    }
    
  • Han, J W; Choi, J; Kim, Y S, Kim, J; Brinkmann, R; Lyu, J and Park, T K: Comparison of the neuroinflammatory responses to selective retina therapy and continuous-wave laser photocoagulation in mouse eyes. Graefe`s Archive for Clinical and Experimental Ophthalmology 256(2), pp. 341-353, 2018
    BibTeX Link
    @article{Brinkmann2018,
       author = {Han, J W; Choi, J; Kim, Y S, Kim, J; Brinkmann, R; Lyu, J and Park, T K},
       title = {Comparison of the neuroinflammatory responses to selective retina therapy and continuous-wave laser photocoagulation in mouse eyes},
       journal = {Graefe's Archive for Clinical and Experimental Ophthalmology} {256(2)},
       
       pages = {341-353},
     
    URL= {https://doi.org/10.1007/s00417-017-3883-7},
       year = {2018},
       type = {Journal Article}
    }
    

2017

  • Buj, C; Münter, M; Schmarbeck, B; Horstmann, J; Hüttmann, G and Brinkmann, R: Noncontact holographic detection for photoacoustic tomography. J Biomed Opt 22(10), pp. 1-14, 2017
    BibTeX Link
    @article{Buj2017,
       author = {Buj, C; Münter, M; Schmarbeck, B; Horstmann, J; Hüttmann, G and Brinkmann, R},
       title = {Noncontact holographic detection for photoacoustic tomography},
       journal = {J Biomed Opt} {22(10)},
       
       pages = {1-14},
       DOI = {10.1117/1.jbo.22.10.106007},
       year = {2017},
       type = {Journal Article}
    }
    
    
    
  • Baade, A; von der Burchard, C; Lawin, M; Koinzer, S; Schmarbeck, B; Schlott, K; Miura, Y; Roider, J; Birngruber, R and Brinkmann, R: Power-controlled temperature guided retinal laser therapy. J Biomed Opt 22(11), pp. 1-11, 2017
    BibTeX Link
    @article{Baade2017,
       author = {Baade, A; von der Burchard, C; Lawin, M; Koinzer, S; Schmarbeck, B; Schlott, K; Miura, Y; Roider, J; Birngruber, R and Brinkmann, R},
       title = {Power-controlled temperature guided retinal laser therapy},
       journal = {J Biomed Opt} {22(11)},
       
       pages = {1-11},
       ISSN = {1083-3668},
       DOI = {10.1117/1.jbo.22.11.118001},
       year = {2017},
       type = {Journal Article}
    }
    
  • Bliedtner, K; Seifert, E; Brinkmann, R and E D Amelink A: Real Time Speckle Monitoring to Control Retinal Photocoagulation. in Proc. SPIE 10413, pp. 1041308-1-7,
    BibTeX Link
    @inproceedings{Bliedtner2017,
       author = {Bliedtner, K; Seifert, E; Brinkmann, R and  Amelink A},
       title = {Real Time Speckle Monitoring to Control Retinal Photocoagulation},
       booktitle = {Proc. SPIE} {10413},
       
       pages = {1041308-1-7},
      
    url = { https://doi.org/10.1117/12.2287815}
  • Miura, Y; Pruessner, J; Mertineit, C L; Kern, K; Muenter, M; Moltmann, M; Danicke, V and Brinkmann, R: Continuous-wave Thulium Laser for Heating Cultured Cells to Investigate Cellular Thermal Effects. J Vis Exp 30(124), 2017
    BibTeX Link
    @article{Miura2017,
       author = {Miura, Y; Pruessner, J; Mertineit, C L; Kern, K; Muenter, M; Moltmann, M; Danicke, V and Brinkmann, R},
       title = {Continuous-wave Thulium Laser for Heating Cultured Cells to Investigate Cellular Thermal Effects},
       journal = {J Vis Exp} {30(124)},
       
       ISSN = {1940-087x},
       DOI = {10.3791/54326},
       year = {2017},
       type = {Journal Article},
    
    
  • Lange, Birgit and Jocham, Dieter and Brinkmann, Ralf and Cordes, Jens: Stone/tissue differentiation for Holmium laser lithotripsy using autofluorescence: Clinical proof of concept study. Lasers in Surgery and Medicine, no. 49, pp. 361-365, 2017
    BibTeX Link
    @article{Lange2017,
       author = {Lange, Birgit and Jocham, Dieter and Brinkmann, Ralf and Cordes, Jens},
       title = {Stone/tissue differentiation for Holmium laser lithotripsy using autofluorescence: Clinical proof of concept study},
       journal = {Lasers in Surgery and Medicine},
       volume = {49},
       number = {4},
       pages = {361-365},
       ISSN = {1096-9101},
       DOI = {10.1002/lsm.22611},
       year = {2017},
       type = {Journal Article}
    }
    
  • Verbytskyi, Ievgen and Münter, Michael and Buj, Christian and Brinkmann, Ralf: A Problem of a Displacement Calculation of Tissue Surface in Non-Contact Photoacoustic Tomography. Naukovi Visti NTUU KPI, pp. 58-64, 2017
    BibTeX Link
    @article{Verbytskyi2017,
       author = {Verbytskyi, Ievgen and Münter, Michael and Buj, Christian and Brinkmann, Ralf},
       title = {A Problem of a Displacement Calculation of Tissue Surface in Non-Contact Photoacoustic Tomography},
       journal = {Naukovi Visti NTUU KPI},
       number = {2},
       pages = {58-64},
       ISSN = {2519-8890},
       url = {http://dx.doi.org/10.20535/1810-0546.2017.2.98021},
       year = {2017},
       type = {Journal Article}
    }
    
  • Tode, J;Richert, E;von der Burchard, C;Koinzer, S;Klettner, A;Brinkmann, R and Roider, J: Schonende retinale Lasertherapien als Behandlungsoption der trockenen AMD. Spitzenforschung in der Ophthalmologie, pp. 170-173, 2017
    BibTeX Link
    @article{Brinkmann2017,
       author = {Tode, J;Richert, E;von der Burchard, C;Koinzer, S;Klettner, A;Brinkmann, R and Roider, J},
       title = {Schonende retinale Lasertherapien als Behandlungsoption der trockenen AMD },
       journal = {Spitzenforschung in der Ophthalmologie},
       pages = {170-173},
       ISSN = {1861-4620},
       url = {https://www.dog.org/wp-content/uploads/2009/12/DOG_Sonderband_WEB-min.pdf#page=1&zoom=auto,-57,877},
       year = {2017},
       type = {Journal Article}
    }
    
  • Kepp, Timo and Koinzer, Stefan and Handels, Heinz and Brinkmann, Ralf: Registrierung von nicht sichtbaren Laserbehandlungsarealen der Retina in Live-Aufnahmen des Fundus. in Bildverarbeitung für die Medizin 2017: Algorithmen - Systeme - Anwendungen. Proceedings des Workshops vom 12. bis 14. März 2017 in Heidelberg, pp. 331-336, Springer Berlin Heidelberg, Berlin, Heidelberg, 2017
    BibTeX Link
    @inbook{Kepp2017,
       author = {Kepp, Timo and Koinzer, Stefan and Handels, Heinz and Brinkmann, Ralf},
       title = {Registrierung von nicht sichtbaren Laserbehandlungsarealen der Retina in Live-Aufnahmen des Fundus},
       booktitle = {Bildverarbeitung für die Medizin 2017: Algorithmen - Systeme - Anwendungen. Proceedings des Workshops vom 12. bis 14. März 2017 in Heidelberg},
       editor = {Maier-Hein, geb Fritzsche Klaus Hermann and Deserno, geb Lehmann Thomas Martin and Handels, Heinz and Tolxdorff, Thomas},
       publisher = {Springer Berlin Heidelberg},
       address = {Berlin, Heidelberg},
       pages = {331-336},
       ISBN = {978-3-662-54345-0},
       url = {http://dx.doi.org/10.1007/978-3-662-54345-0_74},
       year = {2017},
       type = {Book Section}
    }
    

2016

  • Tromberg, B. J. and Anderson, R. R. and Birngruber, R. and Brinkmann, R. and Berns, M. W. and Parrish, J. A. and Apiou-Sbirlea, G.: Biomedical optics centers: forty years of multidisciplinary clinical translation for improving human health. J Biomed Opt, no. 21, pp. 124001, 2016
    BibTeX Link
    @article{RN5034,
       author = {Tromberg, B. J. and Anderson, R. R. and Birngruber, R. and Brinkmann, R. and Berns, M. W. and Parrish, J. A. and Apiou-Sbirlea, G.},
       title = {Biomedical optics centers: forty years of multidisciplinary clinical translation for improving human health},
       journal = {J Biomed Opt},
       volume = {21},
       number = {12},
       pages = {124001},
       ISSN = {1560-2281 (Electronic)
    1083-3668 (Linking)},
       DOI = {10.1117/1.JBO.21.12.124001},   
       year = {2016},
       type = {Journal Article}
    }
    
  • Huttmann, Gereon and Moltmann, Moritz and Spahr, Hendrik and Tode, Jan and de Roeck, Anna and Theisen-Kunde, Dirk and Birngruber, Reginald and Koinzer, Stefan and Brinkmann, Ralf: Retinal lesion formation during photocoagulation investigated by high-speed 1060 nm Doppler-OCT: first clinical results. Investigative Ophthalmology & Visual Science, no. 57, pp. 5852-5852, 2016
    BibTeX Link
    @article{Hüttmann2016,
       author = {Huttmann, Gereon and Moltmann, Moritz and Spahr, Hendrik and Tode, Jan and de Roeck, Anna and Theisen-Kunde, Dirk and Birngruber, Reginald and Koinzer, Stefan and Brinkmann, Ralf},
       title = {Retinal lesion formation during photocoagulation investigated by high-speed 1060 nm Doppler-OCT: first clinical results},
       journal = {Investigative Ophthalmology & Visual Science},
       volume = {57},
       number = {12},
       pages = {5852-5852},
       abstract = {Abstract Purpose : The molecular processes during heating with a photocoagulation laser, particularly in sub-visible or mere thermal stimulation treatment, have only partly been understood, and different theories exist that try to explain its clinical efficacy. Optical coherence tomography (OCT) was successfully used to grade lesions with high accuracy 1 hour after the treatments and beyond. During the irradiation, changes in tissue scattering and, by use of the Doppler signal, tissue motion caused by thermal expansion and coagulation-induced tissue contraction were shown to correlate ex-vivo and in rabbits with the strength of photocoagulation lesions. Aim of this study was to validate feasibility and reproducibility of these results in humans. Methods : In an ongoing study more than 100 lesions of three patients have been imaged with a slitlamp-based OCT (1060 nm, 90,000 A-scans/s) with varying irradiance during laser exposure. Durations of the exposure were 50 ms and 200 ms; spot size was 300 µm. Eye movements and heart beat were corrected by cross-correlation of the images. Increased tissue scattering and movement of the neuronal retina due to thermal expansion were determined from the image sequences with 3 ms temporal resolution. Results : In the first treatments with this prototype device, we received acceptable image quality in 1/3 of the lesions. Changes in the neuronal retina were successful visualized during and after the laser irradiation, demonstrating the feasibility of a real-time assessment of initial effects of photocoagulation in humans. Lesion visibility in standard, reflection-based OCT was much weaker during treatment compared to 1 hour afterwards. Increased tissue scattering was observed in stronger lesions already during the laser irradiation. At reduced irradiance, scattering increase was only observed after the end of irradiation. However, tissue motion towards the vitreous was still observed in these cases. Conclusions : In conclusion, high-speed OCT recording during photocoagulation measures initial tissue changes during photocoagulation in humans. It may enhance our understanding of the tissue dynamics right after laser irradiation. It may provide useful information for a real-time dosage control as well. This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.},
       ISSN = {1552-5783},
       url = {http://dx.doi.org/},
       year = {2016},
       type = {Journal Article}
    }
    
  • Kim, H. D. and Jang, S. Y. and Lee, S. H. and Kim, Y. S. and Ohn, Y. H. and Brinkmann, R. and Park, T. K.: Retinal Pigment Epithelium Responses to Selective Retina Therapy in Mouse Eyes. Invest Ophthalmol Vis Sci, no. 57, pp. 3486-95, 2016
    BibTeX Link
    @article{Kim2016,
       author = {Kim, H. D. and Jang, S. Y. and Lee, S. H. and Kim, Y. S. and Ohn, Y. H. and Brinkmann, R. and Park, T. K.},
       title = {Retinal Pigment Epithelium Responses to Selective Retina Therapy in Mouse Eyes},
       journal = {Invest Ophthalmol Vis Sci},
       volume = {57},
       number = {7},
       pages = {3486-95},
       abstract = {PURPOSE: To investigate the characteristics of retinal pigment epithelium (RPE) and retinal damage induced by selective retina therapy (SRT) in mice, and to elucidate longitudinal changes in RPE cells. METHODS: C57BL/6J mice received SRT and continuous-wave laser photocoagulation (cwPC). The cell death pattern was evaluated using TUNEL assay, and proliferative potential of the RPE cells was evaluated using 5-ethynyl-2'-dexoyuridine (EdU) assay. To investigate the cell-cell integrity of RPE cells, beta-catenin staining was performed. The number and hexagonality of RPE cells in the SRT-treated area were estimated using a Voronoi diagram with time periods of 3 hours to 14 days. Antibodies to microphthalmia-associated transcription factor (MiTF) and orthodenticle homeobox 2 (Otx2) were used to confirm the specific characteristics of RPE cells in the SRT-treated area. RESULTS: The number of TUNEL-positive cells located in the neural retina was significantly lower in lesions treated with SRT compared to those treated with cwPC. EdU-positive RPE cells were first detected 3 to 12 hours after SRT, and increased until 3 to 7 days after SRT. beta-catenin staining showed that hexagonality was compromised and subsequently, RPE cells expanded in size within the targeted location. The number of RPE cells in SRT lesions decreased gradually until 12 hours after SRT and recovered by 14 days. Upregulated expression of MiTF and Otx2 was observed for 2 weeks in the SRT lesions. CONCLUSIONS: Selective retina therapy seems to induce selective RPE damage without collateral thermal injury in the neural retina. Furthermore, SRT-treated lesions recovered by proliferation of RPE cells that were present in the treated lesions and by expansion of adjacent RPE cells.},
       ISSN = {0146-0404},
       DOI = {10.1167/iovs.16-19508},
       year = {2016},
       type = {Journal Article}
    }
    
  • Bliedtner, Katharina and Seifert, Eric and Stockmann, Leoni and Effe, Lisa and Brinkmann, Ralf: Towards real time speckle controlled retinal photocoagulation. no. 9693, pp. 96931A-96931A-6,
    BibTeX Link
    @inproceedings{Bliedtner2016,
       author = {Bliedtner, Katharina and Seifert, Eric and Stockmann, Leoni and Effe, Lisa and Brinkmann, Ralf},
       title = {Towards real time speckle controlled retinal photocoagulation},
       volume = {9693},
       pages = {96931A-96931A-6},
       note = {10.1117/12.2212703},
       abstract = {Photocoagulation is a laser treatment widely used for the therapy of several retinal diseases. Intra- and inter-individual variations of the ocular transmission, light scattering and the retinal absorption makes it impossible to achieve a uniform effective exposure and hence a uniform damage throughout the therapy. A real-time monitoring and control of the induced damage is highly requested. Here, an approach to realize a real time optical feedback using dynamic speckle analysis is presented. A 532 nm continuous wave Nd:YAG laser is used for coagulation. During coagulation, speckle dynamics are monitored by a coherent object illumination using a 633nm HeNe laser and analyzed by a CMOS camera with a frame rate up to 1 kHz. It is obvious that a control system needs to determine whether the desired damage is achieved to shut down the system in a fraction of the exposure time. Here we use a fast and simple adaption of the generalized difference algorithm to analyze the speckle movements. This algorithm runs on a FPGA and is able to calculate a feedback value which is correlated to the thermal and coagulation induced tissue motion and thus the achieved damage. For different spot sizes (50-200 μm) and different exposure times (50-500 ms) the algorithm shows the ability to discriminate between different categories of retinal pigment epithelial damage ex-vivo in enucleated porcine eyes. Furthermore in-vivo experiments in rabbits show the ability of the system to determine tissue changes in living tissue during coagulation.},
       url = {http://dx.doi.org/10.1117/12.2212703},
       type = {Conference Proceedings}
    }
    
  • Schlott, Kerstin and Koinzer, Stefan and Baade, Alexander and Birngruber, Reginald and Roider, Johann and Brinkmann, Ralf: Lesion strength control by automatic temperature guided retinal photocoagulation. Journal of Biomedical Optics, no. 21, pp. 098001-098001, 2016
    BibTeX Link
    @article{Schlott2016,
       author = {Schlott, Kerstin and Koinzer, Stefan and Baade, Alexander and Birngruber, Reginald and Roider, Johann and Brinkmann, Ralf},
       title = {Lesion strength control by automatic temperature guided retinal photocoagulation},
       journal = {Journal of Biomedical Optics},
       volume = {21},
       number = {9},
       pages = {098001-098001},
       note = {10.1117/1.JBO.21.9.098001},
       abstract = {Abstract.  Laser photocoagulation is an established treatment for a variety of retinal diseases. However, when using the same irradiation parameter, the size and strength of the lesions are unpredictable due to unknown inter- and intraindividual optical properties of the fundus layers. The aim of this work is to investigate a feedback system to generate desired lesions of preselectable strengths by automatically controlling the irradiation time. Optoacoustics were used for retinal temperature monitoring. A 532-nm continuous wave Nd:YAG laser was used for photocoagulation. A 75-ns/523-nm Q-switched Nd:YLF laser simultaneously excited temperature-dependent pressure transients, which were detected at the cornea by an ultrasonic transducer embedded in a contact lens. The temperature data were analyzed during the irradiation by a LabVIEW routine. The treatment laser was switched off automatically when the required lesion strength was achieved. Five different feedback control algorithms for different lesion sizes were developed and tested on rabbits in vivo. With a laser spot diameter of 133  μm, five different lesion types with ophthalmoscopically visible diameters ranging mostly between 100 and 200  μm, and different appearances were achieved by automatic exposure time control. The automatically controlled lesions were widely independent of the treatment laser power and the retinal pigmentation.},
       ISSN = {1083-3668},
       DOI = {10.1117/1.JBO.21.9.098001},
       year = {2016},
       type = {Journal Article}
    }
    
  • Yasui, Ayako and Yamamoto, Manabu and Hirayama, Kumiko and Shiraki, Kunihiko and Theisen-Kunde, Dirk and Brinkmann, Ralf and Miura, Yoko and Kohno, Takeya: Retinal sensitivity after selective retina therapy (SRT) on patients with central serous chorioretinopathy. Graefe`s Archive for Clinical and Experimental Ophthalmology, pp. 1-12, 2016
    BibTeX Link
    @article{Yasui2016,
       author = {Yasui, Ayako and Yamamoto, Manabu and Hirayama, Kumiko and Shiraki, Kunihiko and Theisen-Kunde, Dirk and Brinkmann, Ralf and Miura, Yoko and Kohno, Takeya},
       title = {Retinal sensitivity after selective retina therapy (SRT) on patients with central serous chorioretinopathy},
       journal = {Graefe's Archive for Clinical and Experimental Ophthalmology},
       pages = {1-12},
       abstract = {To assess retinal sensitivity after selective retina therapy (SRT) in patients with central serous chorioretinopathy (CSCR).},
       ISSN = {1435-702X},
       url = {http://dx.doi.org/10.1007/s00417-016-3441-8},
       year = {2016},
       type = {Journal Article}
    }
    
  • Ranjbar, Mahdy and Brinkmann, Max Philipp and Tura, Aysegül and Rudolf, Martin and Miura, Yoko and Grisanti, Salvatore: Ranibizumab interacts with the VEGF-A/VEGFR-2 signaling pathway in human RPE cells at different levels. Cytokine, no. 83, pp. 210-216, 2016
    BibTeX Link
    @article{Ranjbar2016,
       author = {Ranjbar, Mahdy and Brinkmann, Max Philipp and Tura, Aysegül and Rudolf, Martin and Miura, Yoko and Grisanti, Salvatore},
       title = {Ranibizumab interacts with the VEGF-A/VEGFR-2 signaling pathway in human RPE cells at different levels},
       journal = {Cytokine},
       volume = {83},
       pages = {210-216},
       abstract = {Vascular endothelial growth factor (VEGF) secreted by the retinal pigment epithelium (RPE) plays an important role in ocular homeostasis, but also in diseases, most notably age-related macular degeneration (AMD). To date, anti-VEGF drugs like ranibizumab have been shown to be most effective in treating these pathologic conditions. However, clinical trials suggest that the RPE could degenerate and perish through anti-VEGF treatment. Herein, we evaluated possible pathways and outcomes of the interaction between ranibizumab and human RPE cells (ARPE-19). Results indicate that ranibizumab affects the VEGF-A metabolism in RPE cells from an extra- as well as intracellular site. The drug is taken up into the cells, with the VEGF receptor 2 (VEGFR-2) being involved, and decreases VEGF-A protein levels within the cells as well as extracellularly. Oxidative stress plays a key role in various inflammatory disorders of the eye. Our results suggest that oxidative stress inhibits RPE cell proliferation. This anti-proliferative effect on RPE cells is significantly enhanced through ranibizumab, which does not inhibit RPE cell proliferation substantially in absence of relevant oxidative stress. Therefore, we emphasize that anti-VEGF treatment should be selected carefully in AMD patients with preexistent extensive RPE atrophy.},
       keywords = {Ranibizumab
    RPE
    VEGF-A
    VEGFR-2
    Oxidative stress},
       ISSN = {1043-4666},
       url = {http://www.sciencedirect.com/science/article/pii/S1043466616300722},
       year = {2016},
       type = {Journal Article}
    }
    
  • Ranjbar, M. and Brinkmann, M. P. and Zapf, D. and Miura, Y. and Rudolf, M. and Grisanti, S.: Fc Receptor Inhibition Reduces Susceptibility to Oxidative Stress in Human RPE Cells Treated with Bevacizumab, but not Aflibercept. Cell Physiol Biochem, no. 38, pp. 737-47, 2016
    BibTeX Link
    @article{Ranjbar2016,
       author = {Ranjbar, M. and Brinkmann, M. P. and Zapf, D. and Miura, Y. and Rudolf, M. and Grisanti, S.},
       title = {Fc Receptor Inhibition Reduces Susceptibility to Oxidative Stress in Human RPE Cells Treated with Bevacizumab, but not Aflibercept},
       journal = {Cell Physiol Biochem},
       volume = {38},
       number = {2},
       pages = {737-47},
       note = {1421-9778
    Ranjbar, Mahdy
    Brinkmann, Max Philipp
    Zapf, Dorinja
    Miura, Yoko
    Rudolf, Martin
    Grisanti, Salvatore
    Journal Article
    Switzerland
    Cell Physiol Biochem. 2016;38(2):737-47. doi: 10.1159/000443030. Epub 2016 Feb 15.},
       abstract = {BACKGROUND/AIMS: VEGF-A is induced by oxidative stress, and functions as a survival factor for various cell types, including retinal pigment epithelial (RPE) cells. Anti-vascular endothelial growth factor (VEGF) drugs like aflibercept and bevacizumab have shown to be most effective in treating neovascular age-related macular degeneration (AMD), however uptake of the drugs might lead to interference with cell physiology. Herein, we evaluated the significance of the Fc receptor (FcR) within this context and moreover explored the impact of VEGF inhibition under normal conditions as well as under oxidative stress, in terms of potential adverse effects. METHODS: ARPE-19 (human RPE) cells were treated with aflibercept and bevacizumab in presence or absence of H2O2 as oxidative stress stimulus. After 24h cells were evaluated for drug uptake, VEGF-A expression and secretion, levels of intracellular reactive oxygen species (ROS) as well as cell proliferation. Experiments were repeated with cells being pre-incubated with an FcR inhibitor prior to drug application. RESULTS: Both drugs inhibited extracellular levels of VEGF-A and were taken up into the RPE, resulting in significantly reduced intracellular levels of VEGF-A. When oxidative stress was applied, intracellular ROS levels in cells treated with both drugs rose, and cell proliferation was reduced. Prior incubation with the FcR inhibitor lessened the uptake of bevacizumab, but not aflibercept into RPE cells, and simultaneously enhanced cell survival under oxidative stress conditions. CONCLUSIONS: Our results indicate that uptake and accumulation of aflibercept and bevacizumab within RPE cells affect the intracellular VEGF-A metabolism negatively, leading to a biologically relevant reduced cell survival under oxidative stress. The FcR plays a substantial role in the uptake of bevacizumab, but not aflibercept, which allows an enhanced RPE cell survival through FcR blockage in an environment dominated by oxidative stress, as clinically significant for various inflammatory retinal disorders.},
       ISSN = {1015-8987},
       DOI = {10.1159/000443030},
       year = {2016},
       type = {Journal Article}
    }
    
  • Park, Y. G. and Kim, J. R. and Kang, S. and Seifert, E. and Theisen-Kunde, D. and Brinkmann, R. and Roh, Y. J.: Safety and efficacy of selective retina therapy (SRT) for the treatment of diabetic macular edema in Korean patients. Graefes Arch Clin Exp Ophthalmol, 2016
    BibTeX Link
    @article{Park2016,
       author = {Park, Y. G. and Kim, J. R. and Kang, S. and Seifert, E. and Theisen-Kunde, D. and Brinkmann, R. and Roh, Y. J.},
       title = {Safety and efficacy of selective retina therapy (SRT) for the treatment of diabetic macular edema in Korean patients},
       journal = {Graefes Arch Clin Exp Ophthalmol},
       note = {1435-702x
    Park, Young Gun
    Kim, Jae Ryun
    Kang, Seungbum
    Seifert, Eric
    Theisen-Kunde, Dirk
    Brinkmann, Ralf
    Roh, Young-Jung
    Journal article
    Graefes Arch Clin Exp Ophthalmol. 2016 Jan 23.},
       abstract = {PURPOSE: Selective retina therapy (SRT) stimulates retinal pigment epithelium (RPE) cell migration and proliferation into irradiated areas. The objective of this study was to evaluate the efficacy and safety of SRT in Korean patients with clinically significant diabetic macular edema (DME). METHODS: Prospective non-randomized interventional case series study. Twenty-three eyes of 21 patients with clinically significant DME were treated with SRT and followed for 6 months. Patients underwent an evaluation of best corrected visual acuity (BCVA) in Early Treatment Diabetic Retinopathy Study (ETDRS) letters. Microperimetry was employed to measure macular sensitivity within the central 10 degrees field, and the central macular thickness (CMT) and maximum macular thickness (MMT) were measured. RESULTS: An improvement in BCVA of one to two ETDRS lines was observed in 41.2 % of patients and an improvement of greater than two lines in 29.4 %. Although there was no significant change in CMT (P > 0.05), MMT decreased from 465.8 +/- 87.4 mum to 434.3 +/- 83.9 mum (P = 0.006), and mean macular sensitivity increased from 20.8 +/- 3.4dB to 22.5 +/- 3.5dB (P = 0.02). CONCLUSIONS: The gains in BCVA and improvement in macular sensitivity demonstrated that SRT may be used as an effective and safe treatment modality in Korean patients with clinically significant DME.},
       keywords = {Diabetic macular edema
    Dosimetry
    Microperimetry
    Retinal pigment epithelium
    Selective retina therapy},
       ISSN = {0721-832x},
       DOI = {10.1007/s00417-015-3262-1},
       year = {2016},
       type = {Journal Article}
    }
    

2015

  • Lange, B. and Cordes, J. and Brinkmann, R.: Stone/tissue differentiation for holmium laser lithotripsy using autofluorescence. Lasers Surg Med, no. 47, pp. 737-44, 2015
    BibTeX Link
    @article{Lange2015,
       author = {Lange, B. and Cordes, J. and Brinkmann, R.},
       title = {Stone/tissue differentiation for holmium laser lithotripsy using autofluorescence},
       journal = {Lasers Surg Med},
       volume = {47},
       number = {9},
       pages = {737-44},
       note = {1096-9101
    Lange, Birgit
    Cordes, Jens
    Brinkmann, Ralf
    Journal Article
    United States
    Lasers Surg Med. 2015 Nov;47(9):737-44. doi: 10.1002/lsm.22418. Epub 2015 Sep 22.},
       abstract = {BACKGROUND AND OBJECTIVES: Holmium laser lithotripsy is a safe and effective method to disintegrate urinary stones of all compositions in an endoscopic procedure. However, handling and safety could be improved by a real-time feedback system permanently monitoring the position of the treatment fiber. The laser is fired only when the fiber is identified as being placed in front of stone. This work evaluates the potential of fluorescence detection with an excitation wavelength of 532 nm for this purpose. MATERIALS AND METHODS: A fiber-based fluorescence measurement was set-up to acquire autofluorescence signals from several human renal calculi, artificial stones, and porcine tissue samples (renal calix and ureter). Three different approaches were investigated. First, experiments were performed with a pulsed laser source with a wavelength of 532 nm, pulse energy 36.5 +/- 1 muJ, pulse duration 1.2 +/- 0.5 nanoseconds, and a repetition rate of 1 kHz with 15 urinary concretions. In the second step, a series of measurements on 42 human urinary calculi samples was carried out using low power continuous wave excitation of 0.4 +/- 0.1 mW. Fluorescence was also measured simultaneously to stone fragmentation by holmium laser pulses (pulse energy 240 +/- 50 mJ, repetition rate 10 Hz). Finally, a modulated excitation/detection scheme (lock-in technique) was implemented to render fluorescence detection insensitive to white background light. RESULTS: Unlike porcine renal calix, ureter, and artificial stone human urinary calculi show a strong fluorescence signal when excited with 532 nm. With pulsed excitation on urinary stone (20,000 +/- 11,000) counts were registered at 587 nm with the CCD-array of a grating spectrometer in an integration time of 50 milliseconds. Tissue gave lower count rates of </=(5,500 +/- 1,100) even with longer integration times (500 milliseconds/1 second). With a cw excitation power of 0.4 mW (13,000 +/- 11,000) counts were registered in an integration time of 200 milliseconds at 587 nm (porcine renal calix: (770 +/- 340)). Modulated excitation (66 Hz) with an average power of 0.3 mW and detection with a photodiode resulted in a lock-in amplifier signal of 1.5-4.3V on stone (background and skin: <0.5V). CONCLUSION: With the lock-in technique, autofluorescence from stones can be detected with only the average excitation power of a green aiming beam overlaid to the Ho:YAG-laser beam (power </= 1 mW). Since tissue shows very little autofluorescence when excited with 532 nm, this fluorescence signal enables monitoring of the correct position of the treatment fiber during ureteroscopic procedures. Lasers Surg. Med. 47:737-744, 2015. (c) 2015 Wiley Periodicals, Inc.},
       keywords = {Holmium laser
    feedback control
    fluorescence
    laser lithotripsy},
       ISSN = {0196-8092},
       DOI = {10.1002/lsm.22418},
       year = {2015},
       type = {Journal Article}
    }
    
  • Steiner, Patrick and Ebneter, Andreas and Berger, Lieselotte Erika and Zinkernagel, Martin and Považay, Boris and Meier, Christoph and Kowal, Jens H. and Framme, Carsten and Brinkmann, Ralf and Wolf, Sebastian and Sznitman, Raphael: Time-Resolved Ultra–High Resolution Optical Coherence Tomography for Real-Time Monitoring of Selective Retina TherapyTime-Resolved Ultra–High Resolution OCT During SRT. Investigative Ophthalmology & Visual Science, no. 56, pp. 6654-6662, 2015
    BibTeX Link
    @article{Steiner2015,
       author = {Steiner, Patrick and Ebneter, Andreas and Berger, Lieselotte Erika and Zinkernagel, Martin and Považay, Boris and Meier, Christoph and Kowal, Jens H. and Framme, Carsten and Brinkmann, Ralf and Wolf, Sebastian and Sznitman, Raphael},
       title = {Time-Resolved Ultra–High Resolution Optical Coherence Tomography for Real-Time Monitoring of Selective Retina TherapyTime-Resolved Ultra–High Resolution OCT During SRT},
       journal = {Investigative Ophthalmology & Visual Science},
       volume = {56},
       number = {11},
       pages = {6654-6662},
       note = {10.1167/iovs.15-17151},
       abstract = {Abstract Purpose: Selective retina therapy (SRT) is a novel treatment for retinal pathologies, solely targeting the RPE. During SRT, the detection of an immediate tissue reaction is challenging, as tissue effects remain limited to intracellular RPE photodisruption. Time-resolved ultra-high axial resolution optical coherence tomography (OCT) is thus evaluated for the monitoring of dynamic optical changes at and around the RPE during SRT. Methods: An experimental OCT system with an ultra-high axial resolution of 1.78 μm was combined with an SRT system and time-resolved OCT M-scans of the target area were recorded from four patients undergoing SRT. Optical coherence tomography scans were analyzed and OCT morphology was correlated with findings in fluorescein angiography, fundus photography, and cross-sectional OCT. Results: In cases in which the irradiation caused RPE damage proven by fluorescein angiography, the lesions were well discernible in time-resolved OCT images but remained invisible in fundus photography and cross-sectional OCT acquired after treatment. If RPE damage was introduced, all applied SRT pulses led to detectable signal changes in the time-resolved OCT images. The extent of optical signal variation seen in the OCT data appeared to scale with the applied SRT pulse energy. Conclusions: The first clinical results proved that successful SRT irradiation induces detectable changes in the OCT M-scan signal while it remains invisible in conventional ophthalmoscopic imaging. Thus, real-time high-resolution OCT is a promising modality to monitor and analyze tissue effects introduced by selective retina therapy and may be used to guide SRT in an automatic feedback mode (www.swissmedic.ch number, 2011-MD-0006).},
       ISSN = {1552-5783},
       DOI = {10.1167/iovs.15-17151},
       year = {2015},
       type = {Journal Article}
    }
    
  • Koinzer, S. and Baade, A. and Schlott, K. and Hesse, C. and Caliebe, A. and Roider, J. and Brinkmann, R.: Temperature-Controlled Retinal Photocoagulation Reliably Generates Uniform Subvisible, Mild, or Moderate Lesions. Transl Vis Sci Technol, no. 4, pp. 9, 2015
    BibTeX Link
    @article{Koinzer2015,
       author = {Koinzer, S. and Baade, A. and Schlott, K. and Hesse, C. and Caliebe, A. and Roider, J. and Brinkmann, R.},
       title = {Temperature-Controlled Retinal Photocoagulation Reliably Generates Uniform Subvisible, Mild, or Moderate Lesions},
       journal = {Transl Vis Sci Technol},
       volume = {4},
       number = {5},
       pages = {9},
       note = {Koinzer, Stefan
    Baade, Alexander
    Schlott, Kerstin
    Hesse, Carola
    Caliebe, Amke
    Roider, Johann
    Brinkmann, Ralf
    Journal article
    Transl Vis Sci Technol. 2015 Oct 6;4(5):9. eCollection 2015 Oct.},
       abstract = {PURPOSE: Conventional retinal photocoagulation produces irregular lesions and does not allow reliable control of ophthalmoscopically invisible lesions. We applied automatically controlled retinal photocoagulation, which allows to apply uniform lesions without titration, and aimed at five different predictable lesion intensities in a study on rabbit eyes. METHODS: A conventional 532-nm photocoagulation laser was used in combination with a pulsed probe laser. They facilitated real-time fundus temperature measurements and automatic exposure time control for different predefined time/temperature dependent characteristics (TTC). We applied 225 control lesions (exposure time 200 ms) and 794 TTC lesions (5 intensities, exposure times 7-800 ms) in six rabbit eyes with variable laser power (20-66.4 mW). Starting after 2 hours, we examined fundus color and optical coherence tomographic (OCT) images over 3 months and classified lesion morphologies according to a seven-stage OCT classifier. RESULTS: Visibility rates in funduscopy (OCT) after 2 hours were 17% (68%) for TTC intensity group 1, 38% (90%) for TTC group 2 and greater than 94% (>98%) for all consecutive groups. TTC groups 1 through 4 correlated to increasing morphological lesion intensities and increasing median funduscopic and OCT diameters. Group 5 lesions were as large as, but more intense than group 4 lesions. CONCLUSIONS: Automatic, temperature controlled photocoagulation allows to apply predictable subvisible, mild, or moderate lesions without manual power titration. TRANSLATIONAL RELEVANCE: The technique will facilitate standardized, automatically controlled low and early treatment of diabetic retinopathy study (ETDRS) intensity photocoagulation independently of the treating physician, the treated eye and lesion location.},
       keywords = {Oct
    animal model
    laser photocoagulation
    optoacoustics
    real-time temperature measurement
    spectral domain
    sub-visible},
       ISSN = {2164-2591 (Print)
    2164-2591},
       DOI = {10.1167/tvst.4.5.9},
       year = {2015},
       type = {Journal Article}
    }
    
  • Park, Young Gun and Kang, Seungbum and Brinkmann, Ralf and Roh, Young-Jung: A Comparative Study of Retinal Function in Rabbits after Panretinal Selective Retina Therapy versus Conventional Panretinal Photocoagulation. Journal of Ophthalmology, no. 2015, pp. 8, 2015
    BibTeX Link
    @article{Park2015,
       author = {Park, Young Gun and Kang, Seungbum and Brinkmann, Ralf and Roh, Young-Jung},
       title = {A Comparative Study of Retinal Function in Rabbits after Panretinal Selective Retina Therapy versus Conventional Panretinal Photocoagulation},
       journal = {Journal of Ophthalmology},
       volume = {2015},
       pages = {8},
       DOI = {10.1155/2015/247259},
       url = {http://dx.doi.org/10.1155/2015/247259},
       year = {2015},
       type = {Journal Article}
    }
    
  • Horstmann, J. and Spahr, H. and Buj, C. and Munter, M. and Brinkmann, R.: Full-field speckle interferometry for non-contact photoacoustic tomography. Phys Med Biol, no. 60, pp. 4045-58, 2015
    BibTeX Link
    @article{Horstmann2015,
       author = {Horstmann, J. and Spahr, H. and Buj, C. and Munter, M. and Brinkmann, R.},
       title = {Full-field speckle interferometry for non-contact photoacoustic tomography},
       journal = {Phys Med Biol},
       volume = {60},
       number = {10},
       pages = {4045-58},
       note = {1361-6560
       abstract = {A full-field speckle interferometry method for non-contact and prospectively high speed Photoacoustic Tomography is introduced and evaluated as proof of concept. Thermoelastic pressure induced changes of the objects topography are acquired in a repetitive mode without any physical contact to the object. In order to obtain high acquisition speed, the object surface is illuminated by laser pulses and imaged onto a high speed camera chip. In a repetitive triple pulse mode, surface displacements can be acquired with nanometre sensitivity and an adjustable sampling rate of e.g. 20 MHz with a total acquisition time far below one second using kHz repetition rate lasers. Due to recurring interferometric referencing, the method is insensitive to thermal drift of the object due to previous pulses or other motion. The size of the investigated area and the spatial and temporal resolution of the detection are scalable. In this study, the approach is validated by measuring a silicone phantom and a porcine skin phantom with embedded silicone absorbers. The reconstruction of the absorbers is presented in 2D and 3D. The sensitivity of the measurement with respect to the photoacoustic detection is discussed. Potentially, Photoacoustic Imaging can be brought a step closer towards non-anaesthetized in vivo imaging and new medical applications not allowing acoustic contact, such as neurosurgical monitoring or burnt skin investigation.},
       ISSN = {0031-9155},
       DOI = {10.1088/0031-9155/60/10/4045},
       year = {2015},
       type = {Journal Article}
    }
    
  • Framme, C. and Walter, A. and Berger, L. and Prahs, P. and Alt, C. and Theisen-Kunde, D. and Kowal, J. and Brinkmann, R.: Selective Retina Therapy in Acute and Chronic-Recurrent Central Serous Chorioretinopathy. Ophthalmologica, no. 234, pp. 177-88, 2015
    BibTeX Link
    @article{Framme2015,
       author = {Framme, C. and Walter, A. and Berger, L. and Prahs, P. and Alt, C. and Theisen-Kunde, D. and Kowal, J. and Brinkmann, R.},
       title = {Selective Retina Therapy in Acute and Chronic-Recurrent Central Serous Chorioretinopathy},
       journal = {Ophthalmologica},
       volume = {234},
       number = {4},
       pages = {177-88},
       note = {1423-0267
    Framme, Carsten
    Walter, Andreas
    Berger, Lieselotte
    Prahs, Philipp
    Alt, Clemens
    Theisen-Kunde, Dirk
    Kowal, Jens
    Brinkmann, Ralf
    Journal Article
    Research Support, Non-U.S. Gov't
    Switzerland
    Ophthalmologica. 2015;234(4):177-88. doi: 10.1159/000439188. Epub 2015 Sep 15.},
       abstract = {PURPOSE: Selective retina therapy (SRT), the confined laser heating and destruction of retinal pigment epithelial cells, has been shown to treat acute types of central serous chorioretinopathy (CSC) successfully without damaging the photoreceptors and thus avoiding laser-induced scotoma. However, a benefit of laser treatment for chronic forms of CSC is questionable. In this study, the efficacy of SRT by means of the previously used 1.7-micros and shorter 300-ns pulse duration was evaluated for both types of CSC, also considering re-treatment for nonresponders. MATERIAL AND METHODS: In a two-center trial, 26 patients were treated with SRT for acute (n = 10) and chronic-recurrent CSC (n = 16). All patients presented with subretinal fluid (SRF) in OCT and leakage in fluorescein angiography (FA). SRT was performed using a prototype SRT laser system (frequency-doubled Q-switched Nd:YLF-laser, wavelength 527 nm) with adjustable pulse duration. The following irradiation settings were used: a train of 30 laser pulses with a repetition rate of 100 Hz and pulse durations of 300 ns and 1.7 micros, pulse energy 120-200 microJ, retinal spot size 200 microm. Because SRT lesions are invisible, FA was always performed 1 h after treatment to demonstrate laser outcome (5-8 single spots in the area of leakage). In cases where energy was too low, as indicated by missing FA leakage, energy was adjusted and the patient re-treated immediately. Observation intervals were after 4 weeks and 3 months. In case of nonimprovement of the disease after 3 months, re-treatment was considered. RESULTS: Of 10 patients with active CSC that presents focal leakage in FA, 5 had completely resolved fluid after 4 weeks and all 10 after 3 months. Mean visual acuity increased from 76.6 ETDRS letters to 85.0 ETDRS letters 3 months after SRT. Chronic-recurrent CSC was characterized by less severe SRF at baseline in OCT and weaker leakage in FA than in acute types. Visual acuity changed from baseline 71.6 to 72.8 ETDRS letters after 3 months. At this time, SRF was absent in 3 out of 16 patients (19%), FA leakage had come to a complete stop in 6 out of 16 patients (38%). In 6 of the remaining chronic CSC patients, repeated SRT with higher pulse energy was considered because of persistent leakage activity. After the re-treatment, SRF resolved completely in 5 patients (83.3%) after only 25 days. CONCLUSION: SRT showed promising results in treating acute CSC, but was less effective in chronic cases. Interestingly, re-treatment resulted in enhanced fluid resolution and dry conditions after a considerably shorter time in most patients. Therefore, SRT including re-treatment if necessary might be a valuable CSC treatment alternative even in chronic-recurrent cases.},
       ISSN = {0030-3755},
       DOI = {10.1159/000439188},
       year = {2015},
       type = {Journal Article}
    }
    
  • Huttmann, Gereon and Koinzer, Stefan Otto Johannes and Müller, Heike and Ellerkamp, Iris and Baade, Alex and Moltmann, Moritz and Theisen-Kunde, Dirk and Lange, Birgit and Brinkmann, Ralf and Birngruber, Reginald: Predicting ophthalmoscopic visibility of retinal photocoagulation lesions byhigh-speedOCT: an animal studyinrabbits. Investigative Ophthalmology & Visual Science, no. 56, pp. 5980-5980, 2015
    BibTeX
    @article{Hüttmann2015,
       author = {Huttmann, Gereon and Koinzer, Stefan Otto Johannes and Müller, Heike and Ellerkamp, Iris and Baade, Alex and Moltmann, Moritz and Theisen-Kunde, Dirk and Lange, Birgit and Brinkmann, Ralf and Birngruber, Reginald},
       title = {Predicting ophthalmoscopic visibility of retinal photocoagulation lesions byhigh-speedOCT: an animal studyinrabbits},
       journal = {Investigative Ophthalmology & Visual Science},
       volume = {56},
       number = {7},
       pages = {5980-5980},
       ISSN = {1552-5783},
       year = {2015},
       type = {Journal Article}
    }
    
  • Kim, H. D. and Han, J. W. and Ohn, Y. H. and Brinkmann, R. and Park, T. K.: Functional evaluation using multifocal electroretinogram after selective retina therapy with a microsecond-pulsed laser. Invest Ophthalmol Vis Sci, no. 56, pp. 122-31, 2015
    BibTeX Link
    @article{Kim2015,
       author = {Kim, H. D. and Han, J. W. and Ohn, Y. H. and Brinkmann, R. and Park, T. K.},
       title = {Functional evaluation using multifocal electroretinogram after selective retina therapy with a microsecond-pulsed laser},
       journal = {Invest Ophthalmol Vis Sci},
       volume = {56},
       number = {1},
       pages = {122-31},
       note = {1552-5783
    Kim, Hoon Dong
    Han, Jung Woo
    Ohn, Young-Hoon
    Brinkmann, Ralf
    Park, Tae Kwann
    Journal Article
    United States
    Invest Ophthalmol Vis Sci. 2014 Dec 11;56(1):122-31. doi: 10.1167/iovs.14-15132.},
       abstract = {PURPOSE: To evaluate the changes of retinal function with multifocal electroretinogram (mfERG), and estimate the association between functional and structural changes after selective retina therapy (SRT) with microsecond-pulsed laser in comparison to continuous wave laser photocoagulation (cwPC). METHODS: Selective retina therapy and cwPC were applied with 10 x 10 shots and 1/2 lesion-width on the retina in the right and left eyes of 20 healthy Chinchilla Bastard rabbits, respectively. Optical coherence tomography (OCT), fundus fluorescein angiography (FFA), and mfERG were performed before, and on days 1, 7, and 30 after both laser treatments. The mean ratios of amplitudes and implicit times of N1 and P1 from eight hexagons covering laser-treated retinal lesions/total retina were measured. Histology was obtained after killing three rabbits at each time period to observe the anatomic changes after both laser treatments. RESULTS: The mean ratios of amplitudes of N1 and P1 in SRT lesions did not change significantly for 30 days after laser treatment. Only subtle reductions of the mean ratios of N1 and P1 amplitudes on day 1, thereafter the amplitudes showed the trend to recover toward baseline values. Histology and OCT revealed temporary and reversible morphologic changes after SRT, which restored to normal within 1 month. However, the mean ratios of N1 amplitudes on days 7 and 30 (P = 0.010, P < 0.001, respectively), and P1 amplitudes on days 7 and 30 (P < 0.001, P < 0.001, respectively) declined significantly in cwPC lesions compared with baseline. Disorganization and atrophic changes were identified on histology and OCT after cwPC. CONCLUSIONS: The results suggest that SRT preserved retinal function as well as anatomical structure after treatment.},
       keywords = {continuous wave laser photocoagulation (cwPC)
    multifocal electroretinogram (mfERG)
    selective retina therapy (SRT)},
       ISSN = {0146-0404},
       DOI = {10.1167/iovs.14-15132},
       year = {2015},
       type = {Journal Article}
    }
    

2014

  • Koinzer, S. and Bajorat, S. and Hesse, C. and Caliebe, A. and Bever, M. and Brinkmann, R. and Roecken, C. and Roider, J.: Calibration of histological retina specimens after fixation in Margo`s solution and paraffin embedding to in-vivo dimensions, using photography and optical coherence tomography. Graefes Arch Clin Exp Ophthalmol, no. 252, pp. 145-53, 2014
    BibTeX Link
    @article{Koinzer2014,
       author = {Koinzer, S. and Bajorat, S. and Hesse, C. and Caliebe, A. and Bever, M. and Brinkmann, R. and Roecken, C. and Roider, J.},
       title = {Calibration of histological retina specimens after fixation in Margo's solution and paraffin embedding to in-vivo dimensions, using photography and optical coherence tomography},
       journal = {Graefes Arch Clin Exp Ophthalmol},
       volume = {252},
       number = {1},
       pages = {145-53},
       note = {1435-702x
    Koinzer, Stefan
    Bajorat, Sandra
    Hesse, Carola
    Caliebe, Amke
    Bever, Marco
    Brinkmann, Ralf
    Roecken, Christoph
    Roider, Johann
    Journal Article
    Research Support, Non-U.S. Gov't
    Germany
    Graefes Arch Clin Exp Ophthalmol. 2014 Jan;252(1):145-53. doi: 10.1007/s00417-013-2457-6. Epub 2013 Sep 14.},
       abstract = {BACKGROUND: The extent of retinal tissue deformation by histological processing needs to be separately measured for every workup protocol. This work presents a simple approach for its quantitative assessment, and shows lateral and axial scaling factors for a common protocol. We calibrated histological measurements by in-vivo photographic and optical coherence tomographic (OCT) measurements, using retinal photocoagulation lesions as calibration markers. METHODS: We evaluated four rabbit eyes that were examined histologically after fixation in Margo's solution (1 % paraformaldehyde:1.25 % glutaraldehyde), isopropanol dehydration, paraffin embedding and hematoxylin and eosin staining. Distances between 51 pairs of laser lesions were compared in photographs and on histological slides. Retinal thickness measurements were performed at 15 anatomically defined sites in these eyes, and related to anatomically matched OCT thickness measurements of six different rabbit eyes. RESULTS: We found that the ratio of histological over photographic lesion distances was 1.17 (95 % CI 1.13-1.22), indicating 17 % lateral retinal stretching or expansion by the processing. Thickness measurements in histology were 65.6 % of the in-vivo thickness as measured in OCT, indicating 1/3 axial tissue compression or shrinkage. CONCLUSIONS: We provide an analysis of retinal tissue deformation after fixation in Margo's solution and paraffin embedding. In spite of protocol optimization for reduced tissue deformation, the workup caused 1/3 axial compression/shrinkage and 17 % lateral elongation, which was unexpected. We show a simple way how to calibrate retina specimens by fundus photography and OCT, two methods that are readily available to most ophthalmologists. Our findings underline the necessity to calibrate specimens prior to morphometry.},
       keywords = {Animals
    Calibration
    *Histological Techniques
    Laser Coagulation
    *Paraffin Embedding
    Photography/*methods
    Rabbits
    *Retina
    *Tissue Fixation
    Tomography, Optical Coherence/*methods},
       ISSN = {0721-832x},
       DOI = {10.1007/s00417-013-2457-6},
       year = {2014},
       type = {Journal Article}
    }
    
  • Rohde, Ingo and Brinkmann, Ralf: Gain broadening and mode-locking in overcoupled second harmonic Q-switched microsecond pulses. Journal of Optics, no. 16, pp. 105209, 2014
    BibTeX
    @article{Rohde2014,
       author = {Rohde, Ingo and Brinkmann, Ralf},
       title = {Gain broadening and mode-locking in overcoupled second harmonic Q-switched microsecond pulses},
       journal = {Journal of Optics},
       volume = {16},
       number = {10},
       pages = {105209},
       abstract = {An intracavity frequency doubled, Q-switched Nd:YLF emitting at a wavelength of 527 nm was designed with the goal to temporally stretch the Q-switched pulses up to some microseconds at pulse energies of several millijoules. With different resonator configurations pulse durations between 12 μ s and 3 μ s with energies of 1 mJ–4.5 mJ have been achieved, which is demanded for an application in ophthalmology. For tighter intracavity foci and high pump power, however, strong power modulations by trains of picosecond pulses on the rear flank of the microsecond pulses were observed, indicating the occurrence of cascading nonlinearities and mode-locking. Simultaneously a significant increase of the fundamental spectrum up to 5 nm was found. A similar effect, which is referred to as gain broadening, has previously been observed by using ppKTP for intracavity second harmonic generation. This is, to the best of our knowledge, the first observation of this effect with unpoled second harmonic media.},
       ISSN = {2040-8986},
       url = {http://stacks.iop.org/2040-8986/16/i=10/a=105209},
       year = {2014},
       type = {Journal Article}
    }
    
  • Buj, C and Horstmann, J and Münter, M and Brinkmann, R: Speckle-based holographic detection for non-contact Photoacoustic Tomography. in 48th annual conference of the German Society for Biomedical Engineering, no. 59, pp. 844-847,
    BibTeX
    @inproceedings{Buj14,
       author = {Buj, C and Horstmann, J and Münter, M and Brinkmann, R},
       title = {Speckle-based holographic detection for non-contact Photoacoustic Tomography},
       booktitle = {48th annual conference of the German Society for Biomedical Engineering},
       volume = {59},
       pages = {844-847},
       type = {Conference Proceedings}
    }
    
    
  • Koinzer, S. and Caliebe, A. and Portz, L. and Saeger, M. and Miura, Y. and Schlott, K. and Brinkmann, R. and Roider, J.: Comprehensive detection, grading, and growth behavior evaluation of subthreshold and low intensity photocoagulation lesions by optical coherence tomographic and infrared image analysis. Biomed Res Int, no. 2014, pp. 492679, 2014
    BibTeX Link
    @article{Koinzer2014,
       author = {Koinzer, S. and Caliebe, A. and Portz, L. and Saeger, M. and Miura, Y. and Schlott, K. and Brinkmann, R. and Roider, J.},
       title = {Comprehensive detection, grading, and growth behavior evaluation of subthreshold and low intensity photocoagulation lesions by optical coherence tomographic and infrared image analysis},
       journal = {Biomed Res Int},
       volume = {2014},
       pages = {492679},
       note = {2314-6141
    Koinzer, Stefan
    Caliebe, Amke
    Portz, Lea
    Saeger, Mark
    Miura, Yoko
    Schlott, Kerstin
    Brinkmann, Ralf
    Roider, Johann
    Journal Article
    Research Support, Non-U.S. Gov't
    United States
    Biomed Res Int. 2014;2014:492679. doi: 10.1155/2014/492679. Epub 2014 May 12.},
       abstract = {PURPOSE: To correlate the long-term clinical effect of photocoagulation lesions after 6 months, as measured by their retinal damage size, to exposure parameters. We used optical coherence tomographic (OCT)-based lesion classes in order to detect and assess clinically invisible and mild lesions. METHODS: In this prospective study, 488 photocoagulation lesions were imaged in 20 patients. We varied irradiation diameters (100/300 microm), exposure-times (20-200 ms), and power. Intensities were classified in OCT images after one hour, and we evaluated OCT and infrared (IR) images over six months after exposure. RESULTS: For six consecutive OCT-based lesion classes, the following parameters increased with the class: ophthalmoscopic, OCT and IR visibility rate, fundus and OCT diameter, and IR area, but not irradiation power. OCT diameters correlated with exposure-time, irradiation diameter, and OCT class. OCT classes discriminated the largest bandwidth of OCT diameters. CONCLUSION: OCT classes represent objective and valid endpoints of photocoagulation intensity even for "subthreshold" intensities. They are suitable to calculate the treated retinal area. As the area is critical for treatment efficacy, OCT classes are useful to define treatment intensity, calculate necessary lesion numbers, and universally categorize lesions in clinical studies.},
       DOI = {10.1155/2014/492679},
       url = {http://dx.doi.org/10.1155/2014/492679},
       year = {2014},
       type = {Journal Article}
    }
    
  • Iwami, H. and Pruessner, J. and Shiraki, K. and Brinkmann, R. and Miura, Y.: Protective effect of a laser-induced sub-lethal temperature rise on RPE cells from oxidative stress. Exp Eye Res, no. 124c, pp. 37-47, 2014
    BibTeX Link
    @article{Iwami2014,
       author = {Iwami, H. and Pruessner, J. and Shiraki, K. and Brinkmann, R. and Miura, Y.},
       title = {Protective effect of a laser-induced sub-lethal temperature rise on RPE cells from oxidative stress},
       journal = {Exp Eye Res},
       volume = {124c},
       pages = {37-47},
       note = {1096-0007
    Iwami, Hisashi
    Pruessner, Joachim
    Shiraki, Kunihiko
    Brinkmann, Ralf
    Miura, Yoko
    Journal article
    Exp Eye Res. 2014 May 5;124C:37-47. doi: 10.1016/j.exer.2014.04.014.},
       abstract = {Recently introduced new technologies that enable temperature-controlled laser irradiation on the RPE allowed us to investigate temperature-resolved RPE cell responses. In this study we aimed primarily to establish an experimental setup that can realize laser irradiation on RPE cell culture with the similar temperature distribution as in the clinical application, with a precise time/temperature history. With this setup, we conducted investigations to elucidate the temperature-dependent RPE cell biochemical responses and the effect of transient hyperthermia on the responses of RPE cells to the secondary-exposed oxidative stress. Porcine RPE cells cultivated in a culture dish (inner diameter = 30 mm) with culture medium were used, on which laser radiation (lambda = 1940 nm, spot diameter = 30 mm) over 10 s was applied as a heat source. The irradiation provides a radially decreasing temperature profile which is close to a Gaussian shape with the highest temperature in the center. Power setting for irradiation was determined such that the peak temperature (Tmax) in the center of the laser spot at the cells reaches from 40 degrees C to 58 degrees C (40, 43, 46, 50, 58 degrees C). Cell viability was investigated with ethidium homodimer III staining at the time points of 3 and 24 h following laser irradiation. Twenty four hours after laser irradiation the cells were exposed to hydrogen peroxide (H2O2) for 5 h, followed by the measurement of intracellular glutathione, intracellular 4-hydroxynonenal (HNE) protein adducts, and secreted vascular endothelial growth factor (VEGF). The mean temperature threshold for RPE cell death after 3 h was found to be around 52 degrees C, and for 24 h around 50 degrees C with the current irradiation setting. A sub-lethal preconditioning on Tmax = 43 degrees C significantly induced the reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio, and decreased H2O2-induced increase of intracellular 4-HNE protein adducts. Although sub-lethal hyperthermia (Tmax = 40 degrees C, 43 degrees C, and 46 degrees C) caused a slight increase of VEGF secretion in 6 h directly following irradiation, secondary exposed H2O2-induced VEGF secretion was significantly reduced in the sub-lethally preheated groups, where the largest effect was seen following the irradiation with Tmax = 43 degrees C. In summary, the current results suggest that sub-lethal thermal laser irradiation on the RPE at Tmax = 43 degrees C for 10 s enhances cell defense system against oxidative stress, with increasing the GSH/GSSG ratio. Together with the results that the decreased amount of H2O2-induced 4-HNE in sub-lethally preheated RPE cells was accompanied by the lower secretion of VEGF, it is also strongly suggested that the sub-lethal hyperthermia may modify RPE cell functionality to protect RPE cells from oxidative stress and associated functional decrease, which are considered to play a significant role in the pathogenesis of age-related macular degeneration and other chorioretinal degenerative diseases.},
       ISSN = {0014-4835},
       DOI = {10.1016/j.exer.2014.04.014},
       year = {2014},
       type = {Journal Article}
    }
    
  • Rohde, I. and Masch, J. M. and Theisen-Kunde, D. and Marczynski-Bühlow, M. and Bombien Quaden, R. and Lutter, G. and Brinkmann, R.: Resection of Calcified Aortic Heart Leaflets In Vitro by Q-Switched 2 µm Microsecond Laser Radiation. Journal of Cardiac Surgery, no. 30, pp. 157-162, 2014
    BibTeX Link
    @article{Rohde2014,
       author = {Rohde, I. and Masch, J. M. and Theisen-Kunde, D. and Marczynski-Bühlow, M. and Bombien Quaden, R. and Lutter, G. and Brinkmann, R.},
       title = {Resection of Calcified Aortic Heart Leaflets In Vitro by Q-Switched 2 µm Microsecond Laser Radiation},
       journal = {Journal of Cardiac Surgery},
       volume = {30},
       number = {2},
       pages = {157-162},
       ISSN = {1540-8191},
       DOI = {10.1111/jocs.12481},
       url = {http://dx.doi.org/10.1111/jocs.12481},
       year = {2014},
       type = {Journal Article}
    }
    

2013

  • Miura, Y and Huettmann, G and Orzekowsky-Schroeder, R and Steven, P and Szaszák, M and Koop, N and Brinkmann, R: Two-photon Microscopy and Fluorescence Lifetime Analysis of Lipid Peroxidation Product in Photoreceptor Outer Segment and in Retinal Pigment Epithelial Cell. ARVO Meeting Abstracts, March 26, 2012, 2013
    BibTeX Link
    @misc{Miura2013,
       author = {Miura, Y and Huettmann, G and Orzekowsky-Schroeder, R and Steven, P and Szaszák, M and Koop, N and Brinkmann, R },
       title = {Two-photon Microscopy and Fluorescence Lifetime Analysis of Lipid Peroxidation Product in Photoreceptor Outer Segment and in Retinal Pigment Epithelial Cell},
       publisher = {ARVO Meeting Abstracts},
       month = {March 26, 2012 },
       url = {http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=57630548-893d-4e45-9ddc-b6f547dd4ff0&cKey=d08a30bc-fe98-40a2-8a1c-1b171e4becd3&mKey=f0fce029-9bf8-4e7c-b48e-9ff7711d4a0e},
       year = {2013},
       type = {Poster}
    }
    
  • Cordes, Jens and Nguyen, Felix and Lange, Birgit and Brinkmann, Ralf and Jocham, Dieter: Damage of Stone Baskets by Endourologic Lithotripters: A Laboratory Study of 5 Lithotripters and 4 Basket Types. Advances in Urology, no. 2013, pp. 6, 2013
    BibTeX Link
    @article{Cordes2013,
       author = {Cordes, Jens and Nguyen, Felix and Lange, Birgit and Brinkmann, Ralf and Jocham, Dieter},
       title = {Damage of Stone Baskets by Endourologic Lithotripters: A Laboratory Study of 5 Lithotripters and 4 Basket Types},
       journal = {Advances in Urology},
       volume = {2013},
       pages = {6},
       DOI = {10.1155/2013/632790},
       url = {http://dx.doi.org/10.1155/2013/632790},
       year = {2013},
       type = {Journal Article}
    }
    
  • Brinkmann, Ralf and Iwami, Hisashi and Pruessner, Joachim and Danicke, Veit and Miura, Yoko: Temperature-dependent response of retinal pigment epithelial cells to laser irradiation. Invest. Ophthalmol. Vis. Sci., no. 54, pp. 1809-, 2013
    BibTeX Link
    @article{Brinkmann2013,
       author = {Brinkmann, Ralf and Iwami, Hisashi and Pruessner, Joachim and Danicke, Veit and Miura, Yoko},
       title = {Temperature-dependent response of retinal pigment epithelial cells to laser irradiation},
       journal = {Invest. Ophthalmol. Vis. Sci.},
       volume = {54},
       number = {6},
       pages = {1809-},
       abstract = {PurposeSublethal thermal therapy of the retinal pigment epithelium (RPE) is discussed as a new prophylactic therapy for age-related macular degeneration. However, temperature-dependent RPE cell effects have not been well elucidated. We investigated the biochemical responses of RPE cells following sublethal to lethal thermal laser irradiation. MethodsPorcine RPE cells cultured in a dish (33mm) were heated with a Thulium laser (1.92{micro}m, 1-20W, 10s) over a spot of 3mm. Temperatures during irradiation were measured with thermocouples. Cell viability was examined using annexin-V, ethidium homodimer III and Hoechst 33342 for detecting apoptotic, necrotic and living cell, respectively, by using fluorescence microscopy for localization and flow cytometry for quantification. Secretion of vascular endothelial growth factor (VEGF) for 6h following irradiation on different temperatures was assessed with Elisa assay. In order to examine a protective effect of sublethal hyperthremia, the cells were heated up to 45C 24h prior to the exposure of 2 mM hydroxyl peroxide (H2O2) for 5 h. The involvement of TRPV (Transient Receptor Potential Vanilloid)-1 receptor, which is activated with temperatures > 43C, was investigated by adding capsazepin, a TRPV-1 inhibitor, before irradiation. ResultsCell apoptosis and necrosis was observed 24 h after irradiation with a central peak temperature [&ge;]52C. Fluorescence microscopy revealed apoptotic cells around the central necrotic area. VEGF secretion for 6h after irradiation was significantly increased at peak temperatures between 40 and 52C in a temperature dependent manner (max. 110%, p<0.05), whereas the total secretion decreases with temperatures > 52C. Pre-irradiation onto 45C significantly reduced H2O2-induced cell death after 5h compared to non-heated cells (total cell death: 15.6% to 10.2%, necrosis: 6% to 4 %, early apoptosis: 5.1% to 3.6%; p<0.01). These effects were not observed in the existence of capsazepin during laser irradiation. ConclusionsThe number of apoptotic and necrotic RPE cells increase at least over 24h following thermal laser irradiation. Sublethal temperatures between 40 and 52C seem to induce various cellular responses as VEGF secretion, which might be related to the protective effect against oxidative stress. Results with capsazepin suggest that TRPV-1 channel activation by hyperthermia is essential to exert this protective effect.},
       url = {http://abstracts.iovs.org/cgi/content/abstract/54/6/1809},
       year = {2013},
       type = {Journal Article}
    }
    
  • Bliedtner, Kathrin and Seifert, Eric and Brinkmann, Ralf: Temperature induced tissue deformation monitored by dynamic speckle interferometry. in Studierendentagung, Universität zu Lübeck,
    BibTeX
    @inproceedings{Bliedtner2013,
       author = {Bliedtner, Kathrin and Seifert, Eric and Brinkmann, Ralf},
       title = {Temperature induced tissue deformation monitored
    by dynamic speckle interferometry},
       booktitle = {Studierendentagung},
       publisher = {Universität zu Lübeck},
       type = {Conference Proceedings}
    }
    
  • Horstmann, Jens and Brinkmann, Ralf: Non-contact photoacoustic tomography using holographic full field detection. no. 8800, pp. 880007-880007-6, Proc. SPIE,
    BibTeX Link
    @inproceedings{Horstmann2013,
       author = {Horstmann, Jens and Brinkmann, Ralf},
       title = {Non-contact photoacoustic tomography using holographic full field detection},
       publisher = {Proc. SPIE},
       volume = {8800},
       pages = {880007-880007-6},
       note = {10.1117/12.2033599},
       abstract = {An innovative very fast non-contact imaging technique for Photoacoustic Tomography is introduced. It is based on holographic optical speckle detection of a transiently altering surface topography for the reconstruction of absorbing targets. The surface movement is obtained by parallel recording of speckle phase changes known as Electronic Speckle Pattern Interferometry. Due to parallelized 2-D camera detection and repetitive excitation with variable delay with respect to the image acquisition, data recording of whole volumes for Photoacoustic Imaging can be completed in times far below one second. The size of the detected area is scalable by optical magnification. As a proof of concept, an interferometric setup is realized, capable of surface displacement detection with an axial resolution of less than 3 nm. The potential of the proposed method for in vivo Photoacoustic Imaging is discussed.},
       url = {http://dx.doi.org/10.1117/12.2033599},
       type = {Conference Proceedings}
    }
    
  • Rohde, Ingo and Masch, Jennifer- M. and Theisen-Kunde, Dirk and Marczynski-Bühlow, Martin and Lutter, Georg and Brinkmann, Ralf: Cardiovascular damage after cw and Q-switched 2μm laser irradiation. no. 8803, pp. 88030I-88030I-6,
    BibTeX Link
    @inproceedings{Rohde2013,
       author = {Rohde, Ingo and Masch, Jennifer- M. and Theisen-Kunde, Dirk and Marczynski-Bühlow, Martin and Lutter, Georg and Brinkmann, Ralf},
       title = {Cardiovascular damage after cw and Q-switched 2μm laser irradiation},
       volume = {8803},
       pages = {88030I-88030I-6},
       note = {10.1117/12.2033550},
       abstract = {Aiming for laser-assisted resection of calcified aortic valve structures for Transcatheter Aortic Valve Implantation (TAVI), a Q-switched Tm:YAG laser emitting at a wavelength of 2.01 μm was used to evaluate the cutting efficiency on highly calcified human aortic leaflets in-vitro. The calcified aortic leaflets were examined regarding ablation rates and debris generation, using a pulse energy of 4.3 mJ, a pulse duration of 0.8-1 μs and a repetition rate of 1 kHz. The radiation was transmitted via a 200 μm core diameter quartz fiber. Resection was performed in a fiber-tissue contact mode on water-covered samples in a dish. The remnant particles were analyzed with respect to quantity and size by light microscopy. Additionally, soft tissue of porcine aortic vessels was examined for histologically detectable thermo-mechanical damage after continuous wave and Q-switched 2μm laser irradiation. An ablation rate of 36.7 ± 25.3 mg/min could be realised on highly calcified aortic leaflets, with 85.4% of the remnant particles being &lt;6 μm in diameter. The maximum damaged area of the soft tissue was &lt; 1 mm for both, cw and pulsed laser irradiation. This limits the expected collateral damage of healthy tissue during the medical procedure. Overall, the Q-switched Tm:YAG laser system showed promising results in cutting calcified aortic valves, transmitting sufficient energy through a small flexible fibre.},
       url = {http://dx.doi.org/10.1117/12.2033550},
       type = {Conference Proceedings}
    }
    
  • Seifert, Eric and Roh, Young-Jung and Fritz, Andreas and Park, Young Gun and Kang, Seungbum and Theisen-Kunde, Dirk and Brinkmann, Ralf: Automatic irradiation control by an optical feedback technique for selective retina treatment (SRT) in a rabbit model. no. 8803, pp. 880303-880303-6,
    BibTeX Link
    @inproceedings{Seifert2013,
       author = {Seifert, Eric and Roh, Young-Jung and Fritz, Andreas and Park, Young Gun and Kang, Seungbum and Theisen-Kunde, Dirk and Brinkmann, Ralf},
       title = {Automatic irradiation control by an optical feedback technique for selective retina treatment (SRT) in a rabbit model},
       volume = {8803},
       pages = {880303-880303-6},
       note = {10.1117/12.2033560},
       abstract = {Selective Retina Therapy (SRT) targets the Retinal Pigment Epithelium (RPE) without effecting neighboring layers as the photoreceptors or the choroid. SRT related RPE defects are ophthalmoscopically invisible. Owing to this invisibility and the variation of the threshold radiant exposure for RPE damage the treating physician does not know whether the treatment was successful or not. Thus measurement techniques enabling a correct dosing are a demanded element in SRT devices. The acquired signal can be used for monitoring or automatic irradiation control. Existing monitoring techniques are based on the detection of micro-bubbles. These bubbles are the origin of RPE cell damage for pulse durations in the ns and μs time regime 5μs. The detection can be performed by optical or acoustical approaches. Monitoring based on an acoustical approach has already been used to study the beneficial effects of SRT on diabetic macula edema and central serous retinopathy. We have developed a first real time feedback technique able to detect micro-bubble induced characteristics in the backscattered laser light fast enough to cease the laser irradiation within a burst. Therefore the laser energy within a burst of at most 30 pulses is increased linearly with every pulse. The laser irradiation is ceased as soon as micro-bubbles are detected. With this automatic approach it was possible to observe invisible lesions, an intact photoreceptor layer and a reconstruction of the RPE within one week.},
       url = {http://dx.doi.org/10.1117/12.2033560},
       type = {Conference Proceedings}
    }
    
  • Baade, Alexander and Schlott, Kerstin and Birngruber, Reginald and Brinkmann, Ralf: A numerical model for heat and pressure propagation for temperature controlled retinal photocoagulation. no. 8803, pp. 88030O-88030O-9,
    BibTeX Link
    @inproceedings{Baade2013,
       author = {Baade, Alexander and Schlott, Kerstin and Birngruber, Reginald and Brinkmann, Ralf},
       title = {A numerical model for heat and pressure propagation for temperature controlled retinal photocoagulation},
       volume = {8803},
       pages = {88030O-88030O-9},
       note = {10.1117/12.2033590},
       abstract = {Retinal photocoagulation is an established treatment for various retinal diseases. The temperature development during a treatment can be monitored by applying short laser pulses in addition to the treatment laser light. The laser pulses induce thermoelastic pressure waves that can be detected at the cornea. We present a numerical model to examine the temperature development during the treatment as well as the formation and propagation of the ultrasonic waves. Using the model, it is possible to determine the peak temperature during retinal photocoagulation from the measured signal, and investigate the behaviour of the temperature profile and the accuracy of the temperature determination under varying conditions such as inhomogeneous pigmentation or change in irradiation parameters. It was shown that there is an uncertainty of 2.5 -9% in the determination of the peak temperature when the absorption coefficient between the absorbing layers is varied by a factor of 2. Furthermore the model was extended in order to incorporate the photoacoustic pressure generation and wave propagation. It was shown that for an irradiation pulse duration of 75 ns the resulting pressure wave energy is attenuated by 76 % due to frequency dependent attenuation in water.},
       url = {http://dx.doi.org/10.1117/12.2033590},
       type = {Conference Proceedings}
    }
    
  • Koinzer, Stefan and Saeger, Mark and Hesse, Carola and Portz, Lea and Kleemann, Susanne and Schlott, Kerstin and Brinkmann, Ralf and Roider, Johann: Correlation with OCT and histology of photocoagulation lesions in patients and rabbits. Acta Ophthalmologica, pp. no-no, 2013
    BibTeX Link
    @article{Koinzer2013,
       author = {Koinzer, Stefan and Saeger, Mark and Hesse, Carola and Portz, Lea and Kleemann, Susanne and Schlott, Kerstin and Brinkmann, Ralf and Roider, Johann},
       title = {Correlation with OCT and histology of photocoagulation lesions in patients and rabbits},
       journal = {Acta Ophthalmologica},
       pages = {no-no},
       abstract = {Purpose:  To examine spectral domain optical coherence tomographic (OCT) and histological images from comparable retinal photocoagulation lesions in rabbits, and to correlate these images with comparable OCT images from patients. Methods:  508 rabbit lesions were examined by HE-stained paraffin histology. 1019 rabbit lesions versus 236 patient lesions were examined by OCT, all at the time-points 1 hr, 1 week and 4 weeks after photocoagulation. We analysed 100 μm lesions (in humans) and 133 μm lesions (in rabbits) of 200 ms exposures at powers titrated from the histological threshold up to intense damage. Lesions were matched according to morphological criteria. Results:  Dome-shaped layer alterations, retinal infiltration by round, pigmented cells, outer nuclear layer interruption, and eventually full thickness retinal coagulation are detectable in histology and OCT. Horizontal damage extensions are found 1½ times larger in OCT. More intense irradiation was necessary to induce comparable layer affection in rabbit OCT as in histology. Restoration of the inner retinal layers is only shown in the OCT images. Comparable primary lesions caused more pronounced OCT changes in patients than in rabbits during healing. Conclusions:  Optical coherence tomographic images indicate different tissue changes than histologic images. After photocoagulation, they show wider horizontal damage diameters, but underestimate axial damage particularly during healing. Conclusions on retinal restoration should not be drawn from OCT findings alone. Retinal recovery after comparable initial lesions appears to be more complete in rabbit than in patient OCTs.},
       keywords = {histology
    laser
    optical coherence tomography
    photocoagulation
    retina
    retinal healing},
       year = {2013}
    }
    
  • Miura, Y. and Huettmann, G. and Orzekowsky-Schroeder, R. and Steven, P. and Szaszak, M. and Koop, N. and Brinkmann, R.: Two-Photon Microscopy and Fluorescence Lifetime Imaging of Retinal Pigment Epithelial Cells under Oxidative Stress. Invest Ophthalmol Vis Sci, 2013
    BibTeX Link
    @article{Miura2013,
       author = {Miura, Y. and Huettmann, G. and Orzekowsky-Schroeder, R. and Steven, P. and Szaszak, M. and Koop, N. and Brinkmann, R.},
       title = {Two-Photon Microscopy and Fluorescence Lifetime Imaging of Retinal Pigment Epithelial Cells under Oxidative Stress},
       journal = {Invest Ophthalmol Vis Sci},
       note = {Miura, Yoko
    Huettmann, Gereon
    Orzekowsky-Schroeder, Regina
    Steven, Philipp
    Szaszak, Marta
    Koop, Norbert
    Brinkmann, Ralf
    ENG
    2013/04/06 06:00
    Invest Ophthalmol Vis Sci. 2013 Apr 4. pii: iovs.13-11808v1. doi: 10.1167/iovs.13-11808.},
       abstract = {PURPOSE: The aim of this study was to investigate the autofluorescence (AF) of the RPE with two-photon microscopy (TPM) and fluorescence lifetime imaging (FLIM) under normal and oxidative stress conditions. METHODS: Porcine RPE-choroid explants were used for investigation. The RPE-choroid tissue was preserved in a perfusion organ culture system. Oxidative stress was induced by laser photocoagulation with frequency-doubled Nd:YAG laser (532 nm) and by exposure to different concentrations (0, 1, 10 mM) of ferrous sulfate (FeSO4) for 1 hr. At indicated time points after exposure, the tissue was examined with TPM and FLIM. Intracellular reactive oxygen species around the photocoagulation lesion were detected with chloromethyl-2'7'-dichlorofluorescein diacetate (CM-H2DCFDA). Melanosomes were isolated from RPE cells and its fluorescence properties were investigated under normal and oxidized conditions. RESULTS: Under normal condition, AF in RPE cells with TPM is mostly originated from melanosomes, which has a very short fluorescence lifetime (FLT) (mean=117 ps). Under oxidative stress induced by laser irradiation and FeSO4 exposure, bright granular AF appears inside and around RPE cells, whose FLT is significantly longer (mean=1388 ps) than the FLT of the melanosome-AF. Excitation and emission peaks are found at 710-750 nm and 450-500 nm, respectively. Oxidative stress increases the fluorescence intensity of the melanosomes but does not change their FLT. CONCLUSION: TPM reveals acute oxidative stress-induced bright AF granules inside and around RPE cells which can be clearly discriminated from melanosomes by FLIM. TPM combined with FLIM is a useful tool of live-cell analysis to investigate functional alterations of the RPE.},
       year = {2013}
    }
    

2012

  • Treumer, F. and Klettner, A. and Baltz, J. and Hussain, A. A. and Miura, Y. and Brinkmann, R. and Roider, J. and Hillenkamp, J.: Vectorial release of matrix metalloproteinases (MMPs) from porcine RPE-choroid explants following selective retina therapy (SRT): towards slowing the macular ageing process. Exp Eye Res, no. 97, pp. 63-72, 2012
    BibTeX Link
    @article{Treumer2012,
       author = {Treumer, F. and Klettner, A. and Baltz, J. and Hussain, A. A. and Miura, Y. and Brinkmann, R. and Roider, J. and Hillenkamp, J.},
       title = {Vectorial release of matrix metalloproteinases (MMPs) from porcine RPE-choroid explants following selective retina therapy (SRT): towards slowing the macular ageing process},
       journal = {Exp Eye Res},
       volume = {97},
       number = {1},
       pages = {63-72},
       note = {1096-0007
    Treumer, F
    Klettner, A
    Baltz, J
    Hussain, A A
    Miura, Y
    Brinkmann, R
    Roider, J
    Hillenkamp, J
    Journal Article
    England
    Exp Eye Res. 2012 Apr;97(1):63-72. doi: 10.1016/j.exer.2012.02.011. Epub 2012 Feb 22.},
       abstract = {The purpose of this study was to investigate release of matrix metalloproteinases (MMP) 2 and 9 during retinal pigment epithelium (RPE) wound healing after Selective Retina Therapy (SRT) with laser energy levels below and above the threshold of RPE cell death. Following exposure to SRT using a prototype pulsed Nd:YLF laser with energies of 80-180 mJ/cm(2) fresh porcine RPE-monolayers with Bruch's membrane and choroid were cultured in modified Ussing chambers which separate the apical (RPE-facing) and basal (choroid facing) sides of the RPE monolayer. Threshold energy for RPE cell death and wound healing were determined with calcein-AM viability test. Inactive and active forms of MMP 2 and 9 were quantified within tissue samples and in the culture medium of the apical and basal compartments of the Ussing chamber using gelatine zymography. Laser energies of 160-180 mJ/cm(2) resulted in cell death within 1 h while 120-140 mJ/cm(2) resulted in delayed death of exposed RPE cells. All cells survived 80 and 100 mJ/cm(2). Laser spots healed within 6 days after SRT accompanied by a transient vectorial increase of MMPs. SRT with 180 mJ/cm(2) increased active MMP 2 by 1.9 (p < 0.05) and 1.6 (p < 0.05) fold in tissue and basal compartments, respectively, without alterations in the apical compartment. Pro-MMP 2 levels were also significantly increased in all compartments (p < 0.05). Release of MMP 9 was not altered. Laser energy below the threshold of RPE cell death did not alter the release of MMP 2 or 9. The findings suggest that the release of active MMP 2 on the basal side of the RPE during wound healing following SRT may address age-related pathological changes of Bruch's membrane with a potential to slow degenerative macular ageing processes before irreversible functional loss has occurred.},
       keywords = {Animals
    Cell Death
    Cell Survival
    Choroid/*enzymology/pathology
    Diffusion Chambers, Culture
    Fluoresceins/metabolism
    *Laser Therapy
    Lasers, Solid-State
    Macular Degeneration/enzymology/pathology/*surgery
    Matrix Metalloproteinase 2/*metabolism
    Matrix Metalloproteinase 9/*metabolism
    Organ Culture Techniques
    Retinal Pigment Epithelium/*enzymology/pathology
    Sensory Thresholds
    Swine
    Wound Healing/*physiology},
       ISSN = {0014-4835},
       DOI = {10.1016/j.exer.2012.02.011},
       year = {2012},
       type = {Journal Article}
    }
    
  • Rohde, Ingo and Brinkmann, Ralf and Theisen-Kunde, Dirk: Temporally stretched Q-switched pulses in the 2 µm spectral range. Laser Physics Letters, no. 9, pp. 808-813, 2012
    BibTeX
    @article{Rohde2012,
       author = {Rohde, Ingo and Brinkmann, Ralf and Theisen-Kunde, Dirk},
       title = {Temporally stretched Q-switched pulses in the 2 µm spectral range},
       journal = {Laser Physics Letters},
       volume = {9},
       number = {11},
       pages = {808-813},
       year = {2012}
    }
    
  • Koinzer, S. and Schlott, K. and Ptaszynski, L. and Bever, M. and Kleemann, S. and Saeger, M. and Baade, A. and Caliebe, A. and Miura, Y. and Birngruber, R. and Brinkmann, R. and Roider, J.: Temperature-controlled retinal photocoagulation - a step toward automated laser treatment. Invest Ophthalmol Vis Sci, no. 53, pp. 3605-14, 2012
    BibTeX
    @article{Koinzer2012,
       author = {Koinzer, S. and Schlott, K. and Ptaszynski, L. and Bever, M. and Kleemann, S. and Saeger, M. and Baade, A. and Caliebe, A. and Miura, Y. and Birngruber, R. and Brinkmann, R. and Roider, J.},
       title = {Temperature-controlled retinal photocoagulation - a step toward automated laser treatment},
       journal = {Invest Ophthalmol Vis Sci},
       volume = {53},
       number = {7},
       pages = {3605-14},
       note = {Using Smart Source Parsing
    Jun 14; Print 2012 Jul},
       abstract = {Purpose. Retinal laser photocoagulation carries the risk of overtreatment due to effect variation of identically applied lesions. The degree of coagulation depends on the induced temperature increase and on exposure time. We introduce temperature controlled photocoagulation (TCP), which uses optoacoustics to determine individually exposure times necessary to create reproducible lesions. Methods. Optoacoustic temperature measurement relies on pressure waves that are excited in the retinal tissue by repetitive low-energy laser pulses. Signal amplitudes correlate with tissue temperature and are detected by a transducer in the laser contact lens. We used a continuous wave (CW) photocoagulator for treatment irradiation and superimposed probe laser pulses for simultaneous temperature measurement. Optoacoustic data of 1500 lesions (rabbit) were evaluated to develop an algorithm that controls exposure times automatically in TCP. Lesion diameters of 156 TCP lesions were compared to 156 non-controlled lesions. Histology was performed after 1 hour, and 1 and 4 weeks. Results. TCP resulted in exposure times from 4 to 800 ms depending on laser power chosen. Ophthalmoscopic and histologic lesion diameters were independent of power between 14 and 200 mW. TCP lesions barely were visible with a mean diameter equal to the treatment beam (130 mum). In contrast, standard lesion diameters increased linearly and statistically significantly with power. Histology confirmed sparing of the ganglion and nerve fiber layers in TCP. Conclusions. TCP facilitates uniform retinal lesions over a wide power range. In a clinical setting, it should generate soft and reproducible lesions independently of local tissue variation and improve safety, particularly at short exposure times.},
       year = {2012}
    }
  • Schlott, Kerstin and Koinzer, Stefan and Ptaszynski, Lars and Bever, Marco and Baade, Alex and Roider, Johann and Birngruber, Reginald and Brinkmann, Ralf: Automatic temperature controlled retinal photocoagulation. Journal of Biomedical Optics, no. 17, pp. 061223, 2012
    BibTeX Link
    @article{Schlott2012,
       author = {Schlott, Kerstin and Koinzer, Stefan and Ptaszynski, Lars and Bever, Marco and Baade, Alex and Roider, Johann and Birngruber, Reginald and Brinkmann, Ralf},
       title = {Automatic temperature controlled retinal photocoagulation},
       journal = {Journal of Biomedical Optics},
       volume = {17},
       number = {6},
       pages = {061223},
       keywords = {AutoPhoN},
       year = {2012}
    }
    
  • Koinzer, Stefan and Schlott, Kerstin and Portz, Lea and Ptaszynski, Lars and Baade, Alexander and Bever, Marco and Saeger, Mark and Caliebe, Amke and Denner, Renè and Birngruber, Reginald and Brinkmann, Ralf and Roider, Johann: Correlation of temperature rise and optical coherence tomography characteristics in patient retinal photocoagulation. Journal of Biophotonics, pp. n/a-n/a, 2012
    BibTeX
    @article{Koinzer,
       author = {Koinzer, Stefan and Schlott, Kerstin and Portz, Lea and Ptaszynski, Lars and Baade, Alexander and Bever, Marco and Saeger, Mark and Caliebe, Amke and Denner, Renè and Birngruber, Reginald and Brinkmann, Ralf and Roider, Johann},
       title = {Correlation of temperature rise and optical coherence tomography characteristics in patient retinal photocoagulation},
       journal = {Journal of Biophotonics},
       pages = {n/a-n/a},
       abstract = {We conducted a study to correlate the retinal temperature rise during photocoagulation to the afterward detected tissue effect in optical coherence tomography (OCT). 504 photocoagulation lesions were examined in 20 patients. The retinal temperature increase was determined in real-time during treatment based on thermoelastic tissue expansion which was probed by repetitively applied ns laser pulses. The tissue effect was examined on fundus images and OCT images of individualized lesions. We discerned seven characteristic morphological OCT lesion classes. Their validity was confirmed by increasing visibility and diameters. Mean peak temperatures at the end of irradiation ranged from approx. 60 °C to beyond 100 °C, depending on burn intensity. (© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)},
       keywords = {laser photocoagulation
    optoacoustics
    photocoagulation
    retinal temperature
    spectral domain optical coherence tomography
    OCT
    subthreshold
    classification},
       year = {2012}
    }
  • Brinkmann, Ralf and Koinzer, Stefan and Schlott, Kerstin and Ptaszynski, Lars and Bever, Marco and Baade, Alexander and Luft, Susanne and Miura, Yoko and Roider, Johann and Birngruber, Reginald: Real-time temperature determination during retinal photocoagulation on patients. Journal of Biomedical Optics, no. 17, pp. 061219, 012
    BibTeX
    @article{Brinkmann2012,
       author = {Brinkmann, Ralf and Koinzer, Stefan and Schlott, Kerstin and Ptaszynski, Lars and Bever, Marco and Baade, Alexander and Luft, Susanne and Miura, Yoko and Roider, Johann and Birngruber, Reginald},
       title = {Real-time temperature determination during retinal photocoagulation on patients},
       journal = {Journal of Biomedical Optics},
       volume = {17},
       number = {6},
       pages = {061219},
       note = {Journal Article},
       year = {2012}
    }
  • Treumer, F. and Klettner, A. and Baltz, J. and Hussain, A. A. and Miura, Y. and Brinkmann, R. and Roider, J. and Hillenkamp, J.: Vectorial release of matrix metalloproteinases (MMPs) from porcine RPE-choroid explants following selective retina therapy (SRT): towards slowing the macular ageing process. Exp Eye Res, no. 97, pp. 63-72, 2012
    BibTeX
    @article{Miura2012,
       author = {Treumer, F. and Klettner, A. and Baltz, J. and Hussain, A. A. and Miura, Y. and Brinkmann, R. and Roider, J. and Hillenkamp, J.},
       title = {Vectorial release of matrix metalloproteinases (MMPs) from porcine RPE-choroid explants following selective retina therapy (SRT): towards slowing the macular ageing process},
       journal = {Exp Eye Res},
       volume = {97},
       number = {1},
       pages = {63-72},
       note = {Treumer, F
    Klettner, A
    Baltz, J
    Hussain, A A
    Miura, Y
    Brinkmann, R
    Roider, J
    Hillenkamp, J
    eng
    England
    2012/03/06 06:00
    Exp Eye Res. 2012 Apr;97(1):63-72. doi: 10.1016/j.exer.2012.02.011. Epub 2012 Feb 22.},
       abstract = {The purpose of this study was to investigate release of matrix metalloproteinases (MMP) 2 and 9 during retinal pigment epithelium (RPE) wound healing after Selective Retina Therapy (SRT) with laser energy levels below and above the threshold of RPE cell death. Following exposure to SRT using a prototype pulsed Nd:YLF laser with energies of 80-180 mJ/cm(2) fresh porcine RPE-monolayers with Bruch's membrane and choroid were cultured in modified Ussing chambers which separate the apical (RPE-facing) and basal (choroid facing) sides of the RPE monolayer. Threshold energy for RPE cell death and wound healing were determined with calcein-AM viability test. Inactive and active forms of MMP 2 and 9 were quantified within tissue samples and in the culture medium of the apical and basal compartments of the Ussing chamber using gelatine zymography. Laser energies of 160-180 mJ/cm(2) resulted in cell death within 1 h while 120-140 mJ/cm(2) resulted in delayed death of exposed RPE cells. All cells survived 80 and 100 mJ/cm(2). Laser spots healed within 6 days after SRT accompanied by a transient vectorial increase of MMPs. SRT with 180 mJ/cm(2) increased active MMP 2 by 1.9 (p < 0.05) and 1.6 (p < 0.05) fold in tissue and basal compartments, respectively, without alterations in the apical compartment. Pro-MMP 2 levels were also significantly increased in all compartments (p < 0.05). Release of MMP 9 was not altered. Laser energy below the threshold of RPE cell death did not alter the release of MMP 2 or 9. The findings suggest that the release of active MMP 2 on the basal side of the RPE during wound healing following SRT may address age-related pathological changes of Bruch's membrane with a potential to slow degenerative macular ageing processes before irreversible functional loss has occurred.},
       keywords = {Animals
    Cell Death
    Cell Survival
    Choroid/*enzymology/pathology
    Diffusion Chambers, Culture
    Fluoresceins/metabolism
    *Laser Therapy
    Lasers, Solid-State
    Macular Degeneration/enzymology/pathology/*surgery
    Matrix Metalloproteinase 2/*metabolism
    Matrix Metalloproteinase 9/*metabolism
    Organ Culture Techniques
    Retinal Pigment Epithelium/*enzymology/pathology
    Sensory Thresholds
    Swine
    Wound Healing/*physiology},
       year = {2012}
    }
    
  • Iwami, Hisashi and Ptaszynski, Lars and Danicke, Veit and Brinkmann, Ralf and Miura, Yoko: Sublethal Hyperthermia-induced Vascular Endothelial Growth Factor Secretion And Its Contribution To Adoptive Response Of Retinal Pigment Epithelial Cell. Invest. Ophthalmol. Vis. Sci., no. 53, pp. 4782-, 2012
    BibTeX Link
    @article{Iwami2012,
       author = {Iwami, Hisashi and Ptaszynski, Lars and Danicke, Veit and Brinkmann, Ralf and Miura, Yoko},
       title = {Sublethal Hyperthermia-induced Vascular Endothelial Growth Factor Secretion And Its Contribution To Adoptive Response Of Retinal Pigment Epithelial Cell},
       journal = {Invest. Ophthalmol. Vis. Sci.},
       volume = {53},
       number = {6},
       pages = {4782-},
       abstract = {PurposeTo investigate temperature increase-induced secretion of vascular endothelial growth factor (VEGF) from retinal pigment epithelial (RPE) cells and its contribution to adoptive response relating to cell defence system against oxidative stress. MethodsPorcine RPE cells on 35 mm culture dish were used in the study. Thulium laser ({lambda}=1940 nm, spot size 33 mm was utilized as a heat source. Temperature increase during irradiation for different power and time setting at cell level was measured with thermocouple, and power and time setting of the experiment was determined based on this calibration. Culture medium was replaced by 1.2 ml phosphate buffer saline and then laser was irradiated with different power settings for 10 seconds, so that the peak temperature reaches from 40{degrees}C to 65{degrees}C. Cellular viability after laser irradiation was examined with MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay immediately after irradiation. VEGF secretion was investigated with enzyme-linked immunosorbent assay (ELISA) at 2 and 24 hrs after irradiation. Contribution of a temperature-dependent calcium channel, TRPV (transient receptor potential vanilloid) channels in laser-induced VEGF secretion was investigated using TRPV channel blocker, ruthenium red (20 {micro}M). TRPV channel blocker-containing medium was replaced by the normal medium soon after laser irradiation. Hydrogen peroxide (H2O2) or advanced glycation endproduct (AGE)-was exposed after 6 hrs of laser irradiation and cell viability was examined with MTT assay. ResultsPeak temperature threshold for immediate RPE cell death was found around 55 {degrees}C with our irradiation setting. VEGF secretion was increased after sub-lethal irradiation in power-dependent manner, which was partially suppressed by TRPV channel blocker. Sublethal laser irradiation reduced H2O2 and AGE-induced cell death and this effect was smaller in the cells treated with TRPV channel inhibitor during laser irradiation. ConclusionsSublethal temperature increase-induced VEGF production might contribute to the enhancement of RPE cell defence system against oxidative stress.},
       url = {http://abstracts.iovs.org/cgi/content/abstract/53/6/4782},
       year = {2012},
       type = {Journal Article}
    }
    
  • Mueller, H. H. and Ptaszynski, L. and Schlott, K. and Debbeler, C. and Bever, M. and Koinzer, S. and Birngruber, R. and Brinkmann, R. and Huettmann, G.: Imaging thermal expansion and retinal tissue changes during photocoagulation by high speed OCT. Biomedical Optics Express, no. 3, pp. 1025-1046, 2012
    BibTeX Link
    @article{Müller2012,
       author = {Mueller, H. H. and Ptaszynski, L. and Schlott, K. and Debbeler, C. and Bever, M. and Koinzer, S. and Birngruber, R. and Brinkmann, R. and Huettmann, G.},
       title = {Imaging thermal expansion and retinal tissue changes during photocoagulation by high speed OCT},
       journal = {Biomedical Optics Express},
       volume = {3},
       number = {5},
       pages = {1025-1046},
       note = {935RH
    Times Cited:8
    Cited References Count:37},
       abstract = {Visualizing retinal photocoagulation by real-time OCT measurements may considerably improve the understanding of thermally induced tissue changes and might enable a better reproducibility of the ocular laser treatment. High speed Doppler OCT with 860 frames per second imaged tissue changes in the fundus of enucleated porcine eyes during laser irradiation. Tissue motion, measured by Doppler OCT with nanometer resolution, was correlated with the temperature increase, which was measured non-invasively by optoacoustics. In enucleated eyes, the increase of the OCT signal near the retinal pigment epithelium (RPE) corresponded well to the macroscopically visible whitening of the tissue. At low irradiance, Doppler OCT revealed additionally a reversible thermal expansion of the retina. At higher irradiance additional movement due to irreversible tissue changes was observed. Measurements of the tissue expansion were also possible in vivo in a rabbit with submicrometer resolution when global tissue motion was compensated. Doppler OCT may be used for spatially resolved measurements of retinal temperature increases and thermally induced tissue changes. It can play an important role in understanding the mechanisms of photocoagulation and, eventually, lead to new strategies for retinal laser treatments. (c) 2012 Optical Society of America},
       keywords = {optical coherence tomography
    laser photocoagulation
    vein occlusion
    management
    diseases
    fundus
    blood},
       ISSN = {2156-7085},
       url = {<Go to ISI>://WOS:000303537400018},
       year = {2012},
       type = {Journal Article}
    }
    

2011

  • Brinkmann, R and Koinzer, S and Schlott, K and Ptaszynski, L and Bever, M and Baade, A and Miura, Y and Birngruber, R and Roider, J: Realtime temperature determination during retinal photocoagulation on patients.. Proc SPIE, no. 7885, pp. 78850R, 2011
    BibTeX
    @article{Brinkmann2011,
       author = {Brinkmann, R and Koinzer, S and Schlott, K and Ptaszynski, L and Bever, M and Baade, A and Miura, Y and Birngruber, R and Roider, J},
       title = {Realtime temperature determination during retinal photocoagulation on patients.},
       journal = {Proc SPIE},
       volume = {7885},
       pages = {78850R},
       abstract = {Retinal photocoagulation is a long time established treatment for a variety of retinal diseases, most commonly applied for diabetic macular edema and diabetic retinopathy. The damage extent of the induced thermal coagulations depend on the temperature increase and the time of irradiation. So far, the induced temperature rise is unknown due to intraocular variations in light transmission and scattering and RPE/choroidal pigmentation, which can vary inter- and intraindividually by more than a factor of four. Thus in clinical practice, often stronger and deeper coagulations are applied than therapeutically needed, which lead to extended retinal damage and strong pain perception. The final goal of this project focuses on a dosimetry control, which automatically generates a desired temperature profile and thus coagulation strength for every individual coagulation spot, ideally unburden the ophthalmologist from any laser settings. In this paper we present the first realtime temperature measurements achieved on patients during retinal photocoagulation by means of an optoacoustic method, making use of the temperature dependence of the thermal expansion coefficient of retinal tissue. Therefore, nanosecond probe laser pulses are repetitively and simultaneously applied with the treatment radiation in order to excite acoustic waves, which are detected at the cornea with an ultrasonic transducer embedded in the contact lens and then are processed by PC.},
       url = {http://proceedings.spiedigitallibrary.org/proceeding.aspx?articleid=732381},
       year = {2011},
       type = {Journal Article}
    }
    
  • Horstmann, Jens and Baade, Alexander and Brinkmann, Ralf: Photoacoustic blood vessel detection during surgical laser interventions. no. 8092, pp. 80920Z-80920Z-6, SPIE ECBO,
    BibTeX Link
    @inproceedings{Horstmann2011,
       author = {Horstmann, Jens and Baade, Alexander and Brinkmann, Ralf},
       title = {Photoacoustic blood vessel detection during surgical laser interventions},
       publisher = {SPIE ECBO},
       volume = {8092},
       pages = {80920Z-80920Z-6},
       note = {10.1117/12.889635},
       abstract = {This paper presents a discussion about the potential of photoacoustics with regard to its application in surgical assistance during minimally invasive, laser assisted interventions. Aim of the work is the detection of obscured large blood vessels in order to prevent unintentional dissection. Based on spectroscopic investigations of the target tissue (liver), a wavelength for the photoacoustic excitation laser was chosen with respect to a high absorption contrast between the vessel and the surrounding liver tissue. An experimental setup featuring a simple liver model is created. Preliminary results show, that vessels with a diameter of 2 mm can be detected up to a distance of 1 mm from the treatment fibre. It is shown, that detection of acoustic waves induced inside liver is feasible over distances higher than 10 cm.},
       url = {http://dx.doi.org/10.1117/12.889635},
       type = {Conference Proceedings}
    }
    
  • Muller, Heike H. and Ptaszynski, Lars and Schlott, Kerstin and Bonin, Tim and Bever, Marco and Koinzer, Stefan and Birngruber, Reginald and Brinkmann, Ralf and Huttmann, Gereon: Imaging of temperature distribution and retinal tissue changes during photocoagulation by high speed OCT. no. 7889, pp. 78890E, SPIE,
    BibTeX
    @inproceedings{Müller2011,
       author = {Muller, Heike H. and Ptaszynski, Lars and Schlott, Kerstin and Bonin, Tim and Bever, Marco and Koinzer, Stefan and Birngruber, Reginald and Brinkmann, Ralf and Huttmann, Gereon},
       title = {Imaging of temperature distribution and retinal tissue changes during photocoagulation by high speed OCT},
       editor = {James, G. Fujimoto and Joseph, A. Izatt and Valery, V. Tuchin},
       publisher = {SPIE},
       volume = {7889},
       pages = {78890E},
    
    }
  • Obana, Akira and Brinkmann, Ralf and Gohto, Yuko and Nishimura, Kasumi: A Case of Retinal Injury By A Violet Light-Emitting Diode. Retinal Cases and Brief Reports, no. 5, pp. 223-226 10.1097/ICB.0b013e3181e180d5, 2011
    BibTeX
    @article{Obana,
       author = {Obana, Akira and Brinkmann, Ralf and Gohto, Yuko and Nishimura, Kasumi},
       title = {A Case of Retinal Injury By A Violet Light-Emitting Diode},
       journal = {Retinal Cases and Brief Reports},
       volume = {5},
       number = {3},
       pages = {223-226 10.1097/ICB.0b013e3181e180d5},
       abstract = {Purpose: To describe the first case of retinal injury by a misuse of a toy using light-emitting diode. Methods: A 15-year-old male Japanese student received irradiation on his right eye by a 5 mW light-emitting diode of 410 nm wavelength for 20 seconds in 2 days. He noticed decreased vision and central scotoma approximately 2 weeks later from these events. The mechanism of injury was evaluated from the estimated irradiance on the retina by comparison with experimental threshold data published. Results: Chorioretinal atrophy with visual loss and central scotoma has remained on the fovea. The patient received an estimated dose of 1.58 J/cm2 2 times, which was close to the experimentally determined radiant exposure for photochemical injury of rat retina. Conclusion: The violet light from light-emitting diodes is a potential hazard for the retina, and thus, direct viewing into the beam should be avoided. Children, especially, should not be allowed to play with such toys without being carefully instructed about their proper use and fully supervised.},
       keywords = {black light
    light-emitting diode
    photochemical damage
    retinal injury
    visual disturbance.
    01271216-201100530-00011},
       year = {2011}
    }
    
  • Klatt, C. and Saeger, M. and Oppermann, T. and Porksen, E. and Treumer, F. and Hillenkamp, J. and Fritzer, E. and Brinkmann, R. and Birngruber, R. and Roider, J.: Selective retina therapy for acute central serous chorioretinopathy. Br J Ophthalmol, no. 95, pp. 83-8, 2011
    BibTeX
    @article{Klatt,
       author = {Klatt, C. and Saeger, M. and Oppermann, T. and Porksen, E. and Treumer, F. and Hillenkamp, J. and Fritzer, E. and Brinkmann, R. and Birngruber, R. and Roider, J.},
       title = {Selective retina therapy for acute central serous chorioretinopathy},
       journal = {Br J Ophthalmol},
       volume = {95},
       number = {1},
       pages = {83-8},
       note = {Using Smart Source Parsing
    Jan; Epub 2010 Jun 15},
       abstract = {AIMS: To evaluate selective retina therapy (SRT) as a treatment of acute central serous chorioretinopathy. METHODS: 30 eyes of 30 patients with central serous chorioretinopathy of at least a 3 months' duration were recruited. 14 eyes were randomised to an SRT group (Q-switched neodymium-doped yttrium lithium fluoride (Nd:YLF) laser, wavelength 527 nm, t=1.7 mus, energy 100-370 muJ, spot diameter 200 mum, pulse repetition rate 100 Hz,) and 16 eyes to a control group. After 3 months of follow-up, patients in the control group with persistence of subretinal fluid (SRF) were allocated to a cross-over group, treated with SRT and followed up for further 3 months. The main outcome measures were change of best-corrected Early Treatment Diabetic Retinopathy Study visual acuity (BCVA) and SRF. RESULTS: At 3 months of follow-up, the mean (SD) improvement of BCVA was significantly greater after SRT than in the control group: 12.7 (7.2) versus 6.3 (8.9) letters (p=0.04). SRF had decreased significantly more after SRT as compared with that the control group: 203 (136) mum versus 41 (150) mum (p=0.005). In eight eyes allocated to the cross-over group, the mean BCVA had increased during 3 months of follow up before SRT by 1.4 (5.2) letters and continued to increase during 3 months following SRT by 7.4 (6.3) letters, while SRF increased by 39.5 (160.2) mum before SRT and decreased by 151.5 (204.9) mum after SRT. In six of the eight eyes, SRF had completely resolved 3 months after SRT. CONCLUSIONS: SRT appears to expedite functional recovery and the re-absorption of SRF as compared with that in untreated controls. A larger prospective, randomised phase 3 confirmative patient study is warranted. TRIAL REGISTRATION NUMBER: NCT00987077.},
       year = {2011}
    }
  • Fritz, Andreas and Zegelin, Andrea and Ptaszynski, Lars and Birngruber, Reginald and Brinkmann, Ralf: Dynamics of laser induced micro bubble clusters on tissue phantoms. no. 7885, pp. 78850S-78850S-6,
    BibTeX
    @inproceedings{Fritz2011,
       author = {Fritz, Andreas and Zegelin, Andrea and Ptaszynski, Lars and Birngruber, Reginald and Brinkmann, Ralf},
       title = {Dynamics of laser induced micro bubble clusters on tissue phantoms},
       volume = {7885},
       pages = {78850S-78850S-6},
       note = {10.1117/12.875031},
       abstract = {Selective retina treatment (SRT) is a laser based method to treat retinal diseases associated with disorders of the retinal pigment epithelium (RPE) while preserving photoreceptors and choroid. Applying microsecond laser pulses to the 100- 200 strongly absorbing melanin granules inside the RPE cells induces transient micro bubbles which disrupt the cells. Aim of this work is to understand bubble dynamics in clusters with respect to the influence of the adjacent retina. Bubble dynamics were investigated in vitro on porcine RPE. An about 200 μm thick layer of agarose gel was applied to the RPE layer in order to simulate the mechanical properties of retina. Different laser pulse durations from 1 ns (532 nm, Nd:YAG) to 1.7 μs (527 nm, Nd:YLF) were used. The bubbles were investigated interferometrically (fiber interferometer @ 830 nm) and with fast flash photography (25 ns flash duration). Bubble lifetimes were measured. The results show that with retina phantoms the bubble formation threshold was reached at 2.5 times higher irradiation than without retina phantom for 1.7 μs laser pulses. The microbubbles generated with 1 ns laser pulses were almost not influenced by the agarose layer. Irradiation twofold over bubble formation threshold resulted in 3.5 times longer bubble lifetimes for μs and 2 times longer for ns pulse durations, respectively.},
       url = {http://dx.doi.org/10.1117/12.875031},
       type = {Conference Proceedings}
    }
    
  • Schlott, Kerstin and Koinzer, Stefan and Ptaszynski, Lars and Luft, Susanne and Baade, Alex and Bever, Marco and Roider, Johann and Birngruber, Reginald and Brinkmann, Ralf: Optoacoustic temperature determination and automatic coagulation control in rabbits. in Ophthalmic Technologies XXI, no. 7885, Proc. SPIE,
    BibTeX Link
    @inproceedings{Schlott2011,
       author = {Schlott, Kerstin and Koinzer, Stefan and Ptaszynski, Lars and Luft, Susanne and Baade, Alex and Bever, Marco and Roider, Johann and Birngruber, Reginald and Brinkmann, Ralf},
       title = {Optoacoustic temperature determination and automatic coagulation control in rabbits},
       booktitle = {Ophthalmic Technologies XXI },
       editor = {Ho, Fabrice Manns; Per G. Söderberg; Arthur},
       publisher = {Proc. SPIE},
       volume = {7885},
       note = {10.1117/12.875104},
       abstract = {Retinal laser photocoagulation is an established treatment method for many retinal diseases like macula edema or diabetic retinopathy. The selection of the laser parameters is so far based on post treatment evaluation of the lesion size and strength. Due to local pigment variations in the fundus and individual transmission the same laser parameters often lead to an overtreatment. Optoacoustic allows a non invasive monitoring of the retinal temperature increase during retinal laser irradiation by measuring the temperature dependent pressure amplitudes, which are induced by short probe laser pulses. A 75 ns/ 523 nm Nd:YLF was used as a probe laser at a repetition rate of 1 kHz, and a cw / 532 nm treatment laser for heating. A contact lens was modified with a ring-shaped ultrasonic transducer to detect the pressure waves at the cornea. Temperatures were collected for irradiations leading to soft or invisible lesions. Based on this data the threshold for denaturation was found. By analyzing the initial temperature increase, the further temperature development during irradiation could be predicted. An algorithm was found to calculate the irradiation time, which is needed for a soft lesion formation, from the temperature curve. By this it was possible to provide a real-time dosimetry by automatically switching off the treatment laser after the calculated irradiation time. Automatically controlled coagulations appear softer and more uniformly.},
       keywords = {AutoPhoN},
       url = {http://dx.doi.org/10.1117/12.875104},
       type = {Conference Proceedings}
    }
    
  • Obana, Akira and Brinkmann, Ralf and Gohto, Yuko and Nishimura, Kasumi: A Case of Retinal Injury By A Violet Light-Emitting Diode. Retinal Cases and Brief Reports, no. 5, pp. 223-226 10.1097/ICB.0b013e3181e180d5, 2011
    BibTeX
    @article{Obana,
       author = {Obana, Akira and Brinkmann, Ralf and Gohto, Yuko and Nishimura, Kasumi},
       title = {A Case of Retinal Injury By A Violet Light-Emitting Diode},
       journal = {Retinal Cases and Brief Reports},
       volume = {5},
       number = {3},
       pages = {223-226 10.1097/ICB.0b013e3181e180d5},
       abstract = {Purpose: To describe the first case of retinal injury by a misuse of a toy using light-emitting diode. Methods: A 15-year-old male Japanese student received irradiation on his right eye by a 5 mW light-emitting diode of 410 nm wavelength for 20 seconds in 2 days. He noticed decreased vision and central scotoma approximately 2 weeks later from these events. The mechanism of injury was evaluated from the estimated irradiance on the retina by comparison with experimental threshold data published. Results: Chorioretinal atrophy with visual loss and central scotoma has remained on the fovea. The patient received an estimated dose of 1.58 J/cm2 2 times, which was close to the experimentally determined radiant exposure for photochemical injury of rat retina. Conclusion: The violet light from light-emitting diodes is a potential hazard for the retina, and thus, direct viewing into the beam should be avoided. Children, especially, should not be allowed to play with such toys without being carefully instructed about their proper use and fully supervised.},
       keywords = {black light
    light-emitting diode
    photochemical damage
    retinal injury
    visual disturbance.
    01271216-201100530-00011},
       year = {2011}
    }
    

2010

  • Bombien, R. and Lesche, C. and Lozonschi, L. and Feucker, M. and Brinkmann, R. and Dahmen, C. and Schunke, M. and Cremer, J. and Lutter, G.: Percutaneous Aortic Valve Replacement: Emerging Tractability for Sufficient Intracardiac Resection of the Aortic Valve. Innovations (Phila), no. 5, pp. 55-59, 2010
    BibTeX
    @article{Bombien,
       author = {Bombien, R. and Lesche, C. and Lozonschi, L. and Feucker, M. and Brinkmann, R. and Dahmen, C. and Schunke, M. and Cremer, J. and Lutter, G.},
       title = {Percutaneous Aortic Valve Replacement: Emerging Tractability for Sufficient Intracardiac Resection of the Aortic Valve},
       journal = {Innovations (Phila)},
       volume = {5},
       number = {1},
       pages = {55-59},
       note = {Philadelphia, Pa.
    Innovations (Phila). 2010 Jan;5(1):55-59.},
       abstract = {OBJECTIVE:: The feasibility of endovascular resection of highly calcified aortic valves has already been demonstrated by our group. Different endovascular and intracardiac tractability methods were applied. In this study, these technologies were analyzed comparing the tractability, the resection time, and the lesions in the surrounding tissue. METHODS:: All aortic valve resections (seven human hearts and 21 porcine hearts) were performed using a Thulium:YAG laser (continuous wave, wavelength of 2.01 mum, 20 watts power rating). In the first resection system, the laser fiber was controlled by a free in-lying flexible endoscope (O 2.5 mm, length of 600 mm). The distal part of the endoscope (40 mm) was moved in one plane by proximal manual control (three degrees of freedom). The resection system was separated into defined rooms assigning one room for one tool. The fiber was controlled by the above-mentioned endoscope (*) (three degrees of freedom). The third resection system was a mechanical microactuator carrying the laser fiber (three degrees of freedom). The fourth resection system contains a rotatable inlay with defined rooms and a newly designed nitinol (NiTi) microactuator that controlled the laser fiber (four degrees of freedom). The resection time per leaflet was measured in minutes. Gross anatomy and histology in the surrounding tissue were evaluated. RESULTS:: The resection time in approaches 1, 2, 3, and 4 was 5.5 +/- 2.3 minutes, 7.4 +/- 2.7 minutes, +/- 6.6 minutes, and2.3 +/- 1.2 minutes, respectively. The gross anatomy and histology of collateral damages revealed only superficial lesions of the surrounding tissue. The amount of lesions and the resection time were lower in the fourth approach with four degrees of freedom. CONCLUSIONS:: This analysis demonstrated that a precise tractability with four degrees of freedom is necessary for a faster and safer endovascular resection of the aortic valve. The analysis will help to optimize the ongoing development of the endovascular and intracardiac resection technology.},
       year = {2010}
    }
  • Miura, Y and Huettmann, G and Orzekowsky-Schroeder, R and Steven, P and Szaszák, M and Koop, N and Brinkmann, R: Appearance of autofluorescence in RPE cells at the rim of photocoagulation. in FLIM 2010 - Symposium Fluorescence Lifetime Imaging of the Human Retina,
    BibTeX
    @inproceedings{Miura2010,
       author = {Miura, Y and Huettmann, G and Orzekowsky-Schroeder, R and Steven, P and Szaszák, M and Koop, N and Brinkmann, R},
       title = {Appearance of autofluorescence in RPE cells at the rim of photocoagulation},
       booktitle = {FLIM 2010 - Symposium "Fluorescence Lifetime Imaging of the Human Retina"},
       type = {Conference Proceedings}
    }
    
    
    
  • Roider, J. and Liew, S. H. and Klatt, C. and Elsner, H. and Poerksen, E. and Hillenkamp, J. and Brinkmann, R. and Birngruber, R.: Selective retina therapy (SRT) for clinically significant diabetic macular edema. Graefes Arch Clin Exp Ophthalmol, no. 248, pp. 1263-72, 2010
    BibTeX
    @article{Roider,
       author = {Roider, J. and Liew, S. H. and Klatt, C. and Elsner, H. and Poerksen, E. and Hillenkamp, J. and Brinkmann, R. and Birngruber, R.},
       title = {Selective retina therapy (SRT) for clinically significant diabetic macular edema},
       journal = {Graefes Arch Clin Exp Ophthalmol},
       volume = {248},
       number = {9},
       pages = {1263-72},
       note = {Using Smart Source Parsing
    Sep},
       abstract = {PURPOSE: To test selective retina therapy (SRT) as a treatment of clinically significant diabetic macular edema (DME). METHODS: Prospective two-center interventional uncontrolled phase II pilot study. Thirty-nine eyes of 39 patients with previously untreated non-ischemic DME were treated with focal laser treatment using a Q-switched frequency doubled Nd:YLF laser which selectively affects the retinal pigment epithelium while sparing the photoreceptor layer. Optoacoustic measurements, fundus fluorescein angiography (FFA), and funduscopy were used to determine the individual threshold of RPE damage of each patient. The pulse energy was adjusted to apply angiographically visible but funduscopically invisible effects. Optoacoustic measurements were correlated with funduscopy and FFA. Follow-up examinations at 3 and 6 months post-treatment included best-corrected ETDRS visual acuity (BCVA), FFA, fundus photography, and retinal thickness measured by optical coherence tomography. The primary outcome measure was change of BCVA. Other outcome measures were change of retinal thickness, presence of hard exudates, leakage in FFA, accuracy of optoacoustic measurements, and correlation of BCVA with change of anatomical and systemic parameters. RESULTS: Mean BCVA improved from 43.7 letters (standard deviation, SD=9.1) at baseline to 46.1 letters (SD=10.5) at the 6-month follow-up (p=0.02). BCVA improved (>5 letters) or remained stable (+/-5 letters) in 84% of eyes. Thirteen percent of eyes improved by > or =10 letters, while 16% of eyes lost more than 5 letters. There was no severe loss of vision (> or =15 letters). Overall, retinal thickness, hard exudates, and leakage in FFA did not change significantly (p> 0.05), while improvement of BCVA correlated with a reduction of hard exudates (p=0.01) and central retinal thickness (p=0.01). Specificity and sensitivity of detecting the angiographic visible threshold of RPE damage by optoacoustic measurements were 86% and 70% respectively. No adverse effects or pain were noted during or after treatment. Conclusions Functional and anatomical improvement or stabilization was observed in most patients. SRT appears to be safe. Optoacoustic measurements accurately detect the individual threshold of RPE damage. A randomized trial is required to further test efficacy and safety of SRT as a treatment of clinically significant diabetic macular edema (DME).},
       year = {2010}
    }
    
  • Prahs, P. and Walter, A. and Regler, R. and Theisen-Kunde, D. and Birngruber, R. and Brinkmann, R. and Framme, C.: Selective retina therapy (SRT) in patients with geographic atrophy due to age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol, no. 248, pp. 651-8, 2010
    BibTeX Link
    @article{Prahs2010,
       author = {Prahs, P. and Walter, A. and Regler, R. and Theisen-Kunde, D. and Birngruber, R. and Brinkmann, R. and Framme, C.},
       title = {Selective retina therapy (SRT) in patients with geographic atrophy due to age-related macular degeneration},
       journal = {Graefes Arch Clin Exp Ophthalmol},
       volume = {248},
       number = {5},
       pages = {651-8},
       note = {1435-702x
    Prahs, Philipp
    Walter, Andreas
    Regler, Roman
    Theisen-Kunde, Dirk
    Birngruber, Reginald
    Brinkmann, Ralf
    Framme, Carsten
    Journal Article
    Germany
    Graefes Arch Clin Exp Ophthalmol. 2010 May;248(5):651-8. doi: 10.1007/s00417-009-1208-1. Epub 2009 Dec 22.},
       abstract = {BACKGROUND: For geographic atrophy (GA) due to age-related macular degeneration (AMD) there is so far no approved treatment option. Usually, increased autofluorescence (AF) levels of different patterns adjacent to the atrophic area indicate lipofuscin-laden retinal pigment epithelium (RPE) cells at a high risk for apoptosis. Herein, SRT was used to selectively treat these cells to stimulate RPE proliferation, in order to reduce or ideally stop further growth of the atrophic area. MATERIAL AND METHODS: Six eyes of six patients with bilateral equally pronounced GA were treated by SRT, while the fellow eye served as control. Irradiation was performed using a prototype SRT laser (Medical Laser Center Lubeck, Nd:YLF laser; 527 nm; 200 ns/1.7 micros pulse duration; 30 repetitive pulses at 100 Hz). Test lesions with increasing energies were applied at the lower vessel arcade to determine the individual angiographic and ophthalmoscopic threshold radiant exposures. Treatment was then performed in the area of increased AF adjacent to the GA using energies between both thresholds. The GA progression rates of treated and fellow eyes were evaluated. RESULTS: After a 1-year follow-up, a progression of the atrophic area was observed in the treated eyes (0.7-8.0 mm(2)/yr, mean 3.0 mm(2)/yr; 46%/yr) whereas the progression rates of the fellow eyes were insignificantly lower (0.46-4.04 mm(2)/yr, mean 1.9 mm(2)/yr; 30%/yr; p = 0.134). The progression rate in the treated eyes of two patients increased significantly, while in the other four patients, the progression rates were nearly the same between both eyes. Moreover, one of these two eyes showed an unexpected RPE reaction after treatment, since all laser lesions led to RPE atrophy and thus an accelerated enlargement of the GA occurred. CONCLUSION: SRT in the hyperautofluorescent areas of GA was not able to stop or slow down the progression of GA. However, modified treatment strategies might be more promising, e.g. placing the spots outside the hyperautofluorescent areas where RPE apoptosis is postulated. Moreover, SRT studies on GA might be more successfully performed on specific subgroups of GA, based on autofluorescence and other findings.},
       keywords = {Aged
    Aged, 80 and over
    Disease Progression
    Fluorescein Angiography
    Fluorescence
    Follow-Up Studies
    Geographic Atrophy/etiology/physiopathology/*surgery
    Humans
    Image Processing, Computer-Assisted
    *Laser Coagulation
    Lasers, Solid-State/therapeutic use
    Lipofuscin/metabolism
    Macular Degeneration/complications/physiopathology/*surgery
    Ophthalmologic Surgical Procedures/*methods
    Pilot Projects
    Prognosis
    Retinal Pigment Epithelium/metabolism},
       ISSN = {0721-832x},
       DOI = {10.1007/s00417-009-1208-1},
       year = {2010},
       type = {Journal Article}
    }
    

2009

  • Bever, M. and Schlott, K. and Ptaszynski, L. and Koinzer, S. and Birngruber, R. and Brinkmann, R.: Automatische Dosimetrie bei der Laserphotokoagulation der Netzhaut. 3. Dresdner Medizintechnik-Symposium mit DFG Forschungsschwerpunkt Protektive Beatmungskonzepte, no. 10, 2009
    BibTeX
    @article{Bever2009,
       author = {Bever, M. and Schlott, K. and Ptaszynski, L. and Koinzer, S. and Birngruber, R. and Brinkmann, R.},
       title = {Automatische Dosimetrie bei der Laserphotokoagulation der Netzhaut},
       journal = {3. Dresdner Medizintechnik-Symposium mit DFG Forschungsschwerpunkt Protektive Beatmungskonzepte},
       volume = {10},
       year = {2009},
       type = {Journal Article}
    }
    
  • Langejürgen, J and Schlott, K and Bever, M and Hausmann, K and Koinzer, S and Ptaszynski, L and Roider, J and Birngruber, R and Brinkmann, R: Dependence of optoacoustic transients on exciting laser parameters for real-time monitoring of retinal photocoagulation. pp. 73730K-73730K,
    BibTeX Link
    @inproceedings{Langejürgen2009,
       author = {Langejürgen, J and Schlott, K and Bever, M and Hausmann, K and Koinzer, S and Ptaszynski, L and Roider, J and Birngruber, R and Brinkmann, R},
       title = {Dependence of optoacoustic transients on exciting laser parameters for real-time monitoring of retinal photocoagulation},
       pages = {73730K-73730K},
       note = {10.1117/12.831913},
       abstract = {The extent of retinal laser coagulations depends on the temperature increase at the fundus and the time of irradiation. Due to light scattering within the eye and variable fundus pigmentation the induced temperature increase and therefore the extent of the coagulations cannot be predicted solely from the laser parameters. We use optoacoustics to monitor the temperature rise in real-time in vivo (rabbit) and ex vivo (porcine eye) and to automatically control the coagulation strength. Continuous wave treatment laser radiation and pulsed probe laser light (1-1100 ns) are coupled into the same fibre and are imaged onto the retina by a laser slit lamp. The temperature dependent pressure waves are detected by an ultrasonic transducer embedded in a customary contact lens. Below the coagulation threshold the increase in acoustic amplitude due to thermal tissue expansion is up to 40 %. Best signal to noise ratios &gt; 10 are achieved with probe pulse durations of 1 to 75 ns. Further a time critical algorithm is developed which automatically ceases laser treatment when a certain preset coagulation strength is achieved. Coagulations with similar extent are obtained with this method in vitro and in vivo even when varying the power of the treatment laser by 50 %. These preliminary results are very promising, thus this method might be suitable for an automatic feedback controlled photocoagulation with adjustable coagulation strength.},
    url = {http://dx.doi.org/10.1117/12.831913},
       type = {Conference Proceedings}
    }
    
  • Schlott, Kerstin and Langejürgen, Jens and Bever, Marco and Koinzer, Stefan and Birngruber, Reginald and Brinkmann, Ralf: Time resolved detection of tissue denaturation during retinal photocoagulation. pp. 73730E-73730E,
    BibTeX Link
    @inproceedings{Schlott2009,
       author = {Schlott, Kerstin and Langejürgen, Jens and Bever, Marco and Koinzer, Stefan and Birngruber, Reginald and Brinkmann, Ralf},
       title = {Time resolved detection of tissue denaturation during retinal photocoagulation},
       editor = {7373, Proc. SPIE},
       pages = {73730E-73730E},
       note = {10.1117/12.831877},
       abstract = {The retinal photocoagulation is an established treatment method for different retinal diseases. The extent of the thermal coagulations depends strongly on the generated temperature increase. Until now the dosage is based on a pool of experience of the treating physicians as well as the appearance of the whitish lesions on the retina. The temperature course during photocoagulation can be measured in real-time by optoacoustics. A frequency-doubled Q-switched Nd:YLF laser (523nm, 75 ns) is used for optoacoustic excitation and a continuous-wave Nd:YAG laser (532nm) with adjustable irradiation time and power for heating of the fundus tissue. The onset of coagulation is determined by a photodiode that is placed directly behind enucleated porcine eyes, which served as a model. The onset of coagulation is observed clearly when scattering sets in. The required power for coagulation increases exponentially with decreasing irradiation time. The first results on rabbit eyes in vivo indicate that the onset of coagulation defined by just barely visibile lesions at a slit lamp sets in at an ED50 threshold temperature of 63°C for an irradiation time of 400 ms. In conclusion, optoacoustics can be used to determine temperatures during retinal laser treatments in real-time. This allows evaluating the time-temperature-dependence of retinal coagulation in vivo.},
       keywords = {AutoPhoN},
       url = {http://dx.doi.org/10.1117/12.831877},
       type = {Conference Proceedings}
    }
    
  • Framme, C. and Walter, A. and Prahs, P. and Regler, R. and Theisen-Kunde, D. and Alt, C. and Brinkmann, R.: Structural changes of the retina after conventional laser photocoagulation and selective retina treatment (SRT) in spectral domain OCT. Curr Eye Res, no. 34, pp. 568-79, 2009
    BibTeX
    @article{Framme,
       author = {Framme, C. and Walter, A. and Prahs, P. and Regler, R. and Theisen-Kunde, D. and Alt, C. and Brinkmann, R.},
       title = {Structural changes of the retina after conventional laser photocoagulation and selective retina treatment (SRT) in spectral domain OCT},
       journal = {Curr Eye Res},
       volume = {34},
       number = {7},
       pages = {568-79},
       note = {Framme, Carsten
    Walter, Andreas
    Prahs, Philipp
    Regler, Roman
    Theisen-Kunde, Dirk
    Alt, Clemens
    Brinkmann, Ralf
    Research Support, Non-U.S. Gov't
    England
    Current eye research
    Curr Eye Res. 2009 Jul;34(7):568-79.},
       abstract = {BACKGROUND: Spectral domain optical coherence tomography (SD-OCT) in patients can deliver retinal cross-sectional images with high resolution. This may allow the evaluation of the extent of damage to the retinal pigment epithelium (RPE) and the neurosensory retina after laser treatment. This article aims to investigate the value of SD-OCT in comparing laser lesions produced by conventional laser photocoagulation and selective retina treatment (SRT). MATERIAL AND METHODS: In a retrospective study, conventional retinal laser (CRL) lesions and SRT laser lesions were evaluated with SD-OCT. One hundred seventy-five CRL lesions were investigated in 10 patients with diabetic maculopathy at timepoints between 1 hr and 4 years after treatment. Ninety-one SRT lesions were examined in 9 patients with central serous retinopathy, geographic atrophy, and diabetic maculopathy at timepoints between 1 hr and 2 years. CRL lesions were applied with an ophthalmoscopically slightly grayish-white appearance (Nd:YAG laser at 532-nm wavelength; power 100-200 mW; retinal spot diameter 100 microm; pulse duration 100 ms). SRT lesions were applied with a Nd:YLF (527 nm; pulse duration 200 ns [30 pulses at 100 Hz]; energy 100-200 microJ/pulse; retinal spot diameter 200 microm) and were visible only angiographically. RESULTS: All CRL lesions were characterized by high reflectivity in OCT images throughout the full thickness of the neurosensory tissue 1 hr after irradiation, suggesting complete neurosensory coagulation. Strong contraction through the full thickness of the neurosensory layers was observed within 7 days after treatment. In contrast, the neural retina appeared unaffected after SRT. For both lesion types, the RPE layer appeared to be regular or thinner immediately after treatment, whereas within a period of 4 weeks, a RPE thickening indicating RPE proliferation was observable. One year and later after treatment, CRL lesions were characterized by RPE atrophy combined with significant damage of the neurosensory tissue. SRT lesions aged one year and older revealed unaffected neurosensory structures and an intact RPE layer. CONCLUSION: Spectral domain OCT can be used clinically to follow the development of laser-induced lesions over time. Postoperative RPE proliferation was observed in both CRL and SRT laser lesions. RPE atrophy appeared subsequently only in CRL lesions, whereas the neurosensory retina appeared unaffected following SRT. These results suggest the selective effect of SRT in humans without causing adverse effects to the neurosensory retina.},
       keywords = {Adult
    Aged
    Aged, 80 and over
    Atrophy
    Humans
    Laser Coagulation/*adverse effects
    Lasers, Solid-State/*adverse effects
    Middle Aged
    *Postoperative Complications
    Retina/*pathology
    Retinal Diseases/*diagnosis/*surgery
    Retinal Pigment Epithelium/pathology
    Retrospective Studies
    *Tomography, Optical Coherence},
       year = {2009}
    }
  • Fritz, A and Ptaszynski, L and Stoehr, H and Brinkmann, R: Dynamic of laser induced transient microbubble clusters. Proc SPIE,
    BibTeX
    @inproceedings{Fritz2009,
       author = {Fritz, A and Ptaszynski, L and Stoehr, H and Brinkmann, R},
       title = {Dynamic of laser induced transient microbubble clusters},
       editor = {(BiOS), Conference on Biomedical Optics},
       publisher = {Proc SPIE},
       type = {Conference Proceedings}
    }
    

2008

  • Framme, C. and Roider, J. and Brinkmann, R. and Birngruber, R. and Gabel, V. P.: Basic principles and clinical application of retinal laser therapy. Klinische Monatsblatter Fur Augenheilkunde, no. 225, pp. 259-268, 2008
    BibTeX Link
    @article{Framme2008,
       author = {Framme, C. and Roider, J. and Brinkmann, R. and Birngruber, R. and Gabel, V. P.},
       title = {Basic principles and clinical application of retinal laser therapy},
       journal = {Klinische Monatsblatter Fur Augenheilkunde},
       volume = {225},
       number = {4},
       pages = {259-268},
       note = {301AZ
    Times Cited:3
    Cited References Count:39},
       abstract = {The scientific background of laser photocoagulation of the ocular fundus was studied extensively by several investigators in the 1970 s and 1980 s. The basic principles were succesfully resolved during that time and clinical consequences for proper application of the laser photocoagulation for various diseases were deduced. The present paper gives an overview about the physical basics of laser-tissue interactions during and after retinal laser treatment and the particular laser strategies in the treatment of different retinal diseases. Thus, it addresses the issue of the impact on tissue of laser parameters as wavelength, spot size, pulse duration and laser power. Additionally, the different biological tissue reactions after laser treatment are presented, such as, e.g., for retinopexia or macular treatments as well as for diabetic retinopathies. Specific laser strategies such as the selective laser treatment of the RPE (SRT) or the transpupillary thermotherapy (TTT) are presented and discussed.},
       keywords = {retina
    anatomy
    vitreous
    subfoveal choroidal neovascularization
    central vein occlusion
    transpupillary thermotherapy
    macular degeneration
    pigment epithelium
    photocoagulation
    argon
    trial
    rpe
    diseases},
       ISSN = {0023-2165},
       DOI = {DOI 10.1055/s-2008-1027202},
       url = {<Go to ISI>://WOS:000255870100001},
       year = {2008},
       type = {Journal Article}
    }
    
  • Neumann, J and Brinkmann, R: Self-limited growth of laser-induced vapor bubbles around single micro-absorbers. Appl Phys Lett, no. 93, pp. 033901, 2008
    BibTeX
    @article{Neumann,
       author = {Neumann, J and Brinkmann, R},
       title = {Self-limited growth of laser-induced vapor bubbles around single micro-absorbers},
       journal = {Appl  Phys Lett},
       volume = {93},
       pages = {033901},
       year = {2008}
    }
  • Sandeau, J. and Caillibotte, G. and Kandulla, J. and Elsner, H. and Brinkmann, R and Birngruber, R. and Apiou-Sbirlea, G.: Numerical Modelling of Conductive and Convective Heat Transfers in Retinal Laser Applications. no. 1, pp. 43-52, 2008
    BibTeX
    @misc{Sandeau,
       author = {Sandeau, J. and Caillibotte, G. and Kandulla, J. and Elsner, H. and Brinkmann, R and Birngruber, R. and Apiou-Sbirlea, G.},
       title = {Numerical Modelling of Conductive and Convective Heat Transfers in Retinal  Laser Applications},
       volume = {1},
       number = {1},
       pages = {43-52},
       year = {2008}
    }
  • Framme, C and Roider, J and Brinkmann, R and Birngruber, R and Gabel, V-P: Grundlagen und klinische Anwendung der Lasertherapie an der Netzhaut. no. 225, pp. 259-268, 2008
    BibTeX
    @misc{Framme,
       author = {Framme, C and Roider, J and Brinkmann, R and Birngruber, R and Gabel, V-P},
       title = {Grundlagen und klinische Anwendung der Lasertherapie an der Netzhaut},
       volume = {225},
       number = {4},
       pages = {259-268},
       year = {2008}
    }
  • Framme, C. and Walter, A. and Prahs, P. and Theisen-Kunde, D. and Brinkmann, R.: Comparison of threshold irradiances and online dosimetry for selective retina treatment (SRT) in patients treated with 200 nanoseconds and 1.7 microseconds laser pulses. Lasers Surg Med, no. 40, pp. 616-24, 2008
    BibTeX
    @article{Framme,
       author = {Framme, C. and Walter, A. and Prahs, P. and Theisen-Kunde, D. and Brinkmann, R.},
       title = {Comparison of threshold irradiances and online dosimetry for selective retina treatment (SRT) in patients treated with 200 nanoseconds and 1.7 microseconds laser pulses},
       journal = {Lasers Surg Med},
       volume = {40},
       number = {9},
       pages = {616-24},
       note = {Framme, Carsten
    Walter, Andreas
    Prahs, Philipp
    Theisen-Kunde, Dirk
    Brinkmann, Ralf
    Clinical Trial
    Comparative Study
    Research Support, Non-U.S. Gov't
    United States
    Lasers Surg Med. 2008 Nov;40(9):616-24.},
       abstract = {BACKGROUND: Selective retina therapy (SRT) solely affecting the RPE while sparing of the photoreceptors is usually performed with a train of repetitive laser pulses of 1.7 microseconds in duration. It was our purpose to evaluate the principle feasibility of SRT with shorter 200 nanoseconds laser pulses in patients. METHODS: Nineteen patients with macular disorders [diabetic maculopathy (DMP), geographic atrophy (GA), drusen maculopathy and central serous chorioretinopathy (CSR)] were treated with a prototype of a SRT laser (Nd:YLF laser; 527 nm; 1.7 microseconds and 200 nanoseconds pulse duration; 30 pulses at 100 Hz; spot size: 200 microm). Test lesions (n = 175) with increasing energy were applied at the lower arcade to determine the individual angiographic and ophthalmoscopic threshold radiant exposures (therapeutic window) before applying the central treatment lesions within these ranges additionally guided by online optoacoustic measurements. Postoperatively RPE damage was visualized and confirmed by fluorescein angiographic leakage and correlated with optoacoustic results. Additionally ED(50) damage thresholds were calculated by probit analysis. RESULTS: None of the short repetitive 200 nanoseconds laser pulses led to retinal hemorrhages or retinal ruptures. Nearly all of the test- and treatment lesions could be visualized by angiography indicating desired RPE damage but were ophthalmoscopically invisible suggesting intact neurosensory retinal structures. ED(50) cell damage threshold energies were significantly lower using 200 nanoseconds (99.6 microJ; n = 122) instead of 1.7 microseconds (196.3 microJ; n = 53) laser pulses. Optoacoustic and angiographic visibility correlated in 83.7% (200 nanoseconds) and 87.5% (1.7 microseconds). CONCLUSIONS: Selective RPE effects can safely be achieved using shorter 200 nanoseconds laser pulses in patients without adverse effects to the neurosensory retina. The required pulse energy compared to the standard 1.7 microseconds regime was reduced by about a factor of 2 suggesting a reduced heat generation and flow into adjacent tissues during the shorter laser impact and thus possibly enhancing selectivity. Optoacoustics also seem to be a viable alternative in 200 nanoseconds treatment for a non-invasive online dosimetry control system.},
       keywords = {Adult
    Aged
    Aged, 80 and over
    Cohort Studies
    Feasibility Studies
    Female
    Humans
    Laser Coagulation/ methods
    Lasers, Semiconductor/ therapeutic use
    Male
    Middle Aged
    Ophthalmoscopy
    Radiometry
    Retinal Diseases/pathology/radiography/ surgery
    Retinal Pigment Epithelium/pathology/radiation effects/radiography},
       year = {2008}
    }
    
  • Framme, C and Schüle, G and Kobuch, K and Flucke, B and Birngruber, R and Brinkmann, R: Investigation of Selective Retina Treatment (SRT) by Means of 8 ns Laser Pulses in a Rabbit Model. no. 40, pp. 20-27, 2008
    BibTeX
    @misc{Framme,
       author = {Framme, C and Schüle, G and Kobuch, K and Flucke, B and Birngruber, R and Brinkmann, R},
       title = {Investigation of Selective Retina Treatment (SRT) by Means of 8 ns Laser Pulses in a Rabbit Model},
       volume = {40},
       pages = {20-27},
       year = {2008}
    }
  • Koinzer, S and Elsner, H and Klatt, C and Brinkmann, R and Birngruber, R and Roider, J: Selective Retina Therapy (SRT) of chronic subfoveal fluid after surgery of rhegmatogenous retinal detachment: three case reports. no. 246, pp. 1373-8, 2008
    BibTeX
    @misc{Koinzer,
       author = {Koinzer, S and Elsner, H and Klatt, C and Brinkmann, R and Birngruber, R and Roider, J},
       title = {Selective Retina Therapy (SRT) of chronic subfoveal fluid after surgery of rhegmatogenous retinal detachment: three case reports},
       volume = {246},
       number = {10},
       pages = {1373-8},
       year = {2008}
    }
  • Kandulla, J and Brinkmann, R: Non invasive real-time temperature determination during laser treatments at the retina. Photonik international, no. 2008/1, pp. 42-45, 2008
    BibTeX
    @article{Kandulla,
       author = {Kandulla, J and Brinkmann, R},
       title = {Non invasive real-time temperature determination during laser treatments at the retina},
       journal = {Photonik international},
       volume = {2008/1},
       pages = {42-45},
       year = {2008}
    }

2007

  • Fritz, Andreas and Ptaszynski, Lars and Stoehr, Hardo and Brinkmann, Ralf: Dynamics and detection of laser induced microbubbles in the retinal pigment epithelium (RPE). no. 6632, pp. 66321C-66321C-11,
    BibTeX Link
    @inproceedings{Fritz2007,
       author = {Fritz, Andreas and Ptaszynski, Lars and Stoehr, Hardo and Brinkmann, Ralf},
       title = {Dynamics and detection of laser induced microbubbles in the retinal pigment epithelium (RPE)},
       volume = {6632},
       pages = {66321C-66321C-11},
       note = {10.1117/12.728344},
       abstract = {Selective Retina Treatment (SRT) is a new method to treat eye diseases associated with disorders of the RPE. Selective RPE cell damage is achieved by applying a train of 1.7 μs laser pulses at 527 nm. The treatment of retinal diseases as e.g. diabetic maculopathy (DMP), is currently investigated within clinical studies, however 200 ns pulse durations are under investigation. Transient micro bubbles in the retinal pigment epithelium (RPE) are expected to be the origin of cell damage due to irradiation with laser pulses shorter than 50 μs. The bubbles emerge at the strongly absorbing RPE melanosomes. Cell membrane disruption caused by the transient associated volume increase is expected to be the origin of the angiographically observed RPE leakage. We investigate micro bubble formation and dynamics in porcine RPE using pulse durations of 150 ns. A laser interferometry system at 830 nm with the aim of an online dosimetry control for SRT was developed. Bubble formation was detected interferometrically and by fast flash photography. A correlation to cell damage observed with a vitality stain is found. A bubble detection algorithm is presented.},
       url = {http://dx.doi.org/10.1117/12.728344},
       type = {Conference Proceedings}
    }
    
  • Herrmann, Katharina and Flöhr, Christian and Stalljohann, Jens and Apiou-Sbirlea, Gabriela and Kandulla, Jochen and Birngruber, Reginald and Brinkmann, Ralf: Influence of choroidal perfusion on retinal temperature increase during retinal laser treatments. no. 6632, pp. 66321D-66321D-7,
    BibTeX Link
    @inproceedings{Herrmann2007,
       author = {Herrmann, Katharina and Flöhr, Christian and Stalljohann, Jens and Apiou-Sbirlea, Gabriela and Kandulla, Jochen and Birngruber, Reginald and Brinkmann, Ralf},
       title = {Influence of choroidal perfusion on retinal temperature increase during retinal laser treatments},
       volume = {6632},
       pages = {66321D-66321D-7},
       note = {10.1117/12.728222},
       abstract = {In most retinal laser treatments the therapeutic effect is initiated by a transient temperature increase at and around the retinal pigment epithelium (RPE). Especially in long exposure time treatments like Transpupillary Thermotherapy (TTT) choroidal perfusion has a strong influence on the realized temperature at the fundus. The fundus blood circulation and therefore the heat dissipation is influenced by the intraocular pressure (IOP), which is investigated in the study presented here. In order to reduce the choroidal perfusion, the IOP is increased by injection of physiological saline solution into the eye of anaesthetized rabbits. The fundus is irradiated with 3.64 W/cm2 by means of a TTT-laser (λ = 810 nm) for t = 20 s causing a retinal temperature increase. Realtime temperature determination at the irradiated spot is achieved by a non invasive optoacoustic technique. Perfusion can be reduced by increasing IOP, which leads to different temperature increases when irradiating the retina. This should be considered for long time laser treatments.},
       url = {http://dx.doi.org/10.1117/12.728222},
       type = {Conference Proceedings}
    }
    
  • Theisen-Kunde, D and Ott, V and Brinkmann, R and Keller, R: Potential of a new cw 2µm laser scalpel for laparoscopic surgery. Med. Laser Appl., no. 22, pp. 139-45, 2007
    BibTeX
    @article{Theisen-Kunde,
       author = {Theisen-Kunde, D and Ott, V and Brinkmann, R and Keller, R},
       title = {Potential of a new cw 2µm laser scalpel for laparoscopic surgery},
       journal = {Med. Laser Appl.},
       volume = {22},
       number = {2},
       pages = {139-45},
       abstract = {Abstract
    The potential of a new continuous-wave (cw) thulium–YAG laser for laparoscopic small intestine resection was investigated in pigs in comparison to standard bipolar scissors.
    
    Method
    A diode-pumped solid-state thulium–YAG laser system emitting at a wavelength of 2.01 µm was used. Laser power up to 25 W in cw mode was transmitted via a quartz fibre (400 µm core diameter). In order to resect 1 m of the small intestine, the accompanied mesentery was dissected with both devices in 12 pigs (six each group). Arteries and veins of 0.25–3.2 mm inner diameter were dissected in vivo and the resistance of the occluded vessels to pressures up to 375 mmHg was measured by an in vitro set-up. Samples were prepared for histological evaluation.
    
    Results
    With respect to intestine resection with bipolar scissors, bleeding occurred significantly less (25%) and dissection time was reduced by 19% using the 2 µm laser scalpel. With the 2 µm laser scalpel, small vessels (<0.5 mm) were successfully occluded up to 100% (arteries) and 89% (veins), larger vessels (1–2.3 mm) to 74% (arteries) and 65% (veins) in vivo. In the in vitro pressure measurement with 375 mmHg, 30% of veins and 35% of arteries stayed closed. In conclusion, the first experiments show that the 2 µm laser scalpel is a promising dissection device for minimally invasive surgery. 
    Zusammenfassung
    In einer vergleichenden Tierstudie wurde das Potential eines neuen cw Thulium–YAG-Lasersystems mit dem einer kommerziell erhältlichen bipolaren Schere zur laparoskopischen Resektion des Dünndarms verglichen.
    
    Methode
    Es wurde ein diodengepumptes Thulium–YAG-Festkörper-Lasersystem mit einer Emissionswellenlänge von 2,01 µm verwendet. Die Laserleistung betrug 25 W (Dauerstrich) und die Laserstrahlung wurde mittels einer Quarzglasfaser (Kerndurchmesser 400 µm) zum Applikationsort transmittiert. Zur Entnahme von 1 m Dünndarm wurde zunächst mit beiden Dissektionsgeräten das angrenzende Mesenterium an 12 Schweinen (6 je Instrument) durchtrennt. Zur Untersuchung der Hämostaseeigenschaften des 2 µm Laserskalpells wurden ausgewählte Arterien und Venen mit einem inneren Durchmesser von 0,25 bis 3,2 mm in vivo durchtrennt. In einer anschließenden in vitro Untersuchung wurde der Gefäßverschluss mit einem Druck von 375 mmHg überprüft. Zur histologischen Auswertung wurden Gewebeproben entnommen, mittels H&E gefärbt und lichtmikroskopisch untersucht.
    
    Ergebnisse
    Im Vergleich zur konventionellen bipolaren Schere konnte in der durchgeführten Studie die Anzahl der auftretenden Blutungen mit dem 2 µm Laserskalpell signifikant (25%) und die gesamte Resektionszeit um 19% (nicht signifikant) reduziert werden. Die Hämostase von Gefäßen, welche mittels des 2 µm Laserskalpells durchtrennt wurden, betrug bei Durchmessern <0.5 mm 100% bei den Arterien und 89% bei den Venen. Bei größeren Gefäßen (1–2.3 mm innerer Durchmesser) wurden 74% der Arterien und 65% der Venen dauerhaft in vivo koaguliert. Bei den in vitro Untersuchungen der koagulierten Gefäße mit einem Druck von 375 mmHg waren noch insgesamt 35% der Arterien und 30% der Venen verschlossen.
    
    In dieser Studie konnte gezeigt werden, dass das 2 µm Laserskalpell ein vielversprechendes Instrument für die laparoskopische Chirurgie darstellt.
    
    Resúmen
    En este estudio se investigó el potencial del nuevo láser cw thulium–YAG comparado al uso de la tijera bipolar estándar en intervenciones laparoscópicas en intestino delgado de cerdos.
    
    Método
    Se utilizó un láser thulium–YAG de estado sólido bombeado por diodos que emite en una longitud de onda de 2.01 µm. Una potencia láser de hasta 25 W de onda continua (cw) fue trasmitida a través de una fibra de cuarzo de 400 µm de diámetro. El mesenterio que acompaña al intestino delgado fue diseccionado utilizando uno de los dos sistemas en 12 cerdos (6 con cada instrumento). Se seccionaron in vivo, arterias y venas de 0.25 a 3.2 mm de diámetro interno y se midió in vitro la resistencia de los vasos ocluídos con una presión de hasta 375 mmHg. Las muestras fueron preparadas luego para evaluaciones histológicas.
    
    Resultados
    En la resección de intestino, el uso del bisturí láser de 2 µm ofrece menor sangrado (25%) y el reduce el tiempo de dissección en un 19% con respecto a las tijeras bipolares. Además, el uso del láser permite la oclusión in vivo de los pequeños vasos (diámetro menor a 0,5 mm) hasta en un 100% en arterias y un 89% en venas. Mientras que para las de mayor diámetro (de 1 a 2.3 mm) se obtuvo un 74% y 65%, respectivamente. En las mediciones in vitro de presión con 375 mmHg, un 30% de las venas y un 35% de las arterias permanecieron cerradas. En conclusión, estos primeros experimentos demuestran que el bisturí láser de 2 µm es una herramienta de disección prometedora para la cirugía laparoscópica. 
    
    Keywords: Thulium laser; Minimally invasive; Vessel sealing; Laser scalpel
    Schlüsselwörter: Thuliumlaser; Minimalinvasiv; Hämostase; Laserskalpell
    Palabras clave: Thulium láser; Cirugía mínimamente invasiva; Oclusión de vasos; Bisturí láser},
       year = {2007}
    }
  • Brinkmann, R. and Birngruber, R.: Selektive Retina-Therapie (SRT). Zeitschrift für Medizinische Physik, no. 17, pp. 6-22, 2007
    BibTeX Link
    @article{Brinkmann2007,
       author = {Brinkmann, R. and Birngruber, R.},
       title = {Selektive Retina-Therapie (SRT)},
       journal = {Zeitschrift für Medizinische Physik},
       volume = {17},
       number = {1},
       pages = {6-22},
       note = {276HP
    Times Cited:0
    Cited References Count:42},
       abstract = {Selective Retina Therapy (SRT) is a new and very gentle laser method developed at the Medical Laser Center Lubeck. It is currently investigated clinically in order to treat retinal disorders associated with a decreased function of the retinal pigment epithelium (RPE). SRT is designed to selectively effect the RPE while sparing the neural retina and the photoreceptors as well as the chorioidea. Aim of the therapy is the rejuvenation of the RPE in the treated areas, which should ideally lead to a long term metabolic increase at the chorio- retinal junction. In contrast to conventional laser photocoagulation, which is associated with a complete thermal necrosis of the treated site, SRT completely retains full vision. This paper reviews the methods and mechanisms behind selective RPE effects and reports the first clinical results. An online dosimetry technique to visualize the ophthalmoscopically invisible effects is introduced.},
       keywords = {selective cellular effects
    optoacoustics
    online dosimetry
    rpe
    mu s-laser pulses
    macula oedema
    rcs
    pigment epithelium
    diabetic maculopathy
    laser irradiation
    time regimen
    damage
    rpe
    photocoagulation
    absorption
    mechanisms
    radiation},
       ISSN = {0939-3889},
       DOI = {DOI 10.1016/j.zemedi.2006.11.002},
       url = {<Go to ISI>://WOS:000254132200002},
       year = {2007},
       type = {Journal Article}
    }
    
  • Schlott, Kerstin and Stalljohann, Jens and Weber, Benjamin and Kandulla, Jochen and Herrmann, Katharina and Birngruber, Reginald and Brinkmann, Ralf: Optoacoustic online temperature determination during retinal laser photocoagulation. no. 6632, pp. 66321B-66321B-8,
    BibTeX Link
    @inproceedings{Schlott2007,
       author = {Schlott, Kerstin and Stalljohann, Jens and Weber, Benjamin and Kandulla, Jochen and Herrmann, Katharina and Birngruber, Reginald and Brinkmann, Ralf},
       title = {Optoacoustic online temperature determination during retinal laser photocoagulation},
       volume = {6632},
       pages = {66321B-66321B-8},
       note = {10.1117/12.728291},
       abstract = {Retinal photocoagulation is an established treatment of different retinal diseases. The treatment relies on a short, local heating of the tissue which induces a denaturation. The resulting scar formation may for example prevent the further detachment of the retina. The extent of the coagulation is besides other parameters mostly dependent on the induced temperature increase. However, until today a temperature based dosimetry for photocoagulation does not exist. The dosage is rather based on the experience of the treating physicians to achieve visible whitish lesions on the retina. In this work a technique is presented, which allows an online temperature monitoring during photocoagulation. If an absorbing material is irradiated with short laser pulses, a thermoelastic expansion of the absorber induces an acoustic wave. Its amplitude is dependent on the temperature of the absorber. For analyzing the applicability of the optoacoustic temperature determination for dosimetry, measurements were performed on enucleated porcine eye globes. The pressure transients are detected by an ultrasonic transducer, which is embedded in an ophthalmologic contact lens. As long as no strong lesions occur, the determined temperatures are almost proportional to the power of the treatment laser. Using a spot diameter of 200 μm and different laser powers, the temperature rise at the end of the 400 ms irradiation was found to be approximately 0.16 °C/mW. The onset of the denaturation was observed around 50°C. The far aim of this project is an automatic regulation of the treatment laser onto a desired temperature course.},
       url = {http://dx.doi.org/10.1117/12.728291},
       type = {Conference Proceedings}
    }
    
  • Stoehr, Hardo and Ptaszynski, Lars and Fritz, Andreas and Brinkmann, Ralf: Interferometric optical online dosimetry for selective retina treatment (SRT). no. 6426, pp. 642619-642619-7,
    BibTeX Link
    @inproceedings{Stoehr2007,
       author = {Stoehr, Hardo and Ptaszynski, Lars and Fritz, Andreas and Brinkmann, Ralf},
       title = {Interferometric optical online dosimetry for selective retina treatment (SRT)},
       volume = {6426},
       pages = {642619-642619-7},
       note = {10.1117/12.708521},
       abstract = {In selective retina treatment (SRT) spatial confined tissue damage in the absorbing retinal pigment epithelium (RPE) is obtained by applying microsecond laser pulses. The damage in the RPE is caused by transient microbubbles forming around the laser heated melanin granules inside the cells. For treatment of RPE related diseases, SRT is thought to share the therapeutic benefits of conventional photocoagulation but without affecting the photoreceptors. A drawback for effective clinical SRT is that the laser-induced lesions are ophthalmoscopically invisible. Therefore, a real-time feedback system for dosimetry is demanded in order to avoid undertreatment or unwanted collateral damage to the adjacent tissue. We develop a dosimetry system which uses optical interferometry for the detection of the transient microbubbles. The system is based on an optical fiber interferometer which is operated with a laser diode at 830nm. We present current results obtained with porcine RPE explants in vitro and complete porcine eye globes ex vivo.},
       url = {http://dx.doi.org/10.1117/12.708521},
       type = {Conference Proceedings}
    }
    
  • Framme, C. and Alt, C. and Schnell, S. and Sherwood, M. and Brinkmann, R. and Lin, C. P.: Selective targeting of the retinal pigment epithelium in rabbit eyes with a scanning laser beam. Invest Ophthalmol Vis Sci, no. 48, pp. 1782-92, 2007
    BibTeX
    @article{Framme,
       author = {Framme, C. and Alt, C. and Schnell, S. and Sherwood, M. and Brinkmann, R. and Lin, C. P.},
       title = {Selective targeting of the retinal pigment epithelium in rabbit eyes with a scanning laser beam},
       journal = {Invest Ophthalmol Vis Sci},
       volume = {48},
       number = {4},
       pages = {1782-92},
       note = {0146-0404 (Print)
    Journal Article
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't},
       abstract = {PURPOSE: Selective targeting of the retinal pigment epithelium (RPE) with repetitive laser pulses that minimize thermal damage to the adjacent photoreceptors is a promising new therapeutic modality for RPE-related retinal diseases. The selectivity of an alternative, more versatile scanning approach was examined in vivo by using a broad range of scanning parameters. METHODS: Acousto-optic deflectors repeatedly scanned the focus of a continuous wave (cw)-laser across the retina of Dutch belted rabbits, producing microsecond irradiation at each RPE cell. Two irradiation patterns forming separated lines (SEP) or interlaced lines (INT), different dwell times (2.5-75 micros), and repetition numbers (10 and 100 scans with 100-Hz repetition rate) were tested. Thresholds were evaluated by fundus imaging and angiography. Histology was performed for selected parameters. RESULTS: Selective RPE cell damage was obtained with moderate laser power. The angiographic threshold power decreased with pulse duration, number of exposures, and applying the INT pattern. Ophthalmoscopic thresholds, indicating onset of thermal coagulation, were higher than twice the angiographic threshold for most tested parameters. Histology confirmed selective RPE cell damage for SEP irradiation with 7.5 and 15 micros; slower scan speeds or closed lines caused photoreceptor damage. CONCLUSIONS: A cw-laser scanner can be set up as a highly compact and versatile device. Selective RPE damage is feasible with dwell times up to 15 micros. Greatest selectivity is achieved with short exposure times and separated scan lines. Interlaced lines and long exposure times facilitate heat conduction into photoreceptors. A scanner is an attractive alternative for pulsed selective targeting, because both selective targeting and thermal photocoagulation can be realized.},
       keywords = {Animals
    Eye Injuries/diagnosis
    Fluorescein Angiography
    Laser Coagulation/adverse effects/instrumentation/*methods
    Ophthalmoscopy
    Photoreceptors, Vertebrate/pathology
    Pigment Epithelium of Eye/injuries/pathology/*surgery
    Rabbits
    Retina/injuries/pathology},
       year = {2007}
    }
  • Kandulla, J and Brinkmann, R: Nicht-invasive Echtzeit-Temperaturbestimmung während Laserbehandlungen an der Netzhaut des Auges. Photonik 2, pp. 42-46, 007
    BibTeX Link
    @article{Kandulla,
       author = {Kandulla, J and Brinkmann, R},
       title = {Nicht-invasive Echtzeit-Temperaturbestimmung während Laserbehandlungen an der Netzhaut des Auges},
       journal = {Photonik} {2},
       URL = {https://www.photonik.de/technologie-applikation/158/21005/22},
       pages = {42-46},
       year = {2007}
    }
  • Neumann, J and Brinkmann, R: Nucleation dynamics around single microabsorbers in water heated by nanosecond irradiation. J Appl Phys, no. 101, 2007
    BibTeX
    @article{Neumann,
       author = {Neumann, J and Brinkmann, R},
       title = {Nucleation dynamics around single microabsorbers in water heated by nanosecond irradiation},
       journal = {J Appl Phys},
       volume = {101},
       number = {114701},
       year = {2007}
    }
  • Brinkmann, R. and Birngruber, R.: [Selective Retina Therapy (SRT)]. Z Med Phys, no. 17, pp. 6-22, 007
    BibTeX
    @article{Brinkmann2007,
       author = {Brinkmann, R. and Birngruber, R.},
       title = {[Selective Retina Therapy (SRT)]},
       journal = {Z Med Phys},
       volume = {17},
       number = {1},
       pages = {6-22},
       note = {Brinkmann, Ralf
    Birngruber, Reginald
    English Abstract
    Review
    Germany
    Z Med Phys. 2007;17(1):6-22.},
       abstract = {Selective Retina Therapy (SRT) is a new and very gentle laser method developed at the Medical Laser Center Lubeck. It is currently investigated clinically in order to treat retinal disorders associated with a decreased function of the retinal pigment epithelium (RPE). SRT is designed to selectively effect the RPE while sparing the neural retina and the photoreceptors as well as the chorioidea. Aim of the therapy is the rejuvenation of the RPE in the treated areas, which should ideally lead to a long term metabolic increase at the chorio-retinal junction. In contrast to conventional laser photocoagulation, which is associated with a complete thermal necrosis of the treated site, SRT completely retains full vision. This paper reviews the methods and mechanisms behind selective RPE effects and reports the first clinical results. An online dosimetry technique to visualize the ophthalmoscopically invisible effects is introduced.},
       keywords = {Humans
    Laser Therapy
    Pigment Epithelium of Eye/pathology
    Regeneration
    Retinal Diseases/pathology/surgery/ therapy},
       year = {2007}
    }
    
  • Brinkmann, R and Stalljohann, J and Weber, B and Schlott, K and Kandulla, J and Birngruber, R: Retinal Temperature Determination During Laser Photocoagulation. Proc SPIE, no. 6632, pp. 8, 2007
    BibTeX
    @article{Brinkmann2007,
       author = {Brinkmann, R and Stalljohann, J and Weber, B  and Schlott, K and Kandulla, J and Birngruber, R},
       title = {Retinal Temperature Determination During Laser Photocoagulation},
       journal = {Proc SPIE},
       volume = {6632},
       pages = {8},
       year = {2007},
       type = {Journal Article}
    }
    
  • Framme, C and Brinkmann, R: Die Selektive Retina Therapie (SRT). Der Augenspiegel, no. 53G1396, 2007
    BibTeX
    @article{Framme,
       author = {Framme, C and Brinkmann, R},
       title = {Die Selektive Retina Therapie (SRT)},
       journal = {Der Augenspiegel},
       volume = {53G1396},
       number = {11},
       year = {2007}
    }
  • Stoehr, Hardo and Ptaszynski, Lars and Fritz, Andreas and Brinkmann, Ralf: Interferometric optical online dosimetry for selective retina treatment (SRT). no. 6426, pp. 642619-642619-7,
    BibTeX
    @inproceedings{Stoehr2007,
       author = {Stoehr, Hardo and Ptaszynski, Lars and Fritz, Andreas and Brinkmann, Ralf},
       title = {Interferometric optical online dosimetry for selective retina treatment (SRT)},
       volume = {6426},
       pages = {642619-642619-7},
       note = {10.1117/12.708521},
       abstract = {In selective retina treatment (SRT) spatial confined tissue damage in the absorbing retinal pigment epithelium (RPE) is obtained by applying microsecond laser pulses. The damage in the RPE is caused by transient microbubbles forming around the laser heated melanin granules inside the cells. For treatment of RPE related diseases, SRT is thought to share the therapeutic benefits of conventional photocoagulation but without affecting the photoreceptors. A drawback for effective clinical SRT is that the laser-induced lesions are ophthalmoscopically invisible. Therefore, a real-time feedback system for dosimetry is demanded in order to avoid undertreatment or unwanted collateral damage to the adjacent tissue. We develop a dosimetry system which uses optical interferometry for the detection of the transient microbubbles. The system is based on an optical fiber interferometer which is operated with a laser diode at 830nm. We present current results obtained with porcine RPE explants in vitro and complete porcine eye globes ex vivo.},
       url = {http://dx.doi.org/10.1117/12.708521},
       type = {Conference Proceedings}
    }
    
  • Fritz, Andreas and Ptaszynski, Lars and Stoehr, Hardo and Brinkmann, Ralf: Dynamics and detection of laser induced microbubbles in the retinal pigment epithelium (RPE). no. 6632, pp. 66321C-66321C-11,
    BibTeX
    @inproceedings{Fritz2007,
       author = {Fritz, Andreas and Ptaszynski, Lars and Stoehr, Hardo and Brinkmann, Ralf},
       title = {Dynamics and detection of laser induced microbubbles in the retinal pigment epithelium (RPE)},
       volume = {6632},
       pages = {66321C-66321C-11},
       note = {10.1117/12.728344},
       abstract = {Selective Retina Treatment (SRT) is a new method to treat eye diseases associated with disorders of the RPE. Selective RPE cell damage is achieved by applying a train of 1.7 μs laser pulses at 527 nm. The treatment of retinal diseases as e.g. diabetic maculopathy (DMP), is currently investigated within clinical studies, however 200 ns pulse durations are under investigation. Transient micro bubbles in the retinal pigment epithelium (RPE) are expected to be the origin of cell damage due to irradiation with laser pulses shorter than 50 μs. The bubbles emerge at the strongly absorbing RPE melanosomes. Cell membrane disruption caused by the transient associated volume increase is expected to be the origin of the angiographically observed RPE leakage. We investigate micro bubble formation and dynamics in porcine RPE using pulse durations of 150 ns. A laser interferometry system at 830 nm with the aim of an online dosimetry control for SRT was developed. Bubble formation was detected interferometrically and by fast flash photography. A correlation to cell damage observed with a vitality stain is found. A bubble detection algorithm is presented.},
       url = {http://dx.doi.org/10.1117/12.728344},
       type = {Conference Proceedings}
    }
    
  • Theisen-Kunde, D and Tedsen, S and Danicke, V and Herrmann, K and Brinkmann, R: Partial kidney resection by use of a 1,94 µm thulium fiber laser. in Proc ECBO, no. 6632, SPIE,
    BibTeX
    @inproceedings{Theisen-Kunde2007,
       author = {Theisen-Kunde, D and Tedsen, S and Danicke, V and Herrmann, K and Brinkmann, R},
       title = {Partial kidney resection by use of a 1,94 µm thulium fiber laser},
       booktitle = {Proc ECBO},
       series = {Therapeutic Laser Applications and Laser-Tissue Interactions},
       publisher = {SPIE},
       volume = {6632},
       type = {Conference Proceedings}
    }
    

2006

  • Elsner, H and Pörksen, E and Klatt, C and Bunse, A and Theisen-Kunde, D and Brinkmann, R and Birngruber, R and Laqua, H and Roider, J: Selective Retina Therapy (SRT) in patients with central serous chorioretinopathy (CSC). Graefes Arch Ophthalmol, in print., no. on-line: DOI 10.1007/s00417-006-0368-5, 2006
    BibTeX
    @article{Elsner2006,
       author = {Elsner, H and Pörksen, E and Klatt, C and Bunse, A and Theisen-Kunde, D and Brinkmann, R and Birngruber, R and Laqua, H and Roider, J},
       title = {Selective Retina Therapy (SRT) in patients with central serous chorioretinopathy (CSC)},
       journal = {Graefes Arch Ophthalmol, in print.},
       volume = {on-line: DOI 10.1007/s00417-006-0368-5},
       year = {2006},
       type = {Journal Article}
    }
    
  • Klatt, C. and Elsner, H. and Porksen, E. and Brinkmann, R. and Bunse, A. and Birngruber, R. and Roider, J.: Selective retina therapy in central serous chorioretinopathy with detachment of the pigmentary epithelium. Ophthalmologe, no. 103, pp. 850-5, 2006
    BibTeX Link
    @article{Klatt2006,
       author = {Klatt, C. and Elsner, H. and Porksen, E. and Brinkmann, R. and Bunse, A. and Birngruber, R. and Roider, J.},
       title = {Selective retina therapy in central serous chorioretinopathy with detachment of the pigmentary epithelium},
       journal = {Ophthalmologe},
       volume = {103},
       number = {10},
       pages = {850-5},
       note = {0941-293X (Print)
    Case Reports
    English Abstract
    Journal Article},
       abstract = {BACKGROUND: Selective Retina Therapy (SRT) is a new and innovative laser treatment modality that selectively treats the retinal pigmentary epithelium while sparing the photoreceptors. This therapeutic concept appears to be particularly suitable for treating patients with acute or chronic central serous chorioretinopathy (CSC). We present preliminary results obtained in five patients who had CSC associated with pigmentary epithelium detachment (PED) and serous subretinal fluid (SRF) and who were treated with SRT. METHODS: This case series was made up of five male patients (mean age 47 years) with chronic CSC and SRF resulting from PED. Examinations performed before and at 1 month and 3 months after the treatment were: BCVA, FLA, OCT (Zeiss OCT III). For SRT, confluent treatment of the PED (area of leakage) was carried out using a pulsed frequency-doubled, Q-switched Nd-YLF prototype laser (lambda=527 nm, t= 1.7 s, 100 Hz, energy = 150-250 J). RESULTS: Best corrected visual acuity at baseline was 0.53, while after 4 weeks it was 0.56 and after 12 weeks, 0.5. At baseline leakage was seen at the PED on fluorescein angiography in all patients. After 4 weeks leakage activity was no longer noted on angiography in 4 of 5 patients. OCT at baseline showed SRF at the edge of the PED in all patients, but in 4 of the 5 patients this was no longer detectable after 4 weeks. CONCLUSION: SRT is a safe and effective treatment for patients with CSC in which PED has caused SRF. Not a single case of rip syndrome was observed in this study, even though the PED was treated confluently. Since SRT spares the photoreceptors it is particularly suitable for the treatment of CSC, especially when the origin of leakage is located close to the fovea. The results indicate that SRT leads to reconstruction of the outer blood-retina barrier.},
       keywords = {Adult
    Chorioretinitis/complications/*surgery
    Humans
    Laser Surgery/*methods
    Lasers/*therapeutic use
    Male
    Middle Aged
    Ophthalmologic Surgical Procedures/*methods
    Preoperative Care/methods
    Retinal Detachment/etiology/*surgery
    Treatment Outcome},
       url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16937094},
       year = {2006},
       type = {Journal Article}
    }
    
  • Kandulla, J. and Elsner, H. and Birngruber, R. and Brinkmann, R.: Noninvasive optoacoustic online retinal temperature determination during continuous-wave laser irradiation. Journal of Biomedical Optics, no. 11, 2006
    BibTeX Link
    @article{Kandulla2006,
       author = {Kandulla, J. and Elsner, H. and Birngruber, R. and Brinkmann, R.},
       title = {Noninvasive optoacoustic online retinal temperature determination during continuous-wave laser irradiation},
       journal = {Journal of Biomedical Optics},
       volume = {11},
       number = {4},
       note = {093IM
    Times Cited:30
    Cited References Count:40},
       abstract = {The therapeutic effect of most retinal laser treatments is initiated by a transient temperature increase. Although crucial to the effectiveness of the treatment, the temperature course is not exactly known due to individually different tissue properties. We develop an optoacoustic method to determine the retinal temperature increase in real time during continuous-wave (cw) laser irradiation, and perform temperature calculations to interpret the results exemplary for transpupillary thermotherapy (TTT). Porcine globes ex vivo and rabbit eyes in vivo are irradiated with a diode laser (lambda=810 nm, P <= 3 W, phi = 2 mm) for 60 s. Simultaneously, pulses from a N-2-laser pumped dye laser (lambda= 500 nm, tau= 3.5 ns, E approximate to 5 mu J) are applied on the retina. Following its absorption, an ultrasonic pressure wave is emitted, which is detected by a transducer embedded in a contact lens. Using the previously measured temperature-dependent Gruneisen coefficient of chorioretinal tissue, a temperature raise in porcine eyes of 5.8 degrees C/ (W/cm(2)) after 60 s is observed and confirmed by simultaneous measurements with an inserted thermocouple. In a rabbit, we find 1.4 degrees C/(W/cm(2)) with, and 2.2 degrees C/(W/cm(2)) without perfusion at the same location. Coagulation of the rabbit's retina occurs at Delta T = 21 degrees C after 40 s. In conclusion, this optoacoustic method seems feasible for an in vivo real-time determination of temperature, opening the possibility for feedback control retinal laser treatments. (c) 2006 Society of Photo-Optical Instrumentation Engineers.},
       keywords = {temperature
    optoacoustics
    transpupillary thermotherapy
    ultrasonic transducer
    laser
    heat diffusion calculations
    retinal laser treatment
    subfoveal choroidal neovascularization
    transpupillary thermotherapy
    macular degeneration
    ocular media
    blood flow
    eye
    fundus
    light
    photocoagulation
    transmission},
       ISSN = {1083-3668},
       DOI = {Artn 041111
    Doi 10.1117/1.2236301},
       url = {<Go to ISI>://WOS:000241162000016},
       year = {2006},
       type = {Journal Article}
    }
    
  • Brinkmann, Ralf and Birngruber, Reginald: Selektive Retina-Therapie (SRT). Zeitschrift für Medizinische Physik, no. 17, pp. 6-22, 006
    BibTeX
    @article{Brinkmann2006,
       author = {Brinkmann, Ralf and Birngruber, Reginald},
       title = {Selektive Retina-Therapie (SRT)},
       journal = {Zeitschrift für Medizinische Physik},
       volume = {17},
       number = {1},
       pages = {6-22},
       abstract = {Zusammenfassung Die am Medizinischen Laserzentrum Lübeck entwickelte selektive Retina-Therapie (SRT) wird zur Zeit als neue, schonende Laser-Behandlungsmethode für verschiedene Erkrankungen des Augenhintergrunds evaluiert, deren Ursachen einer Degradation des Retinalen Pigmentepithels (RPE) zugeschrieben werden. Mit der SRT lässt sich selektiv das RPE behandeln, ohne die angrenzende neurosensorische Netzhaut mit den Photorezeptoren und die unter dem RPE liegende Aderhaut (Choroidea) zu beeinträchtigen. Die Therapie führt idealerweise zu einer Regeneration des RPEs und einem gesteigerten Metabolismus am chorio-retinalen Übergang. Im Gegensatz zur etablierten Laserphotokoagulation, bei der die Netzhaut in und um die bestrahlten Areale komplett verödet wird, bleibt bei der SRT die Sehfähigkeit der Patienten in den bestrahlten Arealen erhalten. Der Artikel gibt einen Überblick über die Idee und die physikalischen Mechanismen selektiver RPE-Behandlung, die online Dosimetrie der optisch nicht sichtbaren Effekte und fasst die ersten klinischen Ergebnisse zusammen. Selective Retina Therapy (SRT) is a new and very gentle laser method developed at the Medical Laser Center Lübeck. It is currently investigated clinically in order to treat retinal disorders associated with a decreased function of the retinal pigment epithelium (RPE). SRT is designed to selectively effect the RPE while sparing the neural retina and the photoreceptors as well as the chorioidea. Aim of the therapy is the rejuvenation of the RPE in the treated areas, which should ideally lead to a long term metabolic increase at the chorio-retinal junction. In contrast to conventional laser photocoagulation, which is associated with a complete thermal necrosis of the treated site, SRT completely retains full vision. This paper reviews the methods and mechanisms behind selective RPE effects and reports the first clinical results. An online dosimetry technique to visualize the ophthalmoscopically invisible effects is introduced.},
       keywords = {Selektive Zelleffekte, Optoakustik, Mikroblasen, Online-Dosimetrie, RPE, ?s-Laserpulse, Makulaödeme, RCS
    Selective cellular effects, optoacoustics, online dosimetry, RPE, ?s-laser pulses, macula oedema, RCS},
       year = {2006}
    }
  • Brinkmann, Ralf and Birngruber, Reginald: Selektive Retina-Therapie (SRT). Zeitschrift für Medizinische Physik, no. 17, pp. 6-22, 006
    BibTeX
    @article{Brinkmann2006,
       author = {Brinkmann, Ralf and Birngruber, Reginald},
       title = {Selektive Retina-Therapie (SRT)},
       journal = {Zeitschrift für Medizinische Physik},
       volume = {17},
       number = {1},
       pages = {6-22},
       abstract = {Zusammenfassung Die am Medizinischen Laserzentrum Lübeck entwickelte selektive Retina-Therapie (SRT) wird zur Zeit als neue, schonende Laser-Behandlungsmethode für verschiedene Erkrankungen des Augenhintergrunds evaluiert, deren Ursachen einer Degradation des Retinalen Pigmentepithels (RPE) zugeschrieben werden. Mit der SRT lässt sich selektiv das RPE behandeln, ohne die angrenzende neurosensorische Netzhaut mit den Photorezeptoren und die unter dem RPE liegende Aderhaut (Choroidea) zu beeinträchtigen. Die Therapie führt idealerweise zu einer Regeneration des RPEs und einem gesteigerten Metabolismus am chorio-retinalen Übergang. Im Gegensatz zur etablierten Laserphotokoagulation, bei der die Netzhaut in und um die bestrahlten Areale komplett verödet wird, bleibt bei der SRT die Sehfähigkeit der Patienten in den bestrahlten Arealen erhalten. Der Artikel gibt einen Überblick über die Idee und die physikalischen Mechanismen selektiver RPE-Behandlung, die online Dosimetrie der optisch nicht sichtbaren Effekte und fasst die ersten klinischen Ergebnisse zusammen. Selective Retina Therapy (SRT) is a new and very gentle laser method developed at the Medical Laser Center Lübeck. It is currently investigated clinically in order to treat retinal disorders associated with a decreased function of the retinal pigment epithelium (RPE). SRT is designed to selectively effect the RPE while sparing the neural retina and the photoreceptors as well as the chorioidea. Aim of the therapy is the rejuvenation of the RPE in the treated areas, which should ideally lead to a long term metabolic increase at the chorio-retinal junction. In contrast to conventional laser photocoagulation, which is associated with a complete thermal necrosis of the treated site, SRT completely retains full vision. This paper reviews the methods and mechanisms behind selective RPE effects and reports the first clinical results. An online dosimetry technique to visualize the ophthalmoscopically invisible effects is introduced.},
       keywords = {Selektive Zelleffekte, Optoakustik, Mikroblasen, Online-Dosimetrie, RPE, ?s-Laserpulse, Makulaödeme, RCS
    Selective cellular effects, optoacoustics, online dosimetry, RPE, ?s-laser pulses, macula oedema, RCS},
       year = {2006}
    }
  • Elsner, H. and Klatt, C. and Liew, S. H. and Porksen, E. and Bunse, A. and Rudolf, M. and Brinkmann, R. and Hamilton, R. P. and Birngruber, R. and Laqua, H. and Roider, J.: Selektive Retina Therapiey (SRT) bei Patienten mit diabetischer Makulopathie. Ophthalmologe, no. 103, pp. 856-860, 2006
    BibTeX
    @article{Elsner2006,
       author = {Elsner, H. and Klatt, C. and Liew, S. H. and Porksen, E. and Bunse, A. and Rudolf, M. and Brinkmann, R. and Hamilton, R. P. and Birngruber, R. and Laqua, H. and Roider, J.},
       title = {Selektive Retina Therapiey (SRT) bei Patienten mit diabetischer Makulopathie},
       journal = {Ophthalmologe},
       volume = {103},
       number = {10},
       pages = {856-860},
       note = {0941-293X (Print)
    Journal article},
       abstract = {Selective Retina Therapy (SRT) is a new laser treatment that selectively targets the retinal pigmen epithelium (RPE). In this study, we treated 39 patients presenting with nonischemic, focal and focal-diffuse diabetic maculopathy with SRT. In the main. the results indicate that SRT had stabilizing effects on visual acuity, angiographic leakage, lipid exudation, and foveal retinal thickness. SRT is safe and is especially useful for treating pathologies that are located close to the fovea, which cannot be treated with conventional argon laser photocoagulation.},
       url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16937095},
       year = {2006},
       type = {Journal Article}
    }
    
  • Kandulla, J and Elsner, H and Sandeau, J and Birngruber, R and Brinkmann, R: Non-invasive optoacoustic temperature determination during retinal cw-laser treatments. in Proc SPIE, no. 6138, pp. 336-343,
    BibTeX
    @inproceedings{Kandulla2006,
       author = {Kandulla, J and Elsner, H and Sandeau, J and Birngruber, R and Brinkmann, R},
       title = {Non-invasive optoacoustic temperature determination during retinal cw-laser treatments},
       booktitle = {Proc SPIE},
       volume = {6138},
       pages = {336-343},
       type = {Conference Proceedings}
    }
    
  • Brinkmann, R. and Roider, J. and Birngruber, R.: Selective retina therapy (SRT): a review on methods, techniques, preclinical and first clinical results. Bull Soc Belge Ophtalmol, pp. 51-69, 006
    BibTeX
    @article{Brinkmann2006,
       author = {Brinkmann, R. and Roider, J. and Birngruber, R.},
       title = {Selective retina therapy (SRT): a review on methods, techniques, preclinical and first clinical results},
       journal = {Bull Soc Belge Ophtalmol},
       number = {302},
       pages = {51-69},
       note = {0081-0746 (Print)
    Journal Article
    Review},
       abstract = {Selective retina therapy (SRT) is a new laser procedure for retinal diseases that are thought to be associated with a degradation of the retinal pigment epithelium (RPE). The aim of the irradiation is to selectively damage the RPE without affecting the neural retina, the photoreceptors and the choroid. Goal of the treatment is to stimulate RPE cell migration and proliferation into the irradiated areas in order to improve the metabolism at the diseased retinal sites. In a pilot study more than 150 patients with soft drusen, retinopathia centralis serosa (RCS) and macular edema were treated. The first 3-center international trial targets diabetic macular edema and branch vein occlusion. In this review, selective RPE effects are motivated and two modalities to achieve selective RPE effects will be introduced: a pulsed and a continuous wave scanning mode. The mechanism behind selective RPE-effects will be discussed reviewing in vitro results and temperature calculations. So far clinical SRT is performed by applying trains of 30 laser pulses from a Nd:YLF-Laser (527 nm, 1.7 micros, 100 Hz) to the diseased fundus areas. In the range of 450-800 mJ/cm(2) per pulse, RPE-defects in patients were proved angiographically by fluorescein or ICG-leakage. The selectivity with respect to surrounding highly sensitive tissue and the safety range of the treatment will be reviewed. With the laser parameters used neither bleeding nor scotoma, proved by microperimetry, were observed thus demonstrating no adverse effects to the choroid and the photoreceptors, respectively. During and after irradiation, it shows that the irradiated locations are ophthalmoscopically invisible, since the effects are very limited and confined to the RPE, thus a dosimetry control is demanded. We report on a non-invasive opto-acoustic on-line technique to monitor successful RPE-irradiation and compare the data to those achieved with standard angiography one-hour post treatment.},
       keywords = {Fluorescein Angiography
    Humans
    Laser Coagulation/adverse effects/*methods
    Multicenter Studies
    Perimetry
    Pigment Epithelium of Eye/pathology/surgery
    Retinal Diseases/diagnosis/pathology/*surgery
    Scotoma/etiology/prevention & control},
       year = {2006}
    }
  • Brinkmann, R. and Roider, J. and Birngruber, R.: Selective retina therapy (SRT): a review on methods, techniques, preclinical and first clinical results. Bull Soc Belge Ophtalmol, pp. 51-69, 006
    BibTeX
    @article{Brinkmann2006,
       author = {Brinkmann, R. and Roider, J. and Birngruber, R.},
       title = {Selective retina therapy (SRT): a review on methods, techniques, preclinical and first clinical results},
       journal = {Bull Soc Belge Ophtalmol},
       number = {302},
       pages = {51-69},
       note = {0081-0746 (Print)
    Journal Article
    Review},
       abstract = {Selective retina therapy (SRT) is a new laser procedure for retinal diseases that are thought to be associated with a degradation of the retinal pigment epithelium (RPE). The aim of the irradiation is to selectively damage the RPE without affecting the neural retina, the photoreceptors and the choroid. Goal of the treatment is to stimulate RPE cell migration and proliferation into the irradiated areas in order to improve the metabolism at the diseased retinal sites. In a pilot study more than 150 patients with soft drusen, retinopathia centralis serosa (RCS) and macular edema were treated. The first 3-center international trial targets diabetic macular edema and branch vein occlusion. In this review, selective RPE effects are motivated and two modalities to achieve selective RPE effects will be introduced: a pulsed and a continuous wave scanning mode. The mechanism behind selective RPE-effects will be discussed reviewing in vitro results and temperature calculations. So far clinical SRT is performed by applying trains of 30 laser pulses from a Nd:YLF-Laser (527 nm, 1.7 micros, 100 Hz) to the diseased fundus areas. In the range of 450-800 mJ/cm(2) per pulse, RPE-defects in patients were proved angiographically by fluorescein or ICG-leakage. The selectivity with respect to surrounding highly sensitive tissue and the safety range of the treatment will be reviewed. With the laser parameters used neither bleeding nor scotoma, proved by microperimetry, were observed thus demonstrating no adverse effects to the choroid and the photoreceptors, respectively. During and after irradiation, it shows that the irradiated locations are ophthalmoscopically invisible, since the effects are very limited and confined to the RPE, thus a dosimetry control is demanded. We report on a non-invasive opto-acoustic on-line technique to monitor successful RPE-irradiation and compare the data to those achieved with standard angiography one-hour post treatment.},
       keywords = {Fluorescein Angiography
    Humans
    Laser Coagulation/adverse effects/*methods
    Multicenter Studies
    Perimetry
    Pigment Epithelium of Eye/pathology/surgery
    Retinal Diseases/diagnosis/pathology/*surgery
    Scotoma/etiology/prevention & control},
       year = {2006}
    }
  • Brinkmann, R and Schuele, G. and Neumann, J. and Framme, C. and Pörkensen, E. and Elsner, H. and Theisen-Kunde, D and Roider, J. and Birngruber, R.: Selektive Retina Therapie - Methodik, Technik und Online-Dosimetrie. Ophthalmologe, no. 103, pp. 839-849, 006
    BibTeX
    @article{Brinkmann2006,
       author = {Brinkmann, R and Schuele, G. and Neumann, J. and Framme, C. and Pörkensen, E. and Elsner, H. and Theisen-Kunde, D and Roider, J. and Birngruber, R.},
       title = {Selektive Retina Therapie - Methodik, Technik und Online-Dosimetrie},
       journal = {Ophthalmologe},
       volume = {103},
       pages = {839-849},
       year = {2006}
    }
  • Neumann, J. and Brinkmann, R: Cell disintegration by laser-induced transient microbubbles and its simultaneous monitoring by interferometry. Journal of Biomedical Optics, no. 11, pp. 041112-1 - 041112-11, 2006
    BibTeX
    @article{Neumann,
       author = {Neumann, J. and Brinkmann, R},
       title = {Cell disintegration by laser-induced transient microbubbles and its simultaneous monitoring by interferometry},
       journal = {Journal of Biomedical Optics},
       volume = {11},
       number = {4},
       pages = {041112-1 - 041112-11},
       year = {2006}
    }
  • Klatt, C. and Elsner, H. and Porksen, E. and Brinkmann, R. and Bunse, A. and Birngruber, R. and Roider, J.: Selektive Retina-Therapie bei Retinopathia centralis serosa mit Pigmentepithelabhebung. Ophthalmologe, no. 103, pp. 850-855, Aug, 2006
    BibTeX
    @article{Klatt,
       author = {Klatt, C. and Elsner, H. and Porksen, E. and Brinkmann, R. and Bunse, A. and Birngruber, R. and Roider, J.},
       title = {Selektive Retina-Therapie bei Retinopathia centralis serosa mit Pigmentepithelabhebung},
       journal = {Ophthalmologe},
       volume = {103},
       number = {10},
       pages = {850-855},
       note = {0941-293X (Print)
    Clinical Trial
    English Abstract
    Journal Article},
       month = {Aug},
       abstract = {Selective Retina Therapy (SRT) is a new laser treatment that selectively targets the retinal pigmen epithelium (RPE). In this study, we treated 39 patients presenting with nonischemic, focal and focal-diffuse diabetic maculopathy with SRT. In the main. the results indicate that SRT had stabilizing effects on visual acuity, angiographic leakage, lipid exudation, and foveal retinal thickness. SRT is safe and is especially useful for treating pathologies that are located close to the fovea, which cannot be treated with conventional argon laser photocoagulation.},
       keywords = {Aged
    Diabetic Retinopathy/*surgery
    Female
    Humans
    Laser Surgery/*methods
    Lasers/*therapeutic use
    Macular Degeneration/*surgery
    Male
    Ophthalmologic Surgical Procedures/*methods
    Preoperative Care/methods
    Treatment Outcome},
       year = {2006}
    }
  • Kandulla, J. and Elsner, H. and Birngruber, R. and Brinkmann, R.: Noninvasive optoacoustic online retinal temperature determination during continuous-wave laser irradiation. J Biomed Opt, no. 11, pp. 041111, 2006
    BibTeX
    @article{Kandulla,
       author = {Kandulla, J. and Elsner, H. and Birngruber, R. and Brinkmann, R.},
       title = {Noninvasive optoacoustic online retinal temperature determination during continuous-wave laser irradiation},
       journal = {J Biomed Opt},
       volume = {11},
       number = {4},
       pages = {041111},
       note = {1083-3668 (Print)
    In Vitro
    Journal Article
    Research Support, Non-U.S. Gov't},
       abstract = {The therapeutic effect of most retinal laser treatments is initiated by a transient temperature increase. Although crucial to the effectiveness of the treatment, the temperature course is not exactly known due to individually different tissue properties. We develop an optoacoustic method to determine the retinal temperature increase in real time during continuous-wave (cw) laser irradiation, and perform temperature calculations to interpret the results exemplary for transpupillary thermotherapy (TTT). Porcine globes ex vivo and rabbit eyes in vivo are irradiated with a diode laser (lambda=810 nm, P< or =3 W, phi=2 mm) for 60 s. Simultaneously, pulses from a N2-laser pumped dye laser (lambda=500 nm, tau=3.5 ns, E approximately 5 microJ) are applied on the retina. Following its absorption, an ultrasonic pressure wave is emitted, which is detected by a transducer embedded in a contact lens. Using the previously measured temperature-dependent Gruneisen coefficient of chorioretinal tissue, a temperature raise in porcine eyes of 5.8 degrees C(Wcm2) after 60 s is observed and confirmed by simultaneous measurements with an inserted thermocouple. In a rabbit, we find 1.4 degrees C(Wcm2) with, and 2.2 degrees C(Wcm2) without perfusion at the same location. Coagulation of the rabbit's retina occurs at DeltaT=21 degrees C after 40 s. In conclusion, this optoacoustic method seems feasible for an in vivo real-time determination of temperature, opening the possibility for feedback control retinal laser treatments.},
       keywords = {Animals
    Body Temperature/physiology/radiation effects
    Equipment Design
    Equipment Failure Analysis
    Feasibility Studies
    Hyperthermia, Induced/*instrumentation
    Lasers/*therapeutic use
    Online Systems
    Rabbits
    Reproducibility of Results
    Retina/*physiology/*radiation effects/ultrasonography
    Sensitivity and Specificity
    Swine
    Thermography/*instrumentation/methods
    Ultrasonography/*instrumentation/methods},
       year = {2006}
    }
  • Elsner, H and Pörksen, E and Klatt, C and Bunse, A and Theisen-Kunde, D and Brinkmann, R and Birngruber, R and Laqua, H and Roider, J: Selective Retina Therapy (SRT) in patients with central serous chorioretinopathy (CSC). Graefes Arch Ophthalmol, in print., no. on-line: DOI 10.1007/s00417-006-0368-5, 2006
    BibTeX
    @article{Elsner,
       author = {Elsner, H and Pörksen, E and Klatt, C and Bunse, A and Theisen-Kunde, D and Brinkmann, R and Birngruber, R and Laqua, H and Roider, J},
       title = {Selective Retina Therapy (SRT) in patients with central serous chorioretinopathy (CSC)},
       journal = {Graefes Arch Ophthalmol, in print.},
       volume = {on-line: DOI 10.1007/s00417-006-0368-5},
       year = {2006}
    }

2005

  • Poerksen, E. and Elsner, H. and Theisen-Kunde, D. and Schuele, G. and Hamilton, P. and Laqua, H. and Birngruber, R. and Brinkmann, R. and Roider, J.: Selective retina treatment (SRT): Clinical investigation of an optoacoustic on-line dosimetry control. Investigative Ophthalmology & Visual Science, no. 46, 2005
    BibTeX Link
    @article{Poerksen2005,
       author = {Poerksen, E. and Elsner, H. and Theisen-Kunde, D. and Schuele, G. and Hamilton, P. and Laqua, H. and Birngruber, R. and Brinkmann, R. and Roider, J.},
       title = {Selective retina treatment (SRT): Clinical investigation of an optoacoustic on-line dosimetry control},
       journal = {Investigative Ophthalmology & Visual Science},
       volume = {46},
       note = {Suppl. S
    911CZ
    294
    Times Cited:0
    Cited References Count:0},
       ISSN = {0146-0404},
       url = {<Go to ISI>://WOS:000227980400286},
       year = {2005},
       type = {Journal Article}
    }
    
  • Neumann, J and Brinkmann, R: Boiling nucleation on melanosomes and microbeads transiently heated by nanosecond and microsecond laser pulses.. J Biomed Optics, no. 10, pp. 024001, 2005
    BibTeX
    @article{Neumann,
       author = {Neumann, J and Brinkmann, R},
       title = {Boiling nucleation on melanosomes and microbeads transiently heated by nanosecond and microsecond laser pulses.},
       journal = {J Biomed Optics},
       volume = {10},
       number = {2},
       pages = {024001},
       year = {2005}
    }
  • Framme, C. and Schuele, G. and Roider, J. and Holz, F. G. and Birngruber, R. and Brinkmann, R.: Temperature dependence of A2-E fluorescence in vitro and detection of fundus autofluorescence during selective RPE laser treatment (SRT). Investigative Ophthalmology & Visual Science, no. 46, 2005
    BibTeX Link
    @article{Framme2005,
       author = {Framme, C. and Schuele, G. and Roider, J. and Holz, F. G. and Birngruber, R. and Brinkmann, R.},
       title = {Temperature dependence of A2-E fluorescence in vitro and detection of fundus autofluorescence during selective RPE laser treatment (SRT)},
       journal = {Investigative Ophthalmology & Visual Science},
       volume = {46},
       note = {Suppl. S
    911CZ
    266
    Times Cited:0
    Cited References Count:0},
       ISSN = {0146-0404},
       url = {<Go to ISI>://WOS:000227980400260},
       year = {2005},
       type = {Journal Article}
    }
    
  • Brinkmann, R; Kandulla, J; Elsner, H; Hilmes, M; Hartert, C and Birngruber, R: Non-invasive real-time retinal temperature determination during TTT. Invest Ophthal & VisScie 46, 2005
    BibTeX Link
    @article{Brinkmann2005,
       author = {Brinkmann, R; Kandulla, J; Elsner, H; Hilmes, M; Hartert, C and Birngruber, R},
       title = {Non-invasive real-time retinal temperature determination during TTT},
       journal = {Invest Ophthal & VisScie} {46},
       
       note = {Suppl. S
    911CZ
    1406
    Times Cited:0
    Cited References Count:0},
       ISSN = {0146-0404},
       url = {<Go to ISI>://WOS:000227980401431},
       year = {2005},
       type = {Journal Article}
    }
    
  • Schuele, G; Elsner, H; Framme, C; Roider, J; Birngruber, R and Brinkmann, R: Optoacoustic real-time dosimetry for selective retina treatment. J Biomed Opt 10(6), 2005
    BibTeX Link Link
    @article{Schuele2005,
       author = {Schuele, G; Elsner, H; Framme, C; Roider, J; Birngruber, R and Brinkmann, R},
       title = {Optoacoustic real-time dosimetry for selective retina treatment},
       journal = {J Biomed Opt} {10(6)},
       
       note = {005XJ
    Times Cited:17
    Cited References Count:37},
       abstract = {The selective retina treatment ( SRT ) targets retinal diseases associated with disorders in the retinal pigment epithelium ( RPE ). Due to the ophthalmoscopic invisibility of the laser- induced RPE effects, we investigate a noninvasive optoacoustic real- time dosimetry system. In vitro porcine RPE is irradiated with a Nd: YLF laser ( 527 nm, 1.7- mu s pulse duration, 5 to 40 mu J, 30 pulses, 100- Hz repetition rate). Generated acoustic transients are measured with a piezoelectric transducer. During 27 patient treatments, the acoustic transients are measured with a transducer embedded in an ophthalmic contact lens. After treatment, RPE damage is visualized by fluorescein angiographic leakage. Below the RPE damage threshold, the optoacoustic transients show no pulse- to- pulse fluctuations within a laser pulse train. Above threshold, fluctuations of the individual transients among each other are observed. If optoacoustic pulse- to- pulse fluctuations are present, RPE leakage is observed in fluorescein angiography. In 96% of the irradiated areas, RPE leakage correlated with the optoacoustic defined threshold value. A noninvasive optoacoustic real- time dosimetry for SRT is developed and proved in vitro and during patient treatment. It detects the ophthalmoscopically invisible laser- induced damage of RPE cells and overcomes practical limitations of SRT for use in private practice. (C) 2005 Society of Photo- Optical Instrumentation Engineers.},
       keywords = {selective retina treatment
    optoacoustic dosimetry
    real-time dosimetry
    laser
    retina
    randomized clinical-trial
    macular degeneration
    diabetic-retinopathy
    photocoagulation
    nanosecond
    eye
    temperature
    generation
    liquids
    regimen},
       ISSN = {1083-3668},
       DOI = {Artn 064022
    Doi 10.1117/1.2136327},
       url = {<Go to ISI>://WOS:000234859400024},
       year = {2005},
    
  • Schuele, G. and Elsner, H. and Framme, C. and Roider, J. and Birngruber, R. and Brinkmann, R.: Optoacoustic real-time dosimetry for selective retina treatment. J Biomed Opt, no. 10, pp. 064022, 2005
    BibTeX
    @article{Schuele,
       author = {Schuele, G. and Elsner, H. and Framme, C. and Roider, J. and Birngruber, R. and Brinkmann, R.},
       title = {Optoacoustic real-time dosimetry for selective retina treatment},
       journal = {J Biomed Opt},
       volume = {10},
       number = {6},
       pages = {064022},
       note = {1083-3668 (Print)
    Journal Article},
       abstract = {The selective retina treatment (SRT) targets retinal diseases associated with disorders in the retinal pigment epithelium (RPE). Due to the ophthalmoscopic invisibility of the laser-induced RPE effects, we investigate a noninvasive optoacoustic real-time dosimetry system. In vitro porcine RPE is irradiated with a Nd:YLF laser (527 nm, 1.7-micros pulse duration, 5 to 40 microJ, 30 pulses, 100-Hz repetition rate). Generated acoustic transients are measured with a piezoelectric transducer. During 27 patient treatments, the acoustic transients are measured with a transducer embedded in an ophthalmic contact lens. After treatment, RPE damage is visualized by fluorescein angiographic leakage. Below the RPE damage threshold, the optoacoustic transients show no pulse-to-pulse fluctuations within a laser pulse train. Above threshold, fluctuations of the individual transients among each other are observed. If optoacoustic pulse-to-pulse fluctuations are present, RPE leakage is observed in fluorescein angiography. In 96% of the irradiated areas, RPE leakage correlated with the optoacoustic defined threshold value. A noninvasive optoacoustic real-time dosimetry for SRT is developed and proved in vitro and during patient treatment. It detects the ophthalmoscopically invisible laser-induced damage of RPE cells and overcomes practical limitations of SRT for use in private practice.},
       keywords = {Acoustics/*instrumentation
    Animals
    Computer Systems
    Dose-Response Relationship, Radiation
    Equipment Design
    Equipment Failure Analysis
    Humans
    Laser Coagulation/*methods
    Lasers/*therapeutic use
    Optics/*instrumentation
    Radiation Dosage
    Radiometry/*instrumentation/methods
    Reproducibility of Results
    Retina/pathology/*radiation effects/*surgery
    Sensitivity and Specificity
    Swine},
       year = {2005}
    }
  • Schüle, G and Rumohr, M and Hüttmann, G and Brinkmann, R: RPE damage thresholds and mechanisms for laser exposure in the µs to ms time regimen. Inv Ophthalmol & Vis Sci, no. 46, pp. 714-719, 2005
    BibTeX
    @article{Schüle,
       author = {Schüle, G and Rumohr, M and Hüttmann, G and Brinkmann, R},
       title = {RPE damage thresholds and mechanisms for laser exposure in the µs to ms time regimen},
       journal = {Inv Ophthalmol & Vis Sci},
       volume = {46},
       number = {2},
       pages = {714-719},
       year = {2005}
    }
  • Framme, C and Roider, J and Sachs, H G and Brinkmann, R and Gabel, V-P: Noninvasive Imaging and Monitoring of Retinal Pigment Epithelium Patterns Using Fundus Autofluorescence - Review. Curr Med Imag Rev, no. 1, pp. 89-103, 2005
    BibTeX
    @article{Framme,
       author = {Framme, C and Roider, J and Sachs, H G and Brinkmann, R and Gabel, V-P},
       title = {Noninvasive Imaging and Monitoring of Retinal Pigment Epithelium Patterns Using Fundus Autofluorescence - Review},
       journal = {Curr Med Imag Rev},
       volume = {1},
       pages = {89-103},
       year = {2005}
    }
  • Alt, C. and Framme, C. and Schnell, S. and Lee, H. and Brinkmann, R. and Lin, C. P.: Selective targeting of the retinal pigment epithelium using an acousto-optic laser scanner. J Biomed Opt, no. 10, pp. 64014, 2005
    BibTeX
    @article{Alt,
       author = {Alt, C. and Framme, C. and Schnell, S. and Lee, H. and Brinkmann, R. and Lin, C. P.},
       title = {Selective targeting of the retinal pigment epithelium using an acousto-optic laser scanner},
       journal = {J Biomed Opt},
       volume = {10},
       number = {6},
       pages = {64014},
       note = {1083-3668 (Print)
    Journal Article},
       abstract = {Selective targeting of the retinal pigment epithelium (RPE) is a new strategy for treating certain retinal disorders while preserving adjacent photoreceptors. The treatment currently relies on a complex laser system to produce the required microsecond pulse structure. In our new approach, we scan the focus of a continuous-wave (cw) laser beam with acousto-optic deflectors to produce microsecond-long exposures at each RPE cell. Experiments were performed in vitro with a bench-top scanner on samples of young bovine RPE and in vivo on Dutch belted rabbits with a slit-lamp adapted scanner. Effective dose 50% (ED(50)) for RPE damage was determined in vitro by fluorescence cell viability assay and in vivo by fluorescein angiography. Damage to individual RPE cells was achieved with laser power on the order of 100 mW. Using separated scan lines, we demonstrate selectivity in the form of alternating lines of dead and surviving cells that resemble the scan pattern. Selectivity is also shown by the absence of retinal thermal coagulation in vivo. Selective RPE damage is feasible by rapidly scanning a cw laser beam. The scanning device is an attractive alternative to conventional laser coagulation and pulsed laser targeting of the RPE.},
       year = {2005}
    }
  • Kandulla, J and Elsner, H and Hilmes, M and Hartert, C and Brinkmann, R: Optoacoustic temperature determination at the fundus of the eye during Transpupillary Thermotherapy. in Proc SPIE, no. 5688, pp. 208-214,
    BibTeX
    @inproceedings{Kandulla2005,
       author = {Kandulla, J and Elsner, H and Hilmes, M and Hartert, C and Brinkmann, R},
       title = {Optoacoustic temperature determination at the fundus of the eye during Transpupillary Thermotherapy},
       booktitle = {Proc SPIE},
       volume = {5688},
       pages = {208-214},
       keywords = {AutoPhoN},
       type = {Conference Proceedings}
    }
    
  • Elsner, H. and Liew, S. H. M. and Klatt, C. and Hamilton, P. and Marshall, J. and Porksen, E. and Laqua, H. and Brinkmann, R. and Birngruber, R. and Roider, J.: Selective-retina-therapy (SRT) multicenter clinical trial: 6 month results in patients with diabetic maculopathy. Investigative Ophthalmology & Visual Science, no. 46, 2005
    BibTeX Link
    @article{Elsner2005,
       author = {Elsner, H. and Liew, S. H. M. and Klatt, C. and Hamilton, P. and Marshall, J. and Porksen, E. and Laqua, H. and Brinkmann, R. and Birngruber, R. and Roider, J.},
       title = {Selective-retina-therapy (SRT) multicenter clinical trial: 6 month results in patients with diabetic maculopathy},
       journal = {Investigative Ophthalmology & Visual Science},
       volume = {46},
       note = {Suppl. S
    911CZ
    1463
    Times Cited:0
    Cited References Count:0},
       ISSN = {0146-0404},
       url = {<Go to ISI>://WOS:000227980401487},
       year = {2005},
       type = {Journal Article}
    }
    

2004

  • Brinkmann, R; Poerksen, E; Elsner, H; Schuele, G; Theisen-Kunde, D, Roider, J. and Birngruber, R.: On-line dosimetry for selective retina treatment (SRT). Invest Ophthal & VisScie 45, pp. U763-U763, 2004
    BibTeX Link
    @article{Brinkmann2004,
       author = {Brinkmann, R; Poerksen, E; Elsner, H; Schuele, G; Theisen-Kunde, D, Roider, J. and Birngruber, R.},
       title = {On-line dosimetry for selective retina treatment (SRT)},
       journal = {Invest Ophthal & VisScie} {45},
      
       pages = {U763-U763},
       note = {Suppl. 1
    846TA
    2032
    Times Cited:0
    Cited References Count:0},
       ISSN = {0146-0404},
       url = {<Go to ISI>://WOS:000223338001991},
       year = {2004},
       type = {Journal Article}
    }
    
  • Schüle, G. and Framme, C. and Roider, J. and Brinkmann, R: Noninvasive optoacoustic temperature determination at the fundus of the eye during laser irradiation. Journal of Biomedical Optics, no. 9, pp. 173-179, 2004
    BibTeX
    @article{Schüle,
       author = {Schüle, G. and Framme, C. and Roider, J. and Brinkmann, R},
       title = {Noninvasive optoacoustic temperature determination at the fundus of the eye during laser irradiation},
       journal = {Journal of Biomedical Optics},
       volume = {9},
       number = {1},
       pages = {173-179},
       year = {2004}
    }
    
  • Roegener, J and Brinkmann, R and Lin, C P: Pump-probe detection of laser-induced microbubble formation in retinal pigment epithelium cells. J Biomedical Optics, no. 9, pp. 367-371, 2004
    BibTeX
    @article{Roegener,
       author = {Roegener, J and Brinkmann, R and Lin, C P},
       title = {Pump-probe detection of laser-induced microbubble formation in retinal pigment epithelium cells},
       journal = {J Biomedical Optics},
       volume = {9},
       number = {2},
       pages = {367-371},
       year = {2004}
    }
    
  • Kracht, D. and Brinkmann, R: Green Q-switched microsecond laser pulses by overcoulped intracavity second harmonic generation. no. 231, pp. 319-324, 2004
    BibTeX
    @misc{Kracht,
       author = {Kracht, D. and Brinkmann, R},
       title = {Green Q-switched microsecond laser pulses by overcoulped intracavity second harmonic generation},
       volume = {231},
       pages = {319-324},
       year = {2004}
    }
    
  • Porksen, E. and Elsner, H. and Theisen-Kunde, D. and Brinkmann, R. and Klatt, C. and Bunse, A. and Hamilton, P. and Birngruber, R. and Lagua, H. and Roider, J.: Clinical application of optoacoustic on-line dosimetry in Selective-RPE-laser-treatment (SRT). Investigative Ophthalmology & Visual Science, no. 45, pp. U363-U363, 2004
    BibTeX Link
    @article{Porksen2004,
       author = {Porksen, E. and Elsner, H. and Theisen-Kunde, D. and Brinkmann, R. and Klatt, C. and Bunse, A. and Hamilton, P. and Birngruber, R. and Lagua, H. and Roider, J.},
       title = {Clinical application of optoacoustic on-line dosimetry in Selective-RPE-laser-treatment (SRT)},
       journal = {Investigative Ophthalmology & Visual Science},
       volume = {45},
       pages = {U363-U363},
       note = {Suppl. 2
    846TC
    4074
    Times Cited:0
    Cited References Count:0},
       ISSN = {0146-0404},
       url = {<Go to ISI>://WOS:000223338201270},
       year = {2004},
       type = {Journal Article}
    }
    
  • Framme, C. and Alt, C. and Schnell, S. and Brinkmann, R. and Lin, C. P.: Selektive RPE-Behandlung (SRT) durch Laserscanning eines CW- Lasers. in 102nd Congress Deutsche Ophthalmologische Gesellschaft,
    BibTeX
    @inproceedings{Framme,
       author = {Framme, C. and Alt, C. and Schnell, S. and Brinkmann, R. and Lin, C. P.},
       title = {Selektive RPE-Behandlung (SRT) durch Laserscanning eines CW- Lasers},
       booktitle = {102nd Congress Deutsche Ophthalmologische Gesellschaft},
    
    }
    
  • Framme, C. and Schuele, G. and Roider, J. and Birngruber, R. and Brinkmann, R.: Influence of pulse duration and pulse number in selective RPE laser treatment. Lasers Surg Med, no. 34, pp. 206-15, 2004
    BibTeX
    @article{Framme,
       author = {Framme, C. and Schuele, G. and Roider, J. and Birngruber, R. and Brinkmann, R.},
       title = {Influence of pulse duration and pulse number in selective RPE laser treatment},
       journal = {Lasers Surg Med},
       volume = {34},
       number = {3},
       pages = {206-15},
       note = {0196-8092 (Print)
    Journal Article
    Research Support, Non-U.S. Gov't},
       abstract = {BACKGROUND AND OBJECTIVES: The therapeutic effect of laser treatment for macular diseases is related to the damage to the retinal pigment epithelium (RPE) and the subsequent restoration of the defect due to RPE proliferation. In contrast to conventional laser treatment, it is possible to damage the RPE selectively and to spare the photoreceptors by using repetitive microsecond laser pulses. It was the aim of the study to investigate the influence of pulse duration and number of pulses on angiographically and ophthalmoscopically visible retinal damage thresholds in order to optimize treatment modalities. STUDY DESIGN/MATERIALS AND METHODS: In total, 625 laser lesions with various parameters were applied to the retina in 11 eyes of 6 Chinchilla breed rabbits using an experimental laser system (Nd:YLF at 527 nm). Pulse duration (1.7 microseconds and 200 nanoseconds) and number of pulses (100, 10, and 1 pulses) were varied at a constant repetition rate of 100 Hz. Damage thresholds were determined in terms of ophthalmoscopic and fluorescein angiographic visibility, and the therapeutic window (TW; angiographic ED(50) vs. ophthalmoscopic ED(50)) as well as the safety range (SR; angiographic ED(84) vs. ophthalmoscopic ED(16)) between both thresholds were calculated. Selected laser lesions were evaluated by histology. RESULTS: Generally, the ED(50) radiant exposure for angiographic visibility decreases for shorter laser pulses and with an increase in the number of pulses. The TW for both pulse durations (1.7 microseconds and 200 nanoseconds) was wider with 100 pulses than with single pulses. The widest TW was found for 100 pulses at 200 nanoseconds pulse duration (5.9-fold above the angiographic threshold), and the smallest TW with a factor of 1.6 was found for 1.7 microseconds single pulses. In terms of SR, only irradiation with 100 pulses at 200 nanoseconds pulse duration was associated with a ratio >2. Independently of pulse duration, histological examination of laser sites 1 hour after irradiation revealed widely intact photoreceptors, while the underlying RPE was damaged. CONCLUSIONS: Pulse duration and number of pulses have a significant influence on RPE damage thresholds and consecutively on TW and SR. Because fundus pigmentation in humans may vary intra- and interindividually by a factor of 2, a large TW and ideally also a large SR should be ensured in a clinical treatment context. In rabbits, the safety range with 200 nanoseconds pulses is higher than with the pulse duration of 1.7 microseconds currently in clinical use. These findings suggest the need for clinical pilot studies to prove whether these results can be transposed to the situation in humans.},
       keywords = {Animals
    *Laser Coagulation/adverse effects
    Pigment Epithelium of Eye/*injuries
    Rabbits
    Time Factors},
       year = {2004}
    }
  • Framme, C. and Schule, G. and Roider, J. and Birngruber, R. and Brinkmann, R.: Online autofluorescence measurements during selective RPE laser treatment. no. 242, pp. 863-9, Oct, 2004
    BibTeX
    @misc{Framme,
       author = {Framme, C. and Schule, G. and Roider, J. and Birngruber, R. and Brinkmann, R.},
       title = {Online autofluorescence measurements during selective RPE laser treatment},
       volume = {242},
       number = {10},
       pages = {863-9},
       month = {Oct},
       note = {0721-832X (Print)
    Journal Article},
       abstract = {BACKGROUND: Fundus autofluorescence (AF) is derived from the lipofuscin contained by the retinal pigment epithelial cells. Using a scanning laser ophthalmoscope, two-dimensional AF measurements of the ocular fundus can be achieved. Directly after conventional photocoagulation and also after selective RPE laser treatment (SRT) with ophthalmoscopically non-visible laser lesions, irradiated areas reveal reduced AF, indicating RPE damage. Since the green treatment laser beam could also be used for AF excitation, the aim of this study was to evaluate whether absolute measurements of AF can be performed, and also possible changes in AF detected, online during SRT. METHODS: SRT was carried out by use of a frequency-doubled Nd:YLF laser (wavelength 527 nm, pulse duration 1.7 micros, repetition rate 500 and 100 Hz, number of pulses 100 and 30, single pulse energy 50-130 microJ) in vitro (porcine RPE; retinal spot size 160 microm) and during patient treatment (retinal spot size 176 microm). During irradiation, fluorescence light from the RPE was decoupled from the laser light inside the slit lamp and detected by a photomultiplier or photodiode at wavelengths above 550 nm. Additionally, temperature-dependent fluorescence intensity measurements of A2-E, the main fluorescent component of lipofuscin, were performed in a different in-vitro setup. RESULTS: The intensity of AF decreased over the number of applied pulses during laser irradiation, and this trend was more pronounced in porcine RPE samples than during human treatment. In vitro, the AF intensity decreased by about 22%; however, only a weak signal was detected. When treating patients, the AF intensity was strong and the rate of decay of fluorescence intensity with number of pulses was greater when irradiating at 500 Hz than at the 100 Hz repetition rate. However, for both repetition rates the AF decay was merely up to 6-8% over the number of pulses per laser spot. Fluorescence intensity of A2-E decreased linearly with increasing temperature at about 1% per 1 degrees C and was completely reversible. CONCLUSIONS: Online measurements of AF during selective RPE laser treatment are possible and reveal a decay in AF as a function of the number of laser pulses applied to the RPE. If A2-E results can be transferred to RPE fluorescence, the AF decay could be related to the temperature increase within the tissue during treatment. Further clinical studies-in SRT as well as in conventional laser photocoagulation-might be able to show online AF changes on different areas of the retina and on different pathologies. Due to the temperature dependence of the fluorescence, on-line AF measurements during laser treatments such as photocoagulation or TTT may be able to be used as a real-time method for temperature monitoring.},
       keywords = {Animals
    Diabetic Retinopathy/*surgery
    *Fluorescence
    Humans
    *Laser Coagulation
    Lasers/diagnostic use
    Lipofuscin/*metabolism
    Ophthalmoscopy/methods
    Pigment Epithelium of Eye/*metabolism/surgery
    Swine},
       year = {2004}
    }
  • Framme, C and Schüle, G and Birngruber, R and Roider, J and Schütt, F and Kopitz, J and Holz, F and Brinkmann, R: Temperature dependent fluorescence of A2-E, the main fluorescent lipofuscin component in the RPE. no. 29, pp. 287-291, 2004
    BibTeX
    @article{Framme,
       author = {Framme, C and Schüle, G and Birngruber, R and Roider, J and Schütt, F and Kopitz, J and Holz, F and Brinkmann, R},
       title = {Temperature dependent fluorescence of A2-E, the main fluorescent lipofuscin component in the RPE},
       journal = {Curr Eye Res},
       volume = {29},
       number = {4-5},
       pages = {287-291},
       year = {2004}
    }
  • Brendel, T and Brinkmann, R: Mid-IR laser induced superheating of water and its quantification by an optical temperature probe. Appl Optics, no. 43, pp. 1856-1862, 2004
    BibTeX
    @article{Brendel,
       author = {Brendel, T and Brinkmann, R},
       title = {Mid-IR laser induced superheating of water and its quantification by an optical temperature probe},
       journal = {Appl Optics},
       volume = {43},
       number = {9},
       pages = {1856-1862},
       year = {2004}
    }

2003

  • Roider, J. and Brinkmann, R. and Birngruber, R.: Selective retinal pigment epithelium laser treatment - Theoretical and clinical aspects. in Lasers in Ophthalmology - Basic, Diagnostic and Surgical Aspects, pp. 119-129, Kugler Publications, The Hague, The Netherlands, 2003
    BibTeX
    @inbook{Roider,
       author = {Roider, J. and Brinkmann, R. and Birngruber, R.},
       title = {Selective retinal pigment epithelium laser treatment -   Theoretical and clinical aspects},
       booktitle = {Lasers in Ophthalmology - Basic, Diagnostic and Surgical Aspects},
       editor = {Fankhauser, F. and Kwasniewska, S.},
       publisher = {Kugler Publications, The Hague, The Netherlands},
       pages = {119-129},
       year = {2003}
    }
    
  • Framme, C. and Alt, C. and Schuele, G. and Brinkmann, R. and Birngruber, R. and Lin, C.: Threshold determinations for selective RPE laser treatment with a laser scanner in rabbits with different scan times in the microsecond regime. Investigative Ophthalmology & Visual Science, no. 44, pp. U663-U663, 2003
    BibTeX Link
    @article{Framme2003,
       author = {Framme, C. and Alt, C. and Schuele, G. and Brinkmann, R. and Birngruber, R. and Lin, C.},
       title = {Threshold determinations for selective RPE laser treatment with a laser scanner in rabbits with different scan times in the microsecond regime},
       journal = {Investigative Ophthalmology & Visual Science},
       volume = {44},
       pages = {U663-U663},
       note = {Suppl. 2
    709CK
    4865
    Times Cited:0
    Cited References Count:0},
       ISSN = {0146-0404},
       url = {<Go to ISI>://WOS:000184607002325},
       year = {2003},
       type = {Journal Article}
    }
    
  • Brinkmann, R. and Koop, N. and Ozdemir, M. and Alt, C. and Schule, G. and Lin, C. P. and Birngruber, R.: Targeting of the retinal pigment epithelium (RPE) by means of a rapidly scanned continuous wave (CW) laser beam. Lasers Surg Med, no. 32, pp. 252-64,
    BibTeX
    @article{Brinkmann2003,
       author = {Brinkmann, R. and Koop, N. and Ozdemir, M. and Alt, C. and Schule, G. and Lin, C. P. and Birngruber, R.},
       title = {Targeting of the retinal pigment epithelium (RPE) by means of a rapidly scanned continuous wave (CW) laser beam},
       journal = {Lasers Surg Med},
       volume = {32},
       number = {4},
       pages = {252-64},
       note = {0196-8092 (Print)
    In Vitro
    

2002

  • Brinkmann, R and Koop, N and Özdemir, M and Alt, C and Schüle, G and Lin, C P and Birngruber, R: Selective damage of pigmented cells by means of a rapidly scanned cw laser beam. Proc SPIE, no. 4617, pp. 134-140, 2002
    BibTeX
    @article{Brinkmann2002,
       author = {Brinkmann, R  and Koop, N and Özdemir, M  and Alt, C and Schüle, G and Lin, C P and Birngruber, R},
       title = {Selective damage of pigmented cells by means of a rapidly scanned cw laser beam},
       journal = {Proc SPIE},
       volume = {4617},
       pages = {134-140},
       year = {2002},
       type = {Journal Article}
    }
    
  • Alt, C and Framme, C and Schnell, S and Schuele, G and Brinkmann, R and Lin, C P: In vivo and in vitro Selective Targeting of the Retinal Pigment Epithelium (RPE) Using a Laser-Scanning Device. in Proc SPIE, no. 4611, pp. 59-63,
    BibTeX
    @inproceedings{Alt2002,
       author = {Alt, C and Framme, C and Schnell, S and Schuele, G and Brinkmann, R and Lin, C P},
       title = {In vivo and in vitro Selective Targeting of the Retinal Pigment Epithelium (RPE) Using a Laser-Scanning Device},
       booktitle = {Proc SPIE},
       volume = {4611},
       pages = {59-63},
       type = {Conference Proceedings}
    }
    
  • Framme, C and Brinkmann, R and Birngruber, R and Roider, J: Autofluorescence imaging after selective RPE treatment in macular diseases and clinical outcome: a pilot study. Br J Ophthalmol, no. 86, pp. 1099-1106, 2002
    BibTeX
    @article{Framme2002,
       author = {Framme, C and Brinkmann, R and Birngruber, R and Roider, J},
       title = {Autofluorescence imaging after selective RPE treatment in macular diseases and clinical outcome: a pilot study},
       journal = {Br J Ophthalmol},
       volume = {86},
       pages = {1099-1106},
       year = {2002},
       type = {Journal Article}
    }
    
  • Framme, C. and Schuele, G. and Roider, J. and Kracht, D. and Birngruber, R. and Brinkmann, R.: Threshold determinations for selective retinal pigment epithelium damage with repetitive pulsed microsecond laser systems in rabbits. Ophthalmic Surgery and Lasers, no. 33, pp. 400-409, 2002
    BibTeX
    @article{Framme2002,
       author = {Framme, C. and Schuele, G. and Roider, J. and Kracht, D. and Birngruber, R. and Brinkmann, R.},
       title = {Threshold determinations for selective retinal pigment epithelium damage with repetitive pulsed microsecond laser systems in rabbits},
       journal = {Ophthalmic Surgery and Lasers},
       volume = {33},
       number = {5},
       pages = {400-409},
       note = {596HY
    Times Cited:18
    Cited References Count:28},
       abstract = {BACKGROUND AND OBJECTIVE: In both clinical and animal studies, it has been shown that repetitive short laser pulses can cause selective retinal pigment epithelium damage (RPE) with sparing of photoreceptors. Our purpose was to determine the ophthalmoscopic and angiographic damage thresholds as a function of pulse durations by using different pulsed laser systems to optimize treatment modalities.
    MATERIALS AND METHODS: Chinchilla-breed rabbits were narcotized and placed in a special holding system. Laser lesions were applied using a commercial laser slit lamp, contact lens, and irradiation with a frequency-doubled Nd:YLF laser (wavelength: 527 nm; repetition rate: 500 Hz; number of pulses: 100; pulse duration: 5 mus, 1.7 mus, 200 ns) and an argon-ion laser (514 nm, 500 Hz, 100 pulses, 5 mus and 200 ins). In all eyes, spots with different energies were placed into the regio macularis with a diameter of 102 mum (tophat profile). After treatment, fundus photography and fluorescein angiography were performed and radiant exposure for ED50 damage determined. Speckle measurements at the fiber tips were performed to determine intensity peaks in the beam profile.
    RESULTS: Using the Nd:YLF laser system, the ophthalmoscopic ED50 threshold energies were 25.4 lJ (5 mus), 32 muJ (1.7 mus), and 30 muJ (200 ns). The angiographic ED50 thresholds were 13.4 muJ (5 mus), 9.2 muJ (1.7 mus), and 6.7 muJ (200 ns). With the argon laser, the angiographic threshold for 5 mus pulses was 5.5 muJ. The ophthalmoscopic threshold could not be determined because of a lack of power; however, it was > 12 muJ. For 200 ms, the ED50 radiant exposures were 20.4 mW ophthalmoscopically and 19.2 mW angiographically. Speckle factors were found to be 1.225 for the Nd:YLF and 3.180 for the argon laser. Thus, the maximal ED50-threshold radiant exposures for the Nd:YLF were calculated to be 362 mJ/cm(2) (5 mus), 478 mJ/cm(2) (1.7 mus), and 438 mJ/cm(2) (200 ns) ophthalmoscopically. Angiographically, the thresholds were 189 mJ/cm(2) (5 mus), 143 mJ/cm(2) (1.7 mus), and 97 mJ/cm(2) (200 ns). For the argon laser, the maximal ED50 radiant exposure threshold was 170 mJ/cm(2) angiographically.
    CONCLUSION: The gap between the angiographic and the ophthalmoscopic thresholds for the 200 ns regime (4.5 times above angiographic ED50) was wider than for the 1.7 mus regime (3.3 times above the angiographic ED50). This would suggest the appropriate treatment would be 200 ns pulses. However, histologies have yet to prove that nonvisible mechanical effects increase with shorter pulse durations and could reduce the "therapeutic window." When comparing the thresholds with 5 mus pulses from the argon and Nd:YLF laser, it demonstrates that intensity modulations in the beam profile must be considered.},
       keywords = {primate eye
    photocoagulation
    neovascularization
    nanosecond
    lesions
    model},
       ISSN = {0022-023X},
       url = {<Go to ISI>://WOS:000178160100008},
       year = {2002},
       type = {Journal Article}
    }
    
  • Brinkmann, R. and Koop, N. and Oezdemir, M. and Alt, C. and Schuele, G. and Lin, C. P. and Birngruber, R.: Selective RPE damage by means of a rapidly scanned cw laser beam. Investigative Ophthalmology & Visual Science, no. 43, pp. U595-U595, 2002
    BibTeX Link
    @article{Brinkmann2002,
       author = {Brinkmann, R. and Koop, N. and Oezdemir, M. and Alt, C. and Schuele, G. and Lin, C. P. and Birngruber, R.},
       title = {Selective RPE damage by means of a rapidly scanned cw laser beam},
       journal = {Investigative Ophthalmology & Visual Science},
       volume = {43},
       pages = {U595-U595},
       note = {Suppl. 1
    709CF
    2535
    Times Cited:0
    Cited References Count:0},
       ISSN = {0146-0404},
       url = {<Go to ISI>://WOS:000184606602467},
       year = {2002},
       type = {Journal Article}
    }
    
  • Framme, C. and Schuele, G. and Roider, J. and Kracht, D. and Birngruber, R. and Brinkmann, R.: Threshold determinations for selective retinal pigment epithelium damage with repetitive pulsed microsecond laser systems in rabbits. no. 33, pp. 400-9, Sep-Oct, 2002
    BibTeX
    @misc{Framme,
       author = {Framme, C. and Schuele, G. and Roider, J. and Kracht, D. and Birngruber, R. and Brinkmann, R.},
       title = {Threshold determinations for selective retinal pigment epithelium damage with repetitive pulsed microsecond laser systems in rabbits},
       volume = {33},
       number = {5},
       pages = {400-9},
       month = {Sep-Oct},
       note = {1082-3069 (Print)
    Comparative Study
    Journal Article},
       abstract = {BACKGROUND AND OBJECTIVE: In both clinical and animal studies, it has been shown that repetitive short laser pulses can cause selective retinal pigment epithelium damage (RPE) with sparing of photoreceptors. Our purpose was to determine the ophthalmoscopic and angiographic damage thresholds as a function of pulse durations by using different pulsed laser systems to optimize treatment modalities. MATERIALS AND METHODS: Chinchilla-breed rabbits were narcotized and placed in a special holding system. Laser lesions were applied using a commercial laser slit lamp, contact lens, and irradiation with a frequency-doubled Nd:YLF laser (wave-length: 527 nm; repetition rate: 500 Hz; number of pulses: 100; pulse duration: 5 micros, 1.7 micros, 200 ns) and an argon-ion laser (514 nm, 500 Hz, 100 pulses, 5 micros and 200 ms). In all eyes, spots with different energies were placed into the regio macularis with a diameter of 102 microm (tophat profile). After treatment, fundus photography and fluorescein angiography were performed and radiant exposure for ED50 damage determined. Speckle measurements at the fiber tips were performed to determine intensity peaks in the beam profile. RESULTS: Using the Nd:YLF laser system, the ophthalmoscopic ED50 threshold energies were 25.4 microJ (5 micros), 32 microJ (1.7 micros), and 30 microJ (200 ns). The angiographic ED50 thresholds were 13.4 microJ (5 micros), 9.2 microJ (1.7 micros), and 6.7 microJ (200 ns). With the argon laser, the angiographic threshold for 5 micros pulses was 5.5 microJ. The ophthalmoscopic threshold could not be determined because of a lack of power; however, it was > 12 microJ. For 200 ms, the ED50 radiant exposures were 20.4 mW ophthalmoscopically and 19.2 mW angiographically. Speckle factors were found to be 1.225 for the Nd:YLF and 3.180 for the argon laser. Thus, the maximal ED50 -threshold radiant exposures for the Nd:YLF were calculated to be 362 mJ/cM2 (5 micros), 478 mJ/cm2 (1.7 micros), and 438 mJ/cm2 (200 ns) ophthalmoscopically. Angiographically, the thresholds were 189 mJ/cm2 (5 micros), 143 mJ/cm2 (1.7 micros), and 97 mJ/cm2 (200 ns). For the argon laser, the maximal ED50 radiant exposure threshold was 170 mJ/cm2 angiographically. CONCLUSION: The gap between the angiographic and the ophthalmoscopic thresholds for the 200 ns regime (4.5 times above angiographic ED50) was wider than for the 1.7 micros regime (3.3 times above the angiographic ED50). This would suggest the appropriate treatment would be 200 ns pulses. However, histologies have yet to prove that nonvisible mechanical effects increase with shorter pulse durations and could reduce the "therapeutic window." When comparing the thresholds with 5 micros pulses from the argon and Nd:YLF laser, it demonstrates that intensity modulations in the beam profile must be considered.},
       keywords = {Animals
    Eye Injuries/diagnosis/*etiology
    Fluorescein Angiography
    Laser Coagulation/*adverse effects
    Ophthalmoscopy
    Photography
    Pigment Epithelium of Eye/*injuries
    Rabbits
    Retina/*surgery
    Threshold Limit Values
    Time Factors},
       year = {2002}
    }
    
  • Framme, C. and Brinkmann, R. and Birngruber, R. and Roider, J.: Autofluorescence imaging after selective RPE laser treatment in macular diseases and clinical outcome: a pilot study. British Journal of Ophthalmology, no. 86, pp. 1099-1106, 2002
    BibTeX Link
    @article{Framme2002,
       author = {Framme, C. and Brinkmann, R. and Birngruber, R. and Roider, J.},
       title = {Autofluorescence imaging after selective RPE laser treatment in macular diseases and clinical outcome: a pilot study},
       journal = {British Journal of Ophthalmology},
       volume = {86},
       number = {10},
       pages = {1099-1106},
       note = {595YE
    Times Cited:47
    Cited References Count:35},
       abstract = {Aim: Selective retinal pigment epithelium (RPE) laser treatment is a new technique which selectively damages the RPE while sparing the neural retina. One difficulty is the inability to visualise the laser lesions, The aim of the study was to investigate whether fundus autofluorescence (AF) is changed because of the RPE damage, and thus might be used for treatment control. Additionally, the clinical course of patients with various macular diseases was evaluated.
    Methods: 26 patients with macular diseases (diabetic maculopathy (DMP), soft drusen maculopathy (AMD), and central serous retinopathy (CSR)) were treated and followed up for at least 6 months. Treatment was performed with a train of repetitive short laser pulses (800 ns) of a frequency doubled Nd:YAG laser (parameters: 532 nm, 50 and 500 pulses at 100 and 500 Hz, retinal spot diameter 200 pm, pulse energies 75-175 muJ). AF was excited by 488 nm and detected by a barrier filter at 500 nm (HRA, Heidelberg Engineering, Germany). Patients were examined by ophthalmoscopy, fluorescein angiography, and autofluorescence measurements at various times after treatment (10 minutes, 1 hour, 1 and 6 weeks, 3, 6, and 12 months).
    Results: Fluorescein angiography showed leakage from the irradiated areas for about I week after treatment. None of the laser lesions was ophthalmoscopically visible during treatment. Identification of the lesions was possible by AF imaging showing an intensity decay in the irradiated area in 22 out of 26 patients, predominantly in patients with CSR and AMD. Lesions could be identified 10 minutes after treatment as hypoautofluorescent spots, which were more pronounced I hour later. During follow up the laser spots became hyperautofluorescent. In patients with DMP some AF images were less helpful because of diffuse oedema and larger retinal thickness. In these cases ICG angiography was able to confirm therapeutic success very well. Most of the patients have had benefit from the treatment, with best results obtained for CSR patients.
    Conclusion: Imaging of non-visible selective RPE laser effects can be achieved by AF measurements predominantly in patients without retinal oedema. Therefore, AF may replace invasive fluorescein angiography in many cases to verify therapeutic laser success, Selective laser treatment has the potential to improve the prognosis of macular diseases without the risk of laser scotomas.},
       keywords = {retinal-pigment epithelium
    primate retina
    fundus autofluorescence
    scanning ophthalmoscope
    photocoagulation
    lipofuscin
    krypton
    fluorescence
    melanin
    lesions},
       ISSN = {0007-1161},
       DOI = {DOI 10.1136/bjo.86.10.1099},
       url = {<Go to ISI>://WOS:000178135200010},
       year = {2002},
       type = {Journal Article}
    }
    
  • Framme, C and Brinkmann, R and Birngruber, R and Roider, J: Autofluorescence imaging after selective RPE treatment in macular diseases and clinical outcome: a pilot study. Br J Ophthalmol, no. 86, pp. 1099-1106, 2002
    BibTeX
    @article{Framme,
       author = {Framme, C and Brinkmann, R and Birngruber, R and Roider, J},
       title = {Autofluorescence imaging after selective RPE treatment in macular diseases and clinical outcome: a pilot study},
       journal = {Br J Ophthalmol},
       volume = {86},
       pages = {1099-1106},
       year = {2002}
    }
    
    
  • Schuele, Georg and Huettmann, Gereon and Brinkmann, Ralf: Noninvasive temperature measurements during laser irradiation of the retina with optoacoustic techniques. no. 4611, pp. 64-71, Proc. SPIE,
    BibTeX
    @inproceedings{Schuele,
       author = {Schuele, Georg and Huettmann, Gereon and Brinkmann, Ralf},
       title = {Noninvasive temperature measurements during laser irradiation of the retina with optoacoustic techniques},
       editor = {Fabrice, Manns and Per, G. Soederberg and Arthur, Ho},
       publisher = {Proc. SPIE},
       volume = {4611},
       pages = {64-71},
    }
    
  • Framme, C. and Schuele, G. and Roider, J. and Birngruber, R. and Brinkmann, R.: Threshold determinations for selective RPE damage with repetitively pulsed microsecond laser systems in rabbits. Investigative Ophthalmology & Visual Science, no. 43, pp. U595-U595, 2002
    BibTeX Link
    @article{Framme2002,
       author = {Framme, C. and Schuele, G. and Roider, J. and Birngruber, R. and Brinkmann, R.},
       title = {Threshold determinations for selective RPE damage with repetitively pulsed microsecond laser systems in rabbits},
       journal = {Investigative Ophthalmology & Visual Science},
       volume = {43},
       pages = {U595-U595},
       note = {Suppl. 1
    709CF
    2530
    Times Cited:0
    Cited References Count:0},
       ISSN = {0146-0404},
       url = {<Go to ISI>://WOS:000184606602462},
       year = {2002},
       type = {Journal Article}
    }
    

2001

  • Roider, J; Brinkmann, R, Framme, C; Schule, G, Joachimeyer, E; Wirbelauer, C; Kracht, D, Laqua, H and Birngruber, R: Selective RPE laser treatment in macular diseases: Clinical results.. Invest Ophthal & VisScie 42(4), pp. S695-S695, 2001
    BibTeX Link
    @article{Roider2001,
       author = {Roider, J; Brinkmann, R, Framme, C; Schule, G, Joachimeyer, E; Wirbelauer, C; Kracht, D, Laqua, H and Birngruber, R},
       title = {Selective RPE laser treatment in macular diseases: Clinical results.},
       journal = {Invest Ophthal & VisScie} {42(4)},
       
       pages = {S695-S695},
       note = {Suppl. S
    427EP
    3741
    Times Cited:0
    Cited References Count:0},
       ISSN = {0146-0404},
       url = {<Go to ISI>://WOS:000168392103704},
       year = {2001},
       type = {Journal Article}
    }
    
  • Rommerscheid, Jan and Theisen, Dirk and Schmuecker, G. and Brinkmann, Ralf and Broll, R.: Myocardial expression of the vascular endothelial growth factor (VEGF) after endocardial laser revascularization (ELR). no. 4433, pp. 39-44,
    BibTeX Link
    @inproceedings{Rommerscheid2001,
       author = {Rommerscheid, Jan and Theisen, Dirk and Schmuecker, G. and Brinkmann, Ralf and Broll, R.},
       title = {Myocardial expression of the vascular endothelial growth factor (VEGF) after endocardial laser revascularization (ELR)},
       volume = {4433},
       pages = {39-44},
       note = {10.1117/12.446529},
       abstract = {Background. Endocardial laser revascularization (ELR) is a new technique to treat patients with severe coronary artery disease (CAD) in a percutaneous approach. The results show a significant improvement of symptoms, but the mechanism of action is still unknown. One main theory is the angiogenesis for which Vascular Endothelial Growth Factor (VEGF) is the keypromotor. We investigated immunohistochemically the VEGF-expression after ELR in porcine hearts over a timeperiod of four weeks. Methods. ELR was performed with a single-pulse Thulium:YAG laser. 15 pigs were treated with ELR and the hearts were harvested at five timeperiods: directly (group I), 3 days (group II), 1 week (group III), 2 weeks (group IV) and 4 weeks (group V) after ELR. Each group consisted of three pigs. Immunohistochemically the VEGF-expression was assessed by staining with a polyclonal antibody against VEGF and cellcounting using an expression index (VEGF-EI) Results. A maximum of VEGF-expression was found three days (group II) after ELR with a VEGF-EI of 97%. At 1 week (group III) the VEGF-EI was similar high with 93%. Along the timecourse the index decreased to 22% at 4 weeks (groupV). Conclusions. Our findings show that ELR leads to an local upregulation of VEGF around the channels. The resulting angiogenesis could be the mechanism for the relief of angina.},
       url = {http://dx.doi.org/10.1117/12.446529},
       type = {Conference Proceedings}
    }
    
  • Schuele, Georg and Joachimmeyer, Elke and Framme, Carsten and Roider, Johann and Birngruber, Reginald and Brinkmann, Ralf: Optoacoustic detection of selective RPE cell damage during μs-laser irradiation. no. 4433, pp. 92-96,
    BibTeX Link
    @inproceedings{Schuele2001,
       author = {Schuele, Georg and Joachimmeyer, Elke and Framme, Carsten and Roider, Johann and Birngruber, Reginald and Brinkmann, Ralf},
       title = {Optoacoustic detection of selective RPE cell damage during μs-laser irradiation},
       volume = {4433},
       pages = {92-96},
       note = {10.1117/12.446507},
       abstract = {Objective: The selective damage of the retinal pigment epithelium (RPE) with repetitive microsecond(s) laser pulses is a new technique for the treatment of several retinal diseases. RPE can selectively be damaged by simultaneously sparing off the adjacent photoreceptor tissue. Objective of this study is to investigate whether optoacoustic (OA) transients occurring during irradiation might be used to control the invisible treatment effect. Setup: A train of frequency doubled Nd:YLF laser pulses (527 nm, 1.7microsecond(s) pulse length, 500Hz rep. rate) were applied via a laser slit lamp on porcine RPE samples. The acoustic transients were recorded with a broadband transducer. Results: At low radiant exposures (&lt;100 mJ/cm2) we found a bipolar pressure transient due to thermo-elastic expansion of the RPE. The pressure waves from the individual pulses of one pulse train show nearly identical transients. The transients differ slightly from different sites on the sample. At higher radiant exposures (&gt;150 mJ/cm2), the OA transients differ from pulse to pulse within a pulse train, which can be attributed to microbubble formation around the strong absorbing melanosomes inside the RPE cells. FFT spectra of the OA transients show slight differences in the frequency spectrum with the different radiant exposures.},
       url = {http://dx.doi.org/10.1117/12.446507},
       type = {Conference Proceedings}
    }
    
  • Schuele, Georg and Joachimmeyer, Elke and Framme, Carsten and Roider, Johann and Birngruber, Reginald and Brinkmann, Ralf: Optoacoustic control system for selective treatment of the retinal pigment epithelium. no. 4256, pp. 71-76,
    BibTeX Link
    @inproceedings{Schuele2001,
       author = {Schuele, Georg and Joachimmeyer, Elke and Framme, Carsten and Roider, Johann and Birngruber, Reginald and Brinkmann, Ralf},
       title = {Optoacoustic control system for selective treatment of the retinal pigment epithelium},
       volume = {4256},
       pages = {71-76},
       note = {10.1117/12.429323},
       abstract = {The selective damage of the retinal pigment epithelium (RPE) is a new treatment method for several retinal diseases. By applying a train of microsecond(s) laser pulses it is possible to selectively damage these cells and simultaneously spare the adjacent photoreceptor and neural tissue. Due to the ophthalmologic invisibility of the RPE cell damage we investigate an optoacoustic (OA) control system to monitor the RPE cell damage. Setup: The irradiation was performed with a frequency doubled Nd:YLF laser by applying a train of +s laser pulses. In vitro, the OA transients were received by an ultrasonic broadband transducer. During treatment an OA contact lens with embedded transducer was used. In vitro: Freshly enucleated porcine RPE samples with CalceinAM as life/death staining were used. Below RPE cell damage threshold a classic thermoelastic transient was found. Above cell damage threshold the OA transient differs form pulse to pulse. This can be explained by microbubble formation around the strong absorbing melanosomes inside the RPE cells. In vivo: We found the same pulse to pulse deviations of the OA transient above the fluoresceine angiographic detectable RPE damage threshold during treatment. This system give us a new approach to non-invasively monitor the selective RPE treatment.},
       url = {http://dx.doi.org/10.1117/12.429323},
       type = {Conference Proceedings}
    }
    
  • Framme, C. and Schuele, G. and Birngruber, R. and Brinkmann, R. and Roider, J.: Autofluorescence imaging after selective RPE laser treatment in macular diseases: A pilot study.. Investigative Ophthalmology & Visual Science, no. 42, pp. S703-S703, 2001
    BibTeX Link
    @article{Framme2001,
       author = {Framme, C. and Schuele, G. and Birngruber, R. and Brinkmann, R. and Roider, J.},
       title = {Autofluorescence imaging after selective RPE laser treatment in macular diseases: A pilot study.},
       journal = {Investigative Ophthalmology & Visual Science},
       volume = {42},
       number = {4},
       pages = {S703-S703},
       note = {Suppl. S
    427EP
    3785
    Times Cited:0
    Cited References Count:0},
       ISSN = {0146-0404},
       url = {<Go to ISI>://WOS:000168392103748},
       year = {2001},
       type = {Journal Article}
    }
    
  • Brinkmann, R. and Schuele, G. and Joachimmeyer, E. and Roider, J. and Birngruber, R.: Determination of absolute fundus temperatures during retinal laser photocoagulation and selective RPE treatment.. Investigative Ophthalmology & Visual Science, no. 42, pp. S696-S696, 2001
    BibTeX Link
    @article{Brinkmann2001,
       author = {Brinkmann, R. and Schuele, G. and Joachimmeyer, E. and Roider, J. and Birngruber, R.},
       title = {Determination of absolute fundus temperatures during retinal laser photocoagulation and selective RPE treatment.},
       journal = {Investigative Ophthalmology & Visual Science},
       volume = {42},
       number = {4},
       pages = {S696-S696},
       note = {Suppl. S
    427EP
    3749
    Times Cited:0
    Cited References Count:0},
       ISSN = {0146-0404},
       url = {<Go to ISI>://WOS:000168392103712},
       year = {2001},
       type = {Journal Article}
    }
    

2000

  • Wirbelauer, C. and Koop, N. and Tuengler, A. and Geerling, G. and Birngruber, R. and Laqua, H. and Brinkmann, R.: Corneal endothelial cell damage after experimental diode laser thermal keratoplasty. J Refract Surg, no. 16, pp. 323-9, 2000
    BibTeX
    @article{Wirbelauer2000,
       author = {Wirbelauer, C. and Koop, N. and Tuengler, A. and Geerling, G. and Birngruber, R. and Laqua, H. and Brinkmann, R.},
       title = {Corneal endothelial cell damage after experimental diode laser thermal keratoplasty},
       journal = {J Refract Surg},
       volume = {16},
       number = {3},
       pages = {323-9},
       note = {Wirbelauer, C
    Koop, N
    Tuengler, A
    Geerling, G
    Birngruber, R
    Laqua, H
    Brinkmann, R
    Journal Article
    United States
    J Refract Surg. 2000 May-Jun;16(3):323-9.},
       abstract = {PURPOSE: To evaluate the safety of diode laser thermal keratoplasty (LTK) with respect to corneal endothelial cell damage. METHODS: In an in vitro animal model system, porcine eyes were irradiated with a continuously emitting laser diode at wavelengths (lambda) of 1.85 or 1.87 microm, corresponding to an absorption coefficient (micro(a)) of 1.1 or 2.0 mm(-1). Different irradiation and application parameters were tested serially. To determine the temperature threshold for endothelial damage, corneal buttons were analyzed separately in a waterbath experiment. The endothelial damage was assessed after trypan blue and alizarin red supravital staining under light microscopy. RESULTS: The thresholds for the 50% probability of thermal damage (ED50) were determined at corneal temperatures of 65 degrees C for a 10-second water-bath immersion, and 59 degrees C for 60 seconds. Coagulations that reached the deeper stromal layers revealed severe endothelial cellular alterations and areas of exposed Descemet's membrane. The thermally induced changes were dependent on laser power and the absorption coefficient (wavelength). Mean diameter of total endothelial cell damage was 245 +/- 154 microm (range, 0 to 594 microm) for an absorption coefficient of 1.1 mm(-1). The maximal lateral extent of endothelial cell damage induced by the laser exposure was 594 microm in diameter. Increasing the absorption coefficient decreased the penetration depth of the laser irradiation, creating a greater temperature rise within the corneal stroma and significantly less endothelial damage (P < .01), when the same laser power was applied. The calculated total area of damage for the paracentral human corneal endothelium ranged from 1.8% to 13.6%. CONCLUSION: Data obtained in this in vitro study were transferred to an endothelial cell damage nomogram, demonstrating that appropriate parameter improvements can minimize the adverse effects to the corneal endothelium. However, model adjustment to the human cornea indicates the potential for endothelial cell damage after diode laser thermal keratoplasty, and should be considered when performing this elective procedure.},
       keywords = {Animals
    Anthraquinones
    Cell Count
    Cell Survival
    Corneal Diseases/*etiology/pathology
    Corneal Stroma/*surgery
    Endothelium, Corneal/*pathology
    Laser Coagulation/*adverse effects/methods
    Necrosis
    Safety
    Swine
    Trypan Blue},
       ISSN = {1081-597X (Print)
    1081-597x},
       year = {2000},
       type = {Journal Article}
    }
    
  • Brinkmann, R. and Radt, B. and Flamm, C. and Kampmeier, J. and Koop, N. and Birngruber, R.: Influence of temperature and time on thermally induced forces in corneal collagen and the effect on laser thermokeratoplasty. J Cataract Refract Surg, no. 26, pp. 744-54, 2000
    BibTeX Link
    @article{Brinkmann2000,
       author = {Brinkmann, R. and Radt, B. and Flamm, C. and Kampmeier, J. and Koop, N. and Birngruber, R.},
       title = {Influence of temperature and time on thermally induced forces in corneal collagen and the effect on laser thermokeratoplasty},
       journal = {J Cataract Refract Surg},
       volume = {26},
       number = {5},
       pages = {744-54},
       note = {0886-3350 (Print)
    Journal Article
    Research Support, Non-U.S. Gov't},
       abstract = {PURPOSE: To investigate thermomechanical aspects of corneal collagen denaturation as a function of temperature and time and the effect of the induced forces on refractive changes with laser thermokeratoplasty (LTK). SETTING: Medical Laser Center Lubeck, Lubeck, Germany. METHODS: In a material-test setup, porcine corneal strips were denatured in paraffin oil at various constant temperatures for 10 and 500 seconds, and the temporal course of the contractive forces was studied under isometric conditions. Typical LTK lesions were performed in porcine eyes in vitro with a continuous-wave infrared laser diode at a wavelength of 1.87 microm for 10 and 60 seconds. The laser power was chosen to achieve comparable denatured volumes at both irradiation times. The refractive changes were measured and analyzed by histologic evaluations and temperature calculations. RESULTS: The time course of the induced forces was characterized by a maximal force, which increased almost linearly with temperature, and a residual lower force. After 500 seconds of heating, the highest force was achieved with a temperature of 75 degrees C. With a limited heating period of only 10 seconds, the forces steadily increased with temperature over the entire observation period. Laser thermokeratoplasty produced less refractive change after 10 seconds of irradiation than after 60 seconds, although the laser power was 25% higher in the short heating period. Polarization light microscopy of LTK lesions revealed different stages of thermal damage. CONCLUSION: The course of the contractive forces during and after heating is a complicated function of the spatial time/temperature profile. Laser thermokeratoplasty lesions produced with 2 irradiation times showed different stages of denaturation and induced refractive change.},
       keywords = {Animals
    Body Temperature
    Collagen/*metabolism
    Cornea/metabolism/pathology/*surgery
    *Laser Coagulation
    Microscopy, Polarization
    Protein Denaturation
    Swine
    Time Factors},
       url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10831907},
       year = {2000},
       type = {Journal Article}
    }
    
  • Roider, J. and Brinkmann, R. and Wirbelauer, C. and Laqua, H. and Birngruber, R.: Subthreshold (retinal pigment epithelium) photocoagulation in macular diseases: a pilot study. Br J Ophthalmol, no. 84, pp. 40-7, 2000
    BibTeX
    @article{Roider,
       author = {Roider, J. and Brinkmann, R. and Wirbelauer, C. and Laqua, H. and Birngruber, R.},
       title = {Subthreshold (retinal pigment epithelium) photocoagulation in macular diseases: a pilot study},
       journal = {Br J Ophthalmol},
       volume = {84},
       number = {1},
       pages = {40-7},
       note = {0007-1161 (Print)
    Journal Article},
       abstract = {BACKGROUND: Subthreshold (retinal pigment epithelium) photocoagulation is a new photocoagulation method, which treats the retinal pigment epithelium (RPE) and avoids damage to the neural retina. The initial results in this prospective pilot study on various macular diseases are presented. METHODS: 12 patients with diabetic maculopathy (group I), 10 with soft drusen (group II), and four with central serous retinopathy (CSR) (group III) were treated and followed up for 1 year. Treatment was achieved using a train of repetitive short laser pulses (1.7 micros) of a green Nd:YLF laser (parameters: 527 nm, 100 and 500 pulses, repetition rate: 500 Hz, spot size: 160 microm, energies: 70-100 microJ). Laser energy was based on the visibility of test lesions on fluorescein angiography (50-130 microJ). Patients were examined at various times by ophthalmoscopy, fluorescein and ICG angiography, and infrared imaging. RESULTS: After 6 months hard exudates disappeared in six out of nine patients in group I and leakage disappeared in six out of 12 diabetic patients. In group II drusen were less in seven out of 10 patients. In group III serous detachment disappeared in three out of four cases. Visual acuity was stable in all cases. None of the laser lesions was clinically visible immediately. After 1 day most lesions were visible as yellowish RPE depigmentation. After 3 months some of the lesions were visible as hyperpigmented areas but most were not. Fluorescein angiography showed leakage only in the first week. Infrared imaging showed that most lesions can be visualised in groups I and II after a period longer than 1 week as hyperreflective areas. CONCLUSION: This study showed that subthreshold (RPE) photocoagulation is effective in some cases of diabetic maculopathy, drusens, and in CSR. Visibility of laser burns is not always necessary in the treatment of macular diseases presented here. Infrared imaging is an effective and non-invasive way of visualising subthreshold (RPE) laser burns.},
       keywords = {Aged
    Diabetic Retinopathy/surgery
    Female
    Fluorescein Angiography
    Follow-Up Studies
    Fundus Oculi
    Humans
    *Laser Coagulation
    Macular Degeneration/pathology/*surgery
    Male
    Middle Aged
    Pigment Epithelium of Eye/*surgery
    Pilot Projects
    Prospective Studies
    Retinal Drusen/surgery
    Treatment Outcome},
       year = {2000}
    }
    
  • Kampmeier, J. and Radt, B. and Birngruber, R. and Brinkmann, R.: Thermal and biomechanical parameters of porcine cornea. Cornea, no. 19, pp. 355-63,
    BibTeX
    @article{Kampmeier,
       author = {Kampmeier, J. and Radt, B. and Birngruber, R. and Brinkmann, R.},
       title = {Thermal and biomechanical parameters of porcine cornea},
       journal = {Cornea},
       volume = {19},
       number = {3},
       pages = {355-63},
       note = {0277-3740 (Print)
    Journal Article
    Research Support, Non-U.S. Gov't},
       abstract = {PURPOSE: New methods in refractive surgery require a considerable understanding of the material "cornea" and are often studied by theoretical modeling in order to gain insight into the procedure and an optimized approach to the technique. The quality of these models is highly dependent on the preciseness of its input parameters. Porcine cornea often is used as a model in preclinical studies because of its similarity to man and its availability. METHODS: The important physical parameters for biomechanical deformation, heat conduction, and collagen denaturation kinetics have been determined for porcine cornea. Experimental methods include densitometry, calorimetry, turbidimetry, tensile tests, stress relaxation, and hydrothermal isometric tension measurements. RESULTS: The density of porcine cornea was measured as p = 1062+/-5 kg/m3, the heat capacity gave c = 3.74+/-0.05 J/gK. The stress-strain relation for corneal strips is represented by a third order approximation where the secant modulus yields about Esec approximately equal to 0.4 MPa for small strains less than 2%. The normalized stress relaxation is described by an exponential fit over time. The denaturation process of cornea is characterized by specific temperatures which can be related to the change of the mechanical properties. Denaturation kinetics are described according to the model of Arrhenius yielding the activation energy deltaEa = 106 kJ/mol and the phase transition entropy deltaS = 39 J/(mol x K). CONCLUSIONS: The established set of parameters characterizes the porcine cornea in a reliable way that creates a basis for corneal models. It furthermore gives direct hints of how to treat cornea in certain refractive techniques.},
       keywords = {Animals
    
  • Brinkmann, R. and Huttmann, G. and Rogener, J. and Roider, J. and Birngruber, R. and Lin, C. P.: Origin of retinal pigment epithelium cell damage by pulsed laser irradiance in the nanosecond to microsecond time regimen. Lasers Surg Med, no. 27, pp. 451-64,
    BibTeX
    @article{Brinkmann2000,
       author = {Brinkmann, R. and Huttmann, G. and Rogener, J. and Roider, J. and Birngruber, R. and Lin, C. P.},
       title = {Origin of retinal pigment epithelium cell damage by pulsed laser irradiance in the nanosecond to microsecond time regimen},
       journal = {Lasers Surg Med},
       volume = {27},
       number = {5},
       pages = {451-64},
       note = {0196-8092 (Print)
    In Vitro
    Journal Article
    Research Support, Non-U.S. Gov't},
       abstract = {BACKGROUND AND OBJECTIVE: Selective photodamage of the retinal pigment epithelium (RPE) is a new technique to treat a variety of retinal diseases without causing adverse effects to surrounding tissues such as the neural retina including the photoreceptors and the choroid. In this study, the mechanism of cell damage after laser irradiation was investigated. STUDY DESIGN/MATERIALS AND METHODS: Single porcine RPE-melanosomes and RPE cells were irradiated with a Nd:YLF laser (wavelength lambda = 527 nm, adjustable pulse duration tau = 250 nsec-3 microsec) and a Nd:YAG laser (lambda = 532 nm, tau = 8 nsec). Fast flash photography was applied to observe vaporization at melanosomes in suspension. A fluorescence viability assay was used to probe the cells vitality. RESULTS: The threshold radiant exposures for vaporization around individual melanosomes and for ED50 cell damage are similar at 8-nsec pulse duration. Both thresholds increase with pulse duration; however, the ED50 cell damage radiant exposure is 40% lower at 3 microsec. Temperature calculations to model the onset of vaporization around the melanosomes are in good agreement with the experimental results when assuming a surface temperature of 150 degrees C to initiate vaporization and a homogeneous melanosome absorption coefficient of 8,000 cm(-1). Increasing the number of pulses delivered to RPE cells at a repetition rate of 500 Hz, the ED50 value 
  • Schüle, G. and Hüttmann, G. and Roider, J. and Wirbelauer, C. and Birngruber, R. and Brinkmann, R.: Optoacoustic measurements during µs-irradiation of the retinal pigment epithelium. Proc. SPIE, no. 3914A, 2000
    BibTeX
    @article{Schüle,
       author = {Schüle, G. and Hüttmann, G. and Roider, J. and Wirbelauer, C. and Birngruber, R. and Brinkmann, R.},
       title = {Optoacoustic measurements during µs-irradiation of the retinal pigment epithelium},
       journal = {Proc. SPIE},
       volume = {3914A},
       year = {2000}
    }
    

1999

  • Koop, N. and Wirbelauer, C. and Tüngler, A. and Geerling, G. and Bastian, G. O. and Brinkmann, R: Thermische Schädigung des Hornhautendothels bei der Dioden-Laserthermokeratoplastik.. Ophthalmologe, no. 96, pp. 392-397, 1999
    BibTeX
    @article{Koop,
       author = {Koop, N. and Wirbelauer, C. and Tüngler, A. and Geerling, G. and Bastian, G. O. and Brinkmann, R},
       title = {Thermische Schädigung des Hornhautendothels bei der Dioden-Laserthermokeratoplastik.},
       journal = {Ophthalmologe},
       volume = {96},
       pages = {392-397},
       year = {1999},
       type = {Journal Article}
    }
    
  • Brinkmann, R. and Rögener, J. and Lin, C.P. and Roider, J. and Birngruber, R. and Hüttmann, G.: Selective RPE-Photodestruction: Mechanism of Cell Damage by pulsed laser irradiance in the ns to µs time regime. Proc. SPIE, no. 3601, pp. 59-65, 1999
    BibTeX
    @article{Brinkmann1999,
       author = {Brinkmann, R. and Rögener, J. and Lin, C.P. and Roider, J. and Birngruber, R. and Hüttmann, G.},
       title = {Selective RPE-Photodestruction: Mechanism of Cell Damage by pulsed laser irradiance in the ns to µs time regime},
       journal = {Proc. SPIE},
       volume = {3601},
       pages = {59-65},
       year = { 1999}
    }
    
  • Theisen, D. and Brendel, T. and Birngruber, R. and Brinkmann, R: Endokardiale Laser Revaskularisation des Myokards mittels 20 J Einzelpuls Holmium Laserstrahlung. Lasermedizin, no. 14, pp. 125-128, 1999
    BibTeX
    @article{Theisen1999,
       author = {Theisen, D. and Brendel, T. and Birngruber, R. and Brinkmann, R},
       title = {Endokardiale Laser Revaskularisation des Myokards mittels 20 J Einzelpuls Holmium Laserstrahlung},
       journal = {Lasermedizin},
       volume = {14},
       pages = {125-128},
       year = {1999},
       type = {Journal Article}
    }
    
  • Roider, J. and Brinkmann, R. and Wirbelauer, C. and Laqua, H. and Birngruber, R.: Retinal sparing by selective retinal pigment epithelial photocoagulation. Arch Ophthalmol, no. 117, pp. 1028-34, 1999
    BibTeX
    @article{Roider1999,
       author = {Roider, J. and Brinkmann, R. and Wirbelauer, C. and Laqua, H. and Birngruber, R.},
       title = {Retinal sparing by selective retinal pigment epithelial photocoagulation},
       journal = {Arch Ophthalmol},
       volume = {117},
       number = {8},
       pages = {1028-34},
       note = {0003-9950 (Print)
    Journal Article},
       abstract = {OBJECTIVE: To investigate whether photocoagulation of the retinal pigment epithelium is possible with sparing of the photoreceptors. METHODS: Mild laser effects of a neodymium:yttrium-lithium-fluoride (Nd:YLF) laser (527 nm) were applied to 17 patients. To establish the necessary energy, test exposures were performed to the lower macula (laser variables: 1.7 microseconds, 100 and 500 pulses applied in a train at 500 Hz, 20-130 microJ, 160 microm). Of 179 test lesions, 73 were followed up at various time intervals up to 1 year by performing microperimetry directly on top of the laser lesions. RESULTS: All of the test lesions were at the threshold of retinal pigment epithelial disruption, and none of the laser effects were visible by ophthalmoscopy during photocoagulation; they were detectable only by fluorescein angiography. After exposure with 500 pulses, retinal defects were detected in up to 73% of the patients (100 microJ) after the first day. Most of these defects were no longer detectable after 3 months. After exposure with 100 pulses, no defects could be detected with 70 and 100 microJ after 1 day. The absence of microscotomas in the follow-up period suggests that retinal damage was minimal or, if it occurred, was functionally repaired. CONCLUSION: By choosing proper energy and number of pulses, it is possible to produce retinal pigment epithelial effects with no subsequent retinal damage detectable by microperimetry.},
       keywords = {Adult
    Eye Injuries/physiopathology/*prevention & control
    Female
    Fluorescein Angiography
    Follow-Up Studies
    Fundus Oculi
    Humans
    *Laser Coagulation/methods
    Male
    Middle Aged
    Ophthalmoscopy
    Perimetry
    Pigment Epithelium of Eye/physiopathology/*surgery
    Retina/injuries/*physiopathology
    Retinal Diseases/physiopathology/*surgery
    Visual Acuity},
       url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10448745},
       year = {1999},
       type = {Journal Article}
    }
    
  • Roider, J. and Brinkmann, R. and Wirbelauer, C. and Birngruber, R. and Laqua, H.: Variability of RPE reaction in two cases after selective RPE laser effects in prophylactic treatment of drusen. Graefes Arch Clin Exp Ophthalmol, no. 237, pp. 45-50, 1999
    BibTeX
    @article{Roider1999,
       author = {Roider, J. and Brinkmann, R. and Wirbelauer, C. and Birngruber, R. and Laqua, H.},
       title = {Variability of RPE reaction in two cases after selective RPE laser effects in prophylactic treatment of drusen},
       journal = {Graefes Arch Clin Exp Ophthalmol},
       volume = {237},
       number = {1},
       pages = {45-50},
       note = {0721-832X (Print)
    Case Reports
    Journal Article},
       abstract = {BACKGROUND: The value of prophylactic photocoagulation of soft drusen is unclear. Photocoagulation is usually performed by a continuous wave laser. METHODS: We report the cases of two patients with age-related macular degeneration with soft drusen who were treated by selective retinal pigment epithelium (RPE) photocoagulation of a pulsed Nd:YLF (527 nm) laser. Laser parameters were: wavelength 527 nm, number of pulses in a train 500, pulse duration 1.7 microseconds, energy per pulse 70 microJ, spot size 160 microns, repetition rate 500 Hz. RESULTS: Dosimetry performed individually showed that in both patients laser photocoagulation was performed at the threshold of RPE disruption. None of the laser effects was visible during photocoagulation. They were detectable only by fluorescein angiography. Despite identical photocoagulation parameters the RPE reaction was completely different. In the first patient RPE hyperpigmentation was notable at most photocoagulation sites and the drusen had disappeared after 6 months. In the second patient the laser effects were not visible after 6 months by biomicroscopy and the drusen stayed unchanged. CONCLUSION: These findings could reflect different repair mechanisms of the RPE after alteration and could represent a sign of a different viable stage in the life of RPE cells. Close attention should be paid to this phenomenon in the various drusen studies currently under way.},
       keywords = {Fluorescein Angiography
    Fundus Oculi
    Humans
    *Laser Coagulation
    Macular Degeneration/complications
    Middle Aged
    Pigment Epithelium of Eye/pathology/*surgery
    Retinal Drusen/complications/pathology/*surgery
    Visual Acuity},
       url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9951641},
       year = {1999},
       type = {Journal Article}
    }
    
  • Geerling, G. and Koop, N. and Tungler, A. and Brinkmann, R. and Wirbelauer, C. and Birngruber, R. and Laqua, H.: Diode laser thermokeratoplasty. Initial clinical experiences. Ophthalmologe, no. 96, pp. 306-11, 1999
    BibTeX
    @article{Geerling1999,
       author = {Geerling, G. and Koop, N. and Tungler, A. and Brinkmann, R. and Wirbelauer, C. and Birngruber, R. and Laqua, H.},
       title = {Diode laser thermokeratoplasty. Initial clinical experiences},
       journal = {Ophthalmologe},
       volume = {96},
       number = {5},
       pages = {306-11},
       abstract = {PURPOSE: Pulsed holmium lasers are currently used to correct hyperopia by means of laser thermokeratoplasty (LTK). Series of microsecond laser pulses are applied with a high repetition rate to induce shrinkage of corneal collagen fibers. The pulsed energy application results in intrastromal temperature peaks of up to 200 degrees C. A continuously emitting laser diode can--as we demonstrated recently in an invivo study on minipigs--be used for LTK and may be of advantage because the temperature rise is more steady. The aim of this study was to examine the safety, amount, and stability of hyperopic correction of diode LTK on blind human eyes. METHODS: We used a laserdiode that was set to continuously emit light at lambda = 1.854 microns/mu a = 1.04 mm-1 (group I, n = 4) or 1.87 microns/mu a = 1.92 mm-1 (group II, n = 4). Radiation energy was 100 to 150 mW for 10 s per coagulation. Eight coagulations on a single ring (group I) and 16 coagulations on a double ring (group II) diameter were applied in the cornea concentric to the entrance pupil by means of a vacuum-fixed application mask (group I = conjunctival fixation; group II = corneal fixation) and a handpiece with a focusing optic. Preoperatively as well as 1 week, 1, 2, 3, 6 12 and 18 months postoperative ophthalmologic controls were performed and the corneal refractive power was measured. RESULTS: In group I initial refractive changes of up to +4.9 D were achieved (1 week postoperative). However, due to the great penetration depth of the laser irradiation, large endothelial defects resulted beneath the stromal coagulations. In group II an initial refractive change of up to +6.8 D was achieved and as a result of the reduced penetration depth, the endothelial cell damage was much reduced. Partial regression of the refractive effect occurred in all subjects, which continued in higher refractive changes during the 2nd postoperative year. The refractive effect at 12 months was +0.6 to +1.5 D in group I and +0.9 to +5.7 D in group II. At 12 months the induced astigmatism was 0.5 to 2.2 D in group I and 0.3 to 1.6 D in group II. No serious adverse effects were noticed. CONCLUSION: A continously emitting laser diode working at a wavelength of 1.87 microns can be used to correct hyperopia by means of LTK safely and effectively. Regression occurs predominantly in the first 6 postoperative months. Further studies must be conducted to determine the importance of patient inherent parameters such as age in establishing a nomogram.},
       keywords = {Adult
    Aged
    Aged, 80 and over
    Blindness/*surgery
    Corneal Topography
    English Abstract
    Equipment Safety
    Female
    Human
    Hyperopia/*surgery
    Keratectomy, Photorefractive, Excimer Laser/*instrumentation
    Laser Coagulation/*instrumentation
    Male
    Middle Age
    Postoperative Complications/etiology
    Refraction, Ocular
    Temperature},
       year = {1999},
       type = {Journal Article}
    }
    
  • Geerling, G. and Koop, N. and Brinkmann, R. and Tungler, A. and Wirbelauer, C. and Birngruber, R. and Laqua, H.: Continuous-wave diode laser thermokeratoplasty: first clinical experience in blind human eyes. J Cataract Refract Surg, no. 25, pp. 32-40, 1999
    BibTeX
    @article{Geerling1999,
       author = {Geerling, G. and Koop, N. and Brinkmann, R. and Tungler, A. and Wirbelauer, C. and Birngruber, R. and Laqua, H.},
       title = {Continuous-wave diode laser thermokeratoplasty: first clinical experience in blind human eyes},
       journal = {J Cataract Refract Surg},
       volume = {25},
       number = {1},
       pages = {32-40},
       note = {0886-3350 (Print)
    Clinical Trial
    Journal Article
    Research Support, Non-U.S. Gov't},
       abstract = {PURPOSE: To evaluate the safety and stability of laser thermokeratoplasty (LTK) with a continuous-wave diode laser in blind human eyes and to optimize parameters for a study in sighted eyes. SETTING: Department of Ophthalmology, Medical University Lubeck, Germany. METHODS: A continuous-wave diode laser was set to emit radiation with a wavelength of 1.854 microns (Group 1, n = 4) or 1.870 microns (Group 2, n = 4) and 100 to 150 mW power for 10 seconds. A focusing handpiece was coupled with an application mask and fixed by partial vacuum to the conjunctiva or cornea. The radiation was focused into the corneal stroma between 400 and 600 microns in Group 1 and set to 1000 microns in Group 2. Eight (Group 1, single ring) or 16 (Group 2, double ring) coagulations were applied. RESULTS: The refractive change increased with higher laser power and smaller ring diameters. Two rings of coagulations provided higher and more stable refractive changes of up to 5.66 diopters (D) than a single ring. The refractive effect stabilized between 3 and 6 months postoperatively. At 1 year, mean refractive change was +0.99 D +/- 0.39 (SD) in Group 1 and +2.32 +/- 2.24 D in Group 2. Extensive endothelial damage occurred in Group 1 but was minimal in Group 2. CONCLUSIONS: Diode LTK was used to treat hyperopia safely and effectively. Regression occurred mainly in the first 3 postoperative months. With a wavelength of 1.870 microns, corneal endothelial damage was limited.},
       keywords = {Adult
    Aged
    Aged, 80 and over
    Blindness/*complications
    Corneal Stroma/pathology/physiopathology/*surgery
    Corneal Topography
    Female
    Humans
    Hyperopia/pathology/physiopathology/*surgery
    Laser Coagulation/adverse effects/*methods
    Male
    Middle Aged
    Postoperative Complications
    Safety},
       url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9888074},
       year = {1999},
       type = {Journal Article}
    }
    
  • Brinkmann, R. and Theisen, D. and Brendel, T. and Birngruber, R.: Single-pulse 30-J holmium laser for myocardial revascularization - A study on ablation dynamics in comparison to CO2 laser-TMR. Ieee Journal of Selected Topics in Quantum Electronics, no. 5, pp. 969-980, 1999
    BibTeX Link
    @article{Brinkmann1999,
       author = {Brinkmann, R. and Theisen, D. and Brendel, T. and Birngruber, R.},
       title = {Single-pulse 30-J holmium laser for myocardial revascularization - A study on ablation dynamics in comparison to CO2 laser-TMR},
       journal = {Ieee Journal of Selected Topics in Quantum Electronics},
       volume = {5},
       number = {4},
       pages = {969-980},
       note = {248CM
    Times Cited:9
    Cited References Count:40},
       abstract = {Endocardial laser revascularization (ELR) is a new technique to treat coronary heart disease in a percutaneous, minimally invasive approach. A holmium laser (lambda = 2.12 mu m) was developed to emit pulse energies of up to 30 J in order to ablate the desired channels in a single laser pulse. The energy was transmitted by multimode flexible optical waveguides as required for ELR, Ablation dynamics were investigated in two model systems, water serving as blood model and polyacrylamide (PAA) as a transparent tissue phantom. Measurements were undertaken using pulse energies of 12 J at pulse durations of 2.2 and 8 ms with a beam diameter of 1 mm, For comparison with the clinically established method of transmyocardial revascularization (TMR), ablations were also investigated with a standard 800 W TMR CO2 laser. The dynamics were recorded with a drum camera and stroboscope illumination providing a high framing rate of a single ablation process. Tissue ablation was quantified with the holmium laser in vitro on porcine heart tissue using pulse energies of up to 20 J, Tissue morphology was evaluated using polarization light microscopy to determine thermal and mechanical collateral damage zones. Oscillating vapor bubble channels were found in water and PAA with all laser systems and parameters used. Quasi-static vapor bubbles are observed in water in the millisecond time range using the holmium laser. CO2 laser radiation performed deeper channels in PAA than holmium laser pulses using the same radiant exposure. Channel depths of up to 10 mm were achieved with the holmium laser in myocardial tissue with pulse energies of 17 J, Thermal damage zones of about 150 mu m for the CO2 and 500 mu m for the holmium laser were found. The orientation of myocardial fibrils significantly influences the shape of the ablated cavities and the thermo-mechanical collateral damage zones. In conclusion, the results are very encouraging and demonstrate the potential of a catheter-based minimal invasive procedure for heart reperfusion using single high energy laser pulses.},
       keywords = {ablation dynamics
    co2 laser
    elr
    fast flash photography
    heart revascularization
    holmium laser
    polyacrylamide
    tmlr
    tmr
    transmyocardial revascularization
    tissue ablation
    channels
    generation
    duration
    water
    blood},
       ISSN = {1077-260X},
       DOI = {Doi 10.1109/2944.796319},
       url = {<Go to ISI>://WOS:000083257800015},
       year = {1999},
       type = {Journal Article}
    }
    
  • Brendel, T. and Brinkmann, R. and Theisen, D. and Birngruber, R.: Ablation Dynamics of High Energy IR Laser Pulses in Myocardial Revascularization. Biomedical Optics, OSA Technical Digest, pp. 152-154, 1999
    BibTeX
    @article{Brendel1999,
       author = {Brendel, T. and Brinkmann, R.  and Theisen, D.  and Birngruber, R.},
       title = {Ablation Dynamics of High Energy IR Laser Pulses in Myocardial Revascularization},
       journal = {Biomedical Optics, OSA Technical Digest},
       pages = {152-154},
       year = {1999},
       type = {Journal Article}
    }
    

1998

  • Brinkmann, R and Theisen, D. and Stubbe, H.M. and Birngruber, R.: Endocardial Laser Revascularization with Single High Energy Laser Pulses. OSA TOPS, no. 22, pp. 272-276, 1998
    BibTeX
    @article{Brinkmann1998,
       author = {Brinkmann, R and Theisen, D. and Stubbe, H.M. and Birngruber, R.},
       title = {Endocardial Laser Revascularization with Single High Energy Laser Pulses},
       journal = {OSA TOPS},
       volume = {22},
       pages = {272-276},
       year = { 1998},
       type = {Journal Article}
    }
    
  • Brinkmann, R and Koop, N. and Kamm, K. and Geerling, G. and Kampmeier, J. and Birngruber, R.: Laser Thermokeratoplastik: eine in vitro- und in vivo-Studie mit kontinuierlich emittierender Laserdiode im mittleren IR-Spektralbereich.. Laser in der Medizin, Proc. Laser 97, pp. 412-416, 1998
    BibTeX
    @article{Brinkmann1998,
       author = {Brinkmann, R and Koop, N. and Kamm, K. and Geerling, G. and Kampmeier, J. and Birngruber, R.},
       title = {Laser Thermokeratoplastik: eine in vitro- und in vivo-Studie mit kontinuierlich emittierender Laserdiode im mittleren IR-Spektralbereich.},
       journal = {Laser in der Medizin, Proc. Laser 97},
       pages = {412-416},
       year = {1998},
       type = {Journal Article}
    }
    
  • Brinkmann, R. and Koop, N. and Geerling, G. and Kampmeier, J. and Borcherding, S. and Kamm, K. and Birngruber, R.: Diode laser thermokeratoplasty: application strategy and dosimetry. J Cataract Refract Surg, no. 24, pp. 1195-207, 1998
    BibTeX
    @article{Brinkmann1998,
       author = {Brinkmann, R. and Koop, N. and Geerling, G. and Kampmeier, J. and Borcherding, S. and Kamm, K. and Birngruber, R.},
       title = {Diode laser thermokeratoplasty: application strategy and dosimetry},
       journal = {J Cataract Refract Surg},
       volume = {24},
       number = {9},
       pages = {1195-207},
       note = {0886-3350 (Print)
    Journal Article
    Research Support, Non-U.S. Gov't},
       abstract = {PURPOSE: To investigate suitable application parameters for efficient hyperopic correction by laser thermokeratoplasty (LTK) using mid-infrared laser diodes. SETTING: Medical Laser Center Lubeck, Lubeck, Germany. METHOD: A tunable continuous-wave laser diode in the spectral range between 1.845 and 1.871 microns was used. Transmitted by waveguides, the laser energy was used to induce coagulations on freshly enucleated porcine eyes to increase corneal curvature. The coagulations were equidistantly applied by a fiber-cornea contact and a noncontact focusing device that were adjusted on a ring concentric to the corneal apex. Different laser parameters and application geometries were evaluated. Refractive changes were measured by computer-assisted corneal topography before and after treatment. Polarization light microscopy and temperature calculations were used to analyze the coagulations. RESULTS: Because of the tunability of the laser diode, the influence of the corneal absorption coefficient (between 0.9 and 1.6 mm-1) on the refractive change could be measured. A laser power between 125 and 200 mW was adequate to achieve refractive changes up to 10.0 diopters. In the preferable focusing device, the refractive change increased almost logarithmically with the irradiation time up to 15 seconds. The number of coagulations on a fixed application ring showed no significant influence on refractive change; however, it showed an almost linear decrease with increasing ring diameter from 5.0 to 10.0 mm. Histological analysis revealed 3 stages of thermal damage. CONCLUSION: Diode LTK provided defined and uniform coagulations when using a well-adapted focusing device, resulting in sufficient refractive change. The results indicate that diode LTK is superior to pulsed holmium LTK.},
       keywords = {Absorption
    Animals
    Cornea/pathology/physiopathology/*surgery
    Hyperopia/pathology/physiopathology/*surgery
    Laser Coagulation/*methods
    Microscopy, Polarization
    Refraction, Ocular
    Swine},
       year = { 1998}
    }
    
  • Brinkmann, R. and Knipper, A. and Dröge, G. and Schroer, F. and Gromoll, B. and Birngruber, R.: Fundamental Studies of Fiber-Guided Soft Tissue Cutting by Means of Pulsed Midinfrared IR lasers and their Application in Ureterotomy. J Biomed Opt, no. 3, pp. 85-95, 1998
    BibTeX
    @article{Brinkmann1998,
       author = {Brinkmann, R. and Knipper, A. and Dröge, G. and Schroer, F. and Gromoll, B. and Birngruber, R.},
       title = {Fundamental Studies of Fiber-Guided Soft Tissue Cutting by Means of Pulsed Midinfrared IR lasers and their Application in Ureterotomy},
       journal = {J Biomed Opt},
       volume = {3},
       number = {1},
       pages = {85-95},
       year = { 1998}
    }
    

1997

  • Wirbelauer, C. and Geerling, G. and Koop, N. and Brinkmann, R. and Tungler, A. and Birngruber, R. and Laqua, H.: Acute endothelial cell changes after laser thermal keratoplasty with a CW-IR laser diode. Investigative Ophthalmology & Visual Science, no. 38, pp. 2516-2516, 1997
    BibTeX
    @article{Wirbelauer1997,
       author = {Wirbelauer, C. and Geerling, G. and Koop, N. and Brinkmann, R. and Tungler, A. and Birngruber, R. and Laqua, H.},
       title = {Acute endothelial cell changes after laser thermal keratoplasty with a CW-IR laser diode},
       journal = {Investigative Ophthalmology & Visual Science},
       volume = {38},
       number = {4},
       pages = {2516-2516},
       note = {1
    Wn186
    Times Cited:0
    Cited References Count:0},
       ISSN = {0146-0404},
       url = {<Go to ISI>://WOS:A1997WN18602508},
       year = {1997},
       type = {Journal Article}
    }
    
  • Koop, Norbert and Brinkmann, Ralf and Lankenau, Eva and Flache, Stefan and Engelhardt, Ralf and Birngruber, Reginald: Optische Kohärenztomographie der Kornea und des vorderen Augenabschnitts. Der Ophthalmologe, no. 94, pp. 481-486, 1997
    BibTeX Link
    @article{Koop1997,
       author = {Koop, Norbert and Brinkmann, Ralf and Lankenau, Eva and Flache, Stefan and Engelhardt, Ralf and Birngruber, Reginald},
       title = {Optische Kohärenztomographie der Kornea und des vorderen Augenabschnitts},
       journal = {Der Ophthalmologe},
       volume = {94},
       number = {7},
       pages = {481-486},
       ISSN = {1433-0423},
       url = {http://dx.doi.org/10.1007/s003470050143},
       year = {1997},
       type = {Journal Article}
    }
    
  • Roider, J. and Brinkmann, R. and Laqua, H. and Birngruber, R.: Therapeutical bandwidth or selective RPE-photocoagulation treatment by repetitive mu s-laser pulses (527 nm) - First clinical results. Investigative Ophthalmology & Visual Science, no. 38, pp. 404-404, 1997
    BibTeX
    @article{Roider1997,
       author = {Roider, J. and Brinkmann, R. and Laqua, H. and Birngruber, R.},
       title = {Therapeutical bandwidth or selective RPE-photocoagulation treatment by repetitive mu s-laser pulses (527 nm) - First clinical results},
       journal = {Investigative Ophthalmology & Visual Science},
       volume = {38},
       number = {4},
       pages = {404-404},
       note = {1
    Wn186
    Times Cited:0
    Cited References Count:0},
       ISSN = {0146-0404},
       url = {<Go to ISI>://WOS:A1997WN18600402},
       year = {1997},
       type = {Journal Article}
    }
    
  • Koop, N. and Brinkmann, R. and Lankenau, E. and Flache, S. and Engelhardt, R. and Birngruber, R.: Optical coherence tomography of cornea and anterior segment of the eye. Ophthalmologe, no. 94, pp. 481-486, 1997
    BibTeX Link
    @article{Koop1997,
       author = {Koop, N. and Brinkmann, R. and Lankenau, E. and Flache, S. and Engelhardt, R. and Birngruber, R.},
       title = {Optical coherence tomography of cornea and anterior segment of the eye},
       journal = {Ophthalmologe},
       volume = {94},
       number = {7},
       pages = {481-486},
       note = {Yp140
    Times Cited:34
    Cited References Count:19},
       abstract = {Target: The method of optical coherence tomography (OCT) was investigated regarding its suitability and limits for measuring the cornea and the anterior segment of the eye. Furthermore, the stromal expansion of thermally induced lesions in the cornea directly after irradiation was determined within the scope of the laser thermokeratoplasty (LTK).
    Material and methods: With the experimental scanning OCT system, x-z sections of the anterior eye segment were made with an optical resolution of about 20 mu m axially and 25 mu m laterally. Freshly enucleated, tonicized porcine eyes were used as model eyes. Thermal lesions were applied with a continuously emitting laser diode (lambda=1.86 mu m) and various radiation parameters, Before and after coagulation, the cornea was viewed from limbus to limbus in a central OCT scan and the individual coagulation source was measured,
    Results: Global and local changes of the thickness of the cornea as well as the distance between cornea and lens were measured with high precision. Thermal lesions in their expansion can be clearly presented and matching well with the histologically stained sections, bur are not as exactly defined at the edges due to the limited optical resolution, as known from histological preparations.
    Conclusion: With the OCT method quantitative measuring of the anterior eye segment can be performed in vitro and with reduced resolutions also in vivo. Due to the qualitatively good correspondence regarding the dimensions of thermal damage of the cornea with histologically obtained morphometric results,this method can be used for supervision of coagulation directly after LTK as well as for examination of the individual healing process.},
       keywords = {optical coherence tomography
    pachometry
    laser thermokeratoplasty
    thermal damage
    tissue},
       ISSN = {0941-293X},
       DOI = {DOI 10.1007/s003470050143},
       url = {<Go to ISI>://WOS:000071246700003},
       year = {1997},
       type = {Journal Article}
    }
    
  • Geerling, G. and Brinkmann, R. and Koop, N. and Wirbelauer, C. and Laqua, H. and Birngruber, R.: Diode-laser thermokeratoplasty - First clinical experiences in human blind eyes. Investigative Ophthalmology & Visual Science, no. 38, pp. 2292-2292, 1997
    BibTeX
    @article{Geerling1997,
       author = {Geerling, G. and Brinkmann, R. and Koop, N. and Wirbelauer, C. and Laqua, H. and Birngruber, R.},
       title = {Diode-laser thermokeratoplasty - First clinical experiences in human blind eyes},
       journal = {Investigative Ophthalmology & Visual Science},
       volume = {38},
       number = {4},
       pages = {2292-2292},
       note = {1
    Wn186
    Times Cited:0
    Cited References Count:0},
       ISSN = {0146-0404},
       url = {<Go to ISI>://WOS:A1997WN18602285},
       year = {1997},
       type = {Journal Article}
    }
    
  • Kampmeier, J. and Brinkmann, R. and Pfleiderer, M. and Schneider, E. and Birngruber, R.: Laser thermokeratoplasty (LTK): A finite element model of the cornea. Investigative Ophthalmology & Visual Science, no. 38, pp. 2515-2515, 1997
    BibTeX
    @article{Kampmeier1997,
       author = {Kampmeier, J. and Brinkmann, R. and Pfleiderer, M. and Schneider, E. and Birngruber, R.},
       title = {Laser thermokeratoplasty (LTK): A finite element model of the cornea},
       journal = {Investigative Ophthalmology & Visual Science},
       volume = {38},
       number = {4},
       pages = {2515-2515},
       note = {1
    Wn186
    Times Cited:0
    Cited References Count:0},
       ISSN = {0146-0404},
       url = {<Go to ISI>://WOS:A1997WN18602507},
       year = {1997},
       type = {Journal Article}
    }
    
  • Brinkmann, R. and Koop, N. and Kampmeier, J. and Bruhns, A. and AsiyoVogel, M. and Engelhardt, R. and Birngruber, R.: Corneal collagen denaturation in laser thermokeratoplasty (LTK). Investigative Ophthalmology & Visual Science, no. 38, pp. 2514-2514, 1997
    BibTeX
    @article{Brinkmann1997,
       author = {Brinkmann, R. and Koop, N. and Kampmeier, J. and Bruhns, A. and AsiyoVogel, M. and Engelhardt, R. and Birngruber, R.},
       title = {Corneal collagen denaturation in laser thermokeratoplasty (LTK)},
       journal = {Investigative Ophthalmology & Visual Science},
       volume = {38},
       number = {4},
       pages = {2514-2514},
       note = {1
    Wn186
    Times Cited:0
    Cited References Count:0},
       ISSN = {0146-0404},
       url = {<Go to ISI>://WOS:A1997WN18602506},
       year = {1997},
       type = {Journal Article}
    }
    
  • Brinkmann, R and Dröge, G and Schroer, F and Scheu, M and Birngruber, R: Ablation Dynamics in Laser Sclerostomy Ab Externo by means of Pulsed Lasers in the Mid-Infrared Spectral Range. Ophth Surg Las, no. 28, pp. 853-865, 1997
    BibTeX
    @article{Brinkmann1997,
       author = {Brinkmann, R and Dröge, G and Schroer, F and Scheu, M and Birngruber, R},
       title = {Ablation Dynamics in Laser Sclerostomy Ab Externo by means of Pulsed Lasers in the Mid-Infrared Spectral Range},
       journal = {Ophth Surg Las},
       volume = {28},
       number = {10},
       pages = {853-865},
       year = {1997},
       type = {Journal Article}
    }
    
  • Asiyo-Vogel, M. N. and Koop, N. and Brinkmann, R. and Engelhardt, R. and Eggers, R. and Birngruber, R. and Vogel, A.: Evaluation of LTK lesions by optical low coherence tomography (OCT) and polarization microscopy after Sirius-Red staining. Ophthalmologe, no. 94, pp. 487-491, 1997
    BibTeX Link
    @article{Asiyo-Vogel1997,
       author = {Asiyo-Vogel, M. N. and Koop, N. and Brinkmann, R. and Engelhardt, R. and Eggers, R. and Birngruber, R. and Vogel, A.},
       title = {Evaluation of LTK lesions by optical low coherence tomography (OCT) and polarization microscopy after Sirius-Red staining},
       journal = {Ophthalmologe},
       volume = {94},
       number = {7},
       pages = {487-491},
       note = {Yp140
    Times Cited:5
    Cited References Count:21},
       abstract = {Background: Information on the extent and degree of the thermal effect produced is of great importance for control of the laser dosage in laser thermokeratoplasty (LTK) and for postoperative follow-up. We investigated on acute LTK effects which information images obtained by optical low coherence tomography (OCT) offer compared to those obtained by polarization microscopy.
    Methods: Porcine eyes were irradiated through a 400 mu m quartz fiber using light from a laser diode emitting up to 300 mW at a wavelength of 1.86 mu m. Thermal lesions of varying strength were scanned using an experimental OCT device with about 25 mu m lateral and 20 mu m axial resolution. Histologic evaluation of the scanned areas was done by polarization microscopy after Sirius-Red staining, and similar lesions were also analyzed by TEM.
    Results: Both methods differentiated three damage zones: a transition zone, a zone of moderate coagulation, and a central zone of strong coagulation. In the transition zone,increased birefringence was seen in polarization microscopy, which correlated with increased light scattering seen in the DCT images,ln the moderately coagulated zone, a decrease in birefringence was associated with an even stronger increase of the OCT signal, In the central zone,a loss of the fibrillar tissue structure was observed, which led to a complete loss of birefringence and a strong reduction of the OCT signal.
    Conclusions: Although OCT does not provide the detailed information on thermal changes of tissue seen by the histologic method, it offers information on the extent and degree of tissue changes without preparation artifacts and provides a non-invasive method of immediate and follow-up control of LTK lesions, A quantitative analysis of changes in corneal thickness and curvature is much simpler than by a slit lamp. Time-resolved measurements of corneal light scattering may be used for on-line control of the laser-light dosage during LTK.},
       keywords = {refractive surgery
    laser thermokeratoplasty
    collagen denaturation
    collagen shrinkage
    optical low coherence tomography
    polarization microscopy
    sirius-red staining
    tissue
    collagen
    eye},
       ISSN = {0941-293X},
       DOI = {DOI 10.1007/s003470050144},
       url = {<Go to ISI>://WOS:000071246700004},
       year = {1997},
       type = {Journal Article}
    }
    
  • Asiyo-Vogel, M and Koop, N and Brinkmann, R and Engelhardt, R and Eggers, R and Birngruber, R and Vogel, A: Darstellung von LTK-Läsionen durch optische Kurzkohärenztomographie (OCT) und Polarisationsmikroskopie nach Sirius-Rot-Färbung. Ophthalmologe, no. 94, pp. 487-491, 1997
    BibTeX
    @article{Asiyo-Vogel1997,
       author = {Asiyo-Vogel, M and Koop, N and Brinkmann, R and Engelhardt, R and Eggers, R and Birngruber, R and Vogel, A},
       title = {Darstellung von LTK-Läsionen durch optische Kurzkohärenztomographie (OCT) und Polarisationsmikroskopie nach Sirius-Rot-Färbung},
       journal = {Ophthalmologe},
       volume = {94},
       pages = {487-491},
       year = {1997}
    }
    
  • Asiyo-Vogel, M. and Brinkmann, R and Notbohm, H. and Eggers, R. and Lubatschowski, H. and Laqua, H. and Vogel, A.: Histologic analysis of thermal effects of laserthermokeratoplasty and corneal ablation using Sirius-Red polarization microscopy. J Cataract Refr Surg, no. 23, pp. 515-526, 1997
    BibTeX
    @article{Asiyo-Vogel,
       author = {Asiyo-Vogel, M. and Brinkmann, R and Notbohm, H. and Eggers, R. and Lubatschowski, H. and Laqua, H. and Vogel, A.},
       title = {Histologic analysis of thermal effects of laserthermokeratoplasty and corneal ablation using Sirius-Red polarization microscopy},
       journal = {J Cataract Refr Surg},
       volume = {23},
       pages = {515-526},
       year = {1997}
    }
    

1996

  • Brinkmann, Ralf and Kampmeier, Juergen and Grotehusmann, Ulf and Vogel, Alfred and Koop, Norbert and Asiyo-Vogel, Mary and Birngruber, Reginald: Corneal collagen denaturation in laser thermokeratoplasty. no. 2681, pp. 56-63,
    BibTeX Link
    @inproceedings{Brinkmann1996,
       author = {Brinkmann, Ralf and Kampmeier, Juergen and Grotehusmann, Ulf and Vogel, Alfred and Koop, Norbert and Asiyo-Vogel, Mary and Birngruber, Reginald},
       title = {Corneal collagen denaturation in laser thermokeratoplasty},
       volume = {2681},
       pages = {56-63},
       note = {10.1117/12.239611},
       abstract = {In laserthermokeratoplasty (LTK) thermal denaturation and shrinkage of corneal collagen is used to correct hyperopia and astigmatism. In order to optimize dosimetry, the temperature at which maximal shrinkage of collagen fibrils occurs is of major interest. Since the exposure time in clinical LTK-treatment is limited to a few seconds, the kinetics of collagen denaturation as a rate process has to be considered, thus the time of exposure is of critical importance for threshold and shrinkage temperatures. We investigated the time-temperature correlation for corneal collagen denaturation within different time domains by turbidimetry of scattered HeNe laser probe light using a temperature controlled water bath and pulsed IR laser irradiation. In the temperature range of 60 degree(s)C to 95 degree(s)C we found an exponential relation between the denaturation time and temperature. For the typical LTK-treatment time of 2 s, a temperature of 95 degree(s)C is needed to induce thermal damage. Use of pulsed Holmium laser radiation gave significant scattering of HeNe laser probe light at calculated temperatures of around 100 degree(s)DC. Rate parameters according to the formalism of Arrhenius were fitted to these results. Force measurements showed the simultaneous onset of light scattering and collagen shrinkage.},
       url = {http://dx.doi.org/10.1117/12.239611},
       type = {Conference Proceedings}
    }
    
  • Geerling, G. and Brinkmann, R. and Koop, N. and Klingemann, I. and Laqua, H. and Birngruber, R.: Laser thermokeratoplasty - Experimental study in minipigs with a cw-IR laser diode. Investigative Ophthalmology & Visual Science, no. 37, pp. 304-304, 1996
    BibTeX
    @article{Geerling1996,
       author = {Geerling, G. and Brinkmann, R. and Koop, N. and Klingemann, I. and Laqua, H. and Birngruber, R.},
       title = {Laser thermokeratoplasty - Experimental study in minipigs with a cw-IR laser diode},
       journal = {Investigative Ophthalmology & Visual Science},
       volume = {37},
       number = {3},
       pages = {304-304},
       note = {Tx397
    Times Cited:0
    Cited References Count:0},
       ISSN = {0146-0404},
       url = {<Go to ISI>://WOS:A1996TX39700304},
       year = {1996},
       type = {Journal Article}
    }
    
  • Kampmeier, J. and Brinkmann, R. and Birngruber, R.: Laser thermokeratoplasty (LTK): Biomechanical properties and IR-laser induced forces in porcine cornea.. Investigative Ophthalmology & Visual Science, no. 37, pp. 301-301, 1996
    BibTeX
    @article{Kampmeier1996,
       author = {Kampmeier, J. and Brinkmann, R. and Birngruber, R.},
       title = {Laser thermokeratoplasty (LTK): Biomechanical properties and IR-laser induced forces in porcine cornea.},
       journal = {Investigative Ophthalmology & Visual Science},
       volume = {37},
       number = {3},
       pages = {301-301},
       note = {Tx397
    Times Cited:0
    Cited References Count:0},
       ISSN = {0146-0404},
       url = {<Go to ISI>://WOS:A1996TX39700301},
       year = {1996},
       type = {Journal Article}
    }
    
  • Brinkmann, R. and Koop, N. and Kamm, K. and Geerling, G. and Kampmeier, J. and Birngruber, R.: Laser thermokeratoplasty: an in vitro and in vivo-study by means of a Continous Wave Mid-IR laser diode.. Lasermedizin, no. 12, pp. 179-186, 1996
    BibTeX
    @article{Brinkmann1996,
       author = {Brinkmann, R. and Koop, N. and Kamm, K. and Geerling, G. and Kampmeier, J. and Birngruber, R.},
       title = {Laser thermokeratoplasty: an in vitro and in vivo-study by means of a Continous Wave Mid-IR laser diode.},
       journal = {Lasermedizin},
       volume = {12},
       pages = {179-186},
       year = {1996},
       type = {Journal Article}
    }
    
  • Wetzel, W. and Brinkmann, R. and Koop, N. and Schroer, F. and Birngruber, R.: Photofragmentation of lens nuclei using the Er:YAG laser: Preliminary report of an in vitro study. German Journal of Ophthalmology, no. 5, pp. 281-284, 1996
    BibTeX Link
    @article{Wetzel1996,
       author = {Wetzel, W. and Brinkmann, R. and Koop, N. and Schroer, F. and Birngruber, R.},
       title = {Photofragmentation of lens nuclei using the Er:YAG laser: Preliminary report of an in vitro study},
       journal = {German Journal of Ophthalmology},
       volume = {5},
       number = {5},
       pages = {281-284},
       note = {Vq341
    Times Cited:13
    Cited References Count:12},
       abstract = {The energy of the erbium:YAG laser (2,940-nm wave-length) can be used for minimally traumatic photoablation due to its high absorption at the tissue water and its consequently low penetration depth. Laser sclerostomy ab externo, an application of this principle, has undergone advanced clinical investigation. Another potential application is photofragmentation of the lens for cataract extraction. A laboratory model Er: YAG laser (flashlamp-pumped, 200-mu s pulse length, 5-Hz repetition frequency) was coupled to a short low-OH quartz fiber (400 mu m in diameter). The laser energy was applied by direct contact of the fiber tip to human lenses with very dense cataract. The lenses rested in a small cuvette filled with an aqueous-humor-analogous fluid. The fragmentablation rate was evaluated in relation to the number of pulses and the pulse energy. A laser-triggered flash-photography unit was engaged to visualize the ablation dynamics. We found tissue-ablation rates to range from 4 to 19 mu g/pulse, depending on the nucleus density and ulse energy. The maximal size of the removed fragments was always below 500 mu m During ablation, rapidly increasing and collapsing cavitation bubbles were photographed at the distal tip of the application fiber. The impact radius of these cavitation effects markedly exceeded the pure penetration depth of laser radiation at a 2.9-mu m wavelength. A clinical application of the method should be possible as judged by the results obtained for tissue-ablation rate and fragment size. Cavitation-bubble dynamics seems to be responsible for the high fragmentation efficiency. Special application probes have to be developed to optimize ablation and to prevent inadvertent destruction of the posterior lens capsule by cavitation effects.},
       keywords = {phacoemulsification
    er:yag laser
    cavitation effects
    ablation
    surgery},
       ISSN = {0941-2921},
       url = {<Go to ISI>://WOS:A1996VQ34100006},
       year = {1996},
       type = {Journal Article}
    }
    
  • Gerling, G. and Vogel, A. and ElHifnawi, E. and Koop, N. and Droge, G. and Birngruber, R. and Brinkmann, R.: Morphological and biomorphometrical observations on laser thermal keratoplasty - Histological and biomorphometrical examination of the relationship between refractive change and the volume of laser thermal keratoplasty lesions following Cr:Tm:Ho:YAG laser treatment. German Journal of Ophthalmology, no. 5, pp. 84-91, 1996
    BibTeX
    @article{Gerling1996,
       author = {Gerling, G. and Vogel, A. and ElHifnawi, E. and Koop, N. and Droge, G. and Birngruber, R. and Brinkmann, R.},
       title = {Morphological and biomorphometrical observations on laser thermal keratoplasty - Histological and biomorphometrical examination of the relationship between refractive change and the volume of laser thermal keratoplasty lesions following Cr:Tm:Ho:YAG laser treatment},
       journal = {German Journal of Ophthalmology},
       volume = {5},
       number = {2},
       pages = {84-91},
       note = {Vf915
    Times Cited:4
    Cited References Count:21},
       abstract = {Laser thermal keratoplasty (LTK) is currently under clinical trial for the correction of hyperopia and hyperopic astigmatism by means of collagen coagulation in the peripheral cornea. The purpose of our study was to optimize the ratio between the volume of damaged corneal stroma and the refractive effect so as to minimize potential side effects such as endothelial damage or induction of glare phenomena. We therefore performed histological and morphometrical examinations of enucleated pig eyes to determine the relationship between the coagulated stromal volume and the refractive change after LTK using a pulsed Cr: Tm: Ho: YAG laser (wavelength 2.12 mu m) on enucleated pig eyes. The refractive change was documented with a Littman ophthalmometer. Morphometrical analysis was performed using polarized light microscopy of sirius red-stained specimens. This special stain separated the thermally changed stroma into a dark, nonbirefringent center and a birefringent peripheral zone. The volume of both zones was positively correlated with the refractive change induced. The volume was in turn influenced by the choice of laser parameters, From the ratio of the volume to the refractive change it was found that pulse energies above 30 mJ led to an enlargement of the coagulation volume without increasing the refractive change effectively. The use of high pulse energies did not improve the effect of LTK but only increased the risk of unwanted side effects. However, an increase in the laser repetition rate at a constant pulse number per spot led to refractive changes with a minimal coagulation volume. The highest relative refractive change was achieved with a dark central zone and a birefringent zone, each having a volume of about 50 - 80 x 10(-3) mm(3).},
       keywords = {laser thermal keratoplasty
    hyperopic correction
    biomorphometry
    sirius red stain
    polarization microscopy
    organization
    microscopy
    collagen},
       ISSN = {0941-2921},
       url = {<Go to ISI>://WOS:A1996VF91500004},
       year = {1996},
       type = {Journal Article}
    }
    
  • Brinkmann, R. and Koop, N. and AsiyoVogel, M. N. and Kaftan, B. and Birngruber, R. and Engelhardt, R.: CW-IR laser thermokeratoplasty: Refractive changes and analysis by optical coherence tomography and light microscopy. Investigative Ophthalmology & Visual Science, no. 37, pp. 305-305, 1996
    BibTeX
    @article{Brinkmann1996,
       author = {Brinkmann, R. and Koop, N. and AsiyoVogel, M. N. and Kaftan, B. and Birngruber, R. and Engelhardt, R.},
       title = {CW-IR laser thermokeratoplasty: Refractive changes and analysis by optical coherence tomography and light microscopy},
       journal = {Investigative Ophthalmology & Visual Science},
       volume = {37},
       number = {3},
       pages = {305-305},
       note = {Tx397
    Times Cited:0
    Cited References Count:0},
       ISSN = {0146-0404},
       url = {<Go to ISI>://WOS:A1996TX39700305},
       year = {1996},
       type = {Journal Article}
    }
    
  • Brinkmann, R and Knipper, A and Dröge, G and Gafumbegete, D and Miller, A and Gromoll, B and Birngruber, R: Ureterotomy with a pulsed Holmium Laser. Proc LASER `95, Springer Verlag, pp. 16-19, 1996
    BibTeX
    @article{Brinkmann1996,
       author = {Brinkmann, R and Knipper, A and Dröge, G and Gafumbegete, D and Miller, A and Gromoll, B and Birngruber, R},
       title = {Ureterotomy with a pulsed Holmium Laser},
       journal = {Proc LASER '95, Springer Verlag},
       pages = {16-19},
       year = {1996},
       type = {Journal Article}
    }
    
  • Brinkmann, R. and Hansen, C. and Mohrenstecher, D. and Scheu, M. and Birngruber, R.: Analysis of cavitation dynamics during pulsed laser tissue ablation by optical on-line monitoring. Ieee Journal of Selected Topics in Quantum Electronics, no. 2, pp. 826-835, 1996
    BibTeX Link
    @article{Brinkmann1996,
       author = {Brinkmann, R. and Hansen, C. and Mohrenstecher, D. and Scheu, M. and Birngruber, R.},
       title = {Analysis of cavitation dynamics during pulsed laser tissue ablation by optical on-line monitoring},
       journal = {Ieee Journal of Selected Topics in Quantum Electronics},
       volume = {2},
       number = {4},
       pages = {826-835},
       note = {Xd616
    Times Cited:20
    Cited References Count:24},
       abstract = {Flashlamp pumped mid-IR laser systems emitting in the 23-mu m wavelength range are widely used for various medical applications, especially for tissue ablation, Explosive evaporation is inevitably associated with this process due to the short pulse durations of these laser systems and the high absorption of tissue and water in this spectral regime, Tissue displacement and dissection occur in liquid environment as a consequence of the induced cavitation, Depending on the application these processes might enhance the tissue ablation but can also cause adverse tissue effects, The ablation dynamics were investigated by evaluating the change in rejected probe-light intensity reemitted from the application fiber tip. The ablated cavity and the signal was correlated to fast-flash photographs of the event. Based on this reflection signal a water/tissue discrimination system is introduced which can widely support medical laser applications. In laser sclerostomy ab externo, for example, this approach can be used as a feedback system to automatically control the ablation process. With such a system, adverse effects to adjacent tissue in the anterior chamber of the eye can be minimized.},
       ISSN = {1077-260X},
       DOI = {Doi 10.1109/2944.577305},
       url = {<Go to ISI>://WOS:A1996XD61600006},
       year = {1996},
       type = {Journal Article}
    }
    

1995

  • Schirner, G. and Brinkmann, R. and Droge, G. and Koop, N. and Elhifnawi, E. S. and Birngruber, R.: Experimental Studies to Optimize Laser-Thermokeratoplasty Using Pulsed and Cw-Laser-Sources. Investigative Ophthalmology & Visual Science, no. 36, pp. S716-S716, 1995
    BibTeX Link
    @article{Schirner1995,
       author = {Schirner, G. and Brinkmann, R. and Droge, G. and Koop, N. and Elhifnawi, E. S. and Birngruber, R.},
       title = {Experimental Studies to Optimize Laser-Thermokeratoplasty Using Pulsed and Cw-Laser-Sources},
       journal = {Investigative Ophthalmology & Visual Science},
       volume = {36},
       number = {4},
       pages = {S716-S716},
       note = {Qm915
    Times Cited:3
    Cited References Count:0},
       ISSN = {0146-0404},
       url = {<Go to ISI>://WOS:A1995QM91503294},
       year = {1995},
       type = {Journal Article}
    }
    
  • Schirner, G. and Koop, N. and Elhifnawi, E. and Birngruber, R. and Brinkmann, R.: Experiments with Pulsed and Continuous-Wave Laser Sources to Optimize Laserthermo-Keratoplasty. Vision Research, no. 35, pp. P167-P167, 1995
    BibTeX Link
    @article{Schirner1995,
       author = {Schirner, G. and Koop, N. and Elhifnawi, E. and Birngruber, R. and Brinkmann, R.},
       title = {Experiments with Pulsed and Continuous-Wave Laser Sources to Optimize Laserthermo-Keratoplasty},
       journal = {Vision Research},
       volume = {35},
       pages = {P167-P167},
       note = {Suppl. S
    Rz562
    Times Cited:0
    Cited References Count:0},
       ISSN = {0042-6989},
       url = {<Go to ISI>://WOS:A1995RZ56200472},
       year = {1995},
       type = {Journal Article}
    }
    
  • Brinkmann, R. and Schroer, F. and Mohrenstecher, D. and Droge, G. and Birngruber, R.: Ablation Dynamics in Laser Sclerostomy Ab-Externo. Investigative Ophthalmology & Visual Science, no. 36, pp. S558-S558, 1995
    BibTeX Link
    @article{Brinkmann1995,
       author = {Brinkmann, R. and Schroer, F. and Mohrenstecher, D. and Droge, G. and Birngruber, R.},
       title = {Ablation Dynamics in Laser Sclerostomy Ab-Externo},
       journal = {Investigative Ophthalmology & Visual Science},
       volume = {36},
       number = {4},
       pages = {S558-S558},
       note = {Qm915
    Times Cited:1
    Cited References Count:0},
       ISSN = {0146-0404},
       url = {<Go to ISI>://WOS:A1995QM91502583},
       year = {1995},
       type = {Journal Article}
    }
    

1994

  • Wetzel, W. and Haring, G. and Brinkmann, R. and Birngruber, R.: Laser sclerostomy ab externo using the erbium: YAG laser. First results of a clinical study. Ger J Ophthalmol, no. 3, pp. 112-5, 1994
    BibTeX
    @article{Wetzel1994,
       author = {Wetzel, W. and Haring, G. and Brinkmann, R. and Birngruber, R.},
       title = {Laser sclerostomy ab externo using the erbium: YAG laser. First results of a clinical study},
       journal = {Ger J Ophthalmol},
       volume = {3},
       number = {2},
       pages = {112-5},
       note = {0941-2921 (Print)
    Clinical Trial
    Journal Article},
       abstract = {A new approach to fistulating glaucoma surgery, laser sclerostomy ab externo, was investigated in a clinical study. A pulsed (200 microseconds) erbium-YAG laser was used, as its wavelength (2940 nm) is very well absorbed by tissue water. The laser energy was transmitted via a fiber to an application probe with a cannula particularly designed to guide another fiber into the subconjunctival space. Nine patients with advanced open-angle or neovascular glaucoma were treated. In all cases a functioning fistula with a prominent filtering bleb and a reduction of the intraocular pressure (from up to 50 mmHg to 8-18 mmHg) could be achieved. The total energy was 60 mJ on average. No complication occurred intraoperatively. Postoperatively, all fistulas in patients with neovascular glaucoma (n = 6) were impatent after approx. 7 days due to iris adherence to the internal ostium and episcleral scarring. In cases of open-angle glaucoma (n = 3) a patent fistula persisted for several months. Variation of the exposure parameters, the use of antiproliferative drugs, and a less restrictive selection of patients could further improve the success rate.},
       keywords = {Fiber Optics
    Follow-Up Studies
    Glaucoma, Neovascular/*surgery
    Glaucoma, Open-Angle/*surgery
    Humans
    Intraocular Pressure
    Laser Surgery/*methods
    Postoperative Complications
    Prognosis
    *Sclerostomy},
       url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8193571},
       year = {1994},
       type = {Journal Article}
    }
    
  • Schirner, G. and Huber, A. and Wordemann, A. and Droge, G. and el-Hifnawi, E. and Birngruber, R. and Brinkmann, R.: [Experimental studies on the effect of the Er:glass and Cr:Tm:Ho:YAG laser in thermokeratoplasty]. Ophthalmologe, no. 91, pp. 638-45, 1994
    BibTeX
    @article{Schirner1994,
       author = {Schirner, G. and Huber, A. and Wordemann, A. and Droge, G. and el-Hifnawi, E. and Birngruber, R. and Brinkmann, R.},
       title = {[Experimental studies on the effect of the Er:glass and Cr:Tm:Ho:YAG laser in thermokeratoplasty]},
       journal = {Ophthalmologe},
       volume = {91},
       number = {5},
       pages = {638-45},
       note = {0941-293X (Print)
    English Abstract
    Journal Article},
       abstract = {So far the dose-effect ratio of the Holmium laser (wavelength 2.12 microns) and the erbium laser (1.54 microns) for laser thermokeratoplasty (LTK) are not defined in detail. Our study was designed not only to compare the erbium contact and the holmium non-contact applications but also to throw light on the influence of different geometrical application patterns, pulse energies, pulses per coagulation site and repetition rates under experimental conditions. Enucleated sheep and pig eyes were used 2-6 h post mortem, pressurized to 25 mmHg and moisturized with saline solution. Before and after LTK, pachymetry and keratometry were performed. Some specimens were prepared for light and scanning microscopy. The coagulation threshold for the erbium laser in a contact mode with a 200-microns fibre was 25 J/cm2 (ca. 8 mJ/pulse) and for the holmium laser 8 J/cm2 (ca. 2.5 mJ/pulse). The erbium laser was used in a single shot per spot mode, the holmium laser in repeated pulse per spot mode. With the single shot per spot mode, we were able to induce a promising hyperopic shift of up to -3.47 +/- 0.61 D, while myopic changes could only be induced up to +1.89 +/- 0.74 D. Higher changes of up to +8.27 +/- 1.3 D could be achieved by means of repeated pulses per spot (20 pulses, 45 mJ, 10 Hz). Our experiments showed an obvious increase of dioptric changes when using a higher repetition rate while pulse energy and number were kept constant.(ABSTRACT TRUNCATED AT 250 WORDS)},
       keywords = {Animals
    Cornea/pathology
    Corneal Transplantation/*instrumentation/pathology
    Laser Coagulation/*instrumentation
    Microscopy, Electron, Scanning
    Myopia/pathology/surgery
    Refraction, Ocular
    Sheep
    Swine},
       url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=7812097},
       year = {1994},
       type = {Journal Article}
    }
    
  • Brinkmann, R. and Dröge, G. and Koop, N. and Wördemann, A. and Schirner, G. and Birngruber, R.: Investigations on laser thermokeratoplasty. Lasers Light Ophthalmol, no. 6, pp. 259 - 270, 1994
    BibTeX
    @article{Binkmann1994,
       author = {Brinkmann, R. and Dröge, G. and Koop, N. and Wördemann, A. and Schirner, G. and Birngruber, R.},
       title = {Investigations on laser thermokeratoplasty},
       journal = {Lasers Light Ophthalmol},
       volume = {6},
       number = {4},
       pages = {259 - 270},
       year = {1994},
       type = {Journal Article}
    }
    

1988

  • Hube, M and Brinkmann, R and Welling, H and Beigang, R and Wellegehausen, B: A Cadmium Photoionization Laser Pumped by Laser Induced Plasma Radiation from a Multi Foci Device. Appl Phys B, no. 45, pp. 197-201, 1988
    BibTeX
    @article{Hube,
       author = {Hube, M and Brinkmann, R and Welling, H and Beigang, R and Wellegehausen, B},
       title = {A Cadmium Photoionization Laser Pumped by Laser Induced Plasma Radiation from a Multi Foci Device},
       journal = {Appl Phys B},
       volume = {45},
       pages = {197-201},
       year = {1988}
    }