Yoko Miura, Regina Orzekowsky-Schröder, Philipp Steven, Márta Szaszák, Norbert Koop, and Ralf Brinkmann,
Two-Photon Microscopy and Fluorescence Lifetime Imaging of Retinal Pigment Epithelial Cells under Oxidative Stress, Invest Ophthalmol Vis Sci , 2013.
DOI:https://doi.org/10.1167/iovs.13-11808
Bibtex: BibTeX
@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}
}
Alexander Baade, Kerstin Schlott, Ralf Brinkmann, and Reginald Birngruber,
A numerical model for heat and pressure propagation for temperature controlled retinal photocoagulation, 2013. pp. 88030O-88030O-9.
File: 12.2033590
Bibtex: BibTeX
@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}, 
year = { 2013}
}
Eric Seifert, Young-Jung Roh, Andreas Fritz, Young Gun Park, Seungbum Kang, Dirk Theisen-Kunde, and Ralf Brinkmann,
Automatic irradiation control by an optical feedback technique for selective retina treatment (SRT) in a rabbit model, 2013. pp. 880303-880303-6.
File: 12.2033560
Bibtex: BibTeX
@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},
year = {2013},
   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}
}
Alexander Oepen, Jens Horstmann, and Ralf Brinkmann,
Characterization of an Electronic Speckle Pattern Detection System, in Studierendentagung , 2013.
Bibtex: BibTeX
@inproceedings{Oepen2013,
   author = {van Oepen, Alexander and Horstmann, Jens and Brinkmann, Ralf},
   title = {Characterization of an Electronic Speckle Pattern Detection System},
   booktitle = {Studierendentagung},
   type = {Conference Proceedings}
}
Ingo Rohde, Jennifer- M. Masch, Dirk Theisen-Kunde, Martin Marczynski-Bühlow, Georg Lutter, and Ralf Brinkmann,
Cardiovascular damage after cw and Q-switched 2μm laser irradiation, 2013. pp. 88030I-88030I-6.
File: 12.2033550
Bibtex: BibTeX
@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 <6 μm in diameter. The maximum damaged area of the soft tissue was < 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},
year = { 2013}
}
Jens Horstmann, and Ralf Brinkmann,
Non-contact photoacoustic tomography using holographic full field detection, Proc. SPIE, 2013. pp. 880007-880007-6.
File: 12.2033599
Bibtex: BibTeX
@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},
year = { 2013}
}
Kathrin Bliedtner, Eric Seifert, and Ralf Brinkmann,
Temperature induced tissue deformation monitored by dynamic speckle interferometry, in Studierendentagung , Universität zu Lübeck, 2013.
File: download
Bibtex: 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},
year = { 2013},
url = { http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.714.8862&rep=rep1&type=pdf}
}
Kerstin Schlott, Stefan Koinzer, Lars Ptaszynski, Marco Bever, Johann Roider, and Ralf Brinkmann,
Automatic temperature controlled retinal photocoagulation, Journal of Biomedical Optics , vol. 17, no. 6, pp. 061223, 2012. SPIE.
DOI:10.1117/1.JBO.17.6.061223
File:
Bibtex: BibTeX
@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}
}
Stefan Koinzer, Kerstin Schlott, Lea Portz, Lars Ptaszynski, Alexander Baade, Marco Bever, Mark Saeger, Amke Caliebe, Renè Denner, Ralf Brinkmann, and Johann Roider,
Correlation of temperature rise and optical coherence tomography characteristics in patient retinal photocoagulation, Journal of Biophotonics , pp. n/a-n/a, 2012.
Bibtex: 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}
}
Kumiko Yoshimoto, Manabu Yamamoto, Takeya Kohno, Tasuku Yoneda, Yusaku Yoshida, Andreas Fritz, Dirk Theisen-Kunde, Yoko Miura, Ralf Brinkmann, and Kunihiko Shiraki,
Detection Of Sub-threshold Laser Irradiation Spots With Various Fundus Imaging Methods And Its Correlation With Irradiation Energy And Optoacoustic Values In Selective Retina Therapy , Investigative Ophthalmology & Visual Science , vol. 53, pp. 5198, 2012.
Bibtex: BibTeX
@article{Yoshimoto,
   author = {Yoshimoto, Kumiko and Yamamoto, Manabu and Kohno, Takeya and Yoneda, Tasuku and Yoshida, Yusaku and Fritz, Andreas and Theisen-Kunde, Dirk and Miura, Yoko and Brinkmann, Ralf and Shiraki, Kunihiko},
   title = {Detection Of Sub-threshold Laser Irradiation Spots With Various Fundus Imaging Methods And Its Correlation With Irradiation Energy And Optoacoustic Values In Selective Retina Therapy },
   journal = {Investigative Ophthalmology & Visual Science},
   volume = {53},
   pages = {5198},
   year = {2012}
}
Ralf Brinkmann, Stefan Koinzer, Kerstin Schlott, Lars Ptaszynski, Marco Bever, Alexander Baade, Susanne Luft, Yoko Miura, and Johann Roider,
Real-time temperature determination during retinal photocoagulation on patients, Journal of Biomedical Optics , vol. 17, no. 6, pp. 061219, 2012.
DOI:10.1117/1.JBO.17.6.061219
Bibtex: 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}
}
Manabu Yamamoto, Takeya Kohno, Yusaku Yoshida, Tasuku Yoneda, Hisashi Iwami, Andreas Fritz, Dirk Theisen-Kunde, Yoko Miura, Ralf Brinkmann, and Kunihiko Shiraki,
Selective Retina Therapy for Patients with Central Serous Chorioretinopathy in Japan, Investigative Ophthalmology & Visual Science , vol. 53, pp. 5222, 2012.
DOI:10.1117/1.JBO.17.6.061219
Bibtex: BibTeX
@article{Yamamoto,
   author = {Yamamoto, Manabu and Kohno, Takeya and Yoshida, Yusaku and Yoneda, Tasuku and Iwami, Hisashi and Fritz, Andreas and Theisen-Kunde, Dirk and Miura, Yoko and Brinkmann, Ralf and Shiraki, Kunihiko},
   title = {Selective Retina Therapy for Patients with Central Serous Chorioretinopathy in Japan },
   journal = {Investigative Ophthalmology & Visual Science},
   volume = {53},
   pages = {5222},
   year = {2012}
}
Hisashi Iwami, Lars Ptaszynski, Veit Danicke, Ralf Brinkmann, and Yoko Miura,
Sublethal Hyperthermia-induced Vascular Endothelial Growth Factor Secretion And Its Contribution To Adoptive Response Of Retinal Pigment Epithelial Cell, Invest. Ophthalmol. Vis. Sci. , vol. 53, no. 6, pp. 4782-, 2012.
File: 4782
Bibtex: BibTeX
@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}
}
Stefan Koinzer, Kerstin Schlott, Lars Ptaszynski, Marco Bever, Susanne Kleemann, Mark Saeger, Alexander Baade, Amke Caliebe, Yoko Miura, Reginald Birngruber, Ralf Brinkmann, and Johann Roider,
Temperature-controlled retinal photocoagulation - a step toward automated laser treatment, Invest Ophthalmol Vis Sci , vol. 53, no. 7, pp. 3605-14, 2012.
DOI:https://doi.org/10.1167/iovs.11-8588
Bibtex: 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}
}
Ingo Rohde, Ralf Brinkmann, and Dirk Theisen-Kunde,
Temporally stretched Q-switched pulses in the 2 µm spectral range, Laser Physics Letters , vol. 9, no. 11, pp. 808-813, 2012.
Bibtex: 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}
}
Felix Treumer, Alexa Klettner, J. Baltz, A. A. Hussain, Yoko Miura, Ralf Brinkmann, Johann Roider, and Jost Hillenkamp,
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 , vol. 97, no. 1, pp. 63-72, 2012.
DOI:10.1016/j.exer.2012.02.011
Bibtex: BibTeX
@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}
}
Ralf Brinkmann, Stefan Koinzer, Kerstin Schlott, Lars Ptaszynski, Marco Bever, Alexander Baade, Yoko Miura, Reginald Birngruber, and Johann Roider,
Realtime temperature determination during retinal photocoagulation on patients, Sep. 2011.
Weblink: https://doi.org/10.1117/12.875276
Bibtex: BibTeX
@book{RN5360,
   author = {Brinkmann, Ralf;Koinzer, Stefan;Schlott, Kerstin;Ptaszynski, Lars;Bever, Marco;Baade, Alex;Miura, Yoko;Birngruber, Reginald and Roider, Johann},
   title = {Realtime temperature determination during retinal photocoagulation on patients},
   publisher = {SPIE},
   volume = {7885},
   series = {SPIE BiOS},
   url = {https://doi.org/10.1117/12.875276},
   year = {2011},
   type = {Book}
}
Akira Obana, Ralf Brinkmann, Yuko Gohto, and Kasumi Nishimura,
A Case of Retinal Injury By A Violet Light-Emitting Diode, Retinal Cases and Brief Reports , vol. 5, no. 3, pp. 223--226 10.1097/ICB.0b013e3181e180d5, 2011.
Bibtex: BibTeX
@article{Obana,
   title        = {A Case of Retinal Injury By A Violet Light-Emitting Diode},
   author       = {Obana, Akira and Brinkmann, Ralf and Gohto, Yuko and Nishimura, Kasumi},
   year         = 2011,
   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}
}
Akira Obana, Ralf Brinkmann, Yuko Gohto, and Kasumi Nishimura,
A Case of Retinal Injury By A Violet Light-Emitting Diode, Retinal Cases and Brief Reports , vol. 5, no. 3, pp. 223-226 10.1097/ICB.0b013e3181e180d5, 2011.
Bibtex: 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}
}
Andreas Fritz, Andrea Zegelin, Lars Ptaszynski, and Ralf Brinkmann,
Dynamics of laser induced micro bubble clusters on tissue phantoms, 2011. pp. 78850S-78850S-6.
File: 12.875031.short
Bibtex: 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 = {https://www.spiedigitallibrary.org/conference-proceedings-of-spie/7885/1/Dynamics-of-laser-induced-micro-bubble-clusters-on-tissue-phantoms/10.1117/12.875031.short},
   type = {Conference Proceedings},
year = { 2011}
}
Heike H. Muller, Lars Ptaszynski, Kerstin Schlott, Tim Bonin, Marco Bever, Stefan Koinzer, and Ralf Brinkmann,
Imaging of temperature distribution and retinal tissue changes during photocoagulation by high speed OCT, James, G. Fujimoto and Joseph, A. Izatt and Valery, V. Tuchin, Eds. SPIE, 2011. pp. 78890E.
File: 12.874788
Bibtex: BibTeX
@inproceedings{Müller-2011-2,
   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},
URL = { https://doi.org/10.1117/12.874788},
year = { 2011}

}
Kerstin Schlott, Stefan Koinzer, Lars Ptaszynski, Susanne Luft, Marco Bever, Johann Roider, and Ralf Brinkmann,
Optoacoustic temperature determination and automatic coagulation control in rabbits, in Ophthalmic Technologies XXI , Ho, Fabrice Manns; Per G. Söderberg; Arthur, Eds. Proc. SPIE, 2011.
File: 12.875104
Bibtex: BibTeX
@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},
year = { 2011}
}
Jens Horstmann, Alexander Baade, and Ralf Brinkmann,
Photoacoustic blood vessel detection during surgical laser interventions, SPIE ECBO, 2011. pp. 80920Z-80920Z-6.
File: 12.889635
Bibtex: BibTeX
@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},
year = { 2011}
}
Yoko Miura, Regina Orzekowsky-Schröder, Norbert Koop, Philipp Steven, Márta Szaszák, and Ralf Brinkmann,
Appearance of autofluorescence in RPE cells at the rim of photocoagulation, in FLIM 2010 - Symposium "Fluorescence Lifetime Imaging of the Human Retina" , 2010.
Bibtex: 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},
Year = { 2010}
}