@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}
}

@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}
}

@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}
}

@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}
}

@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},
year = { 2016}
}

@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}
}

@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}
}

@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}
}

@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}
}

@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}
}

@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}
}

@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}
}

@article{Koinzer2014,
   title        = {Comprehensive detection, grading, and growth behavior evaluation of subthreshold and low intensity photocoagulation lesions by optical coherence tomographic and infrared image analysis},
   author       = {Koinzer, S. and Caliebe, A. and Portz, L. and Saeger, M. and Miura, Y. and Schlott, K. and Brinkmann, R. and Roider, J.},
   year         = 2014,
   journal      = {Biomed Res Int},
   volume       = 2014,
   pages        = 492679,
   doi          = {10.1155/2014/492679},
   url          = {http://dx.doi.org/10.1155/2014/492679},
   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.},
   type         = {Journal Article}
}

@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}
}

@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}
}

@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}
}

@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}
}

@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}
}

@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}
}

@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}
}

@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}
}

@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}
}

@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}
}

@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}
}

@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}
}