@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}
}

@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}
}

@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}
}

@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}

}

@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}
}

@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}
}

@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}
}

@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},
year = { 2009},
url = { https://doi.org/10.1117/12.168030}
}

@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}
}

@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},
year = { 2007}
}

@inproceedings{Stoehr2007-1,
   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},
Year = { 2007}
}

@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},
year = { 2007}
}

@article{Brinkmann2006-1,
   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}
}

@inproceedings{Schuele-2002,
   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},
year = { 2002},
url = { https://doi.org/10.1117/12.470601} 
}

@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}
}

@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}
}

@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},
   
   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}
}

@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},
year = { 2001}
}

@inproceedings{Schuele2001-1,
   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 (<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 (>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},
   year = { 2001}
}

@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},
year = { 2001}
}

@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},
url = {https://www.scopus.com/record/display.uri?eid=2-s2.0-0034040252&origin=inward&txGid=6e537773e3e3f14b9b83f939c4a9ce7d},
   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}
}

@article{Brinkmann2000-1,
   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(5)},
   Year = { 2000},
url = { https://www.researchgate.net/publication/227934019_Origin_of_retinal_pigment_epithelium_cell_damage_by_pulsed_laser_irradiance_in_the_nanosecond_to_microsecond_time_regimen},
   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 }
}

@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(5)},
   Year = {2000},
   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}
}

@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}
}

@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}
}