@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}
}

@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}
}

@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}
}

@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}
}

@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}
}

@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}
}

@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}
}

@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}
}

@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{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{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{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}
}

@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{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} 
}

@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}
}

@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}
}

@article{Koop1997,
   author = {Koop, Norbert and Brinkmann, Ralf and Lankenau, Eva and Flache, Stefan and Engelhardt, Ralf and Birngruber, Reginald},
   title = {Optische Kohärenztomographie der Kornea und des vorderen Augenabschnitts},
   journal = {Der Ophthalmologe},
   volume = {94},
   number = {7},
   pages = {481-486},
   ISSN = {1433-0423},
   url = {http://dx.doi.org/10.1007/s003470050143},
   year = {1997},
   type = {Journal Article}
}

@inproceedings{Brinkmann1996-7,
   author = {Brinkmann, Ralf and Kampmeier, Juergen and Grotehusmann, Ulf and Vogel, Alfred and Koop, Norbert and Asiyo-Vogel, Mary and Birngruber, Reginald},
   title = {Corneal collagen denaturation in laser thermokeratoplasty},
   volume = {2681},
   pages = {56-63},
   note = {10.1117/12.239611},
   abstract = {In laserthermokeratoplasty (LTK) thermal denaturation and shrinkage of corneal collagen is used to correct hyperopia and astigmatism. In order to optimize dosimetry, the temperature at which maximal shrinkage of collagen fibrils occurs is of major interest. Since the exposure time in clinical LTK-treatment is limited to a few seconds, the kinetics of collagen denaturation as a rate process has to be considered, thus the time of exposure is of critical importance for threshold and shrinkage temperatures. We investigated the time-temperature correlation for corneal collagen denaturation within different time domains by turbidimetry of scattered HeNe laser probe light using a temperature controlled water bath and pulsed IR laser irradiation. In the temperature range of 60 degree(s)C to 95 degree(s)C we found an exponential relation between the denaturation time and temperature. For the typical LTK-treatment time of 2 s, a temperature of 95 degree(s)C is needed to induce thermal damage. Use of pulsed Holmium laser radiation gave significant scattering of HeNe laser probe light at calculated temperatures of around 100 degree(s)DC. Rate parameters according to the formalism of Arrhenius were fitted to these results. Force measurements showed the simultaneous onset of light scattering and collagen shrinkage.},
   url = {http://dx.doi.org/10.1117/12.239611},
   type = {Conference Proceedings},
Year ={  1996}
}