@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}
}

@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}
}

@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{Schlott2012,
   author = {Schlott, Kerstin and Koinzer, Stefan and Ptaszynski, Lars and Bever, Marco and Baade, Alex and Roider, Johann and Birngruber, Reginald and Brinkmann, Ralf},
   title = {Automatic temperature controlled retinal photocoagulation},
   journal = {Journal of Biomedical Optics},
   volume = {17},
   number = {6},
   pages = {061223},
   keywords = {AutoPhoN},
   year = {2012}
}

@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{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}
}

@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{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{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{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}
}

@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}
}

@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{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{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,
   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}
}

@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}
}

@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{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}
}

@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{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{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}
}

@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}
}

@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}
}

@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{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}
}

@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}
}

@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}
}

@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{Kampmeier-2000,
   author = {Kampmeier, J. and Radt, B. and Birngruber, R. and Brinkmann, R.},
   title = {Thermal and biomechanical parameters of porcine cornea},
   journal = {Cornea},
   volume = {19(3)},
   year = { 2000},
url = { https://www.researchgate.net/publication/12484883_Thermal_and_Biomechanical_Parameters_of_Porcine_Cornea},
   pages = {355-63},
   note = {0277-3740 (Print)
Journal Article
Research Support, Non-U.S. Gov't},
   abstract = {PURPOSE: New methods in refractive surgery require a considerable understanding of the material "cornea" and are often studied by theoretical modeling in order to gain insight into the procedure and an optimized approach to the technique. The quality of these models is highly dependent on the preciseness of its input parameters. Porcine cornea often is used as a model in preclinical studies because of its similarity to man and its availability. METHODS: The important physical parameters for biomechanical deformation, heat conduction, and collagen denaturation kinetics have been determined for porcine cornea. Experimental methods include densitometry, calorimetry, turbidimetry, tensile tests, stress relaxation, and hydrothermal isometric tension measurements. RESULTS: The density of porcine cornea was measured as p = 1062+/-5 kg/m3, the heat capacity gave c = 3.74+/-0.05 J/gK. The stress-strain relation for corneal strips is represented by a third order approximation where the secant modulus yields about Esec approximately equal to 0.4 MPa for small strains less than 2%. The normalized stress relaxation is described by an exponential fit over time. The denaturation process of cornea is characterized by specific temperatures which can be related to the change of the mechanical properties. Denaturation kinetics are described according to the model of Arrhenius yielding the activation energy deltaEa = 106 kJ/mol and the phase transition entropy deltaS = 39 J/(mol x K). CONCLUSIONS: The established set of parameters characterizes the porcine cornea in a reliable way that creates a basis for corneal models. It furthermore gives direct hints of how to treat cornea in certain refractive techniques.},
   keywords = {Animals}
}

@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}
}

@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{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{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{Brinkmann-1999,
   author = {Theisen, D.;Brendel, T.;Birngrub.R and Brinkman, R},
   title = {Endokardiale Laser Revaskularisation des Myokards mittels 20 J Einzelpuls Holmium Laserstrahlung},
   journal = {Laser-Medizin: eine interdisziplinäre Zeitschrift ; Praxis, Klinik, Forschung},
   volume = {14},
   number = {4},
   pages = {125 - 128},
   ISSN = {0938-765X},
   DOI = {https://doi.org/10.1016/S0938-765X(99)80019-4},
   year = {1999},
   type = {Journal Article}
}

@article{Brendel1999,
   author = {Brendel, T. and Brinkmann, R.  and Theisen, D.  and Birngruber, R.},
   title = {Ablation Dynamics of High Energy IR Laser Pulses in Myocardial Revascularization},
   journal = {Biomedical Optics, OSA Technical Digest},
   pages = {152-154},
   year = {1999},
   type = {Journal Article}
}

@article{Koop,
   author = {Koop, N. and Wirbelauer, C. and Tüngler, A. and Geerling, G. and Bastian, G. O. and Brinkmann, R},
   title = {Thermische Schädigung des Hornhautendothels bei der Dioden-Laserthermokeratoplastik.},
   journal = {Ophthalmologe},
   volume = {96},
   pages = {392-397},
   year = {1999},
   type = {Journal Article}
}

@article{Roider1999,
   author = {Roider, J. and Brinkmann, R. and Wirbelauer, C. and Birngruber, R. and Laqua, H.},
   title = {Variability of RPE reaction in two cases after selective RPE laser effects in prophylactic treatment of drusen},
   journal = {Graefes Arch Clin Exp Ophthalmol},
   volume = {237},
   number = {1},
   pages = {45-50},
   note = {0721-832X (Print)
Case Reports
Journal Article},
   abstract = {BACKGROUND: The value of prophylactic photocoagulation of soft drusen is unclear. Photocoagulation is usually performed by a continuous wave laser. METHODS: We report the cases of two patients with age-related macular degeneration with soft drusen who were treated by selective retinal pigment epithelium (RPE) photocoagulation of a pulsed Nd:YLF (527 nm) laser. Laser parameters were: wavelength 527 nm, number of pulses in a train 500, pulse duration 1.7 microseconds, energy per pulse 70 microJ, spot size 160 microns, repetition rate 500 Hz. RESULTS: Dosimetry performed individually showed that in both patients laser photocoagulation was performed at the threshold of RPE disruption. None of the laser effects was visible during photocoagulation. They were detectable only by fluorescein angiography. Despite identical photocoagulation parameters the RPE reaction was completely different. In the first patient RPE hyperpigmentation was notable at most photocoagulation sites and the drusen had disappeared after 6 months. In the second patient the laser effects were not visible after 6 months by biomicroscopy and the drusen stayed unchanged. CONCLUSION: These findings could reflect different repair mechanisms of the RPE after alteration and could represent a sign of a different viable stage in the life of RPE cells. Close attention should be paid to this phenomenon in the various drusen studies currently under way.},
   keywords = {Fluorescein Angiography
Fundus Oculi
Humans
*Laser Coagulation
Macular Degeneration/complications
Middle Aged
Pigment Epithelium of Eye/pathology/*surgery
Retinal Drusen/complications/pathology/*surgery
Visual Acuity},
   url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9951641},
   year = {1999},
   type = {Journal Article}
}

@article{Brinkmann1999,
   author = {Brinkmann, R. and Theisen, D. and Brendel, T. and Birngruber, R.},
   title = {Single-pulse 30-J holmium laser for myocardial revascularization - A study on ablation dynamics in comparison to CO2 laser-TMR},
   journal = {Ieee Journal of Selected Topics in Quantum Electronics},
   volume = {5},
   number = {4},
   pages = {969-980},
   note = {248CM
Times Cited:9
Cited References Count:40},
   abstract = {Endocardial laser revascularization (ELR) is a new technique to treat coronary heart disease in a percutaneous, minimally invasive approach. A holmium laser (lambda = 2.12 mu m) was developed to emit pulse energies of up to 30 J in order to ablate the desired channels in a single laser pulse. The energy was transmitted by multimode flexible optical waveguides as required for ELR, Ablation dynamics were investigated in two model systems, water serving as blood model and polyacrylamide (PAA) as a transparent tissue phantom. Measurements were undertaken using pulse energies of 12 J at pulse durations of 2.2 and 8 ms with a beam diameter of 1 mm, For comparison with the clinically established method of transmyocardial revascularization (TMR), ablations were also investigated with a standard 800 W TMR CO2 laser. The dynamics were recorded with a drum camera and stroboscope illumination providing a high framing rate of a single ablation process. Tissue ablation was quantified with the holmium laser in vitro on porcine heart tissue using pulse energies of up to 20 J, Tissue morphology was evaluated using polarization light microscopy to determine thermal and mechanical collateral damage zones. Oscillating vapor bubble channels were found in water and PAA with all laser systems and parameters used. Quasi-static vapor bubbles are observed in water in the millisecond time range using the holmium laser. CO2 laser radiation performed deeper channels in PAA than holmium laser pulses using the same radiant exposure. Channel depths of up to 10 mm were achieved with the holmium laser in myocardial tissue with pulse energies of 17 J, Thermal damage zones of about 150 mu m for the CO2 and 500 mu m for the holmium laser were found. The orientation of myocardial fibrils significantly influences the shape of the ablated cavities and the thermo-mechanical collateral damage zones. In conclusion, the results are very encouraging and demonstrate the potential of a catheter-based minimal invasive procedure for heart reperfusion using single high energy laser pulses.},
   keywords = {ablation dynamics
co2 laser
elr
fast flash photography
heart revascularization
holmium laser
polyacrylamide
tmlr
tmr
transmyocardial revascularization
tissue ablation
channels
generation
duration
water
blood},
   ISSN = {1077-260X},
   DOI = {Doi 10.1109/2944.796319},
   url = {<Go to ISI>://WOS:000083257800015},
   year = {1999},
   type = {Journal Article}
}

@article{Brinkmann1999,
   author = {Brinkmann, R. and Rögener, J. and Lin, C.P. and Roider, J. and Birngruber, R. and Hüttmann, G.},
   title = {Selective RPE-Photodestruction: Mechanism of Cell Damage by pulsed laser irradiance in the ns to µs time regime},
   journal = {Proc. SPIE},
   volume = {3601},
   pages = {59-65},
   year = { 1999}
}

@article{Brinkmann1998,
   author = {Brinkmann, R and Koop, N. and Kamm, K. and Geerling, G. and Kampmeier, J. and Birngruber, R.},
   title = {Laser Thermokeratoplastik: eine in vitro- und in vivo-Studie mit kontinuierlich emittierender Laserdiode im mittleren IR-Spektralbereich.},
   journal = {Laser in der Medizin, Proc. Laser 97},
   pages = {412-416},
   year = {1998},
   type = {Journal Article}
}

@article{Brinkmann1998,
   author = {Brinkmann, R. and Knipper, A. and Dröge, G. and Schroer, F. and Gromoll, B. and Birngruber, R.},
   title = {Fundamental Studies of Fiber-Guided Soft Tissue Cutting by Means of Pulsed Midinfrared IR lasers and their Application in Ureterotomy},
   journal = {J Biomed Opt},
   volume = {3},
   number = {1},
   pages = {85-95},
   year = { 1998}
}

@article{Brinkmann1998,
   author = {Brinkmann, R and Theisen, D. and Stubbe, H.M. and Birngruber, R.},
   title = {Endocardial Laser Revascularization with Single High Energy Laser Pulses},
   journal = {OSA TOPS},
   volume = {22},
   pages = {272-276},
   year = { 1998},
   type = {Journal Article}
}

@article{Brinkmann1998,
   author = {Brinkmann, R. and Koop, N. and Geerling, G. and Kampmeier, J. and Borcherding, S. and Kamm, K. and Birngruber, R.},
   title = {Diode laser thermokeratoplasty: application strategy and dosimetry},
   journal = {J Cataract Refract Surg},
   volume = {24},
   number = {9},
   pages = {1195-207},
   note = {0886-3350 (Print)
Journal Article
Research Support, Non-U.S. Gov't},
   abstract = {PURPOSE: To investigate suitable application parameters for efficient hyperopic correction by laser thermokeratoplasty (LTK) using mid-infrared laser diodes. SETTING: Medical Laser Center Lubeck, Lubeck, Germany. METHOD: A tunable continuous-wave laser diode in the spectral range between 1.845 and 1.871 microns was used. Transmitted by waveguides, the laser energy was used to induce coagulations on freshly enucleated porcine eyes to increase corneal curvature. The coagulations were equidistantly applied by a fiber-cornea contact and a noncontact focusing device that were adjusted on a ring concentric to the corneal apex. Different laser parameters and application geometries were evaluated. Refractive changes were measured by computer-assisted corneal topography before and after treatment. Polarization light microscopy and temperature calculations were used to analyze the coagulations. RESULTS: Because of the tunability of the laser diode, the influence of the corneal absorption coefficient (between 0.9 and 1.6 mm-1) on the refractive change could be measured. A laser power between 125 and 200 mW was adequate to achieve refractive changes up to 10.0 diopters. In the preferable focusing device, the refractive change increased almost logarithmically with the irradiation time up to 15 seconds. The number of coagulations on a fixed application ring showed no significant influence on refractive change; however, it showed an almost linear decrease with increasing ring diameter from 5.0 to 10.0 mm. Histological analysis revealed 3 stages of thermal damage. CONCLUSION: Diode LTK provided defined and uniform coagulations when using a well-adapted focusing device, resulting in sufficient refractive change. The results indicate that diode LTK is superior to pulsed holmium LTK.},
   keywords = {Absorption
Animals
Cornea/pathology/physiopathology/*surgery
Hyperopia/pathology/physiopathology/*surgery
Laser Coagulation/*methods
Microscopy, Polarization
Refraction, Ocular
Swine},
   year = { 1998}
}

@article{Brinkmann1997,
   author = {Brinkmann, R. and Koop, N. and Kampmeier, J. and Bruhns, A. and AsiyoVogel, M. and Engelhardt, R. and Birngruber, R.},
   title = {Corneal collagen denaturation in laser thermokeratoplasty (LTK)},
   journal = {Investigative Ophthalmology & Visual Science},
   volume = {38},
   number = {4},
   pages = {2514-2514},
   note = {1
Wn186
Times Cited:0
Cited References Count:0},
   ISSN = {0146-0404},
   url = {<Go to ISI>://WOS:A1997WN18602506},
   year = {1997},
   type = {Journal Article}
}

@article{Brinkmann1997,
   author = {Brinkmann, R and Dröge, G and Schroer, F and Scheu, M and Birngruber, R},
   title = {Ablation Dynamics in Laser Sclerostomy Ab Externo by means of Pulsed Lasers in the Mid-Infrared Spectral Range},
   journal = {Ophth Surg Las},
   volume = {28},
   number = {10},
   pages = {853-865},
   year = {1997},
   type = {Journal Article}
}

@article{Geerling1997,
   author = {Geerling, G. and Brinkmann, R. and Koop, N. and Wirbelauer, C. and Laqua, H. and Birngruber, R.},
   title = {Diode-laser thermokeratoplasty - First clinical experiences in human blind eyes},
   journal = {Investigative Ophthalmology & Visual Science},
   volume = {38},
   number = {4},
   pages = {2292-2292},
   note = {1
Wn186
Times Cited:0
Cited References Count:0},
   ISSN = {0146-0404},
   url = {<Go to ISI>://WOS:A1997WN18602285},
   year = {1997},
   type = {Journal Article}
}

@article{Asiyo-Vogel1997,
   author = {Asiyo-Vogel, M. N. and Koop, N. and Brinkmann, R. and Engelhardt, R. and Eggers, R. and Birngruber, R. and Vogel, A.},
   title = {Evaluation of LTK lesions by optical low coherence tomography (OCT) and polarization microscopy after Sirius-Red staining},
   journal = {Ophthalmologe},
   volume = {94},
   number = {7},
   pages = {487-491},
   note = {Yp140
Times Cited:5
Cited References Count:21},
   abstract = {Background: Information on the extent and degree of the thermal effect produced is of great importance for control of the laser dosage in laser thermokeratoplasty (LTK) and for postoperative follow-up. We investigated on acute LTK effects which information images obtained by optical low coherence tomography (OCT) offer compared to those obtained by polarization microscopy.
Methods: Porcine eyes were irradiated through a 400 mu m quartz fiber using light from a laser diode emitting up to 300 mW at a wavelength of 1.86 mu m. Thermal lesions of varying strength were scanned using an experimental OCT device with about 25 mu m lateral and 20 mu m axial resolution. Histologic evaluation of the scanned areas was done by polarization microscopy after Sirius-Red staining, and similar lesions were also analyzed by TEM.
Results: Both methods differentiated three damage zones: a transition zone, a zone of moderate coagulation, and a central zone of strong coagulation. In the transition zone,increased birefringence was seen in polarization microscopy, which correlated with increased light scattering seen in the DCT images,ln the moderately coagulated zone, a decrease in birefringence was associated with an even stronger increase of the OCT signal, In the central zone,a loss of the fibrillar tissue structure was observed, which led to a complete loss of birefringence and a strong reduction of the OCT signal.
Conclusions: Although OCT does not provide the detailed information on thermal changes of tissue seen by the histologic method, it offers information on the extent and degree of tissue changes without preparation artifacts and provides a non-invasive method of immediate and follow-up control of LTK lesions, A quantitative analysis of changes in corneal thickness and curvature is much simpler than by a slit lamp. Time-resolved measurements of corneal light scattering may be used for on-line control of the laser-light dosage during LTK.},
   keywords = {refractive surgery
laser thermokeratoplasty
collagen denaturation
collagen shrinkage
optical low coherence tomography
polarization microscopy
sirius-red staining
tissue
collagen
eye},
   ISSN = {0941-293X},
   DOI = {DOI 10.1007/s003470050144},
   url = {<Go to ISI>://WOS:000071246700004},
   year = {1997},
   type = {Journal Article}
}

@article{Asiyo-Vogel,
   author = {Asiyo-Vogel, M. and Brinkmann, R and Notbohm, H. and Eggers, R. and Lubatschowski, H. and Laqua, H. and Vogel, A.},
   title = {Histologic analysis of thermal effects of laserthermokeratoplasty and corneal ablation using Sirius-Red polarization microscopy},
   journal = {J Cataract Refr Surg},
   volume = {23},
   pages = {515-526},
   year = {1997}
}

@article{Kampmeier1997,
   author = {Kampmeier, J. and Brinkmann, R. and Pfleiderer, M. and Schneider, E. and Birngruber, R.},
   title = {Laser thermokeratoplasty (LTK): A finite element model of the cornea},
   journal = {Investigative Ophthalmology & Visual Science},
   volume = {38},
   number = {4},
   pages = {2515-2515},
   note = {1
Wn186
Times Cited:0
Cited References Count:0},
   ISSN = {0146-0404},
   url = {<Go to ISI>://WOS:A1997WN18602507},
   year = {1997},
   type = {Journal Article}
}

@article{Koop1997,
   author = {Koop, N. and Brinkmann, R. and Lankenau, E. and Flache, S. and Engelhardt, R. and Birngruber, R.},
   title = {Optical coherence tomography of cornea and anterior segment of the eye},
   journal = {Ophthalmologe},
   volume = {94},
   number = {7},
   pages = {481-486},
   note = {Yp140
Times Cited:34
Cited References Count:19},
   abstract = {Target: The method of optical coherence tomography (OCT) was investigated regarding its suitability and limits for measuring the cornea and the anterior segment of the eye. Furthermore, the stromal expansion of thermally induced lesions in the cornea directly after irradiation was determined within the scope of the laser thermokeratoplasty (LTK).
Material and methods: With the experimental scanning OCT system, x-z sections of the anterior eye segment were made with an optical resolution of about 20 mu m axially and 25 mu m laterally. Freshly enucleated, tonicized porcine eyes were used as model eyes. Thermal lesions were applied with a continuously emitting laser diode (lambda=1.86 mu m) and various radiation parameters, Before and after coagulation, the cornea was viewed from limbus to limbus in a central OCT scan and the individual coagulation source was measured,
Results: Global and local changes of the thickness of the cornea as well as the distance between cornea and lens were measured with high precision. Thermal lesions in their expansion can be clearly presented and matching well with the histologically stained sections, bur are not as exactly defined at the edges due to the limited optical resolution, as known from histological preparations.
Conclusion: With the OCT method quantitative measuring of the anterior eye segment can be performed in vitro and with reduced resolutions also in vivo. Due to the qualitatively good correspondence regarding the dimensions of thermal damage of the cornea with histologically obtained morphometric results,this method can be used for supervision of coagulation directly after LTK as well as for examination of the individual healing process.},
   keywords = {optical coherence tomography
pachometry
laser thermokeratoplasty
thermal damage
tissue},
   ISSN = {0941-293X},
   DOI = {DOI 10.1007/s003470050143},
   url = {<Go to ISI>://WOS:000071246700003},
   year = {1997},
   type = {Journal Article}
}

@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}
}

@article{Roider1997,
   author = {Roider, J. and Brinkmann, R. and Laqua, H. and Birngruber, R.},
   title = {Therapeutical bandwidth or selective RPE-photocoagulation treatment by repetitive mu s-laser pulses (527 nm) - First clinical results},
   journal = {Investigative Ophthalmology & Visual Science},
   volume = {38},
   number = {4},
   pages = {404-404},
   note = {1
Wn186
Times Cited:0
Cited References Count:0},
   ISSN = {0146-0404},
   url = {<Go to ISI>://WOS:A1997WN18600402},
   year = {1997},
   type = {Journal Article}
}

@article{Gerling1996,
   author = {Gerling, G. and Vogel, A. and ElHifnawi, E. and Koop, N. and Droge, G. and Birngruber, R. and Brinkmann, R.},
   title = {Morphological and biomorphometrical observations on laser thermal keratoplasty - Histological and biomorphometrical examination of the relationship between refractive change and the volume of laser thermal keratoplasty lesions following Cr:Tm:Ho:YAG laser treatment},
   journal = {German Journal of Ophthalmology},
   volume = {5},
   number = {2},
   pages = {84-91},
   note = {Vf915
Times Cited:4
Cited References Count:21},
   abstract = {Laser thermal keratoplasty (LTK) is currently under clinical trial for the correction of hyperopia and hyperopic astigmatism by means of collagen coagulation in the peripheral cornea. The purpose of our study was to optimize the ratio between the volume of damaged corneal stroma and the refractive effect so as to minimize potential side effects such as endothelial damage or induction of glare phenomena. We therefore performed histological and morphometrical examinations of enucleated pig eyes to determine the relationship between the coagulated stromal volume and the refractive change after LTK using a pulsed Cr: Tm: Ho: YAG laser (wavelength 2.12 mu m) on enucleated pig eyes. The refractive change was documented with a Littman ophthalmometer. Morphometrical analysis was performed using polarized light microscopy of sirius red-stained specimens. This special stain separated the thermally changed stroma into a dark, nonbirefringent center and a birefringent peripheral zone. The volume of both zones was positively correlated with the refractive change induced. The volume was in turn influenced by the choice of laser parameters, From the ratio of the volume to the refractive change it was found that pulse energies above 30 mJ led to an enlargement of the coagulation volume without increasing the refractive change effectively. The use of high pulse energies did not improve the effect of LTK but only increased the risk of unwanted side effects. However, an increase in the laser repetition rate at a constant pulse number per spot led to refractive changes with a minimal coagulation volume. The highest relative refractive change was achieved with a dark central zone and a birefringent zone, each having a volume of about 50 - 80 x 10(-3) mm(3).},
   keywords = {laser thermal keratoplasty
hyperopic correction
biomorphometry
sirius red stain
polarization microscopy
organization
microscopy
collagen},
   ISSN = {0941-2921},
   url = {<Go to ISI>://WOS:A1996VF91500004},
   year = {1996},
   type = {Journal Article}
}

@article{Brinkmann1996-2,
   author = {Brinkmann, R;Koop, N;Kamm, K;Geerling, G;Kampmeier, J and Birngruber, R},
   title = {Laser Thermokeratoplasty: an in vitro and in vivo study by means of a cw mid-IR laser diode},
   journal = {Laser Medizin},
   volume = {12},
Keywords = {Brechkraftänderung, Denaturierung, Hyperopie-Korrektur, Koagulation, Kollagen-Kontraaktion, Kornea, Temperaturberechnung},
   pages = {179-186},
   year = { 1996},
url = { https://doi.org/10.1007/978-3-642-60306-8_83},
   type = {Journal Article}
}

@article{Brinkmann1996-1,
   author = {Brinkmann, R. and Hansen, C. and Mohrenstecher, D. and Scheu, M. and Birngruber, R.},
   title = {Analysis of cavitation dynamics during pulsed laser tissue ablation by optical on-line monitoring},
   journal = {Ieee Journal of Selected Topics in Quantum Electronics},
   volume = {2(4)},
   
   pages = {826-835},
   note = {Xd616
Times Cited:20
Cited References Count:24},
   abstract = {Flashlamp pumped mid-IR laser systems emitting in the 23-mu m wavelength range are widely used for various medical applications, especially for tissue ablation, Explosive evaporation is inevitably associated with this process due to the short pulse durations of these laser systems and the high absorption of tissue and water in this spectral regime, Tissue displacement and dissection occur in liquid environment as a consequence of the induced cavitation, Depending on the application these processes might enhance the tissue ablation but can also cause adverse tissue effects, The ablation dynamics were investigated by evaluating the change in rejected probe-light intensity reemitted from the application fiber tip. The ablated cavity and the signal was correlated to fast-flash photographs of the event. Based on this reflection signal a water/tissue discrimination system is introduced which can widely support medical laser applications. In laser sclerostomy ab externo, for example, this approach can be used as a feedback system to automatically control the ablation process. With such a system, adverse effects to adjacent tissue in the anterior chamber of the eye can be minimized.},
   ISSN = {1077-260X},
   DOI = {Doi 10.1109/2944.577305},
   url = {<Go to ISI>://WOS:A1996XD61600006},
   year = { 1996},
   type = {Journal Article}
}

@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}
}

@article{Brinkmann1996-2,
   author = {Brinkmann, R. and Koop, N. and AsiyoVogel, M. N. and Kaftan, B. and Birngruber, R. and Engelhardt, R.},
   title = {CW-IR laser thermokeratoplasty: Refractive changes and analysis by optical coherence tomography and light microscopy},
   journal = {Investigative Ophthalmology & Visual Science},
   volume = {37(3)},
   
   pages = {305-305},
   note = {Tx397
Times Cited:0
Cited References Count:0},
   ISSN = {0146-0404},
   url = {<Go to ISI>://WOS:A1996TX39700305},
   year = { 1996},
   type = {Journal Article}
}

@article{Geerling1996,
   author = {Geerling, G. and Brinkmann, R. and Koop, N. and Klingemann, I. and Laqua, H. and Birngruber, R.},
   title = {Laser thermokeratoplasty - Experimental study in minipigs with a cw-IR laser diode},
   journal = {Investigative Ophthalmology & Visual Science},
   volume = {37},
   number = {3},
   pages = {304-304},
   note = {Tx397
Times Cited:0
Cited References Count:0},
   ISSN = {0146-0404},
   url = {<Go to ISI>://WOS:A1996TX39700304},
   year = {1996},
   type = {Journal Article}
}

@article{Kampmeier1996,
   author = {Kampmeier, J. and Brinkmann, R. and Birngruber, R.},
   title = {Laser thermokeratoplasty (LTK): Biomechanical properties and IR-laser induced forces in porcine cornea.},
   journal = {Investigative Ophthalmology & Visual Science},
   volume = {37},
   number = {3},
   pages = {301-301},
   note = {Tx397
Times Cited:0
Cited References Count:0},
   ISSN = {0146-0404},
   url = {<Go to ISI>://WOS:A1996TX39700301},
   year = {1996},
   type = {Journal Article}
}

@article{Brinkmann1996-3,
   author = {Brinkmann, R and Knipper, A and Dröge, G and Gafumbegete, D and Miller, A and Gromoll, B and Birngruber, R},
   title = {Ureterotomy with a pulsed Holmium Laser},
   journal = {Proc LASER '95, Springer Verlag},
   pages = {16-19},
   year = { 1996},
url = { https://link.springer.com/chapter/10.1007/978-3-642-80264-5_3},
   type = {Journal Article}
}

@article{Brinkmann-1996-6,
   author = {Koop, N;Brinkmann, R and Schirner, G},
   title = {Verwendung des konfokalen Laserscanverfahrens zur Bestimmung der Hornhaut-topographie und der kornealen Gewebseffekte bei der refraktiven Hornhautchirurgie: Hornhaut},
   journal = {Der Ophthalmologe (Berlin. Print)},
   volume = {93(3)},
   
   pages = {247-251},
   ISSN = {0941-293X},
   year = { 1996},
   type = {Journal Article}
}

@article{RN5186,
   author = {Gerling, G;Vogel, A;Koop, N;Dröge, G;Birngruber, R and Brinkmann, R},
   title = {Morphological and biomorphometrical observations on laser thermal keratoplasty. Histological and biomorphometrical examination of the relationship between refractive change and the volume following Cr: Tm: Ho: YAG laser treatment},
   journal = {Ger J ophthalmol},
   volume = {5(2)},
  
   pages = {84-91},
   ISSN = {0941-2921},
   year = {1996},
   type = {Journal Article}
}

@article{Brinkmann1996-4,
   author = {Brinkmann, R. and Koop, N. and Kamm, K. and Geerling, G. and Kampmeier, J. and Birngruber, R.},
   title = {Laser thermokeratoplasty: an in vitro and in vivo-study by means of a Continous Wave Mid-IR laser diode.},
   journal = {Lasermedizin},
   volume = {12},
   pages = {179-186},
   year = { 1996},
   type = {Journal Article}
}

@article{Brinkmann1996-5,
   author = {Verges, D;Mentzel, H;Dröge, G;Brinkman, R;Krüger, S and Stange, E F},
   title = {Über die Schnittwirkung des Holmium-Lasers in der Magen-und Darmschleimhaut des Schweines},
   journal = {Lasermedizin},
   volume = {12},
keywords = {Holmium, Endoskopie, Polypktomie, Gewebeabtragung},
   pages = {9-16},
   year = { 1996},
   type = {Journal Article}
}

@article{Wetzel1996,
   author = {Wetzel, W. and Brinkmann, R. and Koop, N. and Schroer, F. and Birngruber, R.},
   title = {Photofragmentation of lens nuclei using the Er:YAG laser: Preliminary report of an in vitro study},
   journal = {Ger J Ophthalmol},
   volume = {5(5)},
  
   pages = {281-284},
   note = {Vq341
Times Cited:13
Cited References Count:12},
   abstract = {The energy of the erbium:YAG laser (2,940-nm wave-length) can be used for minimally traumatic photoablation due to its high absorption at the tissue water and its consequently low penetration depth. Laser sclerostomy ab externo, an application of this principle, has undergone advanced clinical investigation. Another potential application is photofragmentation of the lens for cataract extraction. A laboratory model Er: YAG laser (flashlamp-pumped, 200-mu s pulse length, 5-Hz repetition frequency) was coupled to a short low-OH quartz fiber (400 mu m in diameter). The laser energy was applied by direct contact of the fiber tip to human lenses with very dense cataract. The lenses rested in a small cuvette filled with an aqueous-humor-analogous fluid. The fragmentablation rate was evaluated in relation to the number of pulses and the pulse energy. A laser-triggered flash-photography unit was engaged to visualize the ablation dynamics. We found tissue-ablation rates to range from 4 to 19 mu g/pulse, depending on the nucleus density and ulse energy. The maximal size of the removed fragments was always below 500 mu m During ablation, rapidly increasing and collapsing cavitation bubbles were photographed at the distal tip of the application fiber. The impact radius of these cavitation effects markedly exceeded the pure penetration depth of laser radiation at a 2.9-mu m wavelength. A clinical application of the method should be possible as judged by the results obtained for tissue-ablation rate and fragment size. Cavitation-bubble dynamics seems to be responsible for the high fragmentation efficiency. Special application probes have to be developed to optimize ablation and to prevent inadvertent destruction of the posterior lens capsule by cavitation effects.},
   keywords = {phacoemulsification
er:yag laser
cavitation effects
ablation
surgery},
   ISSN = {0941-2921},
  url = {https://www.osti.gov/etdeweb/biblio/7016223},
   year = {1996},
   type = {Journal Article}
}

@article{Brinkmann1996,
   author = {Wetzel, W;Brinkmann, R;Koop, N;Schröer, F and Birngruber, R},
   title = {Photofragmentation of lens nuclei using the Er: YAG laser: preliminary report of an in vitro study},
   journal = {Ger J ophthalmol},
   volume = {5(5)},
  
   pages = {281-284},
   ISSN = {0941-2921},
   year = {1996},
   type = {Journal Article}
}

@article{Schirner1995,
   author = {Schirner, G. and Koop, N. and Elhifnawi, E. and Birngruber, R. and Brinkmann, R.},
   title = {Experiments with Pulsed and Continuous-Wave Laser Sources to Optimize Laserthermo-Keratoplasty},
   journal = {Vision Research},
   volume = {35},
   pages = {P167-P167},
   note = {Suppl. S
Rz562
Times Cited:0
Cited References Count:0},
   ISSN = {0042-6989},
   url = {<Go to ISI>://WOS:A1995RZ56200472},
   year = {1995},
   type = {Journal Article}
}

@article{Schirner1995,
   author = {Schirner, G. and Brinkmann, R. and Droge, G. and Koop, N. and Elhifnawi, E. S. and Birngruber, R.},
   title = {Experimental Studies to Optimize Laser-Thermokeratoplasty Using Pulsed and Cw-Laser-Sources},
   journal = {Investigative Ophthalmology & Visual Science},
   volume = {36},
   number = {4},
   pages = {S716-S716},
   note = {Qm915
Times Cited:3
Cited References Count:0},
   ISSN = {0146-0404},
   url = {<Go to ISI>://WOS:A1995QM91503294},
   year = {1995},
   type = {Journal Article}
}

@article{Brinkmann1995,
   author = {Brinkmann, R. and Schroer, F. and Mohrenstecher, D. and Droge, G. and Birngruber, R.},
   title = {Ablation Dynamics in Laser Sclerostomy Ab-Externo},
   journal = {Investigative Ophthalmology & Visual Science},
   volume = {36},
   number = {4},
   pages = {S558-S558},
   note = {Qm915
Times Cited:1
Cited References Count:0},
   ISSN = {0146-0404},
   url = {<Go to ISI>://WOS:A1995QM91502583},
   year = {1995},
   type = {Journal Article}
}

@article{Brinkmann1994,
   author = {Knipper, A;Brinkmann, R;Durek, C;Gromoll, B and Jocham, D},
   title = {The Holmium-YAG-laser as a new cutting instrument in the ureter},
   journal = {Investigative urology (Berlin, Germany)},
   volume = {5},
   pages = {233-235},
   year = {1994},
   type = {Journal Article}
}

@article{Brinkmann1994,
   author = {Wetzel, W;Häring, G;Brinkmann, R and Birngruber, R},
   title = {Laser sclerostomy ab externo using the erbium: YAG laser. First results of a clinical study},
   journal = {Germ j ophthal},
   volume = {3(2)},
  
   pages = {112-115},
   ISSN = {0941-2921},
   year = {1994},
   type = {Journal Article}
}

@article{Binkmann1994,
   author = {Brinkmann, R. and Dröge, G. and Koop, N. and Wördemann, A. and Schirner, G. and Birngruber, R.},
   title = {Investigations on laser thermokeratoplasty},
   journal = {Lasers Light Ophthalmol},
   volume = {6},
   number = {4},
   pages = {259 - 270},
   year = {1994},
   type = {Journal Article}
}

@article{Brinkmann1994,
   author = {Schirner, G;Huber, A;Wördemann, A;GRÖGE, G; El-Hifnawi, E; Birngruber, R and Brinkmann, R},
   title = {Experimentelle Untersuchungen zur Wirkung des Er: Glas-und Cr: TM: Ho: YAG-Lasers bei der Thermokeratoplastik},
   journal = {Der Ophthalmologe (Berlin. Print)},
   volume = {91},
   number = {5},
   pages = {638-645},
   ISSN = {0941-293X},
   year = {1994},
   type = {Journal Article}
}

@article{Schirner1994,
   author = {Schirner, G. and Huber, A. and Wordemann, A. and Droge, G. and el-Hifnawi, E. and Birngruber, R. and Brinkmann, R.},
   title = {[Experimental studies on the effect of the Er:glass and Cr:Tm:Ho:YAG laser in thermokeratoplasty]},
   journal = {Ophthalmologe},
   volume = {91},
   number = {5},
   pages = {638-45},
   note = {0941-293X (Print)
English Abstract
Journal Article},
   abstract = {So far the dose-effect ratio of the Holmium laser (wavelength 2.12 microns) and the erbium laser (1.54 microns) for laser thermokeratoplasty (LTK) are not defined in detail. Our study was designed not only to compare the erbium contact and the holmium non-contact applications but also to throw light on the influence of different geometrical application patterns, pulse energies, pulses per coagulation site and repetition rates under experimental conditions. Enucleated sheep and pig eyes were used 2-6 h post mortem, pressurized to 25 mmHg and moisturized with saline solution. Before and after LTK, pachymetry and keratometry were performed. Some specimens were prepared for light and scanning microscopy. The coagulation threshold for the erbium laser in a contact mode with a 200-microns fibre was 25 J/cm2 (ca. 8 mJ/pulse) and for the holmium laser 8 J/cm2 (ca. 2.5 mJ/pulse). The erbium laser was used in a single shot per spot mode, the holmium laser in repeated pulse per spot mode. With the single shot per spot mode, we were able to induce a promising hyperopic shift of up to -3.47 +/- 0.61 D, while myopic changes could only be induced up to +1.89 +/- 0.74 D. Higher changes of up to +8.27 +/- 1.3 D could be achieved by means of repeated pulses per spot (20 pulses, 45 mJ, 10 Hz). Our experiments showed an obvious increase of dioptric changes when using a higher repetition rate while pulse energy and number were kept constant.(ABSTRACT TRUNCATED AT 250 WORDS)},
   keywords = {Animals
Cornea/pathology
Corneal Transplantation/*instrumentation/pathology
Laser Coagulation/*instrumentation
Microscopy, Electron, Scanning
Myopia/pathology/surgery
Refraction, Ocular
Sheep
Swine},
   url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=7812097},
   year = {1994},
   type = {Journal Article}
}

@article{Brinkmann1989,
   author = {Engelhardt, R;Brinkmann, R and Meyer, W},
   title = {1. mu. s Alexandrit-Laser fuer laserinduzierte Schockwellenlithotripsie},
   journal = {Laser und Optoelektronik},
   volume = {21(6)},
   pages = {56-61},
   year = {1989},
   type = {Journal Article}
}

@article{Hube,
   author = {Hube, M and Brinkmann, R and Welling, H and Beigang, R and Wellegehausen, B},
   title = {A Cadmium Photoionization Laser Pumped by Laser Induced Plasma Radiation from a Multi Foci Device},
   journal = {Appl Phys B},
   volume = {45},
   pages = {197-201},
   year = {1988}
}