@inproceedings{Herrmann2007,
   author = {Herrmann, Katharina and Flöhr, Christian and Stalljohann, Jens and Apiou-Sbirlea, Gabriela and Kandulla, Jochen and Birngruber, Reginald and Brinkmann, Ralf},
   title = {Influence of choroidal perfusion on retinal temperature increase during retinal laser treatments},
   volume = {6632},
   pages = {66321D-66321D-7},
   note = {10.1117/12.728222},
   abstract = {In most retinal laser treatments the therapeutic effect is initiated by a transient temperature increase at and around the retinal pigment epithelium (RPE). Especially in long exposure time treatments like Transpupillary Thermotherapy (TTT) choroidal perfusion has a strong influence on the realized temperature at the fundus. The fundus blood circulation and therefore the heat dissipation is influenced by the intraocular pressure (IOP), which is investigated in the study presented here. In order to reduce the choroidal perfusion, the IOP is increased by injection of physiological saline solution into the eye of anaesthetized rabbits. The fundus is irradiated with 3.64 W/cm2 by means of a TTT-laser (λ = 810 nm) for t = 20 s causing a retinal temperature increase. Realtime temperature determination at the irradiated spot is achieved by a non invasive optoacoustic technique. Perfusion can be reduced by increasing IOP, which leads to different temperature increases when irradiating the retina. This should be considered for long time laser treatments.},
   url = {http://dx.doi.org/10.1117/12.728222},
   type = {Conference Proceedings},
year = { 2007}
}

@inproceedings{Stoehr2007-1,
   author = {Stoehr, Hardo and Ptaszynski, Lars and Fritz, Andreas and Brinkmann, Ralf},
   title = {Interferometric optical online dosimetry for selective retina treatment (SRT)},
   volume = {6426},
   pages = {642619-642619-7},
   note = {10.1117/12.708521},
   abstract = {In selective retina treatment (SRT) spatial confined tissue damage in the absorbing retinal pigment epithelium (RPE) is obtained by applying microsecond laser pulses. The damage in the RPE is caused by transient microbubbles forming around the laser heated melanin granules inside the cells. For treatment of RPE related diseases, SRT is thought to share the therapeutic benefits of conventional photocoagulation but without affecting the photoreceptors. A drawback for effective clinical SRT is that the laser-induced lesions are ophthalmoscopically invisible. Therefore, a real-time feedback system for dosimetry is demanded in order to avoid undertreatment or unwanted collateral damage to the adjacent tissue. We develop a dosimetry system which uses optical interferometry for the detection of the transient microbubbles. The system is based on an optical fiber interferometer which is operated with a laser diode at 830nm. We present current results obtained with porcine RPE explants in vitro and complete porcine eye globes ex vivo.},
   url = {http://dx.doi.org/10.1117/12.708521},
   type = {Conference Proceedings},
Year = { 2007}
}

@inproceedings{Schlott2007,
   author = {Schlott, Kerstin and Stalljohann, Jens and Weber, Benjamin and Kandulla, Jochen and Herrmann, Katharina and Birngruber, Reginald and Brinkmann, Ralf},
   title = {Optoacoustic online temperature determination during retinal laser photocoagulation},
   volume = {6632},
   pages = {66321B-66321B-8},
   note = {10.1117/12.728291},
   abstract = {Retinal photocoagulation is an established treatment of different retinal diseases. The treatment relies on a short, local heating of the tissue which induces a denaturation. The resulting scar formation may for example prevent the further detachment of the retina. The extent of the coagulation is besides other parameters mostly dependent on the induced temperature increase. However, until today a temperature based dosimetry for photocoagulation does not exist. The dosage is rather based on the experience of the treating physicians to achieve visible whitish lesions on the retina. In this work a technique is presented, which allows an online temperature monitoring during photocoagulation. If an absorbing material is irradiated with short laser pulses, a thermoelastic expansion of the absorber induces an acoustic wave. Its amplitude is dependent on the temperature of the absorber. For analyzing the applicability of the optoacoustic temperature determination for dosimetry, measurements were performed on enucleated porcine eye globes. The pressure transients are detected by an ultrasonic transducer, which is embedded in an ophthalmologic contact lens. As long as no strong lesions occur, the determined temperatures are almost proportional to the power of the treatment laser. Using a spot diameter of 200 μm and different laser powers, the temperature rise at the end of the 400 ms irradiation was found to be approximately 0.16 °C/mW. The onset of the denaturation was observed around 50°C. The far aim of this project is an automatic regulation of the treatment laser onto a desired temperature course.},
   url = {http://dx.doi.org/10.1117/12.728291},
   type = {Conference Proceedings},
year = { 2007}
}

@article{Brinkmann2006-1,
   author = {Brinkmann, Ralf and Birngruber, Reginald},
   title = {Selektive Retina-Therapie (SRT)},
   journal = {Zeitschrift für Medizinische Physik},
   volume = {17},
   number = {1},
   pages = {6-22},
   abstract = {Zusammenfassung Die am Medizinischen Laserzentrum Lübeck entwickelte selektive Retina-Therapie (SRT) wird zur Zeit als neue, schonende Laser-Behandlungsmethode für verschiedene Erkrankungen des Augenhintergrunds evaluiert, deren Ursachen einer Degradation des Retinalen Pigmentepithels (RPE) zugeschrieben werden. Mit der SRT lässt sich selektiv das RPE behandeln, ohne die angrenzende neurosensorische Netzhaut mit den Photorezeptoren und die unter dem RPE liegende Aderhaut (Choroidea) zu beeinträchtigen. Die Therapie führt idealerweise zu einer Regeneration des RPEs und einem gesteigerten Metabolismus am chorio-retinalen Übergang. Im Gegensatz zur etablierten Laserphotokoagulation, bei der die Netzhaut in und um die bestrahlten Areale komplett verödet wird, bleibt bei der SRT die Sehfähigkeit der Patienten in den bestrahlten Arealen erhalten. Der Artikel gibt einen Überblick über die Idee und die physikalischen Mechanismen selektiver RPE-Behandlung, die online Dosimetrie der optisch nicht sichtbaren Effekte und fasst die ersten klinischen Ergebnisse zusammen. Selective Retina Therapy (SRT) is a new and very gentle laser method developed at the Medical Laser Center Lübeck. It is currently investigated clinically in order to treat retinal disorders associated with a decreased function of the retinal pigment epithelium (RPE). SRT is designed to selectively effect the RPE while sparing the neural retina and the photoreceptors as well as the chorioidea. Aim of the therapy is the rejuvenation of the RPE in the treated areas, which should ideally lead to a long term metabolic increase at the chorio-retinal junction. In contrast to conventional laser photocoagulation, which is associated with a complete thermal necrosis of the treated site, SRT completely retains full vision. This paper reviews the methods and mechanisms behind selective RPE effects and reports the first clinical results. An online dosimetry technique to visualize the ophthalmoscopically invisible effects is introduced.},
   keywords = {Selektive Zelleffekte, Optoakustik, Mikroblasen, Online-Dosimetrie, RPE, ?s-Laserpulse, Makulaödeme, RCS
Selective cellular effects, optoacoustics, online dosimetry, RPE, ?s-laser pulses, macula oedema, RCS},
   year = { 2006}
}

@inproceedings{Schuele-2002,
   author = {Schuele, Georg and Huettmann, Gereon and Brinkmann, Ralf},
   title = {Noninvasive temperature measurements during laser irradiation of the retina with optoacoustic techniques},
   editor = {Fabrice, Manns and Per, G. Soederberg and Arthur, Ho},
   publisher = {Proc. SPIE},
   volume = {4611},
   pages = {64-71},
year = { 2002},
url = { https://doi.org/10.1117/12.470601} 
}

@inproceedings{Rommerscheid2001,
   author = {Rommerscheid, Jan and Theisen, Dirk and Schmuecker, G. and Brinkmann, Ralf and Broll, R.},
   title = {Myocardial expression of the vascular endothelial growth factor (VEGF) after endocardial laser revascularization (ELR)},
   volume = {4433},
   pages = {39-44},
   note = {10.1117/12.446529},
   abstract = {Background. Endocardial laser revascularization (ELR) is a new technique to treat patients with severe coronary artery disease (CAD) in a percutaneous approach. The results show a significant improvement of symptoms, but the mechanism of action is still unknown. One main theory is the angiogenesis for which Vascular Endothelial Growth Factor (VEGF) is the keypromotor. We investigated immunohistochemically the VEGF-expression after ELR in porcine hearts over a timeperiod of four weeks. Methods. ELR was performed with a single-pulse Thulium:YAG laser. 15 pigs were treated with ELR and the hearts were harvested at five timeperiods: directly (group I), 3 days (group II), 1 week (group III), 2 weeks (group IV) and 4 weeks (group V) after ELR. Each group consisted of three pigs. Immunohistochemically the VEGF-expression was assessed by staining with a polyclonal antibody against VEGF and cellcounting using an expression index (VEGF-EI) Results. A maximum of VEGF-expression was found three days (group II) after ELR with a VEGF-EI of 97%. At 1 week (group III) the VEGF-EI was similar high with 93%. Along the timecourse the index decreased to 22% at 4 weeks (groupV). Conclusions. Our findings show that ELR leads to an local upregulation of VEGF around the channels. The resulting angiogenesis could be the mechanism for the relief of angina.},
   url = {http://dx.doi.org/10.1117/12.446529},
   type = {Conference Proceedings},
year = { 2001}
}

@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,
   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{Brinkmann2001,
   author = {Brinkmann, R. and Schuele, G. and Joachimmeyer, E. and Roider, J. and Birngruber, R.},
   title = {Determination of absolute fundus temperatures during retinal laser photocoagulation and selective RPE treatment.},
   journal = {Investigative Ophthalmology & Visual Science},
   volume = {42},
   number = {4},
   pages = {S696-S696},
   note = {Suppl. S
427EP
3749
Times Cited:0
Cited References Count:0},
   ISSN = {0146-0404},
   url = {<Go to ISI>://WOS:000168392103712},
   year = {2001},
   type = {Journal Article}
}

@article{Roider2001,
   author = {Roider, J; Brinkmann, R, Framme, C; Schule, G, Joachimeyer, E; Wirbelauer, C; Kracht, D, Laqua, H and Birngruber, R},
   title = {Selective RPE laser treatment in macular diseases: Clinical results.},
   journal = {Invest Ophthal & VisScie},
   
   pages = {S695-S695},
   note = {Suppl. S
427EP
3741
Times Cited:0
Cited References Count:0},
   ISSN = {0146-0404},
   url = {<Go to ISI>://WOS:000168392103704},
   year = {2001},
   type = {Journal Article}
}

@inproceedings{Schuele2001-1,
   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{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}
}