@article{Dolling:24,
author = {Maron Dolling and Lara Buhl and Reginald Birngruber and Gereon H\"{u}ttmann and Hinnerk Schulz-Hildebrandt},
journal = {Appl. Opt.},
keywords = {Distortion; Imaging systems; Optical aberration; Optical components; Spectral domain optical coherence tomography; Systems design},
number = {10},
pages = {2694--2703},
publisher = {Optica Publishing Group},
title = {Algorithm and software for field distortion correction in a commercial SD-OCT for corneal curvature assessment},
volume = {63},
month = {Apr},
year = {2024},
url = {https://opg.optica.org/ao/abstract.cfm?URI=ao-63-10-2694},
doi = {10.1364/AO.505107},
abstract = {Accurate assessment of corneal curvatures using frequency domain optical coherence tomography (OCT) with galvanometer scanners remains challenging due to the well-known scan field distortion. This paper presents an algorithm and software for correcting the distortion using only two simple measurements in which a readily available standard sphere is positioned in different depths in front of the OCT scanner. This offers a highly accessible and easily reproducible method for the field distortion correction (FDC). The correction was validated by measuring different spherical phantoms and conducting corneal curvature measurements of ex vivo porcine corneas using a commercial spectral-domain OCT system and a clinically approved swept-source OCT as a reference instrument. Thus, the error in radius measurements of spherical phantoms was reduced by \>90\% and astigmatism by \>80\% using FDC. In explanted porcine eyes, the error in astigmatism measurements with the Telesto was reduced by 75\% for power and 70\% for angle. The best fitting sphere radius was determined up to a deviation of 0.4\% from the Anterion. This paper describes a correction algorithm for OCT immanent distortion that is applicable to any scanning OCT setup and enables precise corneal curvature measurements. The MATLAB software for the FDC is publicly available on GitHub.},
}

@article{Schenk-2021,
   author = {Schenk, M S;Wartak, A;Buehler, V;Zhao, J;Tearney, G J;Birngruber, R and Kassumeh, S},
   title = {Advances in Imaging of Subbasal Corneal Nerves With Micro–Optical Coherence Tomography},
   journal = {Tvst},
keywords = {corneal nerves; micro–optical coherence tomography; subbasal plexus},
   volume = {10 (13)},
   pages = {22-22},
   ISSN = {2164-2591},
   DOI = {10.1167/tvst.10.13.22},

   year = {2021},
   type = {Journal Article}
}

@article{Seifert2021,
   author = {Seifert, E;Tode, J;Pielen, A;Theisen-Kunde, D;Framme, C;Roider, J;Miura, Y;Birngruber, R and Brinkmann, R},
   title = {Algorithms for optoacoustically controlled selective retina therapy (SRT)},
   journal = {Photoacoustics},
Keywords = {SRT; Lasers in medicine; Ophthalmology; RPE; Selectivity; Algorithm; Retina therapy; Optoacoustics; Feedback},
   volume = {25},
   pages = {100316},
   ISSN = {2213-5979},
   url = {https://www.sciencedirect.com/science/article/pii/S2213597921000756},
   year = {2021},
   type = {Journal Article}
}

@article{Seifert2021,
   author = {Seifert, E;Sonntag, S R;Kleingarn, P;Theisen-Kunde, D;Grisanti, S;Birngruber, R;Miura, Y and Brinkmann, R},
   title = {Investigations on Retinal Pigment Epithelial Damage at Laser Irradiation in the Lower Microsecond Time Regime},
   journal = {Investigative Ophthalmology & Visual Science},
   volume = {62(3)},
  
   pages = {32-32},
   ISSN = {1552-5783},
   DOI = {10.1167/iovs.62.3.32},
   url = {https://doi.org/10.1167/iovs.62.3.32},
   year = {2021},
   type = {Journal Article}
}

@article{Kassumeh2020,
   author = {Kassumeh, S;Luther, J K.;Wertheimer, C M.;Brandt, K;Schenk, M S.;Priglinger, S G.;Wartak, A;Apiou-Sbirlea, G.;Anderson, R. R. and Birngruber, R},
   title = {Corneal Stromal Filler Injection as a Novel Approach to Correct Presbyopia—An Ex Vivo Pilot Study},
   journal = {TVST},
   volume = {9(7)},
  keywords = { presbyopia correction; corneal filler; refractive surgery; femtosecond laser; hyaluronic acid; bifocality},

   pages = {30-30},
   ISSN = {2164-2591},
   
   url = {https://doi.org/10.1167/tvst.9.7.30},
   year = {2020},
   type = {Journal Article}
}

@article{Wertheimer2020,
author = {Wertheimer, C M; Brandt, K; Kaminsky, S; Elhardt, C; Kassumeh, S A; Pham, L; Schulz-Hildebrandt, H; Priglinger, S; Anderson, R R and Birngruber, R},

url = {https://www.healio.com/ophthalmology/journals/jrs/2020-6-36-6/%7B8e6aaf40-922c-4998-9c7b-39b47135ec61%7D/refractive-changes-after-corneal-stromal-filler-injection-for-the-correction-of-hyperopia},
journal = {J Refractive Surg},
number = {6(36)},
pages = {406--413},
title = {Refractive Changes After Corneal Stromal Filler Injection for the Correction of Hyperopia},

date = {2020-06-14},
year = {2020},
keywords ={mOCT, HSH}
}

@article{Birngruber2020,
   author = {Elhardt, C;Wertheimer, C M.;Wartak, A;Zhao, J;Leung, H M;Kassumeh, S A.;Yin, B;Tearney, G J. and Birngruber, R},
   title = {Stromal Nerve Imaging and Tracking Using Micro-Optical Coherence Tomography},
   journal = {Translational Vision Science & Technology},
   volume = {9(5)},
  
   pages = {6-6},
   ISSN = {2164-2591},
   Keywords = {optical coherence tomography; micro-OCT; imaging;corneal nerves; diabetes},
   url = {https://doi.org/10.1167/tvst.9.5.6},
   year = {2020},
   type = {Journal Article}
}

@inproceedings{10.1117/12.2507866,
author = {Jan Philip Kolb and Daniel Weng and Hubertus Hakert and Matthias Eibl and Wolfgang Draxinger and Tobias Meyer and Thomas Gottschall and Ralf  Brinkmann and Reginald Birngruber and J{\"u}rgen Popp and Jens Limpert and Sebastian Nino Karpf and Robert Huber},
title = {{Virtual HE histology by fiber-based picosecond two-photon microscopy}},
volume = {10882},
booktitle = {Multiphoton Microscopy in the Biomedical Sciences XIX},
editor = {Ammasi Periasamy and Peter T. C. So and Karsten K{\"o}nig},
organization = {International Society for Optics and Photonics},
publisher = {SPIE},
pages = {108822F},
abstract = {Two-Photon Microscopy (TPM) can provide three-dimensional morphological and functional contrast in vivo. Through proper staining, TPM can be utilized to create virtual, HE equivalent images and thus can improve throughput in histology-based applications. We previously reported on a new light source for TPM that employs a compact and robust fiber-amplified, directly modulated laser. This laser is pulse-to-pulse wavelength switchable between 1064 nm, 1122 nm, and 1186 nm with an adjustable pulse duration from 50ps to 5ns and arbitrary repetition rates up to 1MHz at kW-peak powers. Despite the longer pulse duration, it can achieve similar average signal levels compared to fs-setups by lowering the repetition rate to achieve similar cw and peak power levels. The longer pulses lead to a larger number of photons per pulse, which yields single shot fluorescence lifetime measurements (FLIM) by applying a fast 4 GSamples/s digitizer. In the previous setup, the wavelengths were limited to 1064 nm and longer. Here, we use four wave mixing in a non-linear photonic crystal fiber to expand the wavelength range down to 940 nm. This wavelength is highly suitable for imaging green fluorescent proteins in neurosciences and stains such as acridine orange (AO), eosin yellow (EY) and sulforhodamine 101 (SR101) used for histology applications. In a more compact setup, we also show virtual HE histological imaging using a direct 1030 nm fiber MOPA.},
keywords = {Multiphoton Microscopy, Four Wave Mixing, FWM, Histology, Laser, Non Linear Microscopy, Two Photon Microscopy, JenLab Young Investigator Award},
year = {2019},
doi = {10.1117/12.2507866},
URL = {https://doi.org/10.1117/12.2507866}
}

@article{seifert2018,
   author = {Seifert, E; Tode, J; Pielen, A; Theisen-Kunde, D; Framme, C; Roider, J; Miura, Y; Birngruber, R and Brinkmann, R},
   title = {Selective retina therapy: toward an optically controlled automatic dosing},
   journal = {J Biomed Opt},
   
   pages = {1-12},
   ISSN = {1560-2281 (Electronic)
1083-3668 (Linking)},
   DOI = {10.1117/1.JBO.23.11.115002},   
keywords = {algorithm, lasers in medicine, ophthalmology, retinal pigment epithelium, selective retina therapy, selectivity},
   year = {2018},
   type = {Journal Article}
}

@article{Sudkamp2018a,
   author = {Sudkamp, H; Hillmann, D; Koch, P;vom Endt, M; Spahr, H; Münst, M; Pfäffle, C; Birngruber, R and Hüttmann, G},
   title = {Simple approach for aberration-corrected OCT imaging of the human retina},
   journal = {Opt Lett},
   
   pages = {4224},
   ISSN = {0146-9592
1539-4794},
   DOI = {10.1364/ol.43.004224},
   year = {2018},
   type = {Journal Article},
   keyword = {Retome}
}

@article{Baade2017,
   author = {Baade, A; von der Burchard, C; Lawin, M; Koinzer, S; Schmarbeck, B; Schlott, K; Miura, Y; Roider, J; Birngruber, R and Brinkmann, R},
   title = {Power-controlled temperature guided retinal laser therapy},
   journal = {J Biomed Opt},
   
   pages = {1-11},
   ISSN = {1083-3668},
   DOI = {10.1117/1.jbo.22.11.118001},
   year = {2017},
   type = {Journal Article}
}

@article{RN4897,
   author = {Sudkamp, Helge and Koch, Peter and Spahr, Hendrik and Hillmann, Dierck and Franke, Gesa and Münst, Michael and Reinholz, Fred and Birngruber, Reginald and Hüttmann, Gereon},
   title = {In-vivo retinal imaging with off-axis full-field time-domain optical coherence tomography},
   journal = {Optics Letters},
   volume = {41},
   number = {21},
   pages = {4987-4990},
   DOI = {10.1364/OL.41.004987},
   url = {http://ol.osa.org/abstract.cfm?URI=ol-41-21-4987},
   year = {2016},
   type = {Journal Article}
}

@article{Wang2015,
   author = {Wang, S. and Huttmann, G. and Zhang, Z. and Vogel, A. and Birngruber, R. and Tangutoori, S. and Hasan, T. and Rahmanzadeh, R.},
   title = {Light-Controlled Delivery of Monoclonal Antibodies for Targeted Photoinactivation of Ki-67},
   journal = {Mol Pharm},
   note = {1543-8392
Wang, Sijia
Huttmann, Gereon
Zhang, Zhenxi
Vogel, Alfred
Birngruber, Reginald
Tangutoori, Shifalika
Hasan, Tayyaba
Rahmanzadeh, Ramtin
Journal article
Mol Pharm. 2015 Aug 13.},
   abstract = {The selective inhibition of intracellular and nuclear molecules such as Ki-67 holds great promise for the treatment of cancer and other diseases. However, the choice of the target protein and the intracellular delivery of the functional agent remain crucial challenges. Main hurdles are (a) an effective delivery into cells, (b) endosomal escape of the delivered agents, and (c) an effective, externally triggered destruction of cells. Here we show a light-controlled two-step approach for selective cellular delivery and cell elimination of proliferating cells. Three different cell-penetrating nano constructs, including liposomes, conjugates with the nuclear localization sequence (NLS), and conjugates with the cell penetrating peptide Pep-1, delivered the light activatable antibody conjugate TuBB-9-FITC, which targets the proliferation associated protein Ki-67. HeLa cells were treated with the photosensitizer benzoporphyrin monoacid derivative (BPD) and the antibody constructs. In the first optically controlled step, activation of BPD at 690 nm triggered a controlled endosomal escape of the TuBB-9-FITC constructs. In more than 75% of Ki-67 positive, irradiated cells TuBB-9-FITC antibodies relocated within 24 h from cytoplasmic organelles to the cell nucleus and bound to Ki-67. After a second light irradiation at 490 nm, which activated FITC, cell viability decreased to approximately 13%. Our study shows an effective targeting strategy, which uses light-controlled endosomal escape and the light inactivation of Ki-67 for cell elimination. The fact that liposomal or peptide-assisted delivery give similar results leads to the additional conclusion that an effective mechanism for endosomal escape leaves greater variability for the choice of the delivery agent.},
   keywords = {endosomal entrapment
liposome
nanotechnology
nuclear localization sequence (NLS)
photodynamic therapy},
   ISSN = {1543-8384},
   DOI = {10.1021/acs.molpharmaceut.5b00260},
   year = {2015},
   type = {Journal Article}
}

@article{Hüttmann2015,
   author = {Huttmann, Gereon and Koinzer, Stefan Otto Johannes and Müller, Heike and Ellerkamp, Iris and Baade, Alex and Moltmann, Moritz and Theisen-Kunde, Dirk and Lange, Birgit and Brinkmann, Ralf and Birngruber, Reginald},
   title = {Predicting ophthalmoscopic visibility of retinal photocoagulation lesions byhigh-speedOCT: an animal studyinrabbits},
   journal = {Investigative Ophthalmology & Visual Science},
   volume = {56},
   number = {7},
   pages = {5980-5980},
   ISSN = {1552-5783},
   year = {2015},
   type = {Journal Article}
}

@inproceedings{Baade2013,
   author = {Baade, Alexander and Schlott, Kerstin and Birngruber, Reginald and Brinkmann, Ralf},
   title = {A numerical model for heat and pressure propagation for temperature controlled retinal photocoagulation},
   volume = {8803},
   pages = {88030O-88030O-9},
   note = {10.1117/12.2033590},
   abstract = {Retinal photocoagulation is an established treatment for various retinal diseases. The temperature development during a treatment can be monitored by applying short laser pulses in addition to the treatment laser light. The laser pulses induce thermoelastic pressure waves that can be detected at the cornea. We present a numerical model to examine the temperature development during the treatment as well as the formation and propagation of the ultrasonic waves. Using the model, it is possible to determine the peak temperature during retinal photocoagulation from the measured signal, and investigate the behaviour of the temperature profile and the accuracy of the temperature determination under varying conditions such as inhomogeneous pigmentation or change in irradiation parameters. It was shown that there is an uncertainty of 2.5 -9% in the determination of the peak temperature when the absorption coefficient between the absorbing layers is varied by a factor of 2. Furthermore the model was extended in order to incorporate the photoacoustic pressure generation and wave propagation. It was shown that for an irradiation pulse duration of 75 ns the resulting pressure wave energy is attenuated by 76 % due to frequency dependent attenuation in water.},
   url = {http://dx.doi.org/10.1117/12.2033590},
   type = {Conference Proceedings}, 
year = { 2013}
}

@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}
}

@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}
}

@article{Framme2008,
   author = {Framme, C. and Roider, J. and Brinkmann, R. and Birngruber, R. and Gabel, V. P.},
   title = {Basic principles and clinical application of retinal laser therapy},
   journal = {Klinische Monatsblatter Fur Augenheilkunde},
   volume = {225},
   number = {4},
   pages = {259-268},
   note = {301AZ
Times Cited:3
Cited References Count:39},
   abstract = {The scientific background of laser photocoagulation of the ocular fundus was studied extensively by several investigators in the 1970 s and 1980 s. The basic principles were succesfully resolved during that time and clinical consequences for proper application of the laser photocoagulation for various diseases were deduced. The present paper gives an overview about the physical basics of laser-tissue interactions during and after retinal laser treatment and the particular laser strategies in the treatment of different retinal diseases. Thus, it addresses the issue of the impact on tissue of laser parameters as wavelength, spot size, pulse duration and laser power. Additionally, the different biological tissue reactions after laser treatment are presented, such as, e.g., for retinopexia or macular treatments as well as for diabetic retinopathies. Specific laser strategies such as the selective laser treatment of the RPE (SRT) or the transpupillary thermotherapy (TTT) are presented and discussed.},
   keywords = {retina
anatomy
vitreous
subfoveal choroidal neovascularization
central vein occlusion
transpupillary thermotherapy
macular degeneration
pigment epithelium
photocoagulation
argon
trial
rpe
diseases},
   ISSN = {0023-2165},
   DOI = {DOI 10.1055/s-2008-1027202},
   url = {<Go to ISI>://WOS:000255870100001},
   year = {2008},
   type = {Journal Article}
}

@article{Birngruber2001,
   author = {Arnold, J. and Kilmartin, D. and Olson, J. and Neville, S. and Robinson, K. and Birngruber, R. and  Laird, A. and Richmond, C. and Farrow, A. and McKay, S. and Saperstein, D. A. and Aaberg, T. M. and Johnson, J. B. and Waldron, R. and Loupe, D. and Gillman, J. and Myles, B. and Schachat, A. P. and Bressler, N. M. and Bressler, S. B. and Nesbitt, P. and Porter, T. and Hawse, P. and Hartnett, M. and Eager, A. and Belt, J. and Cain, D. and Emmert, D. and George, T. and Herring, M. and McDonald, J. and Mones, J. and Corcostegui, B. and Gilbert, M. and Duran, N. and Sisquella, M. and Nolla, A. and Margalef, A. and Miller, J. W. and Gragoudas, E. S. and Lane, A. M. and Emmanuel, N. and Holbrook, A. and Evans, C. and Lord, U. S. and Walsh, D. K. and Callahan, C. D. and DuBois, J. L. and Lewis, H. and Kaiser, P. K. and Holody, L. J. and Lesak, E. and Lichterman, S. and Siegel, H. and Fattori, A. and Ambrose, G. and Fecko, T. and Ross, D. and Burke, S. and Singerman, L. and Zegarra, H. and Novak, M. and Bartel, M. and Tilocco-DuBois, K. and Iic, M. and Schura, S. and Mayes, S. J. and Tanner, V. and Rowe, P. and Smith-Brewer, S. and Kukula, D. and Greanoff, G. and Daley, G. and DuBois, J. and Lehnhardt, D. and Fish, G. E. and Jost, B. F. and Anand, R. and Callanan, D. and Arceneaux, S. and Arnwine, J. and Ellenich, P. and King, J. and Aguado, H. and Rollins, R. and Jurklies, B. and Pauleikhoff, D. and Hintzmann, A. and Fischer, M. and Sowa, C. and Behne, E. and Pournaras, C. J. and Donati, G. and Kapetanios, A. D. and Cavaliere, K. and Guney-Wagner, S. and Gerber, N. and Sickenberg, M. and Sickenberg, V. and Gans, A. and Hosner, B. and others },
   title = {Photodynamic therapy of subfoveal choroidal neovascularization in pathologic myopia with verteporfin - 1-year results of a randomized clinical trial - VIP report no. 1},
   journal = {Ophthalmology},
   volume = {108},
   number = {5},
   pages = {841-852},
   note = {425WW
Times Cited:272
Cited References Count:12},
   abstract = {Objective: To determine if photodynamic therapy with verteporfin (Visudyne; CIBA Vision Corp, Duluth, GA) can improve the chance of stabilizing or improving vision (<8 letter loss) safely in patients with subfoveal choroidal neovascularization (CNV) caused by pathologic myopia.
Design: Multicenter, double-masked, placebo-controlled, randomized clinical trial at 28 ophthalmology practices in Europe and North America.
Participants: One hundred twenty patients with subfoveal CNV caused by pathologic myopia with a greatest linear dimension no more than 5400 <mu>m and best-corrected visual acuity (Snellen equivalent) of approximately 20/100 or better.
Intervention: Patients were randomly assigned (2:1) to verteporfin (6 mg per square meter of body surface area; n = 81) or placebo (5% dextrose in water, n = 39) administered via intravenous infusion of 30 ml over 10 minutes. Fifteen minutes after the start of the infusion, a laser light at 689 nm was delivered at an intensity of 600 mW/cm(2) over 83 seconds to give a light dose of 50 J/cm(2) to a round spot size on the retina with a diameter of 1000 mum larger than the greatest linear dimension of the choroidal neovascular lesion. At follow-up examinations every 3 months, retreatment with either verteporfin or placebo (as assigned at baseline) was applied to areas of fluorescein leakage if present.
Main Outcome Measures: The primary outcome was the proportion of eyes at the follow-up examination 12 months after study entry with fewer than eight letters (approximately 1.5 lines) of visual acuity lost, adhering to an intent-to-treat analysis.
Results: At baseline, move than 90% of each group had evidence of classic CNV (regardless of whether occult CNV was present) and only 12 (15%) and 5 (13%) cases in the verteporfin and placebo groups, respectively, had occult CNV (regardless of whether classic CNV was present). Seventy-nine of the 81 verteporfin-treated patients (98%) compared with 36 of the 39 placebo-treated patients (92%) completed the month 12 examination. Visual acuity, contrast sensitivity, and fluorescein angiographic outcomes were better in the verteporfin-treated eyes than in the placebo-treated eyes at every follow-up examination through the month 12 examination. At the month 12 examination, 58 (72%) of the verteporfin-treated patients compared with 17 (44%) of the placebo-treated patients lost fewer than eight letters (P < 0.01), including 26 (32%) versus 6 (15%) improving at least five letters (<greater than or equal to>1 line). Seventy (86%) of the verteporfin-treated patients compared with 26 (67%) of the placebo-treated patients lost fewer than 15 letters (P = 0.01), Few ocular or other systemic adverse events were associated with verteporfin therapy compared with placebo treatment.
Conclusions: Because photodynamic therapy with verteporfin can safely increase the chance of stabilizing or improving vision in patients with subfoveal CNV from pathologic myopia compared with a placebo, we recommend ophthalmologists consider verteporfin therapy for treatment of such patients. Ophthalmology 2001; 108:841-852 (C) 2001 by the American Academy of Ophthalmology.},
   ISSN = {0161-6420},
   url = {<Go to ISI>://WOS:000168315500020},
   year = {2001},
   type = {Journal Article}
}

@article{Birngruber2001,
   author = {Arnold, J. and Kilmartin, D. and Olson, J. and Neville, S. and Robinson, K. and Laird, A. and Richmond, C. and Farrow, A. and McKay, S. and McKechnie, R. and Evans, G. and Aaberg, T. M. and Brower, J. and Waldron, R. and Loupe, D. and Gillman, J. and Myles, B. and Saperstein, D. A. and Schachat, A. P. and Bressler, N. M. and Bressler, S. B. and Nesbitt, P. and Porter, T. and Hawse, P. and Harnett, M. and Eager, A. and Belt, J. and Cain, D. and Emmert, D. and George, T. and Herring, M. and McDonald, J. and Mones, J. and Corcostegui, B. and Gilbert, M. and Duran, N. and Sisquella, M. and Nolla, A. and Margalef, A. and Miller, J. W. and Gragoudas, E. S. and Lane, A. M. and Emmanuel, N. and Holbrook, A. and Evans, C. and Lord, U. S. and Walsh, D. K. and Callahan, C. D. and DuBois, J. L. and Moy, J. and Kenney, A. G. and Milde, I. and Platz, E. S. and Lewis, H. and Kaiser, P. K. and Holody, L. J. and Lesak, E. and Lichterman, S. and Siegel, H. and Fattori, A. and Ambrose, G. and Fecko, T. and Ross, D. and Burke, S. and Conway, J. and Singerman, L. and Zegarra, H. and Novak, M. and Bartel, M. and Tilocco-DuBois, K. and Ilc, M. and Schura, S. and Joyce, S. and Tanner, V. and Rowe, P. and Smith-Brewer, S. and Greanoff, G. and Daley, G. and DuBois, J. and Lehnhardt, D. and Kukula, D. and Fish, G. E. and Jost, B. F. and Anand, R. and Callanan, D. and Arceneaux, S. and Arnwine, J. and Ellenich, P. and King, J. and Aguado, H. and Rollins, R. and Anderson, T. and Nork, C. and Duignan, K. and Boleman, B. and Jurklies, B. and Pauleikhoff, D. and Hintzmann, A. and Fischer, M. and Sowa, C. and Birngruber, R. and others },
   title = {Verteporfin therapy of subfoveal choroidal neovascularization in age-related macular degeneration: Two-year results of a randomized clinical trial including lesions with occult with no classic choroidal neovascularization-verteporfin in photodynamic therapy report 2},
   journal = {American Journal of Ophthalmology},
   volume = {131},
   number = {5},
   pages = {541-560},
   note = {431AN
Times Cited:579
Cited References Count:9},
   abstract = {PURPOSE: To determine if photodynamic therapy with verteporfin (Visudyne; Novartis AG, Bulach, Switzerland), termed verteporfin therapy, can safely reduce the risk of vision loss compared with a placebo (with sham treatment) in patients with subfoveal choroidal neovascularization caused by age-related macular degeneration who were identified with a lesion composed of occult with no classic choroidal neovascularization, or with presumed early onset classic choroidal neovascularization with good visual acuity letter score,
METHODS: This was a double-masked, placebo controlled (sham treatment), randomized, multicenter clinical trial involving 28 ophthalmology practices in Europe and North America. The study population was patients with age related macular degeneration, with subfoveal choroidal neovascularization lesions measuring no greater than 5400 mum in greatest linear dimension with either 1) occult with no classic choroidal neovascularization, best-corrected visual acuity score of at least 50 (Snellen equivalent approximately 20/100), and evidence of hemorrhage or recent disease progression; or 2) evidence of classic choroidal neovascularization with a best-corrected visual acuity score of at least 70 (better than a Snellen equivalent of approximately 20/40); assigned randomly (2:1) to verteporfin therapy or placebo therapy. Verteporfin (6 mg per square meter of body surface area) or placebo (5% dextrose in water) was administered by means of intravenous infusion of 30 mi over 10 minutes. Fifteen minutes after the start of the infusion, a laser light at 689 nm delivered 50 J/cm(2) by application of an intensity of 600 mW/cm(2) over 83 seconds using a spot size with a diameter 1000 mum larger than the greatest linear dimension of the choroidal neovascularization lesion on the retina. At follow-up examinations every 3 months, retreatment with the same regimen was applied if angiography showed fluorescein leakage. The main outcome measure was at least moderate vision loss, that is, a loss of at least 15 letters (approximately 3 lines), adhering to an intent-to treat analysis with the last observation carried forward to impute for missing data.
RESULTS: Two hundred ten (93%) and 193 (86%) of the 225 patients in the verteporfin group compared with 104 (91%) and 99 (87%) of the 114 patients in the placebo group completed the month 12 and 24 examinations, respectively. On average, verteporfin-treated patients received five treatments over the 24 months of follow-up. The primary outcome was similar for the verteporfin-treated and the placebo-treated eyes through the month 12 examination, although a number of secondary visual and angiographic outcomes significantly favored the verteporfin-treated group. Between the month 12 and 24 examinations, the treatment benefit grew so that by the month 24 examination, the vertepor-fin-treated eyes were less likely to have moderate or severe vision loss. Of the 225 verteporfin-treated patients, 121 (54%) compared with 76 (67%) of 114 placebo-treated patients lost at least 15 letters (P =.023). Likewise, 61 of the verteporfin-treated patients (30%) compared with 54 of the placebo-treated patients (47%) lost at least 30 letters (P = .001). Statistically significant results favoring verteporfin therapy at the month 24 examination were consistent between the total population and the subgroup of patients with a baseline lesion composition identified as occult choroidal neovascularization with no classic choroidal neovascularization, This subgroup included 166 of the 225 verteporfin-treated patients (74%) and 92 of the 114 placebo-treated patients (81%). In these patients, 91 of the verteporfin-treated group (55%) compared with 63 of the placebo-treated group (68%) lost at least 15 letters (P =.032), whereas 48 of the verteporfin-treated group (29%) and 43 of the placebo-treated group (47%) lost at least 30 letters (P =.004). Other secondary outcomes, including visual acuity letter score worse than 34 (approximate Snellen equivalent of 20/200 or worse), mean change in visual acuity letter score, development of classic choroidal neovascularization, progression of classic choroidal neovascularization and size of lesion, favored the verteporfin-treated group at both the month 12 and month 24 examination for both the entire study group and the subgroup of cases with occult with no classic choroidal neovascularization at baseline. Subgroup analyses of lesions composed of occult with no classic choroidal neovascularization at baseline suggested that the treatment benefit was greater for patients with either smaller lesions (4 disc areas or less) or lower levels of visual acuity (letter score less than 65, an approximate Snellen equivalent of 20/50(-1) or worse) at baseline. Prospectively planned multivariable analyses confirmed that these two baseline variables affected the magnitude of treatment benefit. Of the 123 verteporfin-treated patients and 64 placebo-heated patients with either visual acuity score Less than 65 or lesion size 4 disc areas or less at baseline, 60 (49%) and 48 (75%) lost at least 15 letters (P < .001), respectively, and 26 (21%) and 31 (48%) lost at least 30 letters (P <.001), respectively, at the month 24 examination. Conversely, treatment may not be beneficial for patients with both larger lesions and good visual acuity (both greater than 4 disc areas and letter score 65 or greater, an approximate Snellen equivalent of 20/50 or better). With respect to safety for the entire study group, 10 of 225 verteportin-treated patients (4.
4%) and none of the placebo-treated patients had a severe decrease of vision (at least 20 letters compared with the visual acuity just before the treatment) within 7 days after treatment, judged to be the result of the development of subretinal pigment epithelial blood, marked subretinal fluid associated with choroidal hypofluorescence, or no obvious cause. Five of these 10 patients had recovery of vision to less than a 20-letter loss compared with the pretreatment vision score at 3 months after this event. Photosensitivity reactions occurred in only one patient in each group.
CONCLUSIONS: In this trial of patients with agerelated macular degeneration and subfoveal choroidal neovascularisation lesions composed of occult with no classic choroidal neovascularization, verteporfin therapy significantly reduced the risk of moderate and severe visual acuity loss. Subgroup analyses suggest that a greater benefit was achieved in patients presenting with either smaller lesions (4 disc areas or less) or lower levels of visual acuity (letter score less than 65, an approximate Snellen equivalent of 20/50(-1) or less). The Verteporfin In Photodynamic Therapy Study Group recommends that this therapy should be considered for the treatment of patients with age-related macular degeneration with subfoveal lesions composed of occult with no classic choroidal neovascularization who are presumed to have recent disease progression. Patients to be treated should be aware of a small (4%) risk of acute, severe vision decrease.<(c)> 2001 by Elsevier Science Inc. All rights reserved.).},
   ISSN = {0002-9394},
   url = {<Go to ISI>://WOS:000168609900001},
   year = {2001},
   type = {Journal Article}
}

@article{Sickenberg,
   author = {Sickenberg, M. and Schmidt-Erfurth, U. and Miller, J. W. and Pournaras, C. J. and Zografos, L. and Piguet, B. and Donati, G. and Laqua, H. and Barbazetto, I. and Gragoudas, E. S. and Lane, A. M. and Birngruber, R. and van den Bergh, H. and Strong, H. A. and Manjuris, U. and Gray, T. and Fsadni, M. and Bressler, N. M.},
   title = {A preliminary study of photodynamic therapy using verteporfin for choroidal neovascularization in pathologic myopia, ocular histoplasmosis syndrome, angioid streaks, and idiopathic causes},
   journal = {Arch Ophthalmol},
   volume = {118},
   number = {3},
   pages = {327-36},
year = { 2000},
url = { https://jamanetwork.com/journals/jamaophthalmology/fullarticle/412940},
   note = {0003-9950 (Print)
Case Reports
Clinical Trial
Clinical Trial, Phase I
Clinical Trial, Phase II
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't},
   abstract = {OBJECTIVE: To evaluate short-term safety and the effects on visual acuity and fluorescein angiography of single or multiple sessions of photodynamic therapy with verteporfin for choroidal neovascularization (CNV) not related to age-related macular degeneration (AMD), including pathologic myopia, the ocular histoplasmosis syndrome, angioid streaks, and idiopathic causes. DESIGN: A nonrandomized, multicenter, open-label, dose-escalation phase 1 and 2 clinical trial. SETTING: Four ophthalmic centers in Europe and North America providing retinal care. PARTICIPANTS: Thirteen patients with subfoveal CNV due to pathologic myopia, the ocular histoplasmosis syndrome, angioid streaks, or idiopathic causes. METHODS: Standardized protocol refraction, visual acuity testing, ophthalmic examinations, color photographs, and fluorescein angiograms were used to evaluate the results of photodynamic therapy treatments with verteporfin. Follow-up ranged from 12 weeks for patients who were treated once to 43 weeks for patients who were treated up to 4 times. RESULTS: Verteporfin therapy was well tolerated in patients with CNV not related to AMD. No deterioration in visual acuity was observed; most patients gained at least 1 line of vision. Reduction in the size of leakage area from classic CNV was noted in all patients as early as 1 week after verteporfin therapy, with complete absence of leakage from classic CNV in almost half of the patients. Improvement in visual acuity after verteporfin therapy was greatest (+6, +8, and +9 lines) in 3 patients with relatively poor initial visual acuity (between 20/200 and 20/800). Up to 4 treatments were found to have short-term safety even with retreatment intervals as short as 4 weeks. CONCLUSIONS: Treatment of CNV not related to AMD with verteporfin therapy achieves short-term cessation of fluorescein leakage from CNV in a small number of patients without loss of vision. Further randomized clinical trials including a larger number of patients are under way to confirm whether verteporfin therapy is beneficial for subfoveal CNV not related to AMD.},
   keywords = {Adult}
}

@article{Birngruber2000,
   author = {Birngruber, R. and Schmidt-Erfurth, U. and Teschner, S. and Noack, J.},
   title = {Confocal laser scanning fluorescence topography: a new method for three-dimensional functional imaging of vascular structures},
   journal = {Graefes Archive for Clinical and Experimental Ophthalmology},
   volume = {238},
   number = {7},
   pages = {559-565},
   note = {341NG
Times Cited:10
Cited References Count:16},
   abstract = {Three-dimensional topography of perfused vascular structures is possible via confocal laser scanning of intravascular fluorescence. The lateral resolution is given by the spot size of the scanning laser beam (optimally 10 mu m at the retina). The axial resolution, however, depends on the accuracy of detection of the surface of the fluorescent structure, which is typically one order of magnitude higher (30 mu m at the retina) than the confocal resolution. The vascular structure is stained with an appropriate fluorescent dye prior to the investigation using standard systemic dye injection. Confocal scanning of the fluorescence in planes of different depths within the vascular structure under investigation leads to a three-dimensional data set. Signal processing in eludes passive eye tracking, lateral averaging and axial determination of the surface of the fluorescent structure. The potential of this new technique is demonstrated by showing the topography of physiological vessel structures as well as of selected vascular diseases such as cone dystrophy, RPE detachment, choroidal haemangioma and retinal laser coagulation. Confocal laser angioscopic fluorescence topography (CLAFT) measures the three-dimensional surface structure of functional (perfused) vasculature and surrounding leakage. CLAFT may help to diagnose and quantify status and time course of vascular diseases.},
   keywords = {in-vivo
ophthalmoscope
therapy},
   ISSN = {0721-832X},
   DOI = {DOI 10.1007/s004179900059},
   url = {<Go to ISI>://WOS:000088596000003},
   year = {2000},
   type = {Journal Article}
}

@article{Birngruber2000,
   author = {Birngruber, R. and Schmidt-Erfurth, U. and Hasan, T.},
   title = {Photodynamische Therapie der altersbedingten Makuladegeneration - Nichtthermische Laserbestrahlung aktiviert einen hochselektiven Photosensibilisator},
   journal = {LaserOpto},
   volume = {32},
   pages = {66-70},
   year = {2000},
   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{Birngruber1999,
   author = {Birngruber, R. and Noack, J. and Schmidt-Erfurth, U.},
   title = {Confocal laserscanning fluorescence topography of chorioretinal vascular structures},
   journal = {Investigative Ophthalmology & Visual Science},
   volume = {40},
   number = {4},
   pages = {S571-S571},
   note = {178MF
3007
Times Cited:0
Cited References Count:0},
   ISSN = {0146-0404},
   url = {<Go to ISI>://WOS:000079269203007},
   year = {1999},
   type = {Journal Article}
}

@article{Wirbelauer1997,
   author = {Wirbelauer, C. and Geerling, G. and Koop, N. and Brinkmann, R. and Tungler, A. and Birngruber, R. and Laqua, H.},
   title = {Acute endothelial cell changes after laser thermal keratoplasty with a CW-IR laser diode},
   journal = {Investigative Ophthalmology & Visual Science},
   volume = {38},
   number = {4},
   pages = {2516-2516},
   note = {1
Wn186
Times Cited:0
Cited References Count:0},
   ISSN = {0146-0404},
   url = {<Go to ISI>://WOS:A1997WN18602508},
   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{Toth,
   author = {Toth, C. A. and Narayan, D. G. and Boppart, S. A. and Hee, M. R. and Fujimoto, J. G. and Birngruber, R. and Cain, C. P. and DiCarlo, C. D. and Roach, W. P.},
   title = {A comparison of retinal morphology viewed by optical coherence tomography and by light microscopy},
   journal = {Arch Ophthalmol},
   volume = {115},
   number = {11},
   pages = {1425-8},
   note = {0003-9950 (Print)
Comparative Study
Journal Article
Research Support, U.S. Gov't, Non-P.H.S.},
   abstract = {OBJECTIVE: To compare the cross-sectional images of primate retinal morphology obtained by optical coherence tomography (OCT) with light microscopy to determine the retinal components represented in OCT images. METHODS: Laser pulses were delivered to the retina to create small marker lesions in a Macaca mulatta. These lesions were used to align in vivo OCT scans and ex vivum histologic cross sections for image comparison. RESULTS: The OCT images demonstrated reproducible patterns of retinal morphology that corresponded to the location of retinal layers seen on light microscopic overlays. Layers of relative high reflectivity corresponded to horizontally aligned retinal components such as the nerve fiber layer and plexiform layers, as well as to the retinal pigment epithelium and choroid. In contrast, the nuclear layers and the photoreceptor inner and outer segments demonstrated relative low reflectivity by OCT. CONCLUSIONS: Retinal morphology and macular OCT imaging correlate well, with alignment of areas of high and low reflectivity to specific retinal and choroidal elements. Resolution of retinal structures by OCT depends on the contrast in relative reflectivity of adjacent structures. Use of this tool will enable expanded study of retinal morphology, both normal and pathologic, as it evolves in vivo.},
   keywords = {Animals
Macaca mulatta
Microscopy/*methods
Retina/*cytology
Tomography/*methods},
   year = {1997}
}