@article{RN5506,
   author = {Rahn, U.;Rahn, C. D.;Arora, S.;Ng, E.;Kozak, I.;Chhablani, J.;Miura, Y and Group, Subthreshold Laser Planning},
   title = {Variability of thermal subthreshold retinal laser treatment plans},
   journal = {Sci Rep},
   volume = {14},
   number = {1},
   pages = {22723},
   ISSN = {2045-2322},
   DOI = {10.1038/s41598-024-73763-4},
   year = {2024},
   type = {Journal Article}
}

@article{10.1159/000535930,
    author = {Lange, Clemens A. and Ohlmeier, Charlotte and Kiskämper, Anna and von Schwarzkopf, Christoph and Hufnagel, Hinrich and Gruber, Markus and Schworm, Benedikt and Brocks, Ulrike and Reinking, Franziska and Schreiner, Lisa and Miura, Yoko and Grundel, Milena and Lohmann, Tibor and Clemens, Christoph R. and Gamulescu, Maria-Andreea and Eter, Nicole and Grisanti, Salvatore and Priglinger, Siegfried and Spitzer, Martin S. and Walter, Peter and Agostini, Hansjürgen A. and Stahl, Andreas and Pauleikhoff, Laurenz J.B. and for the Retina.net CSC-Registry-Study Group},
    title = "{Clinical Landscape of Central Serous Chorioretinopathy in Germany: Retina.net CSC Registry Report Number 1}",
    journal = {Ophthalmologica},
    pages = {1-12},
    year = {2024},
    month = {02},
    abstract = "{Introduction: The German Registry of central serous chorioretinopathy (CSC) collects data on CSC patients in a nationwide multicenter approach to analyze epidemiology, risk factors, clinical presentations, as well as diagnosis and treatment patterns. Methods: In this multicenter cohort study, patients with CSC were enrolled in nine tertiary referral centers in Germany between January 2022 and June 2023. After consenting to the study, demographic data, risk factors, reported symptoms, best-corrected visual acuity (BCVA), funduscopic findings, disease severity, and diagnostic and treatment decisions were recorded and analyzed. Results: A total of 539 eyes of 411 CSC patients were enrolled in this study including 308 males (75\\%) and 103 females (25\\%). Patients were predominantly of Caucasian origin and had a mean age of 55.5 years (IQR 41.0–70.0). 28\\% of eyes were classified as acute (\\<4 months duration) CSC, 28\\% as chronic (\\>4 months duration) CSC, 21\\% as inactive CSC, 11\\% as chronic atrophic CSC, and 12\\% as CSC with secondary CNV. 128 patients (31\\%) demonstrated bilateral CSC. The most common risk factors reported were psychological stress (52\\%), smoking (38\\%), arterial hypertension (38\\%), and a history of or current use of steroids (30\\%). Most frequently encountered symptoms included decreased visual acuity (76\\%), metamorphopsia (49\\%), relative scotoma (47\\%), blurred vision (19\\%), and dyschromatopsia (9\\%). The mean logMAR BCVA on initial examination was 0.2 (≈20/30, IQR 0.2–0.4) but showed significant variation with a tendency of lower BCVA in chronic cases. At the baseline visit, 74\\% of the overall cohort received no treatment, while 19\\% underwent local treatment and only 2\\% underwent systemic treatment. Of the local therapies, anti-VEGF injections were the most frequently performed procedure (33\\%, mainly for secondary CNV), followed by micropulse laser (28\\%), focal nonpulsed laser (23\\%), verteporfin photodynamic therapy (14\\%), and nonsteroidal anti-inflammatory eye drops (2\\%). Among intravitreal anti-VEGF agents, aflibercept was used most frequently, followed by bevacizumab and ranibizumab. Conclusion: This registry represents one of the largest cohorts of European patients with CSC to date. Patient age and the proportion of women were higher than expected and bilateral active disease was lower than anticipated, highlighting that neither age nor gender should be overemphasized when diagnosing CSC. Therapeutic interventions are heterogeneous and include verteporfin photodynamic therapy, micropulse laser, and anti-VEGF injections in case of secondary CNV. }",
    issn = {0030-3755},
    doi = {10.1159/000535930},
    url = {https://doi.org/10.1159/000535930},
    eprint = {https://karger.com/oph/article-pdf/doi/10.1159/000535930/4178133/000535930.pdf},
}

@article{10.1167/tvst.13.1.24,
    author = {Sonntag, Svenja Rebecca and Klein, Britta and Brinkmann, Ralf and Grisanti, Salvatore and Miura, Yoko},
    title = "{Fluorescence Lifetime Imaging Ophthalmoscopy of Mouse Models of Age-related Macular Degeneration}",
    journal = {Translational Vision Science & Technology},
    volume = {13},
    number = {1},
    pages = {24-24},
    year = {2024},
    month = {01},
    abstract = "{   To investigate fluorescence lifetime of mouse models of age-related macular degeneration (AMD) by fluorescence lifetime imaging ophthalmoscopy (FLIO).    Two AMD mouse models, apolipoprotein E knockout (ApoE−/−) mice and NF-E2-related factor-2 knockout (Nrf2−/−) mice, and their wild-type mice underwent monthly ophthalmic examinations including FLIO from 3 months of age. After euthanasia at the age of 6 or 11 months, blood plasma was collected to determine total antioxidant capacity and eyes were enucleated for Oil red O (ORO) lipid staining of chorioretinal tissue.    In FLIO, the mean fluorescence lifetime (τm) of wild type shortened with age in both spectral channels. In short spectral channel, τm shortening was observed in both AMD models as well, but its rate was more pronounced in ApoE−/− mice and significantly different from the other strains as months of age progressed. In contrast, in long spectral channel, both model strains showed completely opposite trends, with τm becoming shorter in ApoE−/− and longer in Nrf2−/− mice than the others. Oil red O staining at Bruch's membrane was significantly stronger in ApoE−/− mice at 11 months than the other strains. Plasma total antioxidant capacity was highest in ApoE−/− mice at both 6 and 11 months.    The two AMD mouse models exhibited largely different fundus fluorescence lifetime, which might be related to the different systemic metabolic state. FLIO might be able to indicate different metabolic states of eyes at risk for AMD.    This animal study may provide new insights into the relationship between early AMD-associated metabolic changes and FLIO findings.  }",
    issn = {2164-2591},
    doi = {10.1167/tvst.13.1.24},
    url = {https://doi.org/10.1167/tvst.13.1.24},
    eprint = {https://arvojournals.org/arvo/content\_public/journal/tvst/938660/i2164-2591-13-1-24\_1706520239.75643.pdf},
}

@Article{diagnostics14040431,
AUTHOR = {Thiemann, Natalie and Sonntag, Svenja Rebecca and Kreikenbohm, Marie and Böhmerle, Giulia and Stagge, Jessica and Grisanti, Salvatore and Martinetz, Thomas and Miura, Yoko},
TITLE = {Artificial Intelligence in Fluorescence Lifetime Imaging Ophthalmoscopy (FLIO) Data Analysis—Toward Retinal Metabolic Diagnostics},
JOURNAL = {Diagnostics},
VOLUME = {14},
YEAR = {2024},
NUMBER = {4},
ARTICLE-NUMBER = {431},
URL = {https://www.mdpi.com/2075-4418/14/4/431},
ISSN = {2075-4418},
ABSTRACT = {The purpose of this study was to investigate the possibility of implementing an artificial intelligence (AI) approach for the analysis of fluorescence lifetime imaging ophthalmoscopy (FLIO) data even with small data. FLIO data, including the fluorescence intensity and mean fluorescence lifetime (τm) of two spectral channels, as well as OCT-A data from 26 non-smokers and 28 smokers without systemic and ocular diseases were used. The analysis was performed with support vector machines (SVMs), a well-known AI method for small datasets, and compared with the results of convolutional neural networks (CNNs) and autoencoder networks. The SVM was the only tested AI method, which was able to distinguish τm between non-smokers and heavy smokers. The accuracy was about 80%. OCT-A data did not show significant differences. The feasibility and usefulness of the AI in analyzing FLIO and OCT-A data without any apparent retinal diseases were demonstrated. Although further studies with larger datasets are necessary to validate the results, the results greatly suggest that AI could be useful in analyzing FLIO-data even from healthy subjects without retinal disease and even with small datasets. AI-assisted FLIO is expected to greatly advance early retinal diagnosis.},
DOI = {10.3390/diagnostics14040431}
}

@article{RN5480,
   author = {Sonntag, Svenja Rebecca;Hamann, Maximilian;Seifert, Eric;Grisanti, Salvatore;Brinkmann, Ralf and Miura, Yoko},
   title = {Detection sensitivity of fluorescence lifetime imaging ophthalmoscopy for laser-induced selective damage of retinal pigment epithelium},
   journal = {Graefe's Archive for Clinical and Experimental Ophthalmology},
   ISSN = {1435-702X},
   DOI = {10.1007/s00417-024-06449-2},
   url = {https://doi.org/10.1007/s00417-024-06449-2},
   year = {2024},
   type = {Journal Article}
}

@article{RN5490,
   author = {Kajita, Keisuke;Nishida, Mitsuhiro;Kurimoto, Yasuo;Yokota, Satoshi;Sugita, Sunao;Semba, Toshika;Shirae, Satoshi;Hayashi, Naoko;Ozaki, Atsuta;Miura, Yoko;Maeda, Akiko;Mitamura, Yoshinori;Takahashi, Masayo and Mandai, Michiko},
   title = {Graft cell expansion from hiPSC-RPE strip after transplantation in primate eyes with or without RPE damage},
   journal = {Scientific Reports},
   volume = {14},
   number = {1},
   pages = {10044},
   ISSN = {2045-2322},
   DOI = {10.1038/s41598-024-60895-w},
   url = {https://doi.org/10.1038/s41598-024-60895-w},
   year = {2024},
   type = {Journal Article}
}

@Inbook{Miura2024,
author="Miura, Yoko",
editor="Klettner, Alexa Karina
and Dithmar, Stefan",
title="Organkultur des retinalen Pigmentepithels",
bookTitle="Das Retinale Pigmentepithel -- Physiologie und Pathologie",
year="2024",
publisher="Springer International Publishing",
address="Cham",
pages="337--356",
abstract="Retinales Pigmentepithel (RPE)-Organkultur wird hier als die Erhaltung von Gewebeexplantaten, einschlie{\ss}lich des RPE-Monolayers, in einem lebenden Zustand {\"u}ber einen bestimmten Zeitraum definiert, mit dem Zweck, ein lebendes RPE zu untersuchen. Es gibt haupts{\"a}chlich zwei verschiedene Arten von RPE-Organkulturen; RPE-Choroid-Organkultur und RPE-Choroid-Sklera-Organkultur. Als Kultursystem gibt es statische und Perfusionskultursysteme. Die Kokultivierung mit der neuronalen Retina ist auch eine Option. Da Studien mit RPE-Organkultur eine vermittelnde Rolle als Br{\"u}cke zwischen in vitro und in vivo Studien einnehmen, k{\"o}nnte das richtige Wissen {\"u}ber die RPE-Organkultur f{\"u}r die Wahl des geeigneten experimentellen Modells f{\"u}r jede Studie recht hilfreich sein. In diesem Kapitel werden verschiedene Typen und Systeme von RPE-Organkulturen vorgestellt, zusammen mit ihren morphologischen und funktionellen Eigenschaften sowie Vor- und Nachteilen. Schlie{\ss}lich werden ihre m{\"o}glichen Anwendungen in der ophthalmologischen Forschung aus fr{\"u}heren und laufenden Studien vorgestellt.",
isbn="978-3-031-35055-9",
doi="10.1007/978-3-031-35055-9_18",
url="https://doi.org/10.1007/978-3-031-35055-9_18"
}

@article{https://doi.org/10.1002/lsm.23833,
author = {von der Burchard, Claus and Miura, Yoko and Stanzel, Boris and Chhablani, Jay and Roider, Johann and Framme, Carsten and Brinkmann, Ralf and Tode, Jan},
title = {Regenerative Retinal Laser and Light Therapies (RELITE): Proposal of a New Nomenclature, Categorization, and Trial Reporting Standard},
journal = {Lasers in Surgery and Medicine},
volume = {56},
number = {8},
pages = {693-708},
keywords = {nomenclature, retinal laser therapy, subvisible laser therapy},
doi = {https://doi.org/10.1002/lsm.23833},
url = {https://onlinelibrary.wiley.com/doi/abs/10.1002/lsm.23833},
eprint = {https://onlinelibrary.wiley.com/doi/pdf/10.1002/lsm.23833},
abstract = {ABSTRACT Objectives Numerous laser and light therapies have been developed to induce regenerative processes in the choroid/retinal pigment epithelium (RPE)/photoreceptor complex, leaving the neuroretina undamaged. These therapies are applied to the macula for the treatment of various diseases, most prominently diabetic maculopathy, retinal vein occlusion, central serous chorioretinopathy, and age-related macular degeneration. However, the abundance of technologies, treatment patterns, and dosimetry protocols has made understanding these therapies and comparing different approaches increasingly complex and challenging. To address this, we propose a new nomenclature system with a clear categorization that will allow for better understanding and comparability between different laser and light modalities. We propose this nomenclature system as an open standard that may be adapted in future toward new technical developments or medical advancements. Methods A systematic literature review of reported macular laser and light therapies was conducted. A categorization into a standardized system was proposed and discussed among experts and professionals in the field. This paper does not aim to assess, compare, or evaluate the efficacy of different laser or dosimetry techniques or treatment patterns. Results The literature search yielded 194 papers describing laser techniques, 50 studies describing dosimetry, 272 studies with relevant clinical trials, and 82 reviews. Following the common therapeutic aim, we propose “regenerative retinal laser and light therapies (RELITE)” as the general header. We subdivided RELITE into four main categories that refer to the intended physical and biochemical effects of temperature increase (photothermal therapy, PTT), RPE regeneration (photomicrodisruption therapy, PMT), photochemical processes (photochemical therapy, PCT), and photobiomodulation (photobiomodulation therapy, PBT). Further, we categorized the different dosimetry approaches and treatment regimens. We propose the following nomenclature system that integrates the most important parameters to enable understanding and comparability: Pattern—Dosimetry—Exposure Time/Frequency, Duty Cycle/Irradiation Diameter/Wavelength—Subcategory—Category. Conclusion Regenerative retinal laser and light therapies are widely used for different diseases and may become valuable in the future. A precise nomenclature system and strict reporting standards are needed to allow for a better understanding, reproduceable and comparable clinical trials, and overall acceptance. We defined categories for a systematic therapeutic goal-based nomenclature to facilitate future research in this field.},
year = {2024}
}

@ARTICLE{10.3389/fopht.2024.1340692,
  
AUTHOR={Pfäffle, Clara and Puyo, Léo and Spahr, Hendrik and Hillmann, Dierck and Miura, Yoko and Hüttmann, Gereon},   
	 
TITLE={Unraveling the Functional Signals of Rods and Cones in the Human Retina: Separation and Analysis},      
	
JOURNAL={Frontiers in Ophthalmology},      
	
VOLUME={4},           
	
YEAR={2024},      
	  
URL={https://www.frontiersin.org/articles/10.3389/fopht.2024.1340692},       
	
DOI={10.3389/fopht.2024.1340692},      
	
ISSN={2674-0826}   
   
}

@article{RN5446,
   author = {Sonntag, Svenja Rebecca;Kreikenbohm, Marie;Böhmerle, Giulia;Stagge, Jessica;Grisanti, Salvatore and Miura, Yoko},
   title = {Impact of cigarette smoking on fluorescence lifetime of ocular fundus},
   journal = {Scientific Reports},
   volume = {13},
   number = {1},
   pages = {11484},
   ISSN = {2045-2322},
   DOI = {10.1038/s41598-023-37484-4},
   url = {https://doi.org/10.1038/s41598-023-37484-4},
   year = {2023},
   type = {Journal Article}
}

@article{RN5362,
   author = {Yamamoto, Manabu;Miura, Yoko;Hirayama, Kumiko;Kyo, Akika;Kohno, Takeya;Theisen-Kunde, Dirk;Brinkmann, Ralf and Honda, Shigeru},
   title = {Comparative Treatment Study on Macular Edema Secondary to Branch Retinal Vein Occlusion by Intravitreal Ranibizumab with and without Selective Retina Therapy},
   journal = {Life},
   volume = {13},
   number = {3},
   pages = {769},
   ISSN = {2075-1729},
   DOI = {10.3390/life13030769},
   url = {https://www.mdpi.com/2075-1729/13/3/769},
   year = {2023},
   type = {Journal Article}
}

@inproceedings{10.1117/12.2670902,
author = {Paula Enzian and Birgit Lange and Zuzana Penxov{\'a} and Anke Leichtle and Yoko Miura and Karl-Ludwig Bruchhage and Ralf Brinkmann},
title = {{Fluorescence lifetime imaging microscopy (FLIM) of human middle ear tissue samples}},
volume = {12627},
booktitle = {Translational Biophotonics: Diagnostics and Therapeutics III},
editor = {Zhiwei Huang and Lothar D. Lilge},
organization = {International Society for Optics and Photonics},
publisher = {SPIE},
pages = {126271T},
keywords = {FLIM, autofluorescence, otitis media, cholesteatoma, middle ear, inflammation},
year = {2023},
doi = {10.1117/12.2670902},
URL = {https://doi.org/10.1117/12.2670902}
}

@article{RN5328,
   author = {Pfäffle, C;Spahr, H;Gercke, K;Puyo, L;Höhl, S;Melenberg, D;Miura, Y;Hüttmann, G and Hillmann, D},
   title = {Phase-Sensitive Measurements of Depth-Dependent Signal Transduction in the Inner Plexiform Layer},
   journal = {Frontiers in Medicine},
   volume = {9},
   ISSN = {2296-858X},
   DOI = {10.3389/fmed.2022.885187},
keywords = {optoretinography, optical coherence tomography, phase-sensitive OCT, functional imaging, inner
plexiform layer, retina},
   url = {https://www.frontiersin.org/articles/10.3389/fmed.2022.885187},
   year = {2022},
   type = {Journal Article}
}

@article{Miura2022,
   author = {Miura, Y;Inagaki, K;Hutfilz, A;Seifert, E;Schmarbeck, B;Murakami, A;Ohkoshi, K and Brinkmann, R},
   title = {Temperature Increase and Damage Extent at Retinal Pigment Epithelium Compared between Continuous Wave and Micropulse Laser Application},
   journal = {Life},
   volume = {12(9)},
  
   pages = {1313},
   ISSN = {2075-1729},
   url = {https://www.mdpi.com/2075-1729/12/9/1313},
   year = {2022},
   type = {Journal Article}
}

@inproceedings{RN5321,
   author = {Pfäffle, C;Spahr, H;Gercke, K;Burhan, S;Melenberg, D;Miura, Y;Hüttmann, G and Hillmann, D},
   title = {Phase-sensitive measurements of depth dependent signal transduction in the inner plexiform layer},
   booktitle = {SPIE BiOS},
   publisher = {SPIE},
   volume = {11623},
   url = {https://doi.org/10.1117/12.2577605},
   type = {Conference Proceedings}
}

@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{Kyo-2021,
   author = {Kyo, A.;Yamamoto, M.;Hirayama, K.;Kohno, T.;Theisen-Kunde, D.;Brinkmann, R.;Miura, Y. and Honda, S.},
   title = {Factors affecting resolution of subretinal fluid after selective retina therapy for central serous chorioretinopathy},
   journal = {Sci Rep},
   volume = {11(1)},
  
   pages = {8973},
   ISSN = {2045-2322},
   DOI = {10.1038/s41598-021-88372-8},
   year = {2021},
   type = {Journal Article}
}

@article{Miura2021-2,
   author = {Sonntag, S R;Seifert, E;Hamann, M;Lewke, B;Theisen-Kunde, D;Grisanti, S;Brinkmann, R and Miura, Y},
   title = {Fluorescence Lifetime Changes Induced by Laser Irradiation: A Preclinical Study towards the Evaluation of Retinal Metabolic States},
   journal = {Life},
   volume = {11(6)},
  keywords = {retinal laser treatment; metabolic change; fluorescence lifetime imaging ophthalmoscopy},
   pages = {555},
   ISSN = {2075-1729},
   url = {https://www.mdpi.com/2075-1729/11/6/555},
   year = {2021},
   type = {Journal Article}
}

@article{Miura-3,
   author = {Miura, Y},
   title = {Fluorescence Lifetime Imaging Ophthalmoscopy—FLIO},
   journal = {Nippon Laser Igakkaishi},
   volume = {advpub},
   DOI = {10.2530/jslsm.jslsm-42_0008},
   year = {2021},
   type = {Journal Article}
}

@article{Prasuhn2021,
   author = {Prasuhn, M;Miura, Y;Tura, A.;Rommel, Felix;Kakkassery, V;Sonntag, S;Grisanti, S and Ranjbar, M},
   title = {Influence of Retinal Microsecond Pulse Laser Treatment in Central Serous Chorioretinopathy: A Short-Term Optical Coherence Tomography Angiography Study},
   journal = {J ClinMed},
   volume = {10(11)},
   
   pages = {2418},
   ISSN = {2077-0383},
   url = {https://www.mdpi.com/2077-0383/10/11/2418},
   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{Büttner2021,
   author = {Büttner, M.;Luger, B.;Abou Moulig, W.;Junker, B.;Framme, C.;Jacobsen, C.;Knoll, K. and Pielen, A.; SRT Study Group(Brinkmann, R.; Miura, Y.)},
   title = {Selective retina therapy (SRT) in patients with therapy refractory persistent acute central serous chorioretinopathy (CSC): 3 months functional and morphological results},
   journal = {Graefes Arch Clin Exp Ophthalmol},
   volume = {259},
   number = {6},
   pages = {1401-1410},
   ISSN = {0721-832X (Print)
0721-832x},
   DOI = {10.1007/s00417-020-04999-9},
abstract = { PURPOSE: Central serous chorioretinopathy (CSC) is a disease presenting with detachment of the neurosensory retina and characteristic focal leakage on fluorescein angiography. The spontaneous remission rate is 84% within 6 months. In this study, the efficacy of selective retina therapy (SRT) was examined in patients with therapy refractory persistent acute CSC defined by symptoms for at least 6 months and persistent subretinal fluid (SRF) despite eplerenone therapy. MATERIAL AND METHODS: This is a prospective, monocentric observational study in 17 eyes (16 patients, mean age 42 years, 2 female). SRT was performed with the approved R:GEN laser (Lutronic, South Korea), a micropulsed 527-nm Nd:YLF laser device, with a train of 30 pulses of 1.7 μs at 100-Hz repetition rate at the point of focal leakage determined by fluorescein angiography (FA) at baseline (BSL). Visits on BSL, week 4 (wk4), and week 12 (wk12) included best corrected visual acuity (BCVA, logMar), central retinal thickness (CRT) on spectral domain optical coherence tomography (SD-OCT), and FA. Statistical analysis was performed by pair-by-pair comparisons of multiple observations in each case with Bonferroni correction for multiple testing. (IBM SPSS Statistics 25®). RESULTS: Mean CRT at BSL was 387.69 ± 110.4 μm. CRT significantly decreased by 106.31 μm in wk4 (95%-KI: 21.42-191.2; p = 0.01), by 133.63 μm in wk12 (95%-KI: 50.22-217.03; p = 0.001) and by 133.81 μm (95%-KI: 48.88-218.75; p = 0.001) compared to BSL. Treatment success defined as complete resolution of SRF occurred at wk4 in 7/17 eyes (35.3%) and at wk12 in 10/17 eyes (58.8%). Re-SRT was performed in 7/17 eyes (41.2%) after an average of 107.14 ± 96.59 days. Treatment success after Re-SRT was observed in 4/6 eyes (66.6%, 12 weeks after Re-SRT). Mean BCVA did not change significantly from BSL to any later timepoint after adjusting for multiple testing. Notably, eyes with treatment success showed better BCVA at all timepoints and gained more letters compared to failures. CONCLUSION: Single or repetitive SRT may be an effective and safe treatment in 2 of 3 patients suffering from acute persistent CSC after 6 months of symptoms or more. We observed complete resolution of SRF in around 60% of eyes 12 weeks after first SRT treatment and also 12 weeks after Re-SRT treatment in eyes with persistent or recurrent SRF. Results on the long-term course after SRT are still pending.},
keywords = { Central serous chorioretinopathy; Fluorescein angiography; Micropulse laser; OCT; Persistent acute disease; Selective retina treatment; Subretinal fluid. },
   year = {2021},
   type = {Journal Article}
}

@article{Miura2020-2,
   author = {Yamamoto, M;Miura, Y;Hirayama, K;;Kohno, T;Kabata, D;Theisen-Kunde, D;Brinkmann, R and Honda, S;},
   title = {Predictive factors of outcome of selective retina therapy for diabetic macular edema},
   journal = {International Ophthalmology},
   ISSN = {1573-2630},
   
   url = {https://doi.org/10.1007/s10792-020-01288-6},
   year = {2020},
   type = {Journal Article}
}

@inbook{Miura2020,
   author = {Miura, Yoko},
   title = {Retinal Pigment Epithelium Organ Culture},
   booktitle = {Retinal Pigment Epithelium in Health and Disease},
   publisher = {Springer},
   pages = {307-324},
   year = {2020},
   type = {Book Section},
URL = { https://link.springer.com/chapter/10.1007/978-3-030-28384-1_18}
}

@article{Hirayama2020,
   author = {Hirayama, K.;Yamamoto, M.;Kohno, T.;Kyo, A.;Theisen-Kunde, D.;Brinkmann, R.;Miura, Y. and Honda, S.},
   title = {Selective retina therapy (SRT) for macular serous retinal detachment associated with tilted disc syndrome},
   journal = {Graefes Arch Clin Exp Ophthalmol},
   ISSN = {0721-832x},
 volume = {259},
   pages = {387-393},
   DOI = {10.1007/s00417-020-04931-1},
   year = {2020},
   type = {Journal Article}
}

@article{yamamoto2020,
   author = {Yamamoto, M;Miura, Y;Kyo, A;Hirayama, K;Kohno, T;Theisen-Kunde, D;Brinkmann, R and Honda, S},
   title = {Selective retina therapy for subretinal fluid associated with choroidal nevus},
   journal = {Amer J Ophthalm Case Rep},
   volume = {19},
   pages = {100794},
   ISSN = {2451-9936},
keywords = {Laser therapy, Choroidal tumor, Retinal pigment epithelium, Retinal disorder},
   DOI = {https://doi.org/10.1016/j.ajoc.2020.100794},
   
   year = {2020},
   type = {Journal Article}
}

@inproceedings{10.1117/12.2527123,
author = {Yoko Miura and Wolfgang Draxinger and Christin Grill and Tom Pfeiffer and Salvatore Grisanti and Robert Huber},
title = {{MHz-OCT for low latency virtual reality guided surgery: first wet lab experiments on ex-vivo porcine eye
}},
volume = {11078},
booktitle = {Optical Coherence Imaging Techniques and Imaging in Scattering Media III},
editor = {Maciej Wojtkowski and Stephen A. Boppart and Wang-Yuhl Oh},
organization = {International Society for Optics and Photonics},
publisher = {SPIE},
pages = {110780E},
abstract = {MHz-OCT systems based on FDML swept laser sources combined with the massive parallel processing capabilities of modern computer hardware enable volumetric imaging, processing and stereoscopic display at video rates. The increasing image quality and speed might enable new fields of application where the volumetric OCT completely replaces stereoscopic microscopes instead of being a mere supplement. Aside from the depth resolving capability, a particular advantage is the ability to display a whole image volume from arbitrary points of view without the need to move the actual microscope or to rotate the patient’s eye. Purely digital microscopy is already offered as alternative to traditional through-an-eyepiece surgical microscope. We explore the use of virtual reality to present digital OCT microscopy images to a trained surgeon, carrying out a series of surgical procedures ex-vivo on a porcine eye model.},
keywords = {virtual reality, surgery guidance , real-time OCT, user experience},
year = {2019},
doi = {10.1117/12.2527123},
URL = {https://doi.org/10.1117/12.2527123}
}

@article{Miura2019-2,
   author = {Rudolf, M; Curcio, C A; Schlözer-Schrehardt, U; Sefat, A M M; Tura, A; Aherrahrou, Z; Brinkmann, M; Grisanti, S;  Miura, Y and Ranjbar, M},
   title = {Apolipoprotein A-I mimetic peptide L-4F removes Bruch's membrane lipids in aged nonhuman primates},
   journal = {Invest Ophthalmol Vis Sci},
   pages = {461-472},  
   url = {https://www.ncbi.nlm.nih.gov/pubmed/30707219},
   year = {2019},
   type = {Journal Article}
}

@article{Miura2019/3,
   
   author = {Miura, Y;Lewke, B;Hutfilz, A and Brinkmann, R},
   title = {Change in fluorescence lifetime of retinal pigment epithelium under oxidative stress},
   journal = {Nippon Ganka Gakkai Zasshi },
  
   pages = {105-114},
   url = {http://journal.nichigan.or.jp/Disp?style=abst&vol=123&year=2019&mag=0&number=2&start=105},
   year = {2019},
   type = {Journal Article}
}

@article{Miura2019,
   author = {Hirayama, K;Manabu Yamamoto, M; Takeya Kohno, T; Miura, Y; Brinkmann, R;  Shiraki,K;Theisen-Kunde, D; and Honda, S;},
   title = {Change in the Thickness of Retinal Layers after Selective Retina
Therapy (SRT) in Patients with Central Serous Chorioretinopathy},
   journal = {Osaka City Med.},
   volume = {65},
   pages = {55-63},
   url = {http://dlisv03.media.osaka-cu.ac.jp/il/meta_pub/G0000438repository_00306096-65-1-55},
   year = {2019},
   type = {Journal Article}
}

@article{Hutfilz2019,
   author = {Hutfilz, A;Sonntag, S;Lewke, B;Theisen-Kunde, D;Grisanti, S;Brinkmann, R and Miura, Y},
   title = {Fluorescence Lifetime Imaging Ophthalmoscopy of the Retinal Pigment Epithelium During Wound Healing After Laser Irradiation},
   journal = {Translational Vision Science & Technology},
   volume = {8(5)},
 
   ISSN = {2164-2591},
   DOI = {10.1167/tvst.8.5.12},
   year = {2019},
   type = {Journal Article}
}

@inbook{Miura2019,
   author = {Miura, Y;Bernstein, P S;Dysli, C;Sauer, L and Zinkernagel, M},
   title = {Fluorophores in the Eye},
   booktitle = {Fluorescence Lifetime Imaging Ophthalmoscopy},
   editor = {Zinkernagel, Martin and Dysli, Chantal},
   publisher = {Springer International Publishing},
   address = {Cham},
   pages = {35-48},
   ISBN = {978-3-030-22878-1},
Keywords = {Retinoid cycle Lipofuscin Macular pigment Collagen/elastin Redox coenzyme Melanin Lipid peroxidation endproducts Advanced glycation endproducts (AGE) },
  
   url = {https://doi.org/10.1007/978-3-030-22878-1_7},
   year = {2019},
   type = {Book Section}
}

@inproceedings{Detrez2019,
   author = {Detrez, N;Miura, Y;Seifert, E;Theisen-Kunde, D and Brinkmann, R},
   title = {Heating and optoacoustic temperature determination of cell cultures},
   publisher = {SPIE},
   volume = {11079},
   series = {European Conferences on Biomedical Optics},
booktitle =    {Proc. SPIE 11079, Medical Laser Applications
and Laser-Tissue Interactions IX},
   url = {https://doi.org/10.1117/12.2527024},
keywords = {Laser, Noninvasive thermometry, hyperthermia, temperature measurement, photoacoustics}, optoacoustics,
   year = {2019},
   type = {Conference Proceeding}
}

@book{Miura2019,
   author = {Klettner, A and  Miura, Y},
   title = {Porcine RPE/choroidal explant cultures},
   pages = {109-118 },
journal = {Weber B., Langmann T., Retinal Degeneration. Methods in Molecular Biology: 1834},
   ISBN = {978-1-4939-8669-2},
  URL = {https://doi.org/10.1007/978-1-4939-8669-9_8},
   year = {2019},
   type = {Book}
}

@article{Miura2019/4,
   author = {Miura, Y;Seifert, E;Rehra, J;Kern, K;Theisen-Kunde, D;Denton, M and Brinkmann, R},
   title = {Real-time optoacoustic temperature determination on cell cultures during heat exposure: a feasibility study},
   journal = {Int J Hyperth},
   pages = {1-7},
   ISSN = {0265-6736},
  
   url = {https://doi.org/10.1080/02656736.2019.1590653},
   year = {2019},
   type = {Journal Article}
}

@article{Pfäffle2019,
   author = {Pfäffle, C;Spahr, H;Kutzner, L;Burhan, S;Hilge, F;Miura, Y;Hüttmann, G and Hillmann, D},
   title = {Simultaneous functional imaging of neuronal and photoreceptor layers in living human retina},
   journal = {Optics Letters 44(23)},
 
   pages = {5671-5674},
   DOI = {10.1364/OL.44.005671},
   
   year = {2019},
   type = {Journal Article}
}

@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{Miura2018,
   author = {Kern, K; Mertineit, C L; Brinkmann, R and Miura, Y},
   title = {Expression of heat shock protein 70 and cell death kinetics after different thermal impacts on cultured retinal pigment epithelial cells},
   journal = {Exp Eye Res},
  
   pages = {117-126},
   ISSN = {1096-0007 (Electronic)
0014-4835 (Linking)},
   DOI = {10.1016/j.exer.2018.02.013},
   year = {2018},
   type = {Journal Article}
}

@inbook{Miura2018,
   author = {Miura, Y},
   title = {Two-Photon Microscopy (TPM) and Fluorescence Lifetime Imaging Microscopy (FLIM) of Retinal Pigment Epithelium (RPE) of Mice In Vivo},
   booktitle = {Mouse Retinal Phenotyping: Methods and Protocols},
   editor = {Tanimoto, Naoyuki},
   publisher = {Springer New York},
  
   pages = {73-88},
   ISBN = {978-1-4939-7720-8},
   url={https://doi.org/10.1007/978-1-4939-7720-8_5},
   year = {2018},
   type = {Book Section}
}

@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{Miura2017,
   author = { Ataka,S;Ogawa,S; Miura,Y; Kohno,T and Shiraki, K},
   title = {A Comparison of Intraoperative Metrics between the Infiniti with and the Centurion without Intelligent Phacoemulsification Systems},
   journal = {Journal of Eye & Cataract Surgery},
   volume = {3},
   ISSN = {2571-8300},
Abstract = {Purpose: To compare the efficiency and safety of two
phacoemulsification systems, the Infiniti with intelligent
phacoemulsification (IP) and the Centurion without IP, in
terms of intraoperative metrics of phacoemulsification and
the occurrences of adverse events and intraoperative tip
obstruction.
Design: Comparative case series.
Methods: A consecutive series of 340 eyes (151 eyes with
the Infiniti, 189 eyes with the Centurion) was evaluated. A
2.4 mm sclerocorneal incision was used with the Infiniti, and
a 2.0 mm incision was used with the Centurion.
Phacoemulsification of the nucleus was performed using
the phaco chop technique, with the IP function of the
Infiniti turned on and the IP mode of the Centurion turned
off. From among the parameters displayed on the panels of
both devices, ultrasound (US) time, cumulative dissipated
energy (CDE), aspiration time, and estimated balanced salt
solution (BSS) aspiration volume were investigated and
compared between the devices. Results: A comparison of all
subjects found significant differences between the two
devices in mean CDE (p=0.02) and mean aspiration time
(p=0.003), but not in mean US time (p=0.43) or mean
estimated BSS aspiration volume (p=0.07). For grade 3
nuclei, all parameters of mean US time (p=0.0044), mean
CDE (p ≤ 0.001), mean aspiration time (p<0.001), and mean
estimated BSS aspiration volume (p=0.001) showed
significant differences favoring the Centurion.
Conclusions: Compared to the Infiniti with IP mode, cataract
surgery with the Centurion without IP mode is likely to be
performed with less phacoemulsification energy and higher
efficiency.},
   DOI = {10.21767/2471-8300.100034},
   year = {2017},
   type = {Journal Article}
}

@article{Miura2017,
   author = {Rudolf, M; Mir Mohi Sefat, A; Miura, Y; Tura, A; Raasch, W; Ranjbar, M; Grisanti, S; Aherrahrou, Z; Wagner, A; Messinger, J D; Garber, D W; Anantharamaiah, G M and Curcio, C A},
   title = {ApoA-I Mimetic Peptide 4F Reduces Age-Related Lipid Deposition in Murine Bruch's Membrane and Causes Its Structural Remodeling},
   journal = {Curr Eye Res},
   pages = {1-12},
   ISSN = {0271-3683},
   DOI = {10.1080/02713683.2017.1370118},
   year = {2017},
   type = {Journal Article},

}

@article{Miura2017,
   author = {Miura, Y; Pruessner, J; Mertineit, C L; Kern, K; Muenter, M; Moltmann, M; Danicke, V and Brinkmann, R},
   title = {Continuous-wave Thulium Laser for Heating Cultured Cells to Investigate Cellular Thermal Effects},
   journal = {J Vis Exp},
   
   ISSN = {1940-087x},
   DOI = {10.3791/54326},
   year = {2017},
   type = {Journal Article}
  } 

@article{Ranjbar2016,
   author = {Ranjbar, M. and Brinkmann, M. P. and Zapf, D. and Miura, Y. and Rudolf, M. and Grisanti, S.},
   title = {Fc Receptor Inhibition Reduces Susceptibility to Oxidative Stress in Human RPE Cells Treated with Bevacizumab, but not Aflibercept},
   journal = {Cell Physiol Biochem},
   volume = {38},
   number = {2},
   pages = {737-47},
   note = {1421-9778
Ranjbar, Mahdy
Brinkmann, Max Philipp
Zapf, Dorinja
Miura, Yoko
Rudolf, Martin
Grisanti, Salvatore
Journal Article
Switzerland
Cell Physiol Biochem. 2016;38(2):737-47. doi: 10.1159/000443030. Epub 2016 Feb 15.},
   abstract = {BACKGROUND/AIMS: VEGF-A is induced by oxidative stress, and functions as a survival factor for various cell types, including retinal pigment epithelial (RPE) cells. Anti-vascular endothelial growth factor (VEGF) drugs like aflibercept and bevacizumab have shown to be most effective in treating neovascular age-related macular degeneration (AMD), however uptake of the drugs might lead to interference with cell physiology. Herein, we evaluated the significance of the Fc receptor (FcR) within this context and moreover explored the impact of VEGF inhibition under normal conditions as well as under oxidative stress, in terms of potential adverse effects. METHODS: ARPE-19 (human RPE) cells were treated with aflibercept and bevacizumab in presence or absence of H2O2 as oxidative stress stimulus. After 24h cells were evaluated for drug uptake, VEGF-A expression and secretion, levels of intracellular reactive oxygen species (ROS) as well as cell proliferation. Experiments were repeated with cells being pre-incubated with an FcR inhibitor prior to drug application. RESULTS: Both drugs inhibited extracellular levels of VEGF-A and were taken up into the RPE, resulting in significantly reduced intracellular levels of VEGF-A. When oxidative stress was applied, intracellular ROS levels in cells treated with both drugs rose, and cell proliferation was reduced. Prior incubation with the FcR inhibitor lessened the uptake of bevacizumab, but not aflibercept into RPE cells, and simultaneously enhanced cell survival under oxidative stress conditions. CONCLUSIONS: Our results indicate that uptake and accumulation of aflibercept and bevacizumab within RPE cells affect the intracellular VEGF-A metabolism negatively, leading to a biologically relevant reduced cell survival under oxidative stress. The FcR plays a substantial role in the uptake of bevacizumab, but not aflibercept, which allows an enhanced RPE cell survival through FcR blockage in an environment dominated by oxidative stress, as clinically significant for various inflammatory retinal disorders.},
   ISSN = {1015-8987},
   DOI = {10.1159/000443030},
   year = {2016},
   type = {Journal Article}
}

@article{Ranjbar2016,
   author = {Ranjbar, Mahdy and Brinkmann, Max Philipp and Tura, Aysegül and Rudolf, Martin and Miura, Yoko and Grisanti, Salvatore},
   title = {Ranibizumab interacts with the VEGF-A/VEGFR-2 signaling pathway in human RPE cells at different levels},
   journal = {Cytokine},
   volume = {83},
   pages = {210-216},
   abstract = {Vascular endothelial growth factor (VEGF) secreted by the retinal pigment epithelium (RPE) plays an important role in ocular homeostasis, but also in diseases, most notably age-related macular degeneration (AMD). To date, anti-VEGF drugs like ranibizumab have been shown to be most effective in treating these pathologic conditions. However, clinical trials suggest that the RPE could degenerate and perish through anti-VEGF treatment. Herein, we evaluated possible pathways and outcomes of the interaction between ranibizumab and human RPE cells (ARPE-19). Results indicate that ranibizumab affects the VEGF-A metabolism in RPE cells from an extra- as well as intracellular site. The drug is taken up into the cells, with the VEGF receptor 2 (VEGFR-2) being involved, and decreases VEGF-A protein levels within the cells as well as extracellularly. Oxidative stress plays a key role in various inflammatory disorders of the eye. Our results suggest that oxidative stress inhibits RPE cell proliferation. This anti-proliferative effect on RPE cells is significantly enhanced through ranibizumab, which does not inhibit RPE cell proliferation substantially in absence of relevant oxidative stress. Therefore, we emphasize that anti-VEGF treatment should be selected carefully in AMD patients with preexistent extensive RPE atrophy.},
   keywords = {Ranibizumab
RPE
VEGF-A
VEGFR-2
Oxidative stress},
   ISSN = {1043-4666},
   url = {http://www.sciencedirect.com/science/article/pii/S1043466616300722},
   year = {2016},
   type = {Journal Article}
}

@article{Yasui2016,
   author = {Yasui, Ayako and Yamamoto, Manabu and Hirayama, Kumiko and Shiraki, Kunihiko and Theisen-Kunde, Dirk and Brinkmann, Ralf and Miura, Yoko and Kohno, Takeya},
   title = {Retinal sensitivity after selective retina therapy (SRT) on patients with central serous chorioretinopathy},
   journal = {Graefe's Archive for Clinical and Experimental Ophthalmology},
   pages = {1-12},
   abstract = {To assess retinal sensitivity after selective retina therapy (SRT) in patients with central serous chorioretinopathy (CSCR).},
   ISSN = {1435-702X},
   url = {http://dx.doi.org/10.1007/s00417-016-3441-8},
   year = {2016},
   type = {Journal Article}
}

@article{Iwami2014,
   author = {Iwami, H. and Pruessner, J. and Shiraki, K. and Brinkmann, R. and Miura, Y.},
   title = {Protective effect of a laser-induced sub-lethal temperature rise on RPE cells from oxidative stress},
   journal = {Exp Eye Res},
   volume = {124c},
   pages = {37-47},
   note = {1096-0007
Iwami, Hisashi
Pruessner, Joachim
Shiraki, Kunihiko
Brinkmann, Ralf
Miura, Yoko
Journal article
Exp Eye Res. 2014 May 5;124C:37-47. doi: 10.1016/j.exer.2014.04.014.},
   abstract = {Recently introduced new technologies that enable temperature-controlled laser irradiation on the RPE allowed us to investigate temperature-resolved RPE cell responses. In this study we aimed primarily to establish an experimental setup that can realize laser irradiation on RPE cell culture with the similar temperature distribution as in the clinical application, with a precise time/temperature history. With this setup, we conducted investigations to elucidate the temperature-dependent RPE cell biochemical responses and the effect of transient hyperthermia on the responses of RPE cells to the secondary-exposed oxidative stress. Porcine RPE cells cultivated in a culture dish (inner diameter = 30 mm) with culture medium were used, on which laser radiation (lambda = 1940 nm, spot diameter = 30 mm) over 10 s was applied as a heat source. The irradiation provides a radially decreasing temperature profile which is close to a Gaussian shape with the highest temperature in the center. Power setting for irradiation was determined such that the peak temperature (Tmax) in the center of the laser spot at the cells reaches from 40 degrees C to 58 degrees C (40, 43, 46, 50, 58 degrees C). Cell viability was investigated with ethidium homodimer III staining at the time points of 3 and 24 h following laser irradiation. Twenty four hours after laser irradiation the cells were exposed to hydrogen peroxide (H2O2) for 5 h, followed by the measurement of intracellular glutathione, intracellular 4-hydroxynonenal (HNE) protein adducts, and secreted vascular endothelial growth factor (VEGF). The mean temperature threshold for RPE cell death after 3 h was found to be around 52 degrees C, and for 24 h around 50 degrees C with the current irradiation setting. A sub-lethal preconditioning on Tmax = 43 degrees C significantly induced the reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio, and decreased H2O2-induced increase of intracellular 4-HNE protein adducts. Although sub-lethal hyperthermia (Tmax = 40 degrees C, 43 degrees C, and 46 degrees C) caused a slight increase of VEGF secretion in 6 h directly following irradiation, secondary exposed H2O2-induced VEGF secretion was significantly reduced in the sub-lethally preheated groups, where the largest effect was seen following the irradiation with Tmax = 43 degrees C. In summary, the current results suggest that sub-lethal thermal laser irradiation on the RPE at Tmax = 43 degrees C for 10 s enhances cell defense system against oxidative stress, with increasing the GSH/GSSG ratio. Together with the results that the decreased amount of H2O2-induced 4-HNE in sub-lethally preheated RPE cells was accompanied by the lower secretion of VEGF, it is also strongly suggested that the sub-lethal hyperthermia may modify RPE cell functionality to protect RPE cells from oxidative stress and associated functional decrease, which are considered to play a significant role in the pathogenesis of age-related macular degeneration and other chorioretinal degenerative diseases.},
   ISSN = {0014-4835},
   DOI = {10.1016/j.exer.2014.04.014},
   year = {2014},
   type = {Journal Article}
}

@article{Koinzer2014,
   title        = {Comprehensive detection, grading, and growth behavior evaluation of subthreshold and low intensity photocoagulation lesions by optical coherence tomographic and infrared image analysis},
   author       = {Koinzer, S. and Caliebe, A. and Portz, L. and Saeger, M. and Miura, Y. and Schlott, K. and Brinkmann, R. and Roider, J.},
   year         = 2014,
   journal      = {Biomed Res Int},
   volume       = 2014,
   pages        = 492679,
   doi          = {10.1155/2014/492679},
   url          = {http://dx.doi.org/10.1155/2014/492679},
   note         = {2314-6141 Koinzer, Stefan Caliebe, Amke Portz, Lea Saeger, Mark Miura, Yoko Schlott, Kerstin Brinkmann, Ralf Roider, Johann Journal Article Research Support, Non-U.S. Gov't United States Biomed Res Int. 2014;2014:492679. doi: 10.1155/2014/492679. Epub 2014 May 12.},
   abstract     = {PURPOSE: To correlate the long-term clinical effect of photocoagulation lesions after 6 months, as measured by their retinal damage size, to exposure parameters. We used optical coherence tomographic (OCT)-based lesion classes in order to detect and assess clinically invisible and mild lesions. METHODS: In this prospective study, 488 photocoagulation lesions were imaged in 20 patients. We varied irradiation diameters (100/300 microm), exposure-times (20-200 ms), and power. Intensities were classified in OCT images after one hour, and we evaluated OCT and infrared (IR) images over six months after exposure. RESULTS: For six consecutive OCT-based lesion classes, the following parameters increased with the class: ophthalmoscopic, OCT and IR visibility rate, fundus and OCT diameter, and IR area, but not irradiation power. OCT diameters correlated with exposure-time, irradiation diameter, and OCT class. OCT classes discriminated the largest bandwidth of OCT diameters. CONCLUSION: OCT classes represent objective and valid endpoints of photocoagulation intensity even for "subthreshold" intensities. They are suitable to calculate the treated retinal area. As the area is critical for treatment efficacy, OCT classes are useful to define treatment intensity, calculate necessary lesion numbers, and universally categorize lesions in clinical studies.},
   type         = {Journal Article}
}

@article{Rudolf2014,
   author = {Rudolf, M. and Mohi, A. and Dettbarn, M. C. and Miura, Y. and Aherrahrou, Z. and Ranjbar, M. and Mutus, B. and Knobloch, J. K.},
   title = {Detection of esterified cholesterol in murine Bruch's membrane wholemounts with a perfringolysin O-based cholesterol marker},
   journal = {Invest Ophthalmol Vis Sci},
   volume = {55},
   number = {8},
   pages = {4759-67},
   note = {1552-5783
Rudolf, Martin
Mohi, Armin
Dettbarn, Marie C
Miura, Yoko
Aherrahrou, Zouhair
Ranjbar, Mahdy
Mutus, Bulent
Knobloch, Johannes K M
Journal Article
Research Support, Non-U.S. Gov't
United States
Invest Ophthalmol Vis Sci. 2014 Jul 1;55(8):4759-67. doi: 10.1167/iovs.14-14311.},
   abstract = {PURPOSE: To investigate the effects of Bruch's membrane (BrM) neutral lipid deposition in mouse models and its significance to aging and age-related macular degeneration, it is essential to reliably detect small quantities of neutral lipids including esterified cholesterol (EC). In chorioretinal sections and BrM wholemounts, we tested a novel fluorescent cholesterol marker based on the bacterial toxin perfringolysin O (PFO) and compared results with those obtained with the classic cholesterol dye filipin. METHODS: An engineered plasmid containing the specific cholesterol binding domain (D4) of PFO fused to green fluorescent protein (GFP) was expressed in cultured E. coli, isolated, purified, and concentrated. A total of 150 BrM-choroid wholemounts and chorioretinal sections of 11- to 13-month-old ApoE(null) mice were prepared and stained with PFO/D4-GFP or filipin for EC. Samples were examined by epifluorescence microscopy. RESULTS: The fluorescence intensity of PFO/D4-GFP was strong, stable, and, if small quantities of EC were present, superior to filipin. In all specimens, we could sharply locate the PFO/D4-GFP signal to BrM. A semiquantitative evaluation of BrM lipid deposition is possible by measuring PFO/D4-GFP fluorescence intensity. CONCLUSIONS: The use of PFO/D4-GFP allowed a robust and direct detection of EC in aged murine BrM. In wholemount samples, its strong and stable fluorescence facilitated a semiquantitative evaluation of BrM-EC content over a large area. The patterns of EC deposition in murine BrM wholemounts are comparable with findings in human BrM wholemounts. Perfringolysin O/D4-GFP could be an important tool for investigating the effects of BrM lipid deposition in mouse models.},
   keywords = {Aging/*metabolism/pathology
Animals
Bacterial Toxins
Bruch Membrane/*metabolism/ultrastructure
Cells, Cultured
Cholesterol Esters/*metabolism
Clostridium perfringens
Disease Models, Animal
Feasibility Studies
Female
Hemolysin Proteins/*diagnostic use
Humans
Macular Degeneration/*diagnosis/metabolism
Mice
Mice, Inbred C57BL
Microscopy, Electron, Transmission},
   ISSN = {0146-0404},
   DOI = {10.1167/iovs.14-14311},
   year = {2014},
   type = {Journal Article}
}

@article{Miura2014,
   author = {Yoko, Miura},
   title = {Retinal Laser Therapy: Recent Unique Developments Behind the Brilliant Front Stage of Anti-VEGF Treatment},
   journal = {J Clin Exp Ophthalmol},
   volume = {5},
   number = {6},
   pages = {1-2},
   note = {-},
   DOI = {http://dx.doi.org/10.4172/2155-9570.1000e114},
   year = {2014},
   type = {Journal Article}
}

@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{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}
}

@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{Brinkmann2012,
   author = {Brinkmann, Ralf and Koinzer, Stefan and Schlott, Kerstin and Ptaszynski, Lars and Bever, Marco and Baade, Alexander and Luft, Susanne and Miura, Yoko and Roider, Johann and Birngruber, Reginald},
   title = {Real-time temperature determination during retinal photocoagulation on patients},
   journal = {Journal of Biomedical Optics},
   volume = {17},
   number = {6},
   pages = {061219},
   note = {Journal Article},
   year = { 2012}
}

@article{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{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}
}

@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{Miura2011,
   author = {Miura, Yoko},
   title = {Retinal pigment epithelium-choroid organ culture},
   journal = {Expert Rev  Ophthalmol},
   volume = {6},
   number = {6},
   pages = {669-680},
   abstract = {The retinal pigment epithelium (RPE) plays a vital role in retinal function, and therefore studies on RPE provide a significant benefit for our visual function. In order to obtain useful information from study results, choosing the suitable experimental model for each purpose of study is of great importance. Although RPE cell cultures are widely used, cells in cell culture have significantly different phenotypical characteristics from in vivo cells. The advantage of using native tissue is that cells in the tissue have close biological properties to in vivo conditions. This review describes basic characteristics of native RPE–choroid tissues in comparison to RPE cells in cell culture and introduces the possibility of preserving tissues in different culture systems. Advantages and disadvantages of organ culture and suitable studies with recent study results are also introduced.},
   year = {2011}
}

@inproceedings{Miura2010,
   author = {Miura, Y and Huettmann, G and Orzekowsky-Schroeder, R and Steven, P and Szaszák, M and Koop, N and Brinkmann, R},
   title = {Appearance of autofluorescence in RPE cells at the rim of photocoagulation},
   booktitle = {FLIM 2010 - Symposium "Fluorescence Lifetime Imaging of the Human Retina"},
   type = {Conference Proceedings},
Year = { 2010}
}

@article{Miura2010,
   author = {Miura, Y. and Klettner, A. and Noelle, B. and Hasselbach, H. and Roider, J.},
   title = {Change of morphological and functional characteristics of retinal pigment epithelium cells during cultivation of retinal pigment epithelium-choroid perfusion tissue culture},
   journal = {Ophthalmic Res},
   volume = {43},
   number = {3},
   pages = {122-33},
   note = {1423-0259
Miura, Yoko
Klettner, Alexa
Noelle, Bernhard
Hasselbach, Heike
Roider, Johann
Journal Article
Switzerland
Ophthalmic Res. 2010;43(3):122-33. doi: 10.1159/000252979. Epub 2009 Oct 29.},
   abstract = {AIMS: To evaluate the changes of morphological and functional characteristics of the retinal pigment epithelium (RPE)-choroid perfusion culture during cultivation. METHODS: PorcineRPE-choroid tissue was cultivated in a perfusion tissue culture system. After the indicated times, histology, immunolocalization of collagen IV and von Willebrand factor, RPE cell viability with calcein-AM, TUNEL assay and occludin immunolocalization of RPE cells were examined. The tissue was treated with selective RPE treatment laser after different time periods and the wound healing response was characterized. Vascular endothelial growth factor secretion was measured by enzyme-linked immunosorbent assay. RESULTS: On day 8, prominent morphological degenerative changes of RPE cells were observed in histology. According to the immunohistochemistry for collagen IV, the Bruch's membrane did not display any obvious decomposition until day 8. Von Willebrand factor staining decreased during cultivation, especially at the choriocapillaris. Calcein-AM staining and TUNEL assay displayed the increase of apoptotic changes in only a minority of the cells on day 4, but in many cells on day 8. Occludin delocalization was observed on day 8. Selective RPE treatment laser-produced wounds were completely closed by monolayer RPE when wounded on fresh and 3-day-old cultures, but not when wounded on 6-day-old cultures. Vascular endothelial growth factor secretion was stable between days 2 and 5, but increased after that. CONCLUSION: Under the stated culture perfusion conditions, porcine RPE-choroid tissue was suitable for experimentation up to 5 days of maintenance.},
   keywords = {Animals
*Apoptosis
Bruch Membrane/pathology
Cell Survival
Choroid/metabolism/*pathology/surgery
Collagen Type IV/metabolism
Enzyme-Linked Immunosorbent Assay
Fluoresceins/metabolism
Immunoenzyme Techniques
In Situ Nick-End Labeling
Laser Therapy
Membrane Proteins/metabolism
Occludin
Organ Culture Techniques
Retinal Pigment Epithelium/metabolism/*pathology/surgery
Swine
Time Factors
Vascular Endothelial Growth Factor A/metabolism
Wound Healing
von Willebrand Factor/metabolism},
   ISSN = {0030-3747},
   DOI = { 10.1159/000252979},
   year = {2010},
   type = {Journal Article}
}

@article{Miura2010,
   author = {Miura, Y and Klettner, A and Roider, J},
   title = {VEGF antagonists decrease barrier function of retinal pigment epithelium in vitro: possible participation of intracellular glutathione},
   journal = {Invest Ophthalmol Vis Sci},
   volume = {51},
   number = {9},
   pages = {4848-55},
   note = {Miura, Yoko
Klettner, Alexa
Roider, Johann
United States
Invest Ophthalmol Vis Sci. 2010 Sep;51(9):4848-55. Epub 2010 Apr 30.},
   abstract = {PURPOSE: To investigate the influence of VEGF antagonists on the barrier function of the retinal pigment epithelium and underlying mechanisms. METHODS: Porcine RPE cells were cultured on six-well membrane inserts. The cells were exposed to bevacizumab (62.5 microg/mL) or ranibizumab (25 microg/mL) for 24 hours (short term) or 9 days (long term). Transepithelial flux of FITC-dextran and intracellular levels of reduced glutathione (GSH) at normal and low-glucose conditions were investigated at different points in time. The influence of the addition of triamcinolone acetonide (TA) was investigated. The effect of GSH depletion on RPE permeability was examined using L-buthionine sulfoximine (BSO), a gamma-glutamylcysteine synthethase inhibitor. RESULTS: After short-term exposure, VEGF antagonists increased the transepithelial flux of FITC-dextran significantly on day 2. Bevacizumab, but not ranibizumab, increased permeability up to 9 days. Under long-term exposure, both drugs enhanced permeability for 7 days; bevacizumab had the stronger effect. The addition of TA inhibited this increase. At the ninth day of short- and long-term exposure, bevacizumab-exposed cells, but not ranibizumab-exposed cells, exhibited a significantly lower GSH level. In the low-glucose condition, both drugs accelerated the decrease of intracellular GSH for the first 48 hours. GSH depletion increased the permeability of retinal pigment epithelium. TA had no effect on BSO-induced GSH depletion. CONCLUSIONS: The results suggest that bevacizumab and ranibizumab may decrease RPE barrier function, with bevacizumab exhibiting a prolonged and more profound effect. Combination with TA is thought to be beneficial because of its protective effect on stabilizing RPE junctional integrity.},
   keywords = {Angiogenesis Inhibitors/ pharmacology
Animals
Antibodies, Monoclonal/ pharmacology
Antibodies, Monoclonal, Humanized
Buthionine Sulfoximine/pharmacology
Cell Membrane Permeability/drug effects
Cells, Cultured
Dextrans/pharmacokinetics
Enzyme Inhibitors/pharmacology
Fluorescein-5-isothiocyanate/analogs & derivatives/pharmacokinetics
Glucose/pharmacology
Glutathione/ metabolism
Retinal Pigment Epithelium/cytology/ drug effects/ metabolism
Swine
Tight Junctions/drug effects/metabolism
Vascular Endothelial Growth Factor A/ antagonists & inhibitors/metabolis
AutoPhoN},
   ISSN = {1552-5783 (Electronic)
0146-0404 (Linking)},
   DOI = {10.1167/iovs.09-4699},
   year = { 2010},
   type = {Journal Article}
}

@article{Miura2009,
   author = {Miura, Y. and Roider, J.},
   title = {Triamcinolone acetonide prevents oxidative stress-induced tight junction disruption of retinal pigment epithelial cells},
   journal = {Graefes Arch Clin Exp Ophthalmol},
   volume = {247},
   number = {5},
   pages = {641-9},
   note = {Using Smart Source Parsing
May; Epub 2009 Feb 3},
   abstract = {PURPOSE: Oxidative stress is known to disrupt the integrity of retinal pigment epithelium (RPE) tight junctions. The goal of this study is to evaluate the effect of triamcinolone acetonide (TA) on the junctional integrity of RPE under oxidative stress and to identify the underlying mechanisms. METHODS: Second passage porcine RPE cells were cultured on 6-well membrane inserts until 4 weeks after reaching confluence. Cells were incubated with TA (10(-5) M) for 30 min. FITC-containing medium was added to the upper chamber (cell's apical side). The cells were then challenged with 1 mM Hydrogen Peroxide (H(2)O(2)). After 5 h, the fluorescence intensity of the medium from lower chamber (cell's basolateral side) was measured using a fluorescence spectrofluorophotometer. This transepithelial flux of FITC-dextran was measured until the 21st day. The immunolocalization of occludin and F-actin was examined with fluorescence microscope. Reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio was determined by a colorimetric assay kit. RESULTS: Non-lethal oxidative stress by H(2)O(2) increased transepithelial flux of FITC-dextran significantly. TA inhibited this increase and preserved the lower flux through the whole experimental period. This permeability change by H(2)O(2) was reversible and recovered to the normal level within 3 weeks. In immunohistological study, H(2)O(2) reduced linear occludin staining at the cell border and increased actin stress fibers. TA prevented H(2)O(2)-induced disruption of junctional assembly of occludin and F-actin. Glutathione assay demonstrated that intracellular GSH/GSSG ratio decreased significantly with H(2)O(2), while TA preserved this ratio by up-regulating GSH synthesis. CONCLUSIONS: TA has a protective effect against oxidative stress-induced disruption of RPE tight junction by preserving cellular redox state.},
   year = {2009}
}

@article{Miura2003,
   author = {Miura, Y. and Yanagihara, N. and Imamura, H. and Kaida, M. and Moriwaki, M. and Shiraki, K. and Miki, T.},
   title = {Hepatocyte growth factor stimulates proliferation and migration during wound healing of retinal pigment epithelial cells in vitro},
   journal = {Jpn J Ophthalmol},
   volume = {47},
   number = {3},
   pages = {268-75},
   note = {Miura, Yoko
Yanagihara, Nobuyo
Imamura, Hitoshi
Kaida, Mayumi
Moriwaki, Mitsuyasu
Shiraki, Kunihiko
Miki, Tokuhiko
eng
Research Support, Non-U.S. Gov't
2003/06/05 05:00
Jpn J Ophthalmol. 2003 May-Jun;47(3):268-75.},
   abstract = {PURPOSE: A defect in retinal pigment epithelial (RPE) cells may cause dysfunction of the neural retina, so rapid recovery of differentiated RPE cells is required after RPE injury. We investigated the effect of hepatocyte growth factor (HGF) on wound healing in RPE cells. METHODS: Confluent monolayers of bovine RPE cells were denuded, and the cells were allowed to recover in the presence or absence of HGF. The effect of HGF on RPE cell proliferation was evaluated by a 3-(4;5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulphophenyl)-2H-tet raz olium assay. In a migration assay, mitomycin C was used to inhibit proliferation, and the number of migrated cells was counted. The signaling pathways involved were examined using inhibitors of mitogen-activated protein kinase (MAPK), phosphatidylinositol-3 (PI3) kinase and protein kinase C pathways. RESULTS: At 80 ng/mL, HGF stimulated the wound closure of RPE monolayers and rendered the restituted cells more epithelioid in shape. HGF at 10 ng/mL stimulated RPE cell migration the most, whereas 80 ng/mL of HGF inhibited migration, but stimulated proliferation the most. In particular, PI3 kinase and MAPK inhibitor inhibited PRE cell migration and proliferation, respectively. CONCLUSIONS: HGF stimulated wound closure in cultured RPE cells, and rendered restituted cells epithelioid in shape. HGF may become a therapeutic candidate for RPE wound healing.},
   keywords = {Animals
Cattle
Cell Count
Cell Division/*drug effects
Cell Movement/*drug effects
Cells, Cultured
Enzyme Inhibitors/pharmacology
Hepatocyte Growth Factor/*pharmacology
Mitogen-Activated Protein Kinases/antagonists & inhibitors
Phosphatidylinositol 3-Kinases/antagonists & inhibitors
Pigment Epithelium of Eye/*cytology/physiology
Protein Kinase C/antagonists & inhibitors
Signal Transduction
Wound Healing/*drug effects},
   year = {2003}
}

@article{Miura2002,
   author = {Y, Miura and T, Yokoyma and H, Tabuchi and M, Yamaguchi and N, Hosoda and Y, Miyata},
   title = {Long-term outcome of juvenile-onset myasthenia ocularis treated by systemic corticosteroid. Japanese review of clinical ophthalmology. },
   journal = {Japanese Review of Clinical Ophthalmology},
   volume = {96},
   number = {11},
   pages = {1133-1135},
   year = {2002}
}

@article{Miura2001,
   author = {Obana, A and Goto, Y and Miura, Y and Wada, S and Miki, T},
   title = {Clinical findings and courses of age-related maculopathy.},
   journal = {Japanese Journal of Clinical Ophthalmology},
   volume = {55},
   number = {6},
   pages = {1229-1234},
   year = {2001}
}

@article{Miura2001,
   author = {Yanagihara, N. and Miura, Y. and Moriwaki, M. and Shiraki, K. and Imamura, H. and Kaida, M. and Miki, T.},
   title = {Hepatocyte growth factor promotes epithelial morphogenesis and occludin linkage to the cytoskeleton in cultured retinal pigment epithelial cells},
   journal = {Graefes Arch Clin Exp Ophthalmol},
   volume = {239},
   number = {8},
   pages = {619-27},
   note = {Yanagihara, N
Miura, Y
Moriwaki, M
Shiraki, K
Imamura, H
Kaida, M
Miki, T
eng
Research Support, Non-U.S. Gov't
Germany
2001/10/05 10:00
Graefes Arch Clin Exp Ophthalmol. 2001 Aug;239(8):619-27.},
   abstract = {BACKGROUND: Although hepatocyte growth factor (HGF) is also known as scatter factor, it induces epithelial morphogenesis in cultured bovine retinal pigment epithelial (RPE) cells. To elucidate the mechanism of epithelial morphogenesis, we investigated the influence of HGF on occludin, a major component of tight junctions. METHODS: RPE cells were plated on collagen type 1-coated chamber slides or dishes, 20 ng/ml HGF was added and the cells were incubated for 1 week. Cells were harvested at several time-points, and occludin expression was examined by immunohistochemistry. Detergent extraction protocols to identify the intensity of occludin linkage to the cytoskeleton were also used. Occludin expression was determined semiquantitatively by Western blotting. RESULTS: Fluorescence microscopy revealed that HGF treatment increased the levels of insoluble occludin at the cell borders after detergent extraction. These level of insoluble occludin and the associated epithelial morphology were maintained for more than 3 weeks after withdrawal of HGF, whereas cells not treated with HGF had a fibroblastic appearance. Western blotting also showed that insoluble occludin was more abundant in HGF-treated cells. Furthermore, immunoreactive bands of insoluble occludin were somewhat larger than those of soluble occludin, suggesting that insoluble occludin may be modified in comparison to soluble occludin. CONCLUSION: Our results suggest that HGF promotes linkage of occludin to the cytoskeleton. HGF may become a therapeutic candidate in physiological recovery of RPE cells and in preparation of RPE monolayers for transplantation.},
   keywords = {Animals
Blotting, Western
Cattle
Cells, Cultured
Cytoskeleton/*metabolism
Fluorescent Antibody Technique, Indirect
Hepatocyte Growth Factor/*pharmacology
Membrane Proteins/*metabolism
Microscopy, Fluorescence
Morphogenesis
Occludin
Pigment Epithelium of Eye/cytology/*drug effects/metabolism},
   year = {2001}
}

@article{Miura2001,
   author = {Obana, A and Gohto, Y and Wada, S and Miura, Y and Miki, T and Chou, A},
   title = {Surgical outcomes in removal of epimacular membranes},
   journal = { Journal of ophthalmic surgery},
   volume = {14},
   number = {2},
   pages = {253-256},
   abstract = {Removal of epiretinal membrane of the macula was performed in 49 eyes of 48 consecutive patients, and visual prognosis was analyzed retrospectively. Best-corrected visual acuity improved in 32 eyes (65%), and was unchanged in 17 eyes (35%). Metamorphopsia improved in 27 eyes (60%), and was unchanged in 18 eyes (40%). Eyes having proliferative tissue on the retinal surface after removal of epiretinal membrane showed significantly poorer improvement of metamorphopsia than those having a smooth retinal surface. However, duration of visual disturbance before surgery and preoperative visual acuity were not associated with the outcome of the metamorphopsia. Intentional peeling of the internal-limiting membrane was performed after removal of the epiretinal membrane in 17 of 40 eyes with idiopathic epiretinal membrane, and the effect of this procedure on improvement of metamorphopsia was evaluated. Internal-limiting membrane peeling did not influence the rate of improvement of metamorphopsia, however, its efficacy and safety remain to be determined in larger case series. (author abst.)},
   year = {2001}
}