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Macular choroidal thickness in Chinese preschool children: decrease with axial length but no evident change with age

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International Journal of Ophthalmology(English edition) 2019年第9期12卷 1465-1473页

作者： Xian-Gui He Jun-Jie Deng Yao Yin Bo Zhang Shu-Yu Xiong Jian-Feng Zhu Hai-Dong Zou Xun Xu Ling Wang Department of Maternal and Child Health School of Public HealthKey Laboratory of Public Health SafetyMinistry of EducationFudan UniversityShanghai 200032China Department of Preventative Ophthalmology Shanghai Eye Disease Prevention and Treatment CenterShanghai Eye HospitalShanghai 200040China Department of Ophthalmology Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai Key Laboratory of Ocular Fundus DiseasesShanghai Engineering Center for Visual Science and PhotomedicineShanghai 200080China

AIM: To explore the distribution pattern of macular choroidal thickness(ChT) and its association with age as well as refractive status in Chinese preschoolers.METHODS: School-based, cross-sectional study. A total of 550 healthy preschool children aged 3 to 6 years old from 6 kindergartens were enrolled. Comprehensive ocular examinations, including measurement of visual acuity, axial length, intraocular pressure and slit-lamp examination before cycloplegia, as well as refraction measurement and sweptsource optical coherence tomography(SS-OCT) examination after cycloplegia, were performed. The macular ChT in each sector of the ETDRS grid was measured by the builtin software of SS-OCT.RESULTS: The mean central ChT of the participants was 312±59 μm. The mean axial length and spherical equivalent refraction were 22.36±0.72 mm and 1.51±0.83 D, respectively. Axial length increased with age(P0.05). The central ChT of 3-4, 5 and 6 years old children was 314±59 μm, 312±60 μm and 312±59 μm, respectively(P=0.920). No difference was observed in ChT in most of the sectors between genders. No statistical significant difference was observed among different refractive groups(all P>0.05), though the ChT of each sector seemed to be smaller in myopic children. Axial length and weight were the independent factors of central Ch T. Children with longer axial length(β=-21.184, P<0.001) and smaller weight(β=1.502, P=0.041) tended to have thinner choroid.CONCLUSION: In preschool children, the ChT remains relatively stable with age, while a negative association between ChT and axial length existed. This will be helpful to elucidate the characteristics of ChT during the early refractive development.

关键词： preschool children choroidal thickness refractive error optical coherence tomography

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Rationally designed mariner vectors for functional genomic analysis of Actinobacillus pleuropneumoniae and other Pasteurellaceae species by transposon-directed insertion-site sequencing (TraDIS)

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Animal Diseases 2021年第4期1卷 249-261页

作者： Janine T.Bossé Yanwen Li Leon G.Leanse Liqing Zhou Roy R.Chaudhuri Sarah E.Peters Jinhong Wang Gareth A.Maglennon Matthew T.G.Holden Duncan J.Maskell Alexander W.Tucker Brendan W.Wren Andrew N.Rycroft Paul R.Langford on behalf of the BRaDPT consortium Section of Paediatric Infectious Disease Department of Infectious DiseaseImperial College LondonSt.Mary’s CampusLondonUK wellman center for photomedicine Harvard Medical SchoolBostonUSA The Applied Diagnostic Research and Evaluation Unit St George’s University of LondonLondonUK Department of Veterinary Medicine University of CambridgeCambridgeUK Department of Molecular Biology and Biotechnology University of SheffieldSheffieldUK Department of Pathology and Pathogen Biology The Royal Veterinary CollegeHatfieldUK The Wellcome Trust Sanger Institute CambridgeUK School of Medicine University of St AndrewsSt AndrewsUK The University of Melbourne ParkvilleVictoriaAustralia s Faculty of Infectious&Tropical Diseases London School of Hygiene&Tropical MedicineLondonUK

Comprehensive identification of conditionally essential genes requires efficient tools for generating high-density transposon libraries that, ideally, can be analysed using next-generation sequencing methods such as Transposon Directed Insertion-site Sequencing (TraDIS). The Himar1 (mariner) transposon is ideal for generating near-saturating mutant libraries, especially in AT-rich chromosomes, as the requirement for integration is a TA dinucleotide, and this transposon has been used for mutagenesis of a wide variety of bacteria. However, plasmids for mariner delivery do not necessarily work well in all bacteria. In particular, there are limited tools for functional genomic analysis of Pasteurellaceae species of major veterinary importance, such as swine and cattle pathogens, Actinobacillus pleuropneumoniae and Pasteurella multocida, respectively. Here, we developed plasmids, pTsodCPC9 and pTlacPC9 (differing only in the promoter driving expression of the transposase gene), that allow delivery of mariner into both these pathogens, but which should also be applicable to a wider range of bacteria. Using the pTlacPC9 vector, we have generated, for the first time, saturating mariner mutant libraries in both A. pleuropneumoniae and P. multocida that showed a near random distribution of insertions around the respective chromosomes as detected by TraDIS. A preliminary screen of 5000 mutants each identified 8 and 14 genes, respectively, that are required for growth under anaerobic conditions. Future high-throughput screening of the generated libraries will facilitate identification of mutants required for growth under different conditions, including in vivo, highlighting key virulence factors and pathways that can be exploited for development of novel therapeutics and vaccines.

关键词： Mariner Transposon TraDIS Pasteurellaceae Actinobacillus pleuropneumoniae Pasteurella multocida

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Anti-VEGF therapy prevents Müller intracellular edema by decreasing VEGF-A in diabetic retinopathy

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Eye and Vision 2021年第1期8卷 109-123页

作者： Tianqin Wang Chaoyang Zhang Hai Xie Mengmeng Jiang Haibin Tian Lixia Lu Guo-Tong Xu Lin Liu Jingfa Zhang Department of Ophthalmology Renji HospitalShanghai Jiao Tong University School of Medicine160 Pujian RoadPudong New DistrictShanghai 200127China Department of Ophthalmology Shanghai General Hospital(Shanghai First People’s Hospital)Shanghai Jiao Tong University100 Haining RoadHongkou DistrictShanghai 200080China National Clinical Research center for Eye Diseases Shanghai Key Laboratory of Ocular Fundus DiseasesShanghai Engineering Center for Visual Science and PhotomedicineShanghai Engineering Center for Precise Diagnosis and Treatment of Eye DiseasesShanghaiChina Tongji Eye Institute Tongji University School of Medicine1239 Siping RoadMedical School BuildingRoom 623Shanghai 200092China

Background:Although vascular endothelial growth factor A(VEGF-A)is known to play a key role in causing retinal edema,whether and how VEGF-A induces intracellular edema in the retina still remains unclear.Methods:Sprague-Dawley rats were rendered diabetic with intraperitoneal injection of streptozotocin.Intravitreal injection of ranibizumab was performed 8 weeks after diabetes onset.rMC-1 cells(rat Müller cell line)were treated with glyoxal for 24 h with or without ranibizumab.The expression levels of inwardly rectifying K^(+)channel 4.1(Kir4.1),aquaporin 4(AQP4),Dystrophin 71(Dp71),VEGF-A,glutamine synthetase(GS)and sodium-potassium-ATPase(Na^(+)-K^(+)-ATPase)were examined using Western blot.VEGF-A in the supernatant of the cell culture was detected with ELISA.The intracellular potassium and sodium levels were detected with specific indicators.Results:Compared with normal control,protein expressions of Kir4.1 and AQP4 were down-regulated significantly in diabetic rat retinas,which were prevented by ranibizumab.The above changes were recapitulated in vitro.Similarly,the intracellular potassium level in glyoxal-treated rMC-1 cells was increased,while the intracellular sodium level and Na^(+)-K^(+)-ATPase protein level remained unchanged,compared with control.However,ranibizumab treatment decreased intracellular sodium,but not potassium.Conclusion:Ranibizumab protected Müller cells from diabetic intracellular edema through the up-regulation of Kir4.1 and AQP4 by directly binding VEGF-A.It also caused a reduction in intracellular osmotic pressure.

关键词： Diabetic retinopathy Diabetic macular edema Müller cell Anti-VEGF Intracellular edema

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The measurement of time spent outdoors in child myopia research： a systematic review

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International Journal of Ophthalmology(English edition) 2018年第6期11卷 1045-1052页

作者： Jing Wang Xian-Gui He Xun Xu Department of Ophthalmology Shanghai General Hospital Shanghai Jiao Tong University Shanghai 200080 China Shanghai Key Laboratory of Ocular Fundus Diseases Shanghai General Hospital Shanghai Jiao Tong University Shanghai 200080 China Shanghai Engineering center for Visual Science and photomedicine Shanghai 200080 China Department of Eye Disease Prevention and Treatment Shanghai Eye Disease Prevention and Treatment Center Shanghai Eye Hospital Shanghai 200040 China Department of Matemal and Child Health School of Public Health Key Laboratory of Public Health Safety Ministry of Education Fudan University Shanghai 200032 China

The purpose of this article is to summarize the methods most commonly used to measure time spent outdoors and provide a comprehensive review of time and activity recording methods with the aim of encouraging the development of new methods. PubMed, Embase and the Cochrane Library were searched from Jan. 1st, 1990 to Aug. 31th, 2017. Studies including the following specific terms： “outdoor”, “outside”, “outdoor activity”, “outside activity”, “outdoor time”, “outside time”, and “outdoor AND measurement of time spent outdoors” were considered for this review. In total, three kinds of outdoor time measurements were discussed. Questionnaires have the longest history and are the most thoroughly revised instruments for assessing time spent outdoors, but recall bias is their most substantial drawback. Global positioning system （GPS） tracking can distinguish between indoor and outdoor locations, but its utility is limited due to several factors such as subject compatibility. Light exposure measurement devices are newly emerging, but all of these devices require good subject cooperation. Further efforts and exploration are needed to develop better methods and new tools to record exposure to the outdoors in real time. Moreover, inventing a new device by combining two or more types of devices mentioned above and using the latest technology of en ergy supplementation and autoswitching may make the best use of the advantages and bypass the disadvantages of each tool.

关键词： myopia outdoor （activity） time questionnaire global positioning system light exposure

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Is Iba-1 protein expression a sensitive marker for microglia activation in experimental diabetic retinopathy?

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International Journal of Ophthalmology(English edition) 2021年第2期14卷 200-208页

作者： Fan-Jun Shi Hai Xie Chao-Yang Zhang Hai-Feng Qin Xin-Wei Zeng Hui Lou Lei Zhang Guo-Tong Xu Jing-Fa Zhang Guo-Xu Xu Department of Ophthalmology the Second Affiliated Hospital of Soochow UniversitySuzhou 215004Jiangsu ProvinceChina Department of Ophthalmology Changzhou Laser HospitalChangzhou 213000Jiangsu ProvinceChina Tongji Eye Institute Department of Regenerative Medicineand Department of PharmacologyTongji University School of MedicineShanghai 200092China Department of Ophthalmology Shanghai General Hospital(Shanghai First People’s Hospital)Shanghai Jiao Tong UniversityShanghai 200080China National Clinical Research center for Eye Diseases Shanghai Key Laboratory of Ocular Fundus DiseasesShanghai Engineering Center for Visual Science and PhotomedicineShanghai Engineering Center for Precise Diagnosis and Treatment of Eye DiseasesShanghai 200080China

AIM:To investigate the changes of Iba-1 and other potential markers for microglia activation in experimental diabetic retinopathy(DR).METHODS:Male Sprague-Dawley rats were rendered diabetes via intraperitoneal injection of streptozotocin.The retinas were harvested at 1 to 24 wk after diabetes onset.Hypoxia-treated mouse microglial cell line(BV2 cells)was employed as the in vitro model to mimic diabetic condition.The expressions of Iba-1,CD11 b,ICAM-1 as well as the inflammatory factors were examined with real-time polymerase chain reaction,Western blot and immunofluorescence both in vivo and in vitro.RESULTS:Compared with age-matched normal control,the number of microglia(Iba-1 positive immunostaining)in diabetic rat retinas was increased from 1 to 24 wk of diabetes,which was most obvious at 12 wk of diabetes.Iba-1 protein expression detected by Western blot was increased slightly in diabetic rat retinas compared with that in age-matched normal control;however,there was statistically significant between two groups only at 2 wk after diabetes onset.The m RNA expression of Iba-1 was decreased significantly at 2 and 4 wk of diabetic rat retinas,and remained unchanged at 8 and 12 wk of diabetes.In BV2 cells,there was no significant change for the Iba-1 protein expression between normoxia and hypoxia groups;however,its m RNA level was decreased significantly under hypoxia.To further characterize microglial activation,F4/80,CD11 b and inflammatory factors were detected both in vivo and in vitro.Compared with normal control,the expressions of F4/80 and CD11 b as well as the inflammatory factors,such as ICAM-1,i NOS,COX2,IL-1βand IL-6,were increased significantly both in vivo and in vitro.CONCLUSION:Iba-1 protein expression might not be a sensitive marker to evaluate the activation of microglia in experimental DR.However,Iba-1 immunostaining,in combination with other markers like CD11 b and ICAM-1,could be well reflect the activation of microglia.Thus,it is of great importance to explore other potential marker to evaluat

关键词： microglia activation Iba-1 diabetic rats diabetic retinopathy

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A rare synchrony of adenocarcinoma of the ampulla with an ileal gastrointestinal stromal tumor: A case report

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World Journal of Gastrointestinal Oncology 2022年第11期14卷 2253-2265页

作者： Venkata Vinod Kumar Matli Gazi B Zibari Gregory wellman Poornima Ramadas Sudha Pandit James Morris Department of Internal Medicine Christus Highland Medical CenterShreveportLA 71106United States Division of Hepatobiliary Surgery Willis-Knighton Health SystemShreveportLA 711103United States Department of Gastrointestinal and Liver Pathology Christus Highland Medical CenterShreveportLA 71105United States Division of Hematology and Oncology Louisiana State University Health Sciences CenterShreveportLA 71103United States Division of Gastroenterology and Hepatology Louisiana State University Health Sciences CenterShreveportLA 71103United States

BACKGROUND This is a unique case of a patient who was found to have two extremely rare primary malignancies synchronously,i.e.,an ampullary adenocarcinoma arising from a high-grade dysplastic tubulovillous adenoma of the ampulla of Vater(TVAoA)with a high-grade ileal gastrointestinal stromal tumor(GIST).Based on a literature review and to the best of our knowledge,this is the first report of this synchronicity.Primary ampullary tumors are extremely rare,with an incidence of four cases per million population,which is approximately 0.0004%.Distal duodenal polyps are uncommon and have a preponderance of occurring around the ampulla of Vater.An adenoma of the ampulla(AoA)may occur sporadically or with a familial inheritance pattern,as in hereditary genetic polyposis syndrome such as familial adenomatous polyposis syndrome(FAPS).We report a case of a 77-year-old male who was admitted for painless obstructive jaundice with a 40-pound weight loss over a two-month period and who was subsequently diagnosed with two extremely rare primary malignancies,i.e.,an adenocarcinoma of the ampulla arising from a high-grade TVAoA and a high-grade ileal GIST found synch-ronously.CASE SUMMARY A 77-year-old male was admitted for generalized weakness with an associated weight loss of 40 pounds in the previous two months and was noted to have painless obstructive jaundice.The physical examination was benign except for bilateral scleral and palmar icterus.Lab results were significant for an obstructive pattern on liver enzymes.Serum lipase and carbohydrate antigen-19-9 levels were elevated.Computed tomography(CT)of the abdomen and pelvis and magnetic resonance cholangiopancreatography were consistent with a polypoid mass at the level of the common bile duct(CBD)and the ampulla of Vater with CBD dilatation.The same lesions were visualized with endoscopic retrograde cholangiopancreatography.Histopathology of endoscopic forceps biopsy showed TVAoA.Histopathology of the surgical specimen of the resected ampulla showed an adenocarcinoma arisin

关键词： Tubulovillous adenoma of the ampulla of Vater Ampullary adenocarcinoma Gastrointestinal stromal tumor Ampullary polyp Small bowel mesenchymal tumor Case report

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微囊肿性附件癌:4例患者用Mohs显微外科技术治疗

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世界核心医学期刊文摘（皮肤病学分册） 2005年第9期1卷 53-54页

作者： Khachemoune A. Olbricht S.M. Johnson D.S. wellman centerfor photomedicine Department of Dermatology Harvard Medical School 50 Blossom Street Boston MA 02114 United States Dr.

Background:Microcystic adnexal carcinoma (MAC) is a rare and aggressive malignant tumor of the sweat glands. Clinically, it often presents as a firm subcutaneous nodule on the head and neck regions. On histology, MAC exhibits both pilar and sweat duct differentiation with a stroma of dense collagen. It often extends beyond the clinical margins with local spreading in the dermal, subcutaneous, and perineural tissue planes. It has a high local recurrence rate after standard excision. Recent preliminary reports have indicated more favorable cure rates with Mohs’micrographic surgery (MMS). Objective:To present our data on four cases of MAC treated by MMS. We also compared our findings with more recently reported series in the English language literature. Methods:We reviewed the medical records of four patients (two males and two females) with MAC treated by MMS over the last 3 years. We also obtained follow-up data. Results:In all four patients with MAC treated by MMS, there were no recurrences, with a mean follow-up of 1 year. Conclusion:We report an additional four MAC cases treated by MMS. The accumulated data continue to confirm that, if the diagnosis of MAC is made early, and if the anatomic location is accessible to excision by MMS, a favorable outcome can be expected.

关键词：微囊肿性附件癌 Mohs 显微外科技术局部复发率皮损边缘皮下结节英文文献侵袭性数据分析临床资料

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Synthesis of Sn nanocluster@carbon dots for photodynamic therapy application

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Chinese Chemical Letters 2021年第7期32卷 2287-2291页

作者： Xiaolong Hu Shuna Wang Qinghua Luo Binghui Ge Qin Cheng Chen Dong Jiahui Xu Haizhen Ding Mingsheng Xu Antonio Claudio Tedesco Xin Huang Renquan Zhang Hong Bi School of Chemistry and Chemical Engineering Anhui Key Laboratory of Modem BiomanufacturingAnhui UniversityHefei 230601China Institutes of Physical Science and Information Technology Anhui UniversityHefei 230601China Department of Chemistry Center of Nanotechnology and Tissue Engineering-Photobiology and Photomedicine Research GroupFaculty of PhilosophySciences and Letters of Ribeirao PretoUniversity of Sao PauloRibeirao PretoSao Paulo 14040-901Brazil Department of Thoracic Surgery First Affiliated Hospital of Anhui Medical UniversityHefei 230032China

Recently,photodynamic therapy(PDT)has been extensively applied in clinical and coadjuvant treatment of various kinds of tumors.However,the photosensitizer(PS)of PDT still lack of high production of singlet oxygen(^(1)O_(2)),low cytotoxicity and high biocompatibility.Herein,we propose a facile method for establishing a new core-shell structured Sn nanocluster@carbon dots(CDs)PS.Firstly,Sn^(4+)@S-CDs complex is synthesized using the sulfur-doped CDs(S-CDs)and SnCl4 as raw materials,and subsequently the new PS(Sn nanocluster@CDs)is obtained after vaporization of Sn4+@S-CDs solution.Remarkably,the obtained Sn nanocluster@CDs show an enhanced fluorescence as well as a higher ^(1)O_(2) quantum yield(QY)than S-CDs.The high ^(1)O_(2) QY(58.3%)irradiated by the LED light(400-700 nm,40 mW/cm^(2)),induce the reduction of 4 T1 cancer cells viability by 25%.More intriguingly,no visible damage happens to healthy cells,with little impact on liver tissue due to renal excretion,both in vitro and in vivo experiments demonstrate that Sn nanocluster@CDs may become a promising PS,owning a high potential for application in PDT.

关键词： Sn nanocluster@CDs Photodynamic therapy Photosensitizer Biocompatibility Singlet oxygen

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Synthetic anti-angiogenic genomic therapeutics for treatment of neovascular age-related macular degeneration

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Asian Journal of Pharmaceutical Sciences 2021年第5期16卷 623-632页

作者： Jing Wang Xiang Shi Qiyu Bo Hong Wang Fang Wei Jun Liu Hao Wang Liuwei Zhang Yan Qi Zhen Li Qixian Chen Xiaodong Sun Department of Ophthalmology Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 200080China Shanghai Key Laboratory of Ocular Fundus Diseases Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 200080China Shanghai Engineering center for Visual Science and photomedicine Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 200080China National Clinical Research center for Eye Diseases Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 200080China Ningbo Hygeia Medical Technology Co. Ltd.Ningbo 315201China School of Bioengineering Dalian University of TechnologyDalian 116024China College of Pharmacy Dalian Medical UniversityDalian 116044China

In light of the intriguing potential of anti-angiogenic approach in suppressing choroidal neovascularization, we attempted to elaborate synthetic gene delivery systems encapsulating anti-angiogenic plasmid DNA as alternatives of clinical antibody-based therapeutics. Herein, block copolymer of cyclic Arg-Gly-Asp-poly(ethylene glycol)-poly(lysine-thiol) [RGD-PEG-PLys(thiol)] with multifunctional components was tailored in manufacture of core-shell DNA delivery nanoparticulates. Note that the polycationic PLys segments were electrostatically complexed with anionic plasmid DNA into nanoscaled core, and the tethered biocompatible PEG segments presented as the spatial shell(minimizing non-specific reactions in biological milieu). Furthermore, the aforementioned self-assembly was introduced with redox-responsive disulfide crosslinking due to the thiol coupling. Hence, reversible stabilities, namely stable in extracellular milieu but susceptible to disassemble for liberation of the DNA payloads in intracellular reducing microenvironment, were verified to facilitate transcellular gene transportation. In addition, RGD was installed onto the surface of the proposed self-assemblies with aim of targeted accumulation and internalization into angiogenic endothelial cells given that RGD receptors were specifically overexpressed on their cytomembrane surface. The proposed anti-angiogenic DNA therapeutics were validated to exert efficient expression of anti-angiogenic proteins in endothelial cells and elicit potent inhibition of ocular neovasculature post intravitreous administration. Hence, the present study approved the potential of gene therapy in treatment of choroidal neovascularization. In light of sustainable gene expression properties of DNA therapeutics, our proposed synthetic gene delivery system inspired prosperous potentials in long-term treatment of choroidal neovascularization, which should be emphasized to develop further towards clinical translations.

关键词： Age-related macular degeneration Anti-angiogenesis Gene therapy Polymer Vascular endothelial growth factor

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Dynamic versus static ultra-widefield fluorescein angiography in eyes with diabetic retinopathy:a pilot prospective cross-sectional study

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International Journal of Ophthalmology(English edition) 2021年第3期14卷 409-415页

作者： Hang-Qi Shen Jing Wang Tian Niu Ji-Li Chen Xun Xu Department of Ophthalmology Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 200080China Shanghai Key Laboratory of Ocular Fundus Diseases Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 200080China Shanghai Engineering center for Visual Science and photomedicine Shanghai Gencral HospitalShanghai Jiao Tong University School of MedicineShanghai 200080China Shanghai Engineering center for Precise Diagnosis and Treatment of Eye Diseases Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 200080China National Clinical Research center for Eye Diseases Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 200080China Department of Ophthalmology Shanghai Shibei Hospital of Jing'an DistrictShanghai 200435China

AIM:To analyze differences in ultra-widefield fluorescein angiography(UWFA)findings between dynamic and static images of eyes with diabetic retinopathy(DR).METHODS:This cross-sectional study included 28 eyes of 28 patients with DR undergoing UWFA.A series of UWFA images acquired from each patient were converted into a time-lapse video and used as a dynamic image.A single,clear,arteriovenous phase image was chosen as a static image.Non-perfusion index(NPI)and its correlation with vascular abnormalities in different zones were compared between dynamic and static UWFA imaging.RESULTS:NPI appeared to increase from the center to the far-periphery in both groups.Dynamic NPI was lower in the total retinal area(0.26 vs 0.29,P=0.009)and farperiphery(0.33 vs 0.36,adjusted P=0.042),which was contrary to the static NPI.Far-peripheral NPI was associated with intraretinal microvascular abnormality in the posterior area in both groups.CONCLUSION:Time-lapse dynamic UWFA imaging is a useful modality to differentially diagnose hypofluorescence in the most peripheral region.This modality could provide a reliable method for NPI measurement.

关键词： diabetic retinopathy ultra-widefield fluorescein angiography non-perfusion index time-lapse photography

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