Ophthalmology science最新文献

{"title":"Validation and Repeatability of Differential Light Sensitivity Measurements with the Novel MAIA Microperimetry Device","authors":"Georg Ansari MD ,&nbsp;Nina L. Giudici MD ,&nbsp;Giuseppe Cancian MD ,&nbsp;Petra Rossouw ,&nbsp;Chiara Rui PhD ,&nbsp;Alberto Rosso PhD ,&nbsp;Silvia Gazzina PhD ,&nbsp;Nicolas Feltgen MD ,&nbsp;Kristina Pfau MD ,&nbsp;Maximilian Pfau MD","doi":"10.1016/j.xops.2025.100886","DOIUrl":"10.1016/j.xops.2025.100886","url":null,"abstract":"<div><h3>Objective</h3><div>Microperimetry is critical for the evaluation of macular light sensitivity, enabling disease monitoring in patients with either center-involving scotoma or initial sparing of the center. The purpose of this study was to investigate the validity and repeatability of light sensitivity measurements with the novel Macular Integrity Assessment (MAIA3) microperimeter compared with the established gold standard MAIA 2013 edition device (MAIA2).</div></div><div><h3>Design</h3><div>A prospective, cross-sectional, premarket clinical investigation on a medical device in a tertiary referral center (<span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> ID: NCT06071546).</div></div><div><h3>Participants</h3><div>Thirty-four healthy volunteers (median age: 28 years, interquartile range [IQR]: [26–32] years) and 34 patients with retinal pathologies (66 years, IQR: [50.5–74.5] years) were enrolled. All participants underwent comprehensive ophthalmic evaluation, including best-corrected visual acuity testing and OCT imaging. The diagnosis of retinal disease in patients was confirmed through fundoscopy and imaging.</div></div><div><h3>Main Outcome Measures</h3><div>Agreement between MAIA3 and MAIA2 measurements with mean sensitivity (MS) and at the pointwise sensitivity (PWS) level and test–retest (TRT) repeatability of MAIA3 and MAIA2 devices (using Bland–Altman statistics).</div></div><div><h3>Results</h3><div>The bias for the agreement between MAIA3 and MAIA2 measurements was below the established International Organization for Standardization standard of &lt;1 decibel (dB). Healthy participants showed a bias of 0.39 dB for both MS and PWS, 95% confidence interval (CI): 0.11−0.67 dB for MS, 0.30−0.48 dB for PWS. The bias in retinal patients was 0.76 dB (CI: 0.40−1.12 for MS, 0.59−0.93 dB for PWS). The overall bias was 0.57 dB (CI: 0.35−0.80 dB for MS and 0.48−0.67 dB for PWS). Overall TRT repeatability was similar between MAIA3 and MAIA2 devices for MS (Bland–Altman 95% limits of repeatability: −1.16 to 1.53 dB for MAIA3 and −1.49 to 2.06 dB for MAIA2). The examination duration with the MAIA3 device was shorter by 43 seconds compared with the MAIA2 device (median duration: 482.5 seconds [IQR: 451.8–537.5 seconds] for MAIA3 vs. 525.5 seconds [IQR: 500.8–562.3 seconds] for MAIA2).</div></div><div><h3>Conclusions</h3><div>The MAIA3 microperimetry enables valid and reliable measurements of macular light sensitivity compared with the established device (MAIA2).</div></div><div><h3>Financial Disclosure(s)</h3><div>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</div></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"5 6","pages":"Article 100886"},"PeriodicalIF":4.6,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144889377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"OCT-Defined Atrophic Age-Related Macular Degeneration Changes Associated with Deep Visual Sensitivity Losses: A Multicenter Study","authors":"Zhichao Wu BAppSc(Optom), PhD ,&nbsp;Barbara A. Blodi MD ,&nbsp;Frank G. Holz MD ,&nbsp;Glenn J. Jaffe MD ,&nbsp;Sandra Liakopoulos MD ,&nbsp;Srinivas R. Sadda MD ,&nbsp;Steffen Schmitz-Valckenberg MD ,&nbsp;Mari Bonse BSc ,&nbsp;Tyler Brown COA ,&nbsp;John Choong BS ,&nbsp;Bailey Clifton COA ,&nbsp;Giulia Corradetti MD ,&nbsp;Lauren A.B. Hodgson MPH ,&nbsp;Anna M. Lentzsch MD ,&nbsp;Alireza Mahmoudi MD ,&nbsp;Jeong W. Pak PhD ,&nbsp;Marlene Saßmannshausen MD ,&nbsp;Cindy Skalak RN, COT ,&nbsp;Leon von der Emde MD ,&nbsp;Jordan Winkler BSc ,&nbsp;Robyn H. Guymer MBBS, PhD","doi":"10.1016/j.xops.2025.100884","DOIUrl":"10.1016/j.xops.2025.100884","url":null,"abstract":"<div><h3>Purpose</h3><div>To identify combination(s) of OCT changes that define atrophic age-related macular degeneration (AMD) lesions associated with repeatable deep visual sensitivity defects.</div></div><div><h3>Design</h3><div>Reader study.</div></div><div><h3>Participants</h3><div>One hundred seventy-one OCT scans from 60 eyes of 53 participants.</div></div><div><h3>Methods</h3><div>Participants underwent 2 high-density targeted microperimetry tests (Macular Integrity Assessment device with Goldmann Size III stimuli) per visit of a 3.5° (approximately 1000 μm) diameter region-of-interest that had evidence of at least incomplete retinal pigment epithelium (RPE) and outer retinal atrophy (iRORA). OCT B-scans within the region sampled on microperimetry were annotated by 12 readers from 6 established reading centers for 7 different features related to RPE and outer retinal atrophy. The prevalence of the presence of a repeatable ≤10 decibel (dB) defect on microperimetry for lesions categorized by 18 different combinations of such features, or criteria, was determined.</div></div><div><h3>Main Outcome Measures</h3><div>The criteria for OCT-defined atrophic changes showing a ≥90% prevalence of a repeatable ≤10 dB defect, which has previously shown to be characteristic of regions with a truly nonresponding test location on microperimetry.</div></div><div><h3>Results</h3><div>Sixty percent of complete RPE and outer retinal atrophy (cRORA) lesions—based on the presence of hypertransmission and RPE abnormalities ≥250 μm in width, with evidence of overlying photoreceptor (PR) degeneration, on an OCT B-scan—had a repeatable ≤10 dB defect. However, between 92% and 98% of lesions with both hypertransmission and complete RPE loss ≥500 μm, and with evidence of any size of any feature of overlying PR degeneration, had a repeatable ≤10 dB defect, depending on the criteria considered. Between 92% and 95% of lesions with hypertransmission ≥500 μm and either overlying external limiting membrane disruption, or outer plexiform layer and inner nuclear layer subsidence, and/or hyporeflective wedge-shaped band(s) ≥500 μm, with or without RPE abnormalities, had a repeatable ≤10 dB defect.</div></div><div><h3>Conclusions</h3><div>This study identified various criteria for OCT-defined atrophic AMD lesions with functional characteristics that can be expected of regions with a truly nonresponding test location on high-density targeted microperimetry testing (i.e., having a ≥90% prevalence of a repeatable ≤10 dB defect). Such OCT-defined lesions could thus serve as functionally relevant clinical endpoints of end-stage atrophic AMD to facilitate preventative treatment trials.</div></div><div><h3>Financial Disclosure(s)</h3><div>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</div></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"5 6","pages":"Article 100884"},"PeriodicalIF":4.6,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144880259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Macular Atrophic versus Subretinal Proliferative Changes in Myopic and Age-Related Macular Degeneration","authors":"Jost B. Jonas MD ,&nbsp;Rahul A. Jonas MD ,&nbsp;Mukharram M. Bikbov MD, PhD ,&nbsp;Gyulli M. Kazakbaeva MD ,&nbsp;Ya Xing Wang MD ,&nbsp;Vinay Nangia MD ,&nbsp;Songhomitra Panda-Jonas MD","doi":"10.1016/j.xops.2025.100885","DOIUrl":"10.1016/j.xops.2025.100885","url":null,"abstract":"<div><h3>Objective</h3><div>To assess the prevalences of subfoveal retinal pigment epithelium (RPE) loss versus subfoveal tissue proliferation as causes of vision loss in patients with late-stage age-related macular degeneration (AMD) or myopic macular atrophy.</div></div><div><h3>Design</h3><div>Population-based studies conducted in Russia, China, and India and histological examination of enucleated human globes.</div></div><div><h3>Participants</h3><div>The Russian Ural Eye and Medical Study (<em>n</em> = 5899 participants; age: ≥40 years), Ural Very Old Study (<em>n</em> = 1526; age: 85+ years), Beijing Eye Study (<em>n</em> = 3468; age: ≥40 years), and Central India Eye and Medical Study (<em>n</em> = 4711) were conducted in rural and urban regions in Bashkortostan/Russia, Beijing/China, and Nagpur/India, respectively. The histological study part included human eyes enucleated because of reasons like malignant melanomas, or were post mortem enucleated.</div></div><div><h3>Methods</h3><div>The participants underwent a series of general medical and ophthalmological examinations including OCT of the macula. In the histological study part, the enucleated globes were histomorphometrically examined.</div></div><div><h3>Main Outcome Measures</h3><div>Presence of RPE loss and of subretinal proliferations.</div></div><div><h3>Results</h3><div>In all 4 population-based studies combined, late-stage AMD and myopic macular atrophy were detected in 291 eyes and 46 eyes, respectively. Retinal pigment epithelium cell loss was dominant in 136 (94%) out of 145 eyes with geographic atrophy and in 35 (76%) out of 46 eyes with myopic macular atrophy, whereas subretinal proliferations were predominantly present in 127 (87%) out of 146 eyes with neovascular AMD. Among all 337 eyes with late AMD or myopic macular atrophy, RPE loss was the main cause for vision loss in 190 (56%) eyes and subretinal proliferations in 147 (44%) eyes, with no significant difference (<em>P</em> &gt; 0.05) between the study cohorts. In the histological specimen, subretinal proliferations included melanin-bearing cells in contact with a periodic acid–Schiff-positive membrane, resembling RPE cells.</div></div><div><h3>Conclusions</h3><div>Subretinal proliferations in the foveal region were the main reason for central visual acuity loss in 44% of all eyes with late AMD or myopic macular atrophy in 4 population-based studies. Subretinal foveal RPE cell proliferation and RPE loss are roughly equally important as a cause of vision loss in AMD and myopic macular atrophy.</div></div><div><h3>Financial Disclosure(s)</h3><div>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</div></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"5 6","pages":"Article 100885"},"PeriodicalIF":4.6,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144866777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Generalized and Interpretable Multi-Label Multi-Disease Screening System for Ocular Anterior Segment Disease Detection","authors":"Mingyu Xu MS ,&nbsp;Lisha Wang ME ,&nbsp;Shengzhan Wang MS ,&nbsp;Yifan Zhou MS ,&nbsp;Nuliqiman Maimaiti MS ,&nbsp;Xin Shi MD ,&nbsp;Renshu Gu PhD ,&nbsp;Gangyong Jia PhD ,&nbsp;Zicheng Jiao BE ,&nbsp;Hongyi Gao BE ,&nbsp;Peifang Xu MD ,&nbsp;Juan Ye MD, PhD","doi":"10.1016/j.xops.2025.100883","DOIUrl":"10.1016/j.xops.2025.100883","url":null,"abstract":"<div><h3>Objective</h3><div>To develop and validate a multi-label, multi-disease, well-generalized, and interpretable screening system applied to the detection of common ocular anterior segment diseases based on ocular surface slit-lamp images.</div></div><div><h3>Design</h3><div>A multicenter artificial intelligence diagnostic study.</div></div><div><h3>Participants</h3><div>A total of 1990 patients were randomly selected from 2 medical centers: the Second Affiliated Hospital of Zhejiang University and the Affiliated People’s Hospital of Ningbo University, between November 2016 and March 2022.</div></div><div><h3>Methods</h3><div>The data set was retrospectively collected from 2 clinical centers and composed of 5132 anonymized slit-lamp images of 13 ocular anterior segment diseases. The screening system was trained and validated in the internal data set composing randomly selected phenotypes and was tested in both internal and external data sets with less trained or new phenotypes included. The performance of the model was further compared with ophthalmologists.</div></div><div><h3>Main Outcome Measures</h3><div>The diagnostic accuracy, precision, recall, sensitivity, specificity, F1 score, Matthews correlation coefficient, confusion matrix, and area under the receiver operating characteristics curve.</div></div><div><h3>Results</h3><div>The multi-label multi-disease detection ability of the screening system was evaluated in 3 stepwise levels and reached the average accuracy of 0.969 and 0.923 in binary image-level anomaly detection, 0.940 and 0.827 in the 4-class region-level anomaly detection, and 0.972 and 0.911 in the 13-class lesion-level anomaly detection in the internal and external test data sets, respectively, showing comparable performance with the ophthalmologists. Furthermore, the screening system presented the average accuracy of 0.950 and 0.852 in internal and external test data sets in images of phenotypes that were less trained or untrained.</div></div><div><h3>Conclusions</h3><div>Our screening system showed excellent multi-label and multi-disease detection ability and generalization ability in identifying ocular anterior segment disease, regardless of the limited phenotypes in the training data set. Thus, the screening system is anticipated to offer easily available primary medical information for patients and assist ophthalmologists in clinical practice.</div></div><div><h3>Financial Disclosure(s)</h3><div>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</div></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"5 6","pages":"Article 100883"},"PeriodicalIF":4.6,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144866775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Focal Weakening/Thinnest Corneal Point Proximity in Normal, Subclinical, and Keratoconic Corneas Using Motion-Tracking Brillouin Microscopy","authors":"Bassel Hammoud MD ,&nbsp;Hongyuan Zhang PhD ,&nbsp;Bianca N. Susanna MD ,&nbsp;Barbara A.L. Dutra MD, PhD ,&nbsp;Giuliano Scarcelli PhD ,&nbsp;J. Bradley Randleman MD","doi":"10.1016/j.xops.2025.100882","DOIUrl":"10.1016/j.xops.2025.100882","url":null,"abstract":"<div><h3>Purpose</h3><div>To determine the proximity between the thinnest corneal point (TCP) and focal corneal weakening in normal, subclinical keratoconus (SKC), and manifest keratoconus (KC) eyes using motion-tracking Brillouin microscopy.</div></div><div><h3>Design</h3><div>Prospective cross-sectional study.</div></div><div><h3>Participants</h3><div>Ninety-five eyes from 95 patients were evaluated: 40 from bilaterally normal patients (controls), 40 from patients with SKC, and 15 from patients with manifest KC.</div></div><div><h3>Methods</h3><div>All patients underwent Scheimpflug tomography, anterior segment OCT (AS-OCT), and custom-built motion-tracking Brillouin (MTB) imaging. Mean and minimum MTB shift values were calculated within the anterior plateau region. Euclidean distances between the TCP (identified by AS-OCT) and the minimum Brillouin shift (MTB-Min) were determined. Motion-tracking Brillouin minimum values within 10 MHz of the absolute minimum were considered equivalent (MTB-Min(e)). Receiver operating characteristic curves were generated for both metrics to determine the area under the curve (AUC), sensitivity, and specificity.</div></div><div><h3>Main Outcome Measures</h3><div>Distance between MTB-Min and TCP; group discrimination based on area under the receiver operating characteristic curve, sensitivity, and specificity.</div></div><div><h3>Results</h3><div>No significant differences were found between groups for age, sex, KMean, or KMax. Subclinical keratoconus and KC eyes were significantly thinner than controls. Motion-tracking Brillouin minimum values were significantly lower in SKC and KC eyes compared with controls. Average distances between MTB-Min and TCP were 0.31 ± 0.16 mm (0.04–0.69 mm) in controls, 0.53 ± 0.28 mm (0.11–1.19 mm) in SKC, and 0.54 ± 0.35 mm (0.10–1.36 mm) for KC (<em>P</em> &lt; 0.001). Motion-tracking Brillouin minimum (e) values were within 1 mm of the TCP in 100% of control eyes, 92.5% of SKC eyes, and 86.7% of KC eyes (<em>P</em> = 0.1). Motion-tracking Brillouin minimum values (e) performed nearly equivalently (AUC = 0.999) to the absolute MTB-Min shift (AUC = 1.0) in differentiating SKC from controls.</div></div><div><h3>Conclusions</h3><div>Focal corneal weakening occurs in close proximity to the thinnest corneal point in SKC. This study provides the first experimental confirmation of this relationship and demonstrates focal mechanical localization in subclinical and early KC.</div></div><div><h3>Financial Disclosure(s)</h3><div>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</div></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"5 6","pages":"Article 100882"},"PeriodicalIF":4.6,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144904001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-Term Blood Pressure Variability and Risk of Age-Related Macular Degeneration in Older Adults: The ALIENOR Study","authors":"Blondy Kayembe-Mulumba MD, MPH ,&nbsp;Karen Leffondré PhD ,&nbsp;Bénédicte M.J. Merle PhD ,&nbsp;Jean-François Korobelnik MD, PhD ,&nbsp;Catherine Helmer MD, PhD ,&nbsp;Christophe Tzourio MD, PhD ,&nbsp;Cécile Delcourt PhD ,&nbsp;Audrey Cougnard-Grégoire PhD ,&nbsp;Marie-Noëlle Delyfer MD, PhD","doi":"10.1016/j.xops.2025.100878","DOIUrl":"10.1016/j.xops.2025.100878","url":null,"abstract":"<div><h3>Purpose</h3><div>Long-term blood pressure variability (BPV) has emerged as a risk factor for various health problems, including eye diseases, independent of blood pressure (BP) levels. Yet, its role in age-related macular degeneration (AMD) progression remains unknown. This study aimed to assess associations between long-term BPV and the risk of AMD.</div></div><div><h3>Design</h3><div>Prospective analysis of 14-year data from the ALIENOR (Antioxydants, LIpides Essentiels, Nutrition et maladies OculaiRes) study, a French longitudinal population-based cohort study (2006–2020).</div></div><div><h3>Participants</h3><div>The ALIENOR study included 963 participants aged ≥73 years from the Three-City (3C) study in Bordeaux, for an ophthalmic follow-up.</div></div><div><h3>Methods</h3><div>Systolic BPV (SBPV), diastolic BPV (DBPV), and pulse pressure variability (PPV) were determined as the standard deviation of available BP measurements in 3C visits (1999–2017).</div></div><div><h3>Main Outcome Measures</h3><div>Age-related macular degeneration was assessed using retinal color photographs and OCT imaging every 2 years from 2006 to 2020. Shared random effects joint models fitted BPV current values and quantified their effect on AMD onset. The implemented Bayesian approach yielded the mean of adjusted posterior hazard ratios of AMD and their 95% credibility intervals (CrIs).</div></div><div><h3>Results</h3><div>Of the 692 (median age: 79.0 years; 63.5% female) and 475 (median age: 78.5 years; 61.1% female) at-risk participants, 10% and 36% developed advanced and intermediate AMD, respectively. The hazard of advanced AMD was significantly increased by 54% for a 5-mmHg increase in DBPV (adjusted hazard ratio [aHR]: 1.54, 95% CrI: 1.02–2.44), whereas statistical significance was not reached for a 5-mmHg increase in SBPV (aHR: 1.20, 95% CrI: 0.96–1.51) and PPV (aHR: 1.17, 95% CrI: 0.88–1.54). Conversely, BPV was not significantly associated with intermediate AMD (aHR: 0.96, 95% CrI: 0.83–1.11; aHR: 0.96, 95% CrI: 0.71–1.30; and aHR: 0.92, 95% CrI: 0.77–1.09; for a 5-mmHg increase in SBPV, DBPV, and PPV, respectively).</div></div><div><h3>Conclusions</h3><div>This study suggested that long-term variability in BP may be associated with an increased risk of advanced AMD, particularly for DBP. These findings underscore the need for further research to confirm this association, explore the underlying mechanisms, and propose potential interventions that could mitigate this risk.</div></div><div><h3>Financial Disclosure(s)</h3><div>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</div></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"5 6","pages":"Article 100878"},"PeriodicalIF":4.6,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144779992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Variation in Mesopic Retinal Sensitivity Relative to Distance from Geographic Atrophy in Age-Related Macular Degeneration","authors":"Souvick Mukherjee PhD ,&nbsp;Emily Vance MPH ,&nbsp;Leon von der Emde MD ,&nbsp;Thilaka Arunachalam BS ,&nbsp;Tharindu De Silva PhD ,&nbsp;Alisa T. Thavikulwat MD ,&nbsp;Christine Orndahl PhD ,&nbsp;Caroline Nyaiburi MS ,&nbsp;Maria Abraham ScM ,&nbsp;Keri Hammel MS ,&nbsp;SriniVas R. Sadda MD ,&nbsp;Emily Y. Chew MD ,&nbsp;Maximilian Pfau MD, PhD ,&nbsp;Wai T. Wong MD, PhD ,&nbsp;Brett G. Jeffrey PhD ,&nbsp;Tiarnán D.L. Keenan BM BCh, PhD","doi":"10.1016/j.xops.2025.100879","DOIUrl":"10.1016/j.xops.2025.100879","url":null,"abstract":"<div><h3>Purpose</h3><div>To analyze the relationship between distance from geographic atrophy (GA) lesion borders and mesopic retinal sensitivity in age-related macular degeneration (AMD).</div></div><div><h3>Design</h3><div>Exploratory analyses of the longitudinal microperimetry dataset from a recent phase II, prospective, single-arm, nonrandomized trial of oral minocycline for GA progression.</div></div><div><h3>Participants</h3><div>Individuals with GA from AMD in ≥1 eye.</div></div><div><h3>Methods</h3><div>Mesopic retinal sensitivity was assessed longitudinally with a fundus-guided microperimetry device at baseline, month 3, and every 6 months thereafter, using a custom T-shaped test pattern centered on the fovea. Individual test loci were superimposed on an aligned fundus autofluorescence image and distance from the closest GA lesion border (GA distance) was computed. The relationship between GA distance and retinal sensitivity was analyzed in study eyes using repeated-measures regression.</div></div><div><h3>Main Outcome Measures</h3><div>Mesopic retinal sensitivity.</div></div><div><h3>Results</h3><div>The study population comprised 26 study eyes from 26 participants (mean age 74.2 years). Retinal sensitivity of extralesional testing loci increased steeply, as a quadratic function, between 0° and 2.05° (i.e., knot at 2.05°; 95% confidence interval [CI] 1.26°–2.84°) of GA distance. Beyond 2.05°, it increased linearly and less steeply. In nonlinear analyses accounting for nesting, a significant effect of GA distance on retinal sensitivity was observed. For GA distances &lt;2.05°, sensitivity increased quadratically by approximately 1.99 decibels (dB)/° (95% CI: 1.15, 2.83 dB/°; <em>P</em> &lt; 0.001) or higher. For GA distances ≥2.05°, sensitivity increased at 0.56 dB/° (95% CI: 0.42, 0.70 dB/°; <em>P</em> &lt; 0.001). There was also a significant effect of time on sensitivity (estimate: −0.07 dB/month; 95% CI: −0.08, −0.06 dB/month; <em>P</em> &lt; 0.001).</div></div><div><h3>Conclusions</h3><div>The results demonstrate a perilesional zone 2° (∼580 μm) around the GA border in which retinal sensitivity changes steeply according to GA distance. This zone presents an important focus for closer evaluation in interventional studies examining potential efficacy for the preservation or recovery of retinal function. With GA progression, decreased retinal sensitivity expands ahead of GA expansion itself, as an advancing wave. Overall, the degree and extent of decreased visual function beyond GA borders have important implications for the design of clinical trials, decision-making in clinical practice, and insights into AMD pathophysiology.</div></div><div><h3>Financial Disclosure(s)</h3><div>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</div></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"5 6","pages":"Article 100879"},"PeriodicalIF":4.6,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144828982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and Safety of Voretigene Neparvovec in RPE65-Retinopathy: Results of a Phase III Trial in Japan","authors":"Kaoru Fujinami MD, PhD ,&nbsp;Kunihiko Akiyama MD, PhD ,&nbsp;Kazushige Tsunoda MD, PhD ,&nbsp;Saori Ito ,&nbsp;Noriko Seko PhD ,&nbsp;Shuichi Yamamoto MD, PhD","doi":"10.1016/j.xops.2025.100876","DOIUrl":"10.1016/j.xops.2025.100876","url":null,"abstract":"<div><h3>Purpose</h3><div>We report the efficacy and safety of voretigene neparvovec (VN) as an adeno-associated viral vector–based gene therapy for Japanese patients with inherited retinal dystrophy caused by biallelic pathogenic <em>RPE65</em> variants (<em>RPE65</em>-retinopathy).</div></div><div><h3>Design</h3><div>Open-label, single arm, phase III clinical trial.</div></div><div><h3>Participants</h3><div>Four subjects were recruited based on the following criteria: (1) a clinical and molecular genetic diagnosis of <em>RPE65</em>-retinopathy; (2) age ≥4 years; (3) a best-corrected VA (BCVA) worse than 20/60 or a visual field (VF) &lt;20° by a III4e isopter or equivalent; and (4) sufficient viable retinal cells by OCT or ophthalmoscopy.</div></div><div><h3>Methods</h3><div>All subjects received subretinal injections of VN (1.5 × 10¹¹ vg in 0.3 mL) after vitrectomy in both eyes.</div></div><div><h3>Main Outcome Measures</h3><div>The primary efficacy end point was a change from baseline in full-field light sensitivity threshold (FST) (white light, averaged over both eyes) at days 30, 90, 180, 270, and year 1. The secondary efficacy end points included changes from baseline in VF testing by Goldmann kinetic perimetry (GP) and BCVA in the logarithm of the minimum angle of resolution (LogMAR) unit. Safety was evaluated by adverse events (AEs), laboratory evaluations, and opthalmic examinations.</div></div><div><h3>Results</h3><div>The mean baseline age of 4 subjects was 31.3 years (10, 17, 49, and 49 years). The homozygous pathogenic variants (c.1543C&gt;T, p.Arg515Trp) were identified in 3 subjects. The mean (range) FST averaged over both eyes improved by −1.831 (−3.54 to −0.56) log₁₀(cd.s/m²) from baseline to year 1 after treatment. The mean changes in VF as measured by (GP III4e) and LogMAR BCVA, averaged across both eyes, were 427.8 (−11 to 1014) sum total degrees and −0.033 (−0.15 to 0.17) LogMAR from baseline to year 1, respectively. None of the AEs, including one serious AE (ovarian cyst torsion), were judged to be related to VN.</div></div><div><h3>Conclusions</h3><div>Overall, these data from a phase III trial showed improvements in FST and VF and well-tolerated safety profiles of VN for 1 year, with ongoing follow-up of up to 5 years in Japanese patients with <em>RPE65</em>-retinopathy. These results support the further applicability of VN to the Japanese population.</div></div><div><h3>Financial Disclosure(s)</h3><div>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</div></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"5 6","pages":"Article 100876"},"PeriodicalIF":4.6,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144896161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Longitudinal Assessment of Area of Reticular Pseudodrusen in Eyes with Age-Related Macular Degeneration","authors":"Swetha Bindu Velaga MS ,&nbsp;Ahmed Roshdy Alagorie MD ,&nbsp;Muneeswar Gupta Nittala MPhil ,&nbsp;Noel C. Moore PhD ,&nbsp;Yeunjoo E. Song PhD ,&nbsp;Jonathan Haines PhD ,&nbsp;Margaret A. Pericak-Vance PhD ,&nbsp;Dwight Stambolian MD ,&nbsp;Zhihong Hu PhD ,&nbsp;Ye He MD, PhD ,&nbsp;Srinivas R. Sadda MD","doi":"10.1016/j.xops.2025.100881","DOIUrl":"10.1016/j.xops.2025.100881","url":null,"abstract":"<div><h3>Purpose</h3><div>To evaluate the change in the area of reticular pseudodrusen (RPD) and choroidal thickness over 2 years in eyes with age-related macular degeneration (AMD).</div></div><div><h3>Design</h3><div>Longitudinal cohort study.</div></div><div><h3>Subjects</h3><div>The study reviewed 1332 eyes from 666 subjects with baseline and 2-year follow-up data, of which 108 eyes were graded to have RPD. Among these, 35 eyes from 22 participants (mean age: 72.8 ± 8.9 years; range: 50–84; 37% female) were eligible for this analysis because they had early or intermediate AMD with RPD at baseline, absence of geographic atrophy at 2 years, and images that were gradable for the presence of RPD.</div></div><div><h3>Methods</h3><div>Infrared reflectance (IR), blue-light fundus autofluorescence, and spectral-domain OCT were obtained for all subjects at baseline and at 2 years. Using the instrument software, a certified grader delineated the RPD area (mm²) on the IR image using the free hand tool. Choroidal thickness was measured for both baseline and month 24 using a previously described deep learning algorithm to compute a choroidal volume.</div></div><div><h3>Main Outcome Measures</h3><div>Changes in RPD area (mm²) and mean volumetric choroidal thickness (μm) between baseline and 2 years.</div></div><div><h3>Results</h3><div>The RPD area increased significantly (<em>P</em> &lt; 0.001) by month 24 compared with baseline with a mean increase of 6.23 ± 4.64 mm². The mean volumetric choroidal thickness was not significantly different from baseline 182.2 ± 94.36 (134.20–227.90) to month 24 178.2 ± 41.10 (109–258).</div></div><div><h3>Conclusions</h3><div>In this longitudinal natural history analysis, we observed an increase in RPD area of &gt;6 mm² over 2 years in the absence of a significant change in choroidal thickness. Although AMD eyes with presence of RPD typically have a thinner choroid, the increase in extent of these lesions does not appear to be associated with further thinning of the choroid.</div></div><div><h3>Financial Disclosure(s)</h3><div>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</div></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"5 6","pages":"Article 100881"},"PeriodicalIF":4.6,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144830523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk of Systemic Health Events and Mortality After Vitrectomy for Diabetic Retinopathy in Patients with Type 2 Diabetes","authors":"Dane A. Jester BS ,&nbsp;Muhammad Z. Chauhan MD, MS ,&nbsp;Zain S. Hussain MD ,&nbsp;Sam Karimaghaei MD ,&nbsp;Jawad Muayad BS ,&nbsp;Asad Loya MD ,&nbsp;Ahmed F. Shakarchi MD, MPH ,&nbsp;Ahmed B. Sallam MD, PhD","doi":"10.1016/j.xops.2025.100880","DOIUrl":"10.1016/j.xops.2025.100880","url":null,"abstract":"<div><h3>Purpose</h3><div>To quantify the risk of mortality, myocardial infarction (MI), stroke, and amputation in patients with type 2 diabetes mellitus (T2DM) who underwent pars plana vitrectomy (PPV) for diabetic retinopathy (DR) compared with those not requiring PPV.</div></div><div><h3>Design</h3><div>A retrospective cohort study utilizing the TriNetX US Collaborative Network.</div></div><div><h3>Subjects</h3><div>The study included 9081 patients with T2DM who underwent PPV for DR, 363 116 patients with T2DM with DR but no PPV, 92 645 patients with T2DM without DR, and 3 264 709 healthy individuals, all aged ≥18 years.</div></div><div><h3>Methods</h3><div>We identified cohorts using specific International Classification of Diseases, 10th Revision and Current Procedural Technology codes. We used propensity score matching to adjust for covariates including age, gender, race, ethnicity, systemic pathology, and ocular conditions unrelated to diabetes.</div></div><div><h3>Main Outcome Measures</h3><div>The primary outcome measures were the hazard ratios (HRs) for mortality, MI, stroke, and amputation at 1, 3, and 5 years after PPV compared with the control groups.</div></div><div><h3>Results</h3><div>Patients with T2DM undergoing PPV for DR had higher risk of systemic events and mortality. Compared with patients with DR not requiring PPV, the PPV cohort had a higher risk at 1 year for stroke (HR: 1.51; 95% confidence interval [CI]: 1.03, 2.21) and amputation (HR: 1.85; 95% CI: 1.08, 3.16). At 3 years, the risks for MI (HR: 1.44; 95% CI: 1.17, 1.78), stroke (HR: 1.61; 95% CI: 1.25, 2.07), and amputation (HR: 2.17; 95% CI: 1.54, 3.05) were significantly elevated. At 5 years, the risks for mortality (HR: 1.28; 95% CI: 1.13, 1.43), MI (HR: 1.50; 95% CI: 1.26, 1.78), stroke (HR: 1.54; 95% CI: 1.25, 1.91), and amputation (HR: 2.10; 95% CI: 1.58, 2.81) were all significantly higher. When compared with diabetic patients without DR or healthy patients, the PPV cohort faced higher risk of each health outcome analyzed at intervals of 1, 3, and 5 years.</div></div><div><h3>Conclusions</h3><div>We found a significant association between patients with T2DM with DR requiring PPV and an increased risk of mortality, MI, stroke, and amputation compared with non-PPV patients with DR, diabetics without DR, and healthy individuals. These findings underscore the need for monitoring and management of systemic health in diabetic patients undergoing PPV for advanced DR.</div></div><div><h3>Financial Disclosure(s)</h3><div>The author(s) have no proprietary or commercial interest in any materials discussed in this article.</div></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"5 6","pages":"Article 100880"},"PeriodicalIF":4.6,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144830524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}