<div><h3>Purpose</h3><div>To identify latent phenotypic subgroups of diabetic macular edema (DME) using artificial intelligence–based OCT metrics and evaluate whether treatment responses to anti-VEGF and dexamethasone (DEX) therapies differ across these phenotypic clusters.</div></div><div><h3>Methods</h3><div>Retrospective study including 114 eyes (82 patients) with treatment-naïve DME. Quantitative OCT metrics, including intraretinal fluid (IRF) and subretinal fluid volumes, IRF % distribution within central 0–1, 1–3, and 3–6 mm, hyperreflective foci counts, and ellipsoid zone (EZ) % disruption, were analyzed before and after treatment.</div></div><div><h3>Main Outcome Measures</h3><div>Gaussian finite mixture modeling was used to identify distinct DME subgroups. Changes in visual acuity (VA) and OCT parameters following anti-VEGF or DEX therapy were analyzed using linear and generalized linear mixed-effects models, with false discovery rate correction applied to account for multiple comparisons.</div></div><div><h3>Results</h3><div>Three phenotypic clusters of DME were identified, each demonstrating distinct structural and functional characteristics: cluster 1 (29%, 95% confidence interval [CI]: 20.0%–38.4%), characterized by localized central IRF (mean 0.34 mm<sup>3</sup>, 32% in the 0–1 mm zone), moderate structural damage (EZ disruption: 13%), and better VA (mean logarithm of the minimum angle of resolution [LogMAR] 0.29); cluster 2 (49%, 95% CI: 39.6%–57.9%), with diffuse IRF (60% in the 3–6 mm zone), the highest IRF volume (mean: 3.33 mm<sup>3</sup>), significant structural disruption (EZ disruption: 46%), and the poorest VA (mean LogMAR: 0.63); and cluster 3 (22%, 95% CI: 13.9%–31.2%), showing intermediate fluid levels and minimal structural damage (EZ disruption: 0.5%). Anti-VEGF therapy led to the greatest VA improvement in cluster 2 (–31.5%, standard deviation: 28.6). Pairwise contrasts showed no significant VA differences between DEX and anti-VEGF in cluster 1 (–26.6%, 95% CI: –64.7 to 11.6) or in cluster 3 (–12.4%, 95% CI: –58.2 to 33.4), although the direction of effect suggested a trend toward greater improvement with DEX. In contrast, cluster 2 showed a nonsignificant difference favoring anti-VEGF (+25.0%, 95% CI: –4.6 to 54.6). For central subfield thickness, DEX achieved a significantly greater reduction than anti-VEGF in cluster 3 (–20.9%, 95% CI: –37.0 to –4.9) and was also associated with a relative increase in peripheral IRF distribution in cluster 3 (+26.7%, 95% CI: 6.5 to 46.9), supporting phenotype-dependent treatment effects.</div></div><div><h3>Conclusions</h3><div>Latent heterogeneity in DME presentations may influence treatment responses. Artificial intelligence–derived spectral-domain OCT metrics could support tailored therapeutic approaches to optimize patient outcomes.</div></div><div><h3>Financial Disclosure(s)</h3><div>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end
{"title":"What Lies beneath Diabetic Macular Edema: Latent Phenotypic Clustering and Differential Treatment Responses to Intravitreal Therapies","authors":"Maria Vittoria Cicinelli MD , Beatrice Leonardo MDs , Giacomo Maiucci MDs , Giuliano Martino MDs , Makan Ziafati MD , Soufiane Bousyf MD , Luisa Frizziero MD , Rosangela Lattanzio MD , Edoardo Midena MD , Francesco Bandello MD","doi":"10.1016/j.xops.2025.100975","DOIUrl":"10.1016/j.xops.2025.100975","url":null,"abstract":"<div><h3>Purpose</h3><div>To identify latent phenotypic subgroups of diabetic macular edema (DME) using artificial intelligence–based OCT metrics and evaluate whether treatment responses to anti-VEGF and dexamethasone (DEX) therapies differ across these phenotypic clusters.</div></div><div><h3>Methods</h3><div>Retrospective study including 114 eyes (82 patients) with treatment-naïve DME. Quantitative OCT metrics, including intraretinal fluid (IRF) and subretinal fluid volumes, IRF % distribution within central 0–1, 1–3, and 3–6 mm, hyperreflective foci counts, and ellipsoid zone (EZ) % disruption, were analyzed before and after treatment.</div></div><div><h3>Main Outcome Measures</h3><div>Gaussian finite mixture modeling was used to identify distinct DME subgroups. Changes in visual acuity (VA) and OCT parameters following anti-VEGF or DEX therapy were analyzed using linear and generalized linear mixed-effects models, with false discovery rate correction applied to account for multiple comparisons.</div></div><div><h3>Results</h3><div>Three phenotypic clusters of DME were identified, each demonstrating distinct structural and functional characteristics: cluster 1 (29%, 95% confidence interval [CI]: 20.0%–38.4%), characterized by localized central IRF (mean 0.34 mm<sup>3</sup>, 32% in the 0–1 mm zone), moderate structural damage (EZ disruption: 13%), and better VA (mean logarithm of the minimum angle of resolution [LogMAR] 0.29); cluster 2 (49%, 95% CI: 39.6%–57.9%), with diffuse IRF (60% in the 3–6 mm zone), the highest IRF volume (mean: 3.33 mm<sup>3</sup>), significant structural disruption (EZ disruption: 46%), and the poorest VA (mean LogMAR: 0.63); and cluster 3 (22%, 95% CI: 13.9%–31.2%), showing intermediate fluid levels and minimal structural damage (EZ disruption: 0.5%). Anti-VEGF therapy led to the greatest VA improvement in cluster 2 (–31.5%, standard deviation: 28.6). Pairwise contrasts showed no significant VA differences between DEX and anti-VEGF in cluster 1 (–26.6%, 95% CI: –64.7 to 11.6) or in cluster 3 (–12.4%, 95% CI: –58.2 to 33.4), although the direction of effect suggested a trend toward greater improvement with DEX. In contrast, cluster 2 showed a nonsignificant difference favoring anti-VEGF (+25.0%, 95% CI: –4.6 to 54.6). For central subfield thickness, DEX achieved a significantly greater reduction than anti-VEGF in cluster 3 (–20.9%, 95% CI: –37.0 to –4.9) and was also associated with a relative increase in peripheral IRF distribution in cluster 3 (+26.7%, 95% CI: 6.5 to 46.9), supporting phenotype-dependent treatment effects.</div></div><div><h3>Conclusions</h3><div>Latent heterogeneity in DME presentations may influence treatment responses. Artificial intelligence–derived spectral-domain OCT metrics could support tailored therapeutic approaches to optimize patient outcomes.</div></div><div><h3>Financial Disclosure(s)</h3><div>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end ","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"6 1","pages":"Article 100975"},"PeriodicalIF":4.6,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145618170","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}
Pub Date : 2025-10-10DOI: 10.1016/j.xops.2025.100964
Yun Hsia MD, MS , Hsiao-Lien Chang MD , Tsing-Hong Wang MD, PhD , Jehn-Yu Huang MD, MPH , Chien-Chia Su MD, PhD
Purpose
To investigate the prevalence and types of artifacts in OCT angiography (OCTA) among patients with different glaucoma severities.
Design
Prospective cross-sectional study.
Subjects
Patients with open-angle glaucoma from a tertiary center were prospectively categorized into mild (mean deviation [MD] of 24-2 visual field ≥ –6 decibels [dB]), moderate (–6 to ≥ –12 dB), advanced (–12 to ≥ –20 dB), and severe glaucoma group (MD < –20 dB).
Methods
AngioVue OCTA was performed three times within a single visit to obtain superficial and deep macular vessel density (VD) with 3 x 3–mm macular scans, and peripapillary VD with 4.5 x 4.5–mm scans centered on the optic disc. The intrasession variability was assessed by the coefficient of variation (CoV). Different types of image artifacts were identified.
Main Outcome Measures
The prevalence of artifacts in patients with varying glaucoma severities, patient-related factors associated with artifact occurrence, and their impact on scan quality index (SQI) and variability of OCTA parameters.
Results
Among the 57 mild, 46 moderate, 46 advanced, and 39 severe glaucoma eyes, half of OCTA images exhibited artifacts. Their prevalence increased from 30% in mild to 67% in severe glaucoma (P < 0.001) for peripapillary scans and from 39% to 62% (P = 0.001) for macular scans. Defocus was the most common artifact (26%) and increased with worsening MD (P = 0.006), contributing to greater CoV of superficial (P = 0.043) and deep (P = 0.024) macular VD and reduced macular SQI (P = 0.018). Peripapillary scans were more affected by artifacts, with defocus (P < 0.001) and eye movement (P = 0.025) increasing as MD worsened, which reduced the peripapillary SQI (P = 0.003 and P < 0.001, respectively). Lower SQI (P < 0.001), eye movement (P = 0.042), and quilt (P = 0.047) were linked to greater CoV of peripapillary VD.
Conclusions
Defocus is the most common OCTA artifact in glaucoma patients, increasing variability in OCTA metrics. Its prevalence rises with glaucoma severity and remains high even in scans with acceptable image quality, emphasizing the need for careful artifact assessment.
Financial Disclosure(s)
The authors have no proprietary or commercial interest in any materials discussed in this article.
{"title":"The Artifacts in Macular and Peripapillary OCT Angiography in Patients with Different Severities of Glaucoma","authors":"Yun Hsia MD, MS , Hsiao-Lien Chang MD , Tsing-Hong Wang MD, PhD , Jehn-Yu Huang MD, MPH , Chien-Chia Su MD, PhD","doi":"10.1016/j.xops.2025.100964","DOIUrl":"10.1016/j.xops.2025.100964","url":null,"abstract":"<div><h3>Purpose</h3><div>To investigate the prevalence and types of artifacts in OCT angiography (OCTA) among patients with different glaucoma severities.</div></div><div><h3>Design</h3><div>Prospective cross-sectional study.</div></div><div><h3>Subjects</h3><div>Patients with open-angle glaucoma from a tertiary center were prospectively categorized into mild (mean deviation [MD] of 24-2 visual field ≥ –6 decibels [dB]), moderate (–6 to ≥ –12 dB), advanced (–12 to ≥ –20 dB), and severe glaucoma group (MD < –20 dB).</div></div><div><h3>Methods</h3><div>AngioVue OCTA was performed three times within a single visit to obtain superficial and deep macular vessel density (VD) with 3 x 3–mm macular scans, and peripapillary VD with 4.5 x 4.5–mm scans centered on the optic disc. The intrasession variability was assessed by the coefficient of variation (CoV). Different types of image artifacts were identified.</div></div><div><h3>Main Outcome Measures</h3><div>The prevalence of artifacts in patients with varying glaucoma severities, patient-related factors associated with artifact occurrence, and their impact on scan quality index (SQI) and variability of OCTA parameters.</div></div><div><h3>Results</h3><div>Among the 57 mild, 46 moderate, 46 advanced, and 39 severe glaucoma eyes, half of OCTA images exhibited artifacts. Their prevalence increased from 30% in mild to 67% in severe glaucoma (<em>P</em> < 0.001) for peripapillary scans and from 39% to 62% (<em>P</em> = 0.001) for macular scans. Defocus was the most common artifact (26%) and increased with worsening MD (<em>P</em> = 0.006), contributing to greater CoV of superficial (<em>P</em> = 0.043) and deep (<em>P</em> = 0.024) macular VD and reduced macular SQI (<em>P</em> = 0.018). Peripapillary scans were more affected by artifacts, with defocus (<em>P</em> < 0.001) and eye movement (<em>P</em> = 0.025) increasing as MD worsened, which reduced the peripapillary SQI (<em>P</em> = 0.003 and <em>P</em> < 0.001, respectively). Lower SQI (<em>P</em> < 0.001), eye movement (<em>P</em> = 0.042), and quilt (<em>P</em> = 0.047) were linked to greater CoV of peripapillary VD.</div></div><div><h3>Conclusions</h3><div>Defocus is the most common OCTA artifact in glaucoma patients, increasing variability in OCTA metrics. Its prevalence rises with glaucoma severity and remains high even in scans with acceptable image quality, emphasizing the need for careful artifact assessment.</div></div><div><h3>Financial Disclosure(s)</h3><div>The authors have no proprietary or commercial interest in any materials discussed in this article.</div></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"6 1","pages":"Article 100964"},"PeriodicalIF":4.6,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145618260","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}
Pub Date : 2025-10-10DOI: 10.1016/j.xops.2025.100976
Hemal P. Patel MD, Cason B. Robbins MD, Jamie J. Karl MD, Peter Weng MD, PhD, Lejla Vajzovic MD, FASRS, Sharon Fekrat MD, FASRS
{"title":"Corrigendum to “Oral Antithrombotic Medication Is Associated with Improved Visual Outcomes in Eyes with Submacular Hemorrhage from Wet Age-Related Macular Degeneration” [Ophthalmology Science. 2025;5:100796]","authors":"Hemal P. Patel MD, Cason B. Robbins MD, Jamie J. Karl MD, Peter Weng MD, PhD, Lejla Vajzovic MD, FASRS, Sharon Fekrat MD, FASRS","doi":"10.1016/j.xops.2025.100976","DOIUrl":"10.1016/j.xops.2025.100976","url":null,"abstract":"","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"6 2","pages":"Article 100976"},"PeriodicalIF":4.6,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145925894","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}
In total, 142 eyes were included in the study: 72 in the RP group and 70 in the control group. Global pRNFL thicknesses were 89.3 ± 38.9, 86.5 ± 35.2, 84.6 ± 31.8, and 81.6 ± 31.3 μm at baseline, 1 year, 2 years, and 3 years in the RP group (P = 0.022), and 100.9 ± 6.3, 100.8 ± 7.0, 100.0 ± 6.3, and 100.3 ± 6.9 μm in the control group ( = 0.079), respectively. The reduction rate of pRNFL thickness was –2.45 μm/y in the RP group and –0.25 μm/y in the control group. In multivariate analysis, age (estimate = –0.55, P = 0.021) and RP stage (estimate = –15.42, P = 0.005) were significant factors associated with changes in pRNFL thickness in RP patients.
Conclusions
Retinitis pigmentosa patients exhibited a thinner pRNFL and a faster rate of thinning over time compared with healthy controls. In RP patients, pRNFL thinning was significantly associated with age and disease stage, possibly reflecting accelerated damage with disease progression.
Financial Disclosure(s)
The authors have no proprietary or commercial interest in any materials discussed in this article.
{"title":"Longitudinal Changes in Peripapillary Retinal Nerve Fiber Layer Thickness in Patients with Retinitis Pigmentosa","authors":"Jae-Yun Sung MD, PhD , Jung-Tae Kim MD, PhD , Yun-Sang Roh MD , Min-Woo Lee MD, PhD","doi":"10.1016/j.xops.2025.100966","DOIUrl":"10.1016/j.xops.2025.100966","url":null,"abstract":"<div><h3>Purpose</h3><div>To perform a longitudinal analysis of peripapillary retinal nerve fiber layer (pRNFL) thickness in retinitis pigmentosa (RP) patients.</div></div><div><h3>Design</h3><div>A retrospective, longitudinal study.</div></div><div><h3>Subjects</h3><div>We enrolled patients diagnosed with RP and normal controls.</div></div><div><h3>Methods</h3><div>After the baseline visit, 3 additional measurements of pRNFL thickness at 1-year intervals were analyzed.</div></div><div><h3>Main Outcome Measures</h3><div>Peripapillary retinal nerve fiber layer thickness.</div></div><div><h3>Results</h3><div>In total, 142 eyes were included in the study: 72 in the RP group and 70 in the control group. Global pRNFL thicknesses were 89.3 ± 38.9, 86.5 ± 35.2, 84.6 ± 31.8, and 81.6 ± 31.3 μm at baseline, 1 year, 2 years, and 3 years in the RP group (<em>P</em> = 0.022), and 100.9 ± 6.3, 100.8 ± 7.0, 100.0 ± 6.3, and 100.3 ± 6.9 μm in the control group ( = 0.079), respectively. The reduction rate of pRNFL thickness was –2.45 μm/y in the RP group and –0.25 μm/y in the control group. In multivariate analysis, age (estimate = –0.55, <em>P</em> = 0.021) and RP stage (estimate = –15.42, <em>P</em> = 0.005) were significant factors associated with changes in pRNFL thickness in RP patients.</div></div><div><h3>Conclusions</h3><div>Retinitis pigmentosa patients exhibited a thinner pRNFL and a faster rate of thinning over time compared with healthy controls. In RP patients, pRNFL thinning was significantly associated with age and disease stage, possibly reflecting accelerated damage with disease progression.</div></div><div><h3>Financial Disclosure(s)</h3><div>The authors have no proprietary or commercial interest in any materials discussed in this article.</div></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"6 1","pages":"Article 100966"},"PeriodicalIF":4.6,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145579184","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}
To assess the efficacy and safety of orally administered calpain inhibitor SJP-0008 in Japanese patients with central retinal artery occlusion (CRAO), to establish a disease registry for the prospective tracking of observational data from patients with CRAO, intended for regulatory use, and to support the development of new therapeutic agents for CRAO.
Design
This was a 2-part study. Part 1 was a physician-/investigator-initiated, phase IIa, single-center, randomized, double-blinded, parallel-group study. Part 2 was a prospective cohort study, during which the CRAO registry was established, and included patients diagnosed with CRAO (including a nonrandomized registry cohort, the non-SJP group, which did not receive SJP-0008). Additionally, in part 2, a combined analysis was performed using data from part 1 patients.
Participants
The study participants were patients recruited within 48 hours of developing CRAO.
Methods
SJP-0008 administration was initiated at least 3 hours but no more than 48 hours after the onset of CRAO. Patients were randomized in a 1:1 ratio using masked randomization to receive either 100-mg or 200-mg doses of SJP-0008. The dosing period was defined as the 4-week postinitiation period (up to 29 days), followed by an 8-week postobservation phase.
Main Outcome Measures
The main outcome measure was to determine the efficacy of SJP-0008 treatment; the primary endpoint was the change in ETDRS visual acuity at 12 weeks in the target eye of patients with CRAO.
Results
The study included 28 patients (mean age: 68.8 ± 14.9 years; 78.6% male). ETDRS scores (mean [95% confidence interval]) were higher at week 12 than at baseline in both the 100-mg (27.9 letters [10.14, 45.61]) and 200-mg (25.7 letters [12.02, 39.40]) SJP-0008 groups, in contrast to the non-SJP group (10.2 letters [4.58, 15.76]). The improvement in the 200-mg SJP-0008 group was greater than in the nonrandomized non-SJP group (P = 0.040). No safety concerns were identified.
Conclusions
The preliminary study supports the safety and efficacy of oral administration of SJP-0008 for treating CRAO, with greater improvement compared with the nonrandomized registry cohort. However, large-scale, multicenter randomized controlled trials are warranted to validate the findings of this study.
Financial Disclosure(s)
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
{"title":"Safety and Efficacy of Orally Administered SJP-0008 in Central Retinal Artery Occlusion: A Phase IIa Randomized Clinical Trial","authors":"Satoru Tsuda MD, PhD , Hiroshi Kunikata MD, PhD , Kazuki Hashimoto MD, PhD , Toshifumi Asano MD, PhD , Azusa Ito MD, PhD , Mitsuhide Yoshida DDS, PhD , Masayuki Yasuda MD, PhD , Fumihiko Nitta MD, PhD , Toru Nakazawa MD, PhD","doi":"10.1016/j.xops.2025.100965","DOIUrl":"10.1016/j.xops.2025.100965","url":null,"abstract":"<div><h3>Purpose</h3><div>To assess the efficacy and safety of orally administered calpain inhibitor SJP-0008 in Japanese patients with central retinal artery occlusion (CRAO), to establish a disease registry for the prospective tracking of observational data from patients with CRAO, intended for regulatory use, and to support the development of new therapeutic agents for CRAO.</div></div><div><h3>Design</h3><div>This was a 2-part study. Part 1 was a physician-/investigator-initiated, phase IIa, single-center, randomized, double-blinded, parallel-group study. Part 2 was a prospective cohort study, during which the CRAO registry was established, and included patients diagnosed with CRAO (including a nonrandomized registry cohort, the non-SJP group, which did not receive SJP-0008). Additionally, in part 2, a combined analysis was performed using data from part 1 patients.</div></div><div><h3>Participants</h3><div>The study participants were patients recruited within 48 hours of developing CRAO.</div></div><div><h3>Methods</h3><div>SJP-0008 administration was initiated at least 3 hours but no more than 48 hours after the onset of CRAO. Patients were randomized in a 1:1 ratio using masked randomization to receive either 100-mg or 200-mg doses of SJP-0008. The dosing period was defined as the 4-week postinitiation period (up to 29 days), followed by an 8-week postobservation phase.</div></div><div><h3>Main Outcome Measures</h3><div>The main outcome measure was to determine the efficacy of SJP-0008 treatment; the primary endpoint was the change in ETDRS visual acuity at 12 weeks in the target eye of patients with CRAO.</div></div><div><h3>Results</h3><div>The study included 28 patients (mean age: 68.8 ± 14.9 years; 78.6% male). ETDRS scores (mean [95% confidence interval]) were higher at week 12 than at baseline in both the 100-mg (27.9 letters [10.14, 45.61]) and 200-mg (25.7 letters [12.02, 39.40]) SJP-0008 groups, in contrast to the non-SJP group (10.2 letters [4.58, 15.76]). The improvement in the 200-mg SJP-0008 group was greater than in the nonrandomized non-SJP group (<em>P</em> = 0.040). No safety concerns were identified.</div></div><div><h3>Conclusions</h3><div>The preliminary study supports the safety and efficacy of oral administration of SJP-0008 for treating CRAO, with greater improvement compared with the nonrandomized registry cohort. However, large-scale, multicenter randomized controlled trials are warranted to validate the findings of this study.</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":"6 1","pages":"Article 100965"},"PeriodicalIF":4.6,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145519899","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}
Pub Date : 2025-10-10DOI: 10.1016/j.xops.2025.100967
Jizhou Tian MS , Diep Tran MS , Zainab Rustam MBBS , Gina Zhu BS , Paul Nagy PhD , Hadi Kharrazi MD, PhD , Deidra C. Crews MD, ScM , Zitong Wang PhD , Scott L. Zeger PhD , Cindy X. Cai MD, MS
Objective
To predict lapses in diabetic retinopathy (DR) care.
Design
Retrospective cohort study.
Subjects
Adults ≥18 years with diabetes seen at the Wilmer Eye Institute for DR screening or treatment between 2012 and 2022.
Main Outcome Measures
Whether an office visit for DR screening or treatment was followed by a lapse in care.
Methods
Three versions of prediction algorithms were constructed using random forests (RFs). XGBoost (XGB) was used as a confirmatory analysis. Random forest-A and XGB-A included electronic health record (EHR) variables alone (e.g., sociodemographic, insurance, ophthalmic diagnoses, lead time, and recommended follow-up time). Random forest-B and XGB-B added location-based social determinants of health (SDoH) variables (e.g., Area Deprivation Index). Random forest-C and XGB-C added history of lapses in care (e.g., whether the patient has ever had lapses in care before). The area under the receiver operating characteristic curve (AUROC) and the area under the precision-recall curve (AUPRC) were calculated for each algorithm.
Results
A total of 36 995 patients (mean age 62 years, 53% female, 47% non-Hispanic White, 38% non-Hispanic Black, and 4% Hispanic) and 141 930 office visits were included. The best performing model was RF-C with an AUROC of 0.774 (0.772–0.776) and AUPRC of 0.707 (0.704–0.711), outperforming RF-A and RF-B in AUROC and AUPRC (P < 0.001 for each comparison). XGB-C similarly outperformed XGB-A and XGB-B (P < 0.001 for each comparison).
Conclusions
We developed RF algorithms, as well as XGB confirmatory models, to predict whether patients with diabetes will experience a lapse in DR care. The best prediction was achieved using EHR variables, location-based SDoH variables, and history of lapses in care. These models offer the opportunity to identify high-risk patients and offer additional resources to reduce lapses in care and potentially vision loss from DR.
Financial Disclosure(s)
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
{"title":"Identifying Patients at High Risk of Lapses in Diabetic Retinopathy Care: A Machine Learning Study","authors":"Jizhou Tian MS , Diep Tran MS , Zainab Rustam MBBS , Gina Zhu BS , Paul Nagy PhD , Hadi Kharrazi MD, PhD , Deidra C. Crews MD, ScM , Zitong Wang PhD , Scott L. Zeger PhD , Cindy X. Cai MD, MS","doi":"10.1016/j.xops.2025.100967","DOIUrl":"10.1016/j.xops.2025.100967","url":null,"abstract":"<div><h3>Objective</h3><div>To predict lapses in diabetic retinopathy (DR) care.</div></div><div><h3>Design</h3><div>Retrospective cohort study.</div></div><div><h3>Subjects</h3><div>Adults ≥18 years with diabetes seen at the Wilmer Eye Institute for DR screening or treatment between 2012 and 2022.</div></div><div><h3>Main Outcome Measures</h3><div>Whether an office visit for DR screening or treatment was followed by a lapse in care.</div></div><div><h3>Methods</h3><div>Three versions of prediction algorithms were constructed using random forests (RFs). XGBoost (XGB) was used as a confirmatory analysis. Random forest-A and XGB-A included electronic health record (EHR) variables alone (e.g., sociodemographic, insurance, ophthalmic diagnoses, lead time, and recommended follow-up time). Random forest-B and XGB-B added location-based social determinants of health (SDoH) variables (e.g., Area Deprivation Index). Random forest-C and XGB-C added history of lapses in care (e.g., whether the patient has ever had lapses in care before). The area under the receiver operating characteristic curve (AUROC) and the area under the precision-recall curve (AUPRC) were calculated for each algorithm.</div></div><div><h3>Results</h3><div>A total of 36 995 patients (mean age 62 years, 53% female, 47% non-Hispanic White, 38% non-Hispanic Black, and 4% Hispanic) and 141 930 office visits were included. The best performing model was RF-C with an AUROC of 0.774 (0.772–0.776) and AUPRC of 0.707 (0.704–0.711), outperforming RF-A and RF-B in AUROC and AUPRC (<em>P</em> < 0.001 for each comparison). XGB-C similarly outperformed XGB-A and XGB-B (<em>P</em> < 0.001 for each comparison).</div></div><div><h3>Conclusions</h3><div>We developed RF algorithms, as well as XGB confirmatory models, to predict whether patients with diabetes will experience a lapse in DR care. The best prediction was achieved using EHR variables, location-based SDoH variables, and history of lapses in care. These models offer the opportunity to identify high-risk patients and offer additional resources to reduce lapses in care and potentially vision loss from DR.</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":"6 1","pages":"Article 100967"},"PeriodicalIF":4.6,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145466347","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}
Pub Date : 2025-10-10DOI: 10.1016/j.xops.2025.100971
Elise Rochet PhD , Feargal J. Ryan PhD , Yuefang Ma PhD , Liam M. Ashander BS , Shashikanth Marri PhD , Janet M. Matthews BS , João M. Furtado MD, PhD , Binoy Appukuttan PhD , David J. Lynn PhD , Justine R. Smith FRANZCO, PhD
Purpose
Ocular toxoplasmosis, caused by infection with Toxoplasma gondii, is characterized by retinal necrosis and reactive intraocular inflammation. Müller glial cells are a principal retinal host cell population for T. gondii. The goal of this research was to delineate potential involvements of Müller glial cells in ocular toxoplasmosis at a molecular level.
Design
Laboratory-based study.
Samples
Human retinal Müller glial cells infected with T. gondii plus noninfected cells.
Methods
Monolayers of Müller glial cells isolated from human retina (6 donor eye pairs) were infected for 24 hours with GT1 or GPHT strain T. gondii tachyzoites (multiplicity of infection of 5), or incubated in parallel without infection. Total RNA and small RNA were extracted from cell monolayers, sequenced on the Illumina NovaSeq 6000 and NextSeq 550 platforms, respectively, and aligned to GRCh38. Transcriptomic responses to infection with each strain were compared for differential expression (false discovery rate <5% and twofold change). These data were interrogated for enrichment of Reactome and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and Gene Ontology in InnateDB; putative transcription factor binding sites in HOMER; and potential microRNA–mRNA interactions in multiMiR.
Main Outcome Measures
Total and small RNA transcriptomes.
Results
6.3% of total RNA and 2.4% of small RNA changed in GT1-infected cells (582 upregulated and 210 downregulated transcripts and 20 upregulated microRNAs) versus 4.3% of total RNA and 1.5% of small RNA in GPHT-infected cells (400 upregulated and 137 downregulated transcripts and 12 upregulated microRNAs). Seventy-six transcripts and 4 microRNAs were different between strains; most were increased by both, but GT1 induced higher levels than GPHT. Enriched pathways and ontologies were dominated by DNA replication and intracellular metabolic activities, and the immune response for GT1 and GPHT. Seven of 8 transcription factor binding sites were shared for GT1 and GPHT infections, all overexpressed, including sites for p65/RELA and E2F family members. Across the strains, miR-18a-5p was the most connected microRNA in predicted mRNA target networks.
Conclusions
This work demonstrates that human retinal Müller glial cells shift to a proliferative and inflammatory phenotype when infected with T. gondii tachyzoites, consistent with a central role in the characteristic pathology of ocular toxoplasmosis.
Financial Disclosure(s)
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
{"title":"Total RNA and MicroRNA Transcriptomic Responses of Human Retinal Müller Glial Cells to Infection with Toxoplasma gondii Tachyzoites","authors":"Elise Rochet PhD , Feargal J. Ryan PhD , Yuefang Ma PhD , Liam M. Ashander BS , Shashikanth Marri PhD , Janet M. Matthews BS , João M. Furtado MD, PhD , Binoy Appukuttan PhD , David J. Lynn PhD , Justine R. Smith FRANZCO, PhD","doi":"10.1016/j.xops.2025.100971","DOIUrl":"10.1016/j.xops.2025.100971","url":null,"abstract":"<div><h3>Purpose</h3><div>Ocular toxoplasmosis, caused by infection with <em>Toxoplasma gondii</em>, is characterized by retinal necrosis and reactive intraocular inflammation. Müller glial cells are a principal retinal host cell population for <em>T. gondii</em>. The goal of this research was to delineate potential involvements of Müller glial cells in ocular toxoplasmosis at a molecular level.</div></div><div><h3>Design</h3><div>Laboratory-based study.</div></div><div><h3>Samples</h3><div>Human retinal Müller glial cells infected with <em>T. gondii</em> plus noninfected cells.</div></div><div><h3>Methods</h3><div>Monolayers of Müller glial cells isolated from human retina (6 donor eye pairs) were infected for 24 hours with GT1 or GPHT strain <em>T. gondii</em> tachyzoites (multiplicity of infection of 5), or incubated in parallel without infection. Total RNA and small RNA were extracted from cell monolayers, sequenced on the Illumina NovaSeq 6000 and NextSeq 550 platforms, respectively, and aligned to GRCh38. Transcriptomic responses to infection with each strain were compared for differential expression (false discovery rate <5% and twofold change). These data were interrogated for enrichment of Reactome and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and Gene Ontology in InnateDB; putative transcription factor binding sites in HOMER; and potential microRNA–mRNA interactions in multiMiR.</div></div><div><h3>Main Outcome Measures</h3><div>Total and small RNA transcriptomes.</div></div><div><h3>Results</h3><div>6.3% of total RNA and 2.4% of small RNA changed in GT1-infected cells (582 upregulated and 210 downregulated transcripts and 20 upregulated microRNAs) versus 4.3% of total RNA and 1.5% of small RNA in GPHT-infected cells (400 upregulated and 137 downregulated transcripts and 12 upregulated microRNAs). Seventy-six transcripts and 4 microRNAs were different between strains; most were increased by both, but GT1 induced higher levels than GPHT. Enriched pathways and ontologies were dominated by DNA replication and intracellular metabolic activities, and the immune response for GT1 and GPHT. Seven of 8 transcription factor binding sites were shared for GT1 and GPHT infections, all overexpressed, including sites for p65/RELA and E2F family members. Across the strains, miR-18a-5p was the most connected microRNA in predicted mRNA target networks.</div></div><div><h3>Conclusions</h3><div>This work demonstrates that human retinal Müller glial cells shift to a proliferative and inflammatory phenotype when infected with <em>T. gondii</em> tachyzoites, consistent with a central role in the characteristic pathology of ocular toxoplasmosis.</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":"6 1","pages":"Article 100971"},"PeriodicalIF":4.6,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145789917","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":"Re: Pushpanathan et al.: Can OpenAI’s New o1 Model Outperform Its Predecessors in Common Eye Care Queries?","authors":"Yusuke Kameda MD, PhD , Yutaka Kaneko MD, PhD , Saki Takada","doi":"10.1016/j.xops.2025.100968","DOIUrl":"10.1016/j.xops.2025.100968","url":null,"abstract":"","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"6 1","pages":"Article 100968"},"PeriodicalIF":4.6,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145466348","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}
Pub Date : 2025-10-10DOI: 10.1016/j.xops.2025.100973
James Loughman PhD , Gareth Lingham PhD , Hakan Kaymak MD , Katrin Lorenz MD , Jan Roelof Polling PhD , Anna Beck MD , Gonzalo Carracedo PhD , Annegret H. Dahlmann-Noor MD, PhD , Philipp L. Müller MD , Ian Flitcroft MBBS, DPhil
Purpose
To investigate the safety, tolerability, and signals of effect of MyopiaX, a smartphone app that selectively delivers blue light to the optic nerve head to control myopia progression in children and adolescents.
Eligible children aged 6 to 12 years, with myopia of cycloplegic spherical equivalent refraction (SER) between –0.75 and –5.00 diopters (D) at baseline. Children were screened and enrolled between November 2021 and September 2023.
Methods
Children were randomly assigned in a 2:1 ratio to MyopiaX or active control. Participants were instructed to use MyopiaX for 10 minutes twice daily for the first 6 months and, during the second 6 months of the trial, also wear defocus incorporated multiple segments (DIMS) myopia control spectacles. The active control group wore DIMS spectacles for the entire 12-month trial.
Main Outcome Measures
The primary outcome was change in axial length (AL) and change in SER at month 6. Clinical safety examinations and the frequency and severity of device-related adverse events (AEs) were analyzed for all participants who began treatment.
Results
Of the 124 randomized participants, 101 were enrolled under the 12-month active-control study design (MyopiaX: n = 66, DIMS: n = 35). After 6 months, the mean AL change from baseline in the MyopiaX (n = 50) and DIMS (n = 34) groups, respectively, was 0.14 ± 0.11 mm and 0.08 ± 0.09 mm. The 6-month change in SER was –0.18 ± 0.39 D in the MyopiaX group and –0.16 ± 0.41 D in DIMS participants. Among the 73 participants who used MyopiaX, including those randomized under the original study design (prior to introduction of an active control), there were 23 related AEs among the 16 participants (22%), including transient ocular discomfort and headache, all of which resolved without any need for treatment.
Conclusions
MyopiaX was safe and well tolerated over 12 months in treatment-naive children with myopia. This exploratory study provides the first clinical data on the impact of MyopiaX’s selective blue light stimulation on myopia progression and ocular growth. This novel approach may offer a complementary therapeutic solution for the clinical management of progressive myopia.
Financial Disclosures
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
{"title":"MyopiaX-1 Safety and Efficacy of a Novel Approach to Slow Juvenile Myopia Progression: A Multicenter, Randomized, Controlled Trial","authors":"James Loughman PhD , Gareth Lingham PhD , Hakan Kaymak MD , Katrin Lorenz MD , Jan Roelof Polling PhD , Anna Beck MD , Gonzalo Carracedo PhD , Annegret H. Dahlmann-Noor MD, PhD , Philipp L. Müller MD , Ian Flitcroft MBBS, DPhil","doi":"10.1016/j.xops.2025.100973","DOIUrl":"10.1016/j.xops.2025.100973","url":null,"abstract":"<div><h3>Purpose</h3><div>To investigate the safety, tolerability, and signals of effect of MyopiaX, a smartphone app that selectively delivers blue light to the optic nerve head to control myopia progression in children and adolescents.</div></div><div><h3>Design</h3><div>Multicenter, randomized, active-controlled, examiner-masked proof-of-concept clinical trial (<span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> identifier NCT04967287).</div></div><div><h3>Participants</h3><div>Eligible children aged 6 to 12 years, with myopia of cycloplegic spherical equivalent refraction (SER) between –0.75 and –5.00 diopters (D) at baseline. Children were screened and enrolled between November 2021 and September 2023.</div></div><div><h3>Methods</h3><div>Children were randomly assigned in a 2:1 ratio to MyopiaX or active control. Participants were instructed to use MyopiaX for 10 minutes twice daily for the first 6 months and, during the second 6 months of the trial, also wear defocus incorporated multiple segments (DIMS) myopia control spectacles. The active control group wore DIMS spectacles for the entire 12-month trial.</div></div><div><h3>Main Outcome Measures</h3><div>The primary outcome was change in axial length (AL) and change in SER at month 6. Clinical safety examinations and the frequency and severity of device-related adverse events (AEs) were analyzed for all participants who began treatment.</div></div><div><h3>Results</h3><div>Of the 124 randomized participants, 101 were enrolled under the 12-month active-control study design (MyopiaX: n = 66, DIMS: n = 35). After 6 months, the mean AL change from baseline in the MyopiaX (n = 50) and DIMS (n = 34) groups, respectively, was 0.14 ± 0.11 mm and 0.08 ± 0.09 mm. The 6-month change in SER was –0.18 ± 0.39 D in the MyopiaX group and –0.16 ± 0.41 D in DIMS participants. Among the 73 participants who used MyopiaX, including those randomized under the original study design (prior to introduction of an active control), there were 23 related AEs among the 16 participants (22%), including transient ocular discomfort and headache, all of which resolved without any need for treatment.</div></div><div><h3>Conclusions</h3><div>MyopiaX was safe and well tolerated over 12 months in treatment-naive children with myopia. This exploratory study provides the first clinical data on the impact of MyopiaX’s selective blue light stimulation on myopia progression and ocular growth. This novel approach may offer a complementary therapeutic solution for the clinical management of progressive myopia.</div></div><div><h3>Financial Disclosures</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":"6 1","pages":"Article 100973"},"PeriodicalIF":4.6,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145684240","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}
Pub Date : 2025-10-10DOI: 10.1016/j.xops.2025.100970
Junran Sun , Mengxi Shen , Jieqiong Chen , Yidong Wu , Yanping Zhou , Jingyang Feng , Yuxuan Cheng , Huixun Jia , Xiaolu Yang , YuanYuan Gong , Yang Liu , Hong Wang , Ruikang K. Wang , Philip J. Rosenfeld , Tong Li , Fenghua Wang , Xiaodong Sun
Purpose
To assess the safety, tolerability, and preliminary efficacy of a single intravitreal injection of LX102-C01 in eyes with neovascular age-related macular degeneration (nAMD) followed up to 52 weeks.
Design
Open-label, single-center, dose-escalation investigator-initiated trial (NCT05831007) with 2 cohorts (3E10 vector genome [vg] and 1E11 vg per eye).
Subjects
Eyes with choroidal neovascularization secondary to nAMD, subretinal or intraretinal fluid, and a history of >2 anti-VEGF treatments in the past 6 months with a good response.
Methods
All patients received 1 injection of aflibercept 2 weeks before LX102-C01. Dose escalation started with 3E10 vg and increased to 1E11 vg per eye. Visual acuity, anatomy, and adverse events (AEs) were assessed. Macular choroidal thickness (CT) and vascularity were measured using a 6 × 6 mm scan on swept-source OCT angiography imaging.
Main Outcome Measures
The primary endpoint was AEs at 1 year. The secondary endpoints were best-corrected visual acuity (BCVA), central subfield thickness (CST), and incidence of rescue treatment. Exploratory endpoints included the macular hypoautofluorescent area, CT, and choroidal vascularity index (CVI).
Results
Six eyes of 6 patients were included. There were no LX102-C01–related nonocular AEs. All LX102-C01–related ocular AEs were mild, predominantly anterior inflammation. There was no evidence of vasculitis, retinitis, choroiditis, vascular occlusions, or endophthalmitis. Two eyes from 2 patients developed recurrent subretinal fluid or hemorrhages that did not meet rescue criteria and resolved spontaneously after 1 to 2 months. All patients were free of rescue anti-VEGF treatments till the latest visit. Compared to baseline, BCVA maintained and CST decreased up to 12 months in both cohorts. The area of hypo-autofluorescence remained stable in both groups. The mean choroidal thickness (MCT) decreased from 162.1 μm to 147.1 μm (P = 0.03), but the CVI measurement showed no significant change (P = 0.6) up to 12 months. Changes in the MCT and CVI showed no statistically significant differences compared with the control group receiving standard aflibercept treatment.
Conclusions
LX102-C01 showed a favorable safety profile and potential efficacy in this preliminary 52-week study, with no observed macular atrophy, suggesting short-term tolerability of gene therapy associated anti-VEGF expression.
Financial Disclosures
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
{"title":"Intravitreal Gene Therapy with LX102-C01 in Neovascular Age-Related Macular Degeneration: A Phase I Dose-Escalation Study of 12-Month Safety and Efficacy Outcomes","authors":"Junran Sun , Mengxi Shen , Jieqiong Chen , Yidong Wu , Yanping Zhou , Jingyang Feng , Yuxuan Cheng , Huixun Jia , Xiaolu Yang , YuanYuan Gong , Yang Liu , Hong Wang , Ruikang K. Wang , Philip J. Rosenfeld , Tong Li , Fenghua Wang , Xiaodong Sun","doi":"10.1016/j.xops.2025.100970","DOIUrl":"10.1016/j.xops.2025.100970","url":null,"abstract":"<div><h3>Purpose</h3><div>To assess the safety, tolerability, and preliminary efficacy of a single intravitreal injection of LX102-C01 in eyes with neovascular age-related macular degeneration (nAMD) followed up to 52 weeks.</div></div><div><h3>Design</h3><div>Open-label, single-center, dose-escalation investigator-initiated trial (NCT05831007) with 2 cohorts (3E10 vector genome [vg] and 1E11 vg per eye).</div></div><div><h3>Subjects</h3><div>Eyes with choroidal neovascularization secondary to nAMD, subretinal or intraretinal fluid, and a history of >2 anti-VEGF treatments in the past 6 months with a good response.</div></div><div><h3>Methods</h3><div>All patients received 1 injection of aflibercept 2 weeks before LX102-C01. Dose escalation started with 3E10 vg and increased to 1E11 vg per eye. Visual acuity, anatomy, and adverse events (AEs) were assessed. Macular choroidal thickness (CT) and vascularity were measured using a 6 × 6 mm scan on swept-source OCT angiography imaging.</div></div><div><h3>Main Outcome Measures</h3><div>The primary endpoint was AEs at 1 year. The secondary endpoints were best-corrected visual acuity (BCVA), central subfield thickness (CST), and incidence of rescue treatment. Exploratory endpoints included the macular hypoautofluorescent area, CT, and choroidal vascularity index (CVI).</div></div><div><h3>Results</h3><div>Six eyes of 6 patients were included. There were no LX102-C01–related nonocular AEs. All LX102-C01–related ocular AEs were mild, predominantly anterior inflammation. There was no evidence of vasculitis, retinitis, choroiditis, vascular occlusions, or endophthalmitis. Two eyes from 2 patients developed recurrent subretinal fluid or hemorrhages that did not meet rescue criteria and resolved spontaneously after 1 to 2 months. All patients were free of rescue anti-VEGF treatments till the latest visit. Compared to baseline, BCVA maintained and CST decreased up to 12 months in both cohorts. The area of hypo-autofluorescence remained stable in both groups. The mean choroidal thickness (MCT) decreased from 162.1 μm to 147.1 μm (<em>P</em> = 0.03), but the CVI measurement showed no significant change (<em>P</em> = 0.6) up to 12 months. Changes in the MCT and CVI showed no statistically significant differences compared with the control group receiving standard aflibercept treatment.</div></div><div><h3>Conclusions</h3><div>LX102-C01 showed a favorable safety profile and potential efficacy in this preliminary 52-week study, with no observed macular atrophy, suggesting short-term tolerability of gene therapy associated anti-VEGF expression.</div></div><div><h3>Financial Disclosures</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":"6 2","pages":"Article 100970"},"PeriodicalIF":4.6,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145884430","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}
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