American Journal of Ophthalmology最新文献

{"title":"New Insights into Imaging Patterns of Autoimmune Retinopathies: A Cluster-Based Update","authors":"Luca De Simone ,&nbsp;Rocco Bruno ,&nbsp;Fabrizio Gozzi ,&nbsp;Elena Bolletta ,&nbsp;Pietro Gentile ,&nbsp;Chantal Adani ,&nbsp;Rodolfo Mastropasqua ,&nbsp;Luca Cimino","doi":"10.1016/j.ajo.2025.12.030","DOIUrl":"10.1016/j.ajo.2025.12.030","url":null,"abstract":"<div><h3>Purpose</h3><div>To describe multimodal imaging (MMI) features in autoimmune retinopathies (AIR) and characterize distinct phenotypic clusters.</div></div><div><h3>Design</h3><div>Retrospective observational case series.</div></div><div><h3>Participants</h3><div>Ten patients diagnosed with AIR between November 2017 and August 2025 were evaluated at the Ocular Immunology Unit, Azienda Unità Sanitaria Locale–IRCCS, Reggio Emilia, Italy.</div></div><div><h3>Methods</h3><div>Patients with paraneoplastic and nonparaneoplastic AIR underwent full-field electroretinography and MMI, including retinography, fundus autofluorescence (FAF), optical coherence tomography (OCT), fluorescein angiography (FA), and indocyanine green angiography. Qualitative pattern analysis was performed to identify recurring imaging features.</div></div><div><h3>Main Outcome Measures</h3><div>MMI characteristics of AIR.</div></div><div><h3>Results</h3><div>Of 30 referred patients, 10 (14 eyes) met inclusion criteria (median age 42 years, range 28 to 65; 70% female; median follow-up 40 months). Three recurring imaging clusters were identified. One cluster showed features within the acute zonal occult outer retinopathy spectrum, including monozonal, bizonal, and trizonal configurations on FAF and OCT. A second cluster was characterized by predominant posterior pole photoreceptoritis with subtle FAF changes and diffuse outer retinal alterations on OCT. A third cluster showed unilateral, peripheral, retinitis pigmentosa–like degeneration with centripetal progression on FAF and mild capillary leakage on fluorescein angiography.</div></div><div><h3>Conclusions</h3><div>In this small case series, MMI revealed recurring phenotypic clusters in AIR that may help contextualize the heterogeneity of this condition. These observations are exploratory and hypothesis-generating, and warrant validation in larger, multicenter studies.</div></div>","PeriodicalId":7568,"journal":{"name":"American Journal of Ophthalmology","volume":"284 ","pages":"Pages 30-42"},"PeriodicalIF":4.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145893648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Postoperative Epiretinal Membrane After Fovea-sparing Versus Standard Internal Limiting Membrane Peeling for Myopic Traction Maculopathy","authors":"Akihiko Shiraki ,&nbsp;Nobuhiko Shiraki ,&nbsp;Kotaro Tsuboi ,&nbsp;Masaki Fukushima ,&nbsp;Ryota Akai ,&nbsp;Tomoko Ueda-Consolvo ,&nbsp;Yuichiro Ishida ,&nbsp;Keita Baba ,&nbsp;Kentaro Abe ,&nbsp;Hisashi Fukuyama ,&nbsp;Yuki Yamamoto ,&nbsp;Yuki Otsuka ,&nbsp;Ryuya Hashimoto ,&nbsp;Motohiro Kamei ,&nbsp;Hirokazu Sakaguchi ,&nbsp;Fumi Gomi ,&nbsp;Yasushi Ikuno ,&nbsp;Takatoshi Maeno ,&nbsp;Yusuke Oshima ,&nbsp;Jay Chhablani ,&nbsp;Taku Wakabayashi","doi":"10.1016/j.ajo.2025.12.028","DOIUrl":"10.1016/j.ajo.2025.12.028","url":null,"abstract":"<div><h3>Purpose</h3><div>To compare the incidence and outcomes of postoperative epiretinal membrane (ERM) formation after fovea-sparing internal limiting membrane peeling (FSIP) and standard internal limiting membrane (ILM) peeling in eyes with myopic traction maculopathy (MTM).</div></div><div><h3>Design</h3><div>Multicenter, retrospective clinical cohort study (Schisis report no. 4).</div></div><div><h3>Methods</h3><div>Patients with MTM who underwent pars plana vitrectomy (PPV) at 10 institutions between June 2008 and July 2024, with at least 12 months of follow-up, were included. Postoperative ERM was identified on optical coherence tomography (OCT) and graded using the Govetto classification. The main outcomes were the 12-month incidence of postoperative ERM and postoperative visual outcomes.</div></div><div><h3>Results</h3><div>We included a total of 206 eyes (201 patients); 46 eyes treated with FSIP and 160 eyes treated with standard ILM peeling. Of the 206 eyes, postoperative ERM developed in 16 eyes (7.8%) at 12 months: 8 eyes (17.4%) in the FSIP group and 8 eyes (5.0%) in the standard ILM peeling group. The incidence of postoperative ERM was significantly higher in the FSIP group than in the standard ILM peeling group (<em>P</em> = .014), and univariable logistic regression analysis revealed that FSIP was significantly associated with postoperative ERM at 12 months (OR = 4.00, 95% CI = 1.39-11.55, <em>P</em> = .009). Of the 8 eyes with postoperative ERM after FSIP, 6 eyes showed stage 1 ERM and 2 eyes showed stage 2 ERM. Of the 8 eyes with postoperative ERM after standard ILM peeling, 7 eyes showed stage 1 ERM and 1 eye showed stage 2 ERM. No additional surgery was required for postoperative ERM during 12 months. Postoperative logarithm of minimum angle of resolution visual acuity at 12 months did not differ significantly between eyes with (0.50 ± 0.43) and without ERM (0.42 ± 0.52; <em>P</em> = .517). The incidence of postoperative macular hole (MH) was lower in the FSIP group (2.2%) than in the standard ILM peeling group (12.8%), although the difference was not statistically significant (<em>P</em> = .071).</div></div><div><h3>Conclusions</h3><div>FSIP increased the incidence of postoperative ERM compared with standard ILM peeling, but most ERMs were subclinical and did not affect vision. Despite the elevated ERM risk, the potential benefit of FSIP in reducing postoperative macular hole formation may outweigh its drawbacks.</div></div>","PeriodicalId":7568,"journal":{"name":"American Journal of Ophthalmology","volume":"284 ","pages":"Pages 123-132"},"PeriodicalIF":4.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145893651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comment on: Safety and Efficiency reducing ROP Guideline sensitivity: An external validation using a large US-based dataset","authors":"Eugenia C. Greig, Darius M. Moshfeghi","doi":"10.1016/j.ajo.2026.03.034","DOIUrl":"https://doi.org/10.1016/j.ajo.2026.03.034","url":null,"abstract":"","PeriodicalId":7568,"journal":{"name":"American Journal of Ophthalmology","volume":"6 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147597915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Geographic and Phenotypic Variability in RHO-Associated Retinopathy: Evidence From a Chinese Cohort and Global Literature","authors":"CHENYUE HANG ,&nbsp;TIANYUAN ZHAO ,&nbsp;ZHIXUAN CHEN ,&nbsp;HONG WANG ,&nbsp;LIN CHEN ,&nbsp;TING ZHANG ,&nbsp;YUTIAN JIAO ,&nbsp;TONG LI ,&nbsp;JUNRAN SUN ,&nbsp;SUQIN YU ,&nbsp;YUANYUAN GONG ,&nbsp;HAO ZHOU ,&nbsp;XUJUN JIANG ,&nbsp;XINXIN LIU ,&nbsp;HUIXUN JIA ,&nbsp;KAIRONG ZHENG ,&nbsp;XIAOLING WAN ,&nbsp;JIEQIONG CHEN ,&nbsp;XIAODONG SUN","doi":"10.1016/j.ajo.2025.12.020","DOIUrl":"10.1016/j.ajo.2025.12.020","url":null,"abstract":"<div><h3>Purpose</h3><div>To investigate the genotype-phenotype correlation in <em>RHO</em>-associated retinopathy, with a focus on delineating an ethnic-specific variant spectrum and comparing clinical severity across biological classes and common variants.</div></div><div><h3>Design</h3><div>Retrospective cohort study and literature review.</div></div><div><h3>Methods</h3><div>We systematically reviewed all published cases of <em>RHO</em>-associated retinal diseases (2196 patients, 1278 probands) and analyzed clinical, genetic, and imaging data from our institutional cohort (80 probands). Variants were categorized by type and by biological class (Class 1-7), and phenotypes were compared across different biological classes and three common variants.</div></div><div><h3>Results</h3><div>A marked geographic divergence was observed: P23H was common in North America but rare in other populations, whereas P347L and R135W were major common variants in European and Asian populations. Genotype-phenotype analysis revealed that Class 2 variants were associated with later onset and slower visual decline, whereas Class 1 and Class 3 variants correlated with earlier onset (<em>P</em> &lt; .0001) and more aggressive phenotypes. Notably, R135W (Class 3) emerged as an under-recognized but highly aggressive variant, with earlier onset (<em>P</em> &lt; .01) and potentially earlier macular involvement.</div></div><div><h3>Conclusions</h3><div>Our study represents the largest study integrating ethnic, genotypic, and clinical data in <em>RHO</em>-associated retinopathy. The findings highlight substantial inter-ethnic differences in common variants and underscore the clinical relevance of biological classification in predicting disease course. In particular, R135W and P347L warrants closer clinical attention due to their aggressive trajectory, which may inform prioritization in gene therapy trials and individualized patient management.</div></div>","PeriodicalId":7568,"journal":{"name":"American Journal of Ophthalmology","volume":"284 ","pages":"Pages 1-11"},"PeriodicalIF":4.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145823647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artificial Intelligence-Guided Endpoint Selection for Neuroprotection Trials in Glaucoma","authors":"Douglas R. da Costa ,&nbsp;Rafael Scherer ,&nbsp;Swarup S. Swaminathan ,&nbsp;Henry Tseng ,&nbsp;Felipe A. Medeiros","doi":"10.1016/j.ajo.2025.12.038","DOIUrl":"10.1016/j.ajo.2025.12.038","url":null,"abstract":"<div><h3>Objective</h3><div>Standard Automated Perimetry (SAP) is the primary method for monitoring glaucoma progression and an established functional endpoint in clinical trials. A ≥7 dB loss in at least five prespecified test locations has been proposed as a potential endpoint for glaucoma trials, but identifying such vulnerable points in advance remains a major challenge. We developed an artificial intelligence model that uses baseline SAP data to predict the locations most likely to progress, enabling a targeted approach to endpoint selection in neuroprotection trials.</div></div><div><h3>Design</h3><div>Retrospective cohort study to predict progression.</div></div><div><h3>Subjects</h3><div>A total of 82,449 SAP tests from 14,237 eyes of 10,533 subjects with open-angle glaucoma across three independent datasets: the Bascom Palmer Ophthalmic Registry, the Duke Glaucoma Registry, and the University of Washington Humphrey Visual Field.</div></div><div><h3>Methods</h3><div>A graph attention network was trained on Bascom Palmer Ophthalmic Registry data, split at the patient level into development and internal validation datasets, to predict progression risk at each SAP location using baseline total deviation values and anatomically informed graph connectivity. For each eye, the five highest-risk points (High-5) were identified and compared with global mean deviation (MD) and the five lowest-risk points (Low-5). The model was applied without retraining to the Duke Glaucoma Registry and University of Washington Humphrey Visual Field cohorts for external validation.</div></div><div><h3>Main Outcome Measures</h3><div>Model ranking performance, neighborhood hit rate, rates of change at High-5, Low-5, and MD, discrimination by area under the receiver operating characteristic curve, and time to repeatable ≥7 dB decline.</div></div><div><h3>Results</h3><div>In progressing eyes, mean slopes at High-5 were −2.05 to −2.32 dB/y, four to five times steeper than Low-5 (−0.45 to −0.66; <em>P</em> &lt; .001) and approximately twice that of MD (−0.93 to −1.14; <em>P</em> &lt; .001). Area under the receiver operating characteristic curve for discriminating progressors from nonprogressors ranged from 0.883 to 0.937 for High-5, outperforming Low-5 (0.668-0.731; <em>P</em> &lt; .001) and MD (0.871-0.911; <em>P</em> = .003). Nearly all progressors reached the High-5 ≥7 dB threshold during follow-up.</div></div><div><h3>Conclusions</h3><div>The artificial intelligence-based model identified the most vulnerable visual field locations from baseline data. The High-5 metric provides a proof-of-concept framework consistent with regulatory concepts of functional endpoints and shows improved sensitivity to progression, supporting more efficient neuroprotection trials and personalized glaucoma monitoring.</div></div>","PeriodicalId":7568,"journal":{"name":"American Journal of Ophthalmology","volume":"284 ","pages":"Pages 88-100"},"PeriodicalIF":4.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145893645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Racial Disparities in Ophthalmology in Training and Practice: A Systematic Review","authors":"Angel Gao ,&nbsp;Tasha Miller ,&nbsp;Arturo Ortin-Martinez ,&nbsp;Radha P. Kohly","doi":"10.1016/j.ajo.2026.01.008","DOIUrl":"10.1016/j.ajo.2026.01.008","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Topic&lt;/h3&gt;&lt;div&gt;Ophthalmology remains one of the least diverse medical specialties, with persistent racial and ethnic disparities throughout training and practice. This review examines experiences of individuals from underrepresented racial minorities (URiM) in ophthalmology within high-income countries, focusing on barriers to representation, discrimination, and equity initiatives.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Clinical Relevance&lt;/h3&gt;&lt;div&gt;Identifying and addressing barriers faced by URiM in ophthalmology is essential to advancing workforce diversity, equitable patient care, and institutional inclusivity. Understanding where inequities persist can inform systemic interventions.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;A systematic review of the literature was conducted in MEDLINE, Embase, PsycINFO, CINAHL, Web of Science, and Cochrane Library from inception to November 2024. Eligible studies included English-language publications from 2000 onwards focusing on racial or ethnic minority individuals in ophthalmology. Two reviewers independently screened studies, extracted data, and assessed risk of bias using the Newcastle-Ottawa Scale and Joanna Briggs Institute Checklist. Data were synthesized descriptively and thematically. The protocol was registered on PROSPERO (CRD42025640520).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Forty-one eligible studies involving 500,823 responses were included. Most studies were cross-sectional, published after 2021 and conducted in the United States. Across all career stages, URiM individuals were underrepresented and faced structural barriers. In medical school, fewer URiM students pursued ophthalmology, citing lack of mentorship and role models. Minority representation among applicants has increased modestly, particularly among Hispanic students, though overall growth remains limited.&lt;/div&gt;&lt;div&gt;During residency and fellowship, racial disparities persisted in research access, fellowship application outcomes, and interview offers. URiM trainees reported negative experiences related to program culture and inclusivity. In practice, racialized ophthalmologists reported higher discrimination rates, reduced advancement into leadership, and underrepresentation on faculty and editorial boards.&lt;/div&gt;&lt;div&gt;While URiM match rates have improved, progress has been uneven. Asian representation has approached parity, while Black, Native American, and Pacific Islander individuals remain severely underrepresented. National ophthalmology mentorship programs have demonstrated high match success and participation. Residency programs that implemented structured interviews, holistic review and targeted equity strategies reported improved URiM representation, though implementation varied.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;Racial and ethnic disparities remain pervasive in ophthalmology. While overall progress has occurred, gains have been concentrated among Asian individuals. Coordinated systemic reforms are urgently needed for a more represent","PeriodicalId":7568,"journal":{"name":"American Journal of Ophthalmology","volume":"284 ","pages":"Pages 196-207"},"PeriodicalIF":4.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145986455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dazdotuftide: Novel Treatment for Noninfectious Uveitis with Superior Intraocular Pressure Safety Profile: A Randomized Clinical Trial","authors":"DAVID S CHU ,&nbsp;EDMUND TSUI ,&nbsp;LANA M RIFKIN ,&nbsp;ALAN G PALESTINE ,&nbsp;CADMUS RICH ,&nbsp;JENNIFER E THORNE ,&nbsp;DAPHNE HAIM-LANGFORD ,&nbsp;ZOHAR MILMAN ,&nbsp;EMILEE FULCHER ,&nbsp;RON NEUMANN ,&nbsp;MARC D DE SMET","doi":"10.1016/j.ajo.2025.12.034","DOIUrl":"10.1016/j.ajo.2025.12.034","url":null,"abstract":"<div><h3>PURPOSE</h3><div>To evaluate the safety and efficacy of dazdotuftide (TRS01 eye drops), a novel, steroid-free, anti-inflammatory drug in patients with active anterior noninfectious uveitis (NIU), following previous studies in which it had shown a favorable risk/benefit profile with regards to safety and specifically intraocular pressure (IOP) safety profile.</div></div><div><h3>DESIGN</h3><div>A randomized, double-masked, multicenter, active-controlled phase 3 trial.</div></div><div><h3>PARTICIPANTS</h3><div>Adults (≤75 years of age) and pediatric patients, with active anterior NIU, with or without uveitic glaucoma, on stable medical therapy for NIU or who had received no prior therapy, requiring further treatment for an active NIU flare-up. Patients eligible for inclusion had Anterior Chamber Cell (ACC) Grade 2 or Grade 3 on Visual Analog Scale in the study eye.</div></div><div><h3>METHODS</h3><div>Patients were randomized 2:1 to topical TRS01 1% or prednisolone acetate 1% administered 4 times daily for 28 days. Key ocular assessments included slit-lamp examination, ocular pain, Best Corrected Visual Acuity, IOP and dilated ophthalmoscopy.</div></div><div><h3>MAIN OUTCOME MEASURES</h3><div>Resolution of inflammation (ACC = 0), clinically meaningful improvement of ACC, ocular pain, flare, and IOP changes on Day 28.</div></div><div><h3>RESULTS</h3><div>The Full Analysis Set included 136 patients; the mean age was 43 years in the TRS01 arm and 42 years in the prednisolone acetate arm. 48% of TRS01 vs 68% of prednisolone acetate patients achieved ACC Grade = 0 on Day 28 (95.1% Confidence Interval (CI): −0.37, −0.02; <em>P</em> = .0311) and 64% of TRS01 vs 89% prednisolone acetate patients experienced clinically meaningful improvement of ACC Grade = 0 or 1, ie, ≤5 cells (95.1% CI: −0.33, −0.06; <em>P</em> = .0049). While TRS01 was found to be inferior to topical steroids to control ACC, TRS01 was noninferior to topical steroids to control flare and ocular pain and exhibited a superior IOP safety compared to topical steroids. For patients who reached ACC = 0, TRS01-treated patients benefited from statistically significantly improved safety outcomes for IOP (including change from baseline and at each IOP threshold evaluated [<em>P</em> &lt; .05]) versus steroid-treated patients.</div></div><div><h3>CONCLUSIONS</h3><div>TRS01 offers the potential to serve as an effective and safe treatment option in NIU that meets the urgent need for a drug that controls inflammation without the steroids’ associated risk of IOP elevation.</div></div>","PeriodicalId":7568,"journal":{"name":"American Journal of Ophthalmology","volume":"284 ","pages":"Pages 78-87"},"PeriodicalIF":4.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145893646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reduced Risk of Non-Neovascular AMD in Cancer Patients Treated With Immune Checkpoint Inhibitors: A Propensity-Matched Cohort Study","authors":"Natan Lishinsky-Fischer ,&nbsp;Sima Gharra ,&nbsp;Itay Nitzan,&nbsp;Itay Chowers,&nbsp;Jaime Levy","doi":"10.1016/j.ajo.2025.12.035","DOIUrl":"10.1016/j.ajo.2025.12.035","url":null,"abstract":"<div><h3>Purpose</h3><div>To evaluate whether immune checkpoint inhibitors (ICIs), which modulate T-cell activity in cancer therapy, influence the risk of developing age-related macular degeneration (AMD).</div></div><div><h3>Design</h3><div>Retrospective cohort study.</div></div><div><h3>Participants</h3><div>Adults aged ≥60 years with a history of cancer, identified from the TriNetX Global Collaborative Network. Only patients who remained alive throughout the follow-up period were included.</div></div><div><h3>Methods</h3><div>Two cohorts were constructed: patients who received ICIs and those who did not. Sub-analyses were conducted for patients with melanoma and for those with metastatic disease. Propensity score matching (1:1) was performed using demographic and clinical covariates. Kaplan-Meier estimates and Cox proportional hazards models assessed the association between ICI exposure and AMD incidence over 5 years.</div></div><div><h3>Main Outcome Measures</h3><div>Incidence of non-neovascular and neovascular AMD after ICI therapy.</div></div><div><h3>Results</h3><div>After matching, 36,037 patients were included in each cohort. ICI-treated patients had a significantly lower risk of developing non-neovascular AMD (hazard ratio [HR], 0.77; 95% CI, [0.63, 0.93]; log-rank <em>P</em> = .0084) over a 5-year follow-up. No significant association was observed between ICI exposure and neovascular AMD. The protective association persisted in melanoma and metastatic subgroups.</div></div><div><h3>Conclusions</h3><div>In this large, multicenter cohort, ICI therapy was associated with a reduced risk of non-neovascular AMD in older adults with cancer. These findings suggest a potential protective role of T-cell modulation in AMD pathogenesis and highlight the need for further research into the retinal effects of ICIs.</div></div>","PeriodicalId":7568,"journal":{"name":"American Journal of Ophthalmology","volume":"284 ","pages":"Pages 153-160"},"PeriodicalIF":4.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145937813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"En Face Optical Coherence Tomography and OCT Angiography in the Pathoanatomy of Inflammatory Macular Disease","authors":"Alessandro Feo ,&nbsp;David Sarraf","doi":"10.1016/j.ajo.2025.12.031","DOIUrl":"10.1016/j.ajo.2025.12.031","url":null,"abstract":"<div><h3>Purpose</h3><div>To review the pivotal role of en face optical coherence tomography (OCT) and OCT angiography (OCTA) in elucidating the pathoanatomy, diagnostic markers, and clinical management of inflammatory macular diseases. These noninvasive modalities provide depth-resolved, layer-specific visualization of structural and vascular alterations, enhancing our understanding of disease mechanisms and facilitating monitoring of disease activity and therapeutic response.</div></div><div><h3>Methods</h3><div>This perspective article synthesizes recent advances in multimodal imaging (MMI) with emphasis on en face OCT and OCTA across the spectrum of posterior noninfectious and infectious uveitic disorders. Representative diseases include multiple evanescent white dot syndrome (MEWDS), punctate inner choroidopathy (PIC), and idiopathic multifocal choroiditis (iMFC), acute zonal occult outer retinopathy (AZOOR), acute posterior multifocal placoid pigment epitheliopathy (APMPPE) and its chronic variants, serpiginous choroiditis (SC), acute syphilitic posterior placoid chorioretinopathy (ASPPC), and Vogt-Koyanagi-Harada (VKH) disease. Imaging signatures were reviewed in relation to pathophysiology, differential diagnosis, and clinical management.</div></div><div><h3>Results</h3><div>En face OCT delineates disease-specific topographic patterns: “dots and spots” in MEWDS, hyperreflective plaques in PIC/iMFC, trizonal maps in AZOOR, sharply demarcated placoid lesions in APMPPE, geographic patterns in SC, and concentric hyperreflective “fingerprint” rings in VKH. OCTA provides complementary vascular insights, distinguishing preserved vs impaired choriocapillaris (CC) flow and revealing disease-driven ischemia. MEWDS typically demonstrates preserved CC perfusion, in contrast to the flow deficits of APMPPE, relentless placoid chorioretinitis, and SC. In PIC/iMFC, OCTA enables detection of inflammatory choroidal neovascularization (iCNV), while in ASPPC and VKH, it captures reversible or persistent CC flow voids following appropriate systemic therapy. Structural-vascular correlation permits differentiation between ischemic and nonischemic disorders, recognition of masquerades, and monitoring of subclinical disease activity.</div></div><div><h3>Conclusions</h3><div>En face OCT and OCTA have redefined the diagnostic and management landscape of inflammatory macular diseases by providing rapid, reproducible, and layer-specific structural-vascular information. Their disease-specific signatures enhance accuracy, support treatment decisions, and improve monitoring of progression and complications such as inflammatory CNV. Integration of these tools into routine multimodal imaging protocols is essential, while future research should prioritize standardization of acquisition and interpretation criteria, quantitative biomarkers, and expanded use of widefield technologies to capture peripheral and longitudinal disease dynamics.</div></div>","PeriodicalId":7568,"journal":{"name":"American Journal of Ophthalmology","volume":"284 ","pages":"Pages 110-122"},"PeriodicalIF":4.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145893643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunopathology of the Outer Retina: Crosstalk With the Immune System","authors":"Gerhild Wildner ,&nbsp;Miranda Gehrke ,&nbsp;Olaf Strauß","doi":"10.1016/j.ajo.2025.12.032","DOIUrl":"10.1016/j.ajo.2025.12.032","url":null,"abstract":"<div><h3>Objective</h3><div>The retinal pigment epithelium (RPE) forms the outer blood-retina barrier. This barrier separates the retina from the choriocapillaris, as well as the immune system. The RPE contributes to the immune privilege of the eye by communicating with the local and systemic immune systems via various receptors and soluble factors. We recently described the expression and upregulation of the transcription factor FoxP3 in stressed RPE cells <em>in vivo</em> and <em>in vitro</em>. FoxP3 was initially described as being specific to regulatory T cells. Based on the hypothesis that different FoxP3 variants are expressed in RPE cells, we investigated the subcellular localization of FoxP3 using a panel of nine antibodies raised against different FoxP3 epitopes in ARPE-19 cells.</div></div><div><h3>Design</h3><div>We investigated cytokine secretion and FoxP3 expression in stressed and unstressed ARPE-19 cells.</div></div><div><h3>Methods</h3><div>Culture supernatants from ARPE-19 cells treated with LPS or with mechanical disruption of the cell layer were investigated for cytokine secretion using a multiplex assay. The cells were then stained with immunofluorescent antibodies that target different FoxP3 domains and phosphorylation sites to detect the intracellular localization of FoxP3.</div></div><div><h3>Main outcome measures</h3><div>Detection of FoxP3 at the subcellular level by identifying different epitopes on the protein.</div></div><div><h3>Results</h3><div>Stressed ARPE-19 cells upregulate inflammatory cytokines (IL-6 and MCP-1), which correspond with FoxP3 localization patterns in the cytoplasm and nucleus (phosphorylated FoxP3), depending on the epitope detected by the antibodies.</div></div><div><h3>Conclusions</h3><div>Stressed RPE cells switch from a tolerogenic to an effector phenotype, yet they immediately re-establish immune privilege by upregulating the transcription factor FoxP3, similar to T cells in the immune system. These different FoxP3 detection patterns suggest an RPE-specific role in maintaining the immune barrier, as well as in other non-T cell tissues that express FoxP3.</div></div>","PeriodicalId":7568,"journal":{"name":"American Journal of Ophthalmology","volume":"284 ","pages":"Pages 56-65"},"PeriodicalIF":4.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145897374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}