Am. J. Ophthalmol. [JOURNAL]
Sun
200 papers
Immune Checkpoint Inhibitor-Associated Uveitis: Insights From Comparative Analyses Across Malignancies and Drug Classes.
Bellanda V, Schulgit MJ, Hassan KA … +7 more , Kennedy LB, Barbosa GCS, Mizuno Y, Mohan N, Kaelber DC, Srivastava SK, Sharma S
Am J Ophthalmol · 2026 Jun · PMID 42229563 · Publisher ↗
PURPOSE: Understanding how the risk of immune checkpoint inhibitor (ICI)-associated noninfectious uveitis (NIU) differs by malignancy and drug class may help understand its pathophysiology and guide targeted ophthalmic s...
PURPOSE: Understanding how the risk of immune checkpoint inhibitor (ICI)-associated noninfectious uveitis (NIU) differs by malignancy and drug class may help understand its pathophysiology and guide targeted ophthalmic surveillance. This study aims to evaluate the comparative risk of ICI-associated NIU across different malignancies and drug classes. DESIGN: Retrospective, multicenter clinical cohort study. SUBJECTS: Adults with metastatic melanoma, lung cancer, renal cell carcinoma (RCC), urothelial carcinoma, hepatocellular carcinoma, Hodgkin lymphoma, or nonmelanoma skin cancer. Propensity score matching was performed for demographics, comorbidities, and socioeconomic factors. EXPOSURES: Prescription of an ICI agent of any class (anti-PD-1, anti-PD-L1, or anti-cytotoxic T-lymphocyte-associated protein 4 [CTLA-4]). MAIN OUTCOME MEASURES: The primary outcome was new-onset NIU within 24 months of first ICI prescription. Relative risks (RR) with 95% confidence intervals (CIs) were calculated. Subgroup analyses compared outcomes across malignancies, with and without ipilimumab or nivolumab exposure, and between ICI subclasses when used in monotherapy. RESULTS: After matching, 16,834 patients with melanoma and 16,834 with lung cancer were included. Melanoma patients had a higher risk of NIU compared with lung cancer (1.10% vs 0.18%; RR, 6.17; 95% CI, 4.20-9.08). Excluding ipilimumab/nivolumab, melanoma remained associated with increased risk (0.53% vs 0.16%; RR, 3.40; 95% CI, 1.68-6.88). Across malignancies, melanoma consistently demonstrated elevated risk relative to other cohorts. Lung cancer showed borderline decreased risk compared to RCC (0.19% vs 0.36%; RR, 0.53; 95% CI, 0.31-0.90), but this effect was not significant after excluding ipilimumab/nivolumab. In drug-class analyses, anti-PD-1 agents did not demonstrate a significantly different risk of NIU compared with anti-PD-L1 agents (0.26% vs 0.20%; RR, 1.33; 95% CI, 0.89-1.99). Anti-cytotoxic T-lymphocyte-associated protein 4 agents could not be compared due to limited use as monotherapy. CONCLUSIONS: Both malignancy type and ICI subclass influence the risk of ICI-associated uveitis. Melanoma carries an intrinsically higher risk independent of ipilimumab/nivolumab exposure, whereas RCC's risk appears largely ipilimumab/nivolumab-driven. These findings underscore the need for careful monitoring of melanoma patients initiating ICIs and suggest that the pathophysiology of ICI-related uveitis is driven by both drug- and disease-specific factors.
Conjunctival Biopsy in Ocular Mucous Membrane Pemphigoid.
Kate A, Wannapanich T, Huang AJW … +1 more , Jhanji V
Am J Ophthalmol · 2026 Jun · PMID 42229562 · Publisher ↗
OBJECTIVE: Ocular mucous membrane pemphigoid (oMMP) is a chronic autoimmune disorder that manifests primarily as progressive conjunctival scarring. We reviewed the published literature on the role of conjunctival biopsy...
OBJECTIVE: Ocular mucous membrane pemphigoid (oMMP) is a chronic autoimmune disorder that manifests primarily as progressive conjunctival scarring. We reviewed the published literature on the role of conjunctival biopsy in oMMP. DESIGN: Perspective. METHODS: Review of literature. RESULTS: The disease can result in progressive ocular surface discomfort, conjunctival scarring, and potential vision loss if timely systemic immunosuppression is not initiated. The diagnosis is typically contingent on positive findings on direct immunofluorescence of conjunctival biopsy samples. This is affected by several factors, which include but are not limited to the site of biopsy, stage of disease, tissue size, and expertise of the interpreting pathologist. Relying solely on the outcome of conjunctival biopsy can delay the institution of the required treatment, and this can adversely affect visual function and clinical outcome. When a thorough history and clinical examination effectively exclude common mimickers of oMMP, the observation of progressive conjunctival cicatrization in the absence of features suggestive of alternative etiologies may be sufficient to establish the diagnosis and mandate timely clinical management. In this context, conjunctival biopsy can be reserved for cases with atypical presentations or when differentiation from other entities, such as drug-induced cicatrization, is required. CONCLUSIONS: This perspective highlights the practical considerations, limitations, and evolving role of conjunctival biopsy in oMMP, underscoring its selective role within a multidisciplinary approach to the diagnosis and management of cicatricial conjunctivitis.
Vitrectomy Versus Observation for Lamellar Macular Holes With Epiretinal Proliferation: A Systematic Review and Meta-Analysis.
Sabage LE, Miranda JVC, DO Amaral Antunes ABF … +2 more , Meneghete BP, Moreira-Neto CA
Am J Ophthalmol · 2026 Jun · PMID 42229561 · Publisher ↗
TOPIC: To compare the visual and anatomical outcomes of vitrectomy with those of observation in eyes with lamellar macular holes associated with epiretinal proliferation (LHEP). CLINICAL RELEVANCE: LHEP is increasingly r...
TOPIC: To compare the visual and anatomical outcomes of vitrectomy with those of observation in eyes with lamellar macular holes associated with epiretinal proliferation (LHEP). CLINICAL RELEVANCE: LHEP is increasingly recognized in clinical practice, yet uncertainty persists regarding the visual benefits and full-thickness macular hole (FTMH) progression risk of surgical versus observational management. Reliable outcome estimates are essential for patient counseling and treatment planning. METHODS: A systematic review and meta-analysis. Literature search of PubMed, Embase, Scopus, Cochrane Library, and Web of Science were performed according to PRISMA guidelines and registered prospectively on PROSPERO (CRD420251089664). Eligible studies included adult patients with lamellar macular holes and LHEP managed with either vitrectomy or observation. The primary outcome was the change in best-corrected visual acuity (BCVA, logMAR). The secondary outcomes included progression to FTMH. Random-effects meta-analyses were conducted separately for surgical and observational cohorts due to limited direct comparative data. The risk of bias was assessed via the Newcastle-Ottawa Scale and the RoB 2 tool. Publication bias was evaluated via funnel plots, Egger's test, and trim-and-fill analysis. RESULTS: Seventeen studies encompassing 610 eyes met the inclusion criteria. In surgically treated eyes (14 studies; 328 eyes), vitrectomy was associated with significant visual improvement (pooled mean difference in BCVA -0.170 logMAR; 95% CI [-0.254, -0.086]; P < .001), with minimal heterogeneity (I² = 0%). In the observational cohort (5 studies; 282 eyes), no significant change in visual acuity was observed (-0.029 logMAR; 95% CI [-0.118, 0.176]; P = .695). The pooled rate of progression to FTMH was 7.5% (95% CI [4.0%,13.6%]) after vitrectomy and 4.2% (95% CI [1.4%, 11.8%]) after observation, with overlapping confidence intervals. Bias-adjusted analyses suggested a wider confidence interval for FTMH progression in the vitrectomy cohort, 12.4% (95% CI [7.4%, 20.1%]), and observational cohort, 10.1% (95% CI [3.3%, 27.2%]). CONCLUSION: In eyes with LHEP, vitrectomy is associated with clinically meaningful visual acuity improvement, whereas no significant change was observed in pooled observational data, without a clear increase in progression to FTMH. These findings support consideration of surgical intervention in appropriately selected patients, guided by symptoms and OCT-based features.
Comment on: Imaging Biomarkers for Early Differentiation of Candida and Aspergillus Endogenous Fungal Endophthalmitis: Multicenter Optical Coherence Tomography-Based Analysis.
Yuan Y
Am J Ophthalmol · 2026 Jun · PMID 42229560 · Publisher ↗
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Implementing Community-Based Adult Eye Screening in the United States: A CFIR-Guided Qualitative Study.
Ramachandran R, Bracy D, Doiphode A … +1 more , Newman-Casey PA
Am J Ophthalmol · 2026 Jun · PMID 42225246 · Publisher ↗
PURPOSE: Community-based eye disease screening programs can reduce preventable vision loss but often remain fragmented and difficult to sustain. To guide the development of screening efforts, this study applied the Conso...
PURPOSE: Community-based eye disease screening programs can reduce preventable vision loss but often remain fragmented and difficult to sustain. To guide the development of screening efforts, this study applied the Consolidated Framework for Implementation Research (CFIR) to identify determinants influencing the design, implementation, and sustainability of adult community-based eye disease screening programs across the United States. DESIGN: A qualitative, multi-site study using semi-structured interviews. PARTICIPANTS: Seventeen US eye care leaders representing 17 adult vision screening programs across 11 states participated. Programs varied in design, including clinical setting, workforce composition, and diagnostic testing modalities. METHODS: Participants completed 50- to 75-minute Zoom interviews (May-August 2024) focused on program design and implementation processes. Transcripts were coded in NVivo and thematically analyzed using a CFIR-guided codebook. Analytic rigor was maintained through double coding, consensus reconciliation, and an audit trail. Inter-rater reliability exceeded κ > 0.8. MAIN OUTCOME MEASURES: Key CFIR constructs and cross-cutting themes characterizing design and implementation determinants for community-based eye screening programs. RESULTS: Twenty-two themes emerged across the 5 CFIR domains. Innovation (program) characteristics reflected programs grounded in public health equity yet constrained by complexity and competing stakeholder priorities. Inner setting factors involved limited physical space, workforce shortages, and limited eye-care knowledge. Outer setting influencers centered on the necessity of community partnerships, the impact of federal and state policy, and unstable funding streams. Themes around individual characteristics highlighted the essential roles of both local champions within an organization as well as strong institutional support. Within the implementation (process) domain, successful programs relied on systematic needs assessments, tailored strategies, and iterative adaptation. CONCLUSIONS: Community eye screening is highly context-dependent and frequently sustained by motivated individuals rather than durable systems. CFIR analysis revealed how policy gaps, unclear and inconsistent "screening" definitions and best practices, fragile referral pathways, and tensions between research fidelity and real-world feasibility create persistent barriers. Future success will require coordinated policy support, sustainable financing, integration within existing health infrastructures, and flexible implementation toolkits. A CFIR-guided framework can inform such adaptable, equity-driven models that bridge evidence and real-world practice to advance population eye health.
Comment on "Nonmydriatic Ocular Fundus Imaging in a General Emergency Department: Feasibility and Novel Considerations for Systematic Screening".
Mohiuddin MA, Misbah Ul Haq M
Am J Ophthalmol · 2026 Jun · PMID 42219077 · Publisher ↗
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Risk of Retinal Detachment After Intravitreal Injection of Anti-VEGF: A Systematic Review and Meta-Analysis.
Mikhail D, Tao BK, Yu P … +15 more , Calicchia L, Butt FR, Dhivagaran T, Al-Qattan HM, Feo A, Quarta A, Mishra AV, Seamone ME, Navajas EV, Kertes PJ, Wong DT, Muni RH, Kaplan AJ, Yan P, Popovic MM
Am J Ophthalmol · 2026 May · PMID 42219076 · Publisher ↗
TOPIC: This systematic review and meta-analysis evaluated the literature-pooled risk of retinal detachment (RD) following intravitreal injection (IVI) of anti-vascular endothelial growth factor (anti-VEGF) agents. CLINIC...
TOPIC: This systematic review and meta-analysis evaluated the literature-pooled risk of retinal detachment (RD) following intravitreal injection (IVI) of anti-vascular endothelial growth factor (anti-VEGF) agents. CLINICAL RELEVANCE: Intravitreal anti-VEGF injections are the most frequently performed intraocular procedure, with RD remaining a poorly quantified complication. Pooled estimates equip clinicians to contextualize RD risk during informed consent. METHODS: This systematic review and meta-analysis followed PRISMA guidelines (PROSPERO: CRD420251175527). MEDLINE, Embase, and Cochrane CENTRAL were searched from inception to January 18, 2026. Included studies reported RD risk after anti-VEGF IVI for neovascular age-related macular degeneration (nAMD), diabetic macular edema, macular edema from retinal vein occlusion, proliferative diabetic retinopathy, or myopic choroidal neovascularization. Paired reviewers independently extracted data and assessed risk of bias using ROBINS-I and the Joanna Briggs Institute checklist for case series. A random-effects single-arm meta-analysis of proportions using a generalized linear mixed model generated pooled risk estimates per injection and per eye. RESULTS: Twelve studies comprising 834,814 injections and 119 RD events were included. In the meta-analysis of 9 studies (787,849 injections), there were 92 rhegmatogenous RD (RRD) events, with a pooled risk of 0.012% [95% CI (0.009-0.015%), I²: 14.4%], equivalent to 1 in 8675 injections. An acute ≤90-day postprocedural sensitivity analysis yielded a consistent RRD risk of 0.013% [95% CI (0.010-0.016%), I²: 36.8%] (approximately 1 in 7692 injections). An eye-level sensitivity analysis yielded a per-eye risk of 0.08% [95% CI (0.02-0.31%), I²: 66.7%] (approximately 1 in 1250 eyes). Exploratory subgroup analyses showed no differences in RRD risk by injection number (≥100,000 vs. <100,000; P=0.520), study setting (single-center vs. multicenter; P=0.258), injection indication (nAMD only vs. mixed; P=0.061), injection provider (ophthalmologist vs. mixed; P=0.259), or risk of bias (P=0.356). One study evaluating severe PDR reported tractional RD risk as 3.6% [95% CI (2.3-5.2%)] (approximately 1 in 28 injections), likely reflecting disease-specific fibrovascular contraction. CONCLUSION: Low-certainty evidence indicates RRD following anti-VEGF IVI is uncommon, with a per-injection risk of 0.012% (1 in 8675 injections). Per-eye risk was 0.08% (1 in 1250 eyes), which was subject to wider uncertainty but more relevant to patients undergoing long-term treatment; notably, the pooled mean of 13.8 injections per eye in the contributing studies likely underestimates real-world cumulative exposure. Future work should incorporate eye-level denominators and standardized reporting of RD subtypes, ocular characteristics, and injection technique to enable risk stratification and identification of modifiable procedural contributors.
Progression in Preperimetric Glaucoma Eyes With and Without Microvasculature Dropout.
Hashemi SM, Nishida T, Moghimi S … +6 more , Soltani G, Pereira AO, Micheletti E, Mittal R, Zangwill LM, Weinreb RN
Am J Ophthalmol · 2026 May · PMID 42214583 · Publisher ↗
PURPOSE: To investigate whether baseline microvasculature dropout (MvD) is associated with subsequent structural and functional changes in preperimetric glaucoma. DESIGN: Subgroup analysis of prospective cohort study dat...
PURPOSE: To investigate whether baseline microvasculature dropout (MvD) is associated with subsequent structural and functional changes in preperimetric glaucoma. DESIGN: Subgroup analysis of prospective cohort study data. METHODS: This study included 93 eyes from 70 participants with a glaucomatous optic disk appearance but no repeatable visual field defects, who were followed with optical coherence tomography, optical coherence tomography angiography, and visual field (VF) over a mean of 4.9 years. Circumpapillary retinal nerve fiber layer thickness and circumpapillary capillary density (cpCD) were assessed. Eyes were grouped based on the presence or absence of MvD at baseline. Mixed-effects models were used to identify factors associated with structural and functional progression. RESULTS: Mean age was 67.7 (95% CI, 65.4-70.0) years. Among the 93 eyes, those with baseline MvD (32 eyes) showed faster loss of cpCD (-0.88 [95% CI, -1.08 to -0.67] %/year) compared to eyes without MvD (-0.23 [95% CI, -0.42 to -0.04] %/year). In multivariable models, the presence of MvD was independently associated with faster cpCD loss (-0.63 [95% CI, -0.95 to -0.32] %/year, P < .001). In contrast, it was not associated with circumpapillary retinal nerve fiber layer loss (0.03 [95% CI, -0.33 to 0.38] µm/year, P = .886). Moreover, PPG eyes that had MvD at baseline developed VF loss more frequently than those without MvD. (62.5% vs 26.2%, P < .001). CONCLUSIONS: Baseline MvD in PPG is associated with both faster vessel density loss and subsequent VF loss, and higher rates of developing glaucomatous visual field damage. Assessment of MvD can be used to estimate risk and guide the frequency of follow-up in patients with PPG.
Ocular Safety Signals of Fibroblast Growth Factor Receptor Inhibitors in Postmarketing Surveillance.
Abu Osba A, Ahmad S, Abu Osba R … +7 more , Hendy AEA, Bondok M, Mihalache A, Kohly RP, Wong D, Muni RH, Popovic MM
Am J Ophthalmol · 2026 May · PMID 42214582 · Publisher ↗
OBJECTIVE: To evaluate postmarketing ocular adverse events (oAEs) associated with fibroblast growth factor receptor inhibitors (FGFRi). DESIGN: Population-based pharmacovigilance study. PARTICIPANTS: Ocular AE reports fr...
OBJECTIVE: To evaluate postmarketing ocular adverse events (oAEs) associated with fibroblast growth factor receptor inhibitors (FGFRi). DESIGN: Population-based pharmacovigilance study. PARTICIPANTS: Ocular AE reports from the US Food and Drug Administration Adverse Event Reporting System for individuals treated with erdafitinib, pemigatinib, or futibatinib. METHODS: US Food and Drug Administration Adverse Event Reporting System data from April 19, 2019 to June 30, 2025 were analyzed using OpenVigil 2.1. Disproportionality analyses were conducted to calculate reporting odds ratios for drug-oAE pairs compared with all other drugs. MAIN OUTCOME MEASURES: Disproportionality of reported ocular AEs among erdafitinib, pemigatinib, and futibatinib. RESULTS: A total of 1582 FGFR inhibitor-associated adverse events were identified, of which 200 (12.6%) were ocular. Erdafitinib accounted for the majority of ocular adverse events (75%), followed by pemigatinib (22%) and futibatinib (3%). The oAEs reported with the highest disproportionality signal with erdafitinib included corneal thinning (ROR 321; 95% CI 102-1009), ocular toxicity (ROR 225; 95% CI 117-439), and xerophthalmia (ROR 138; 95% CI 44-432). The oAEs with the greatest disproportionality signals with pemigatinib were serous retinal detachment (ROR 180; 95% CI 67-484), subretinal fluid (ROR 165; 95% CI 68-398), and retinal pigment epithelium detachment (ROR 110; 95% CI 35-344). Only 1 oAE was reported for futibatinib, which was dry eye (ROR 36.12; 95% CI 15.76-82.74). CONCLUSIONS: This pharmacovigilance analysis identified oAEs associated with FGFR inhibitors in real-world use, extending beyond those reported in clinical trials and regulatory labeling. However, findings are hypothesis-generating and reflect disproportional reporting rather than incidence or causal risk.
Comment on "Macular OCTA Biomarkers Predict Regional Retinal Nonperfusion Patterns on Ultra-Widefield Angiography in Diabetes".
Wang LU
Am J Ophthalmol · 2026 May · PMID 42191104 · Publisher ↗
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Optical Coherence Tomography (OCT) Features of Inactive Multifocal Choroiditis With Panuveitis and Punctate Inner Choroidopathy (MFCPU/PIC) Lesions.
Trinco A, Ferdeghini D, Zicarelli F … +5 more , Oldani M, Sadda S, Staurenghi G, Agarwal A, Invernizzi A
Am J Ophthalmol · 2026 May · PMID 42191103 · Publisher ↗
PURPOSE: To identify optical coherence tomography (OCT) biomarkers of inactive multifocal choroiditis with panuveitis and punctate inner choroidopathy (MFCPU/PIC) and to compare them with atrophic chorioretinal scars sec...
PURPOSE: To identify optical coherence tomography (OCT) biomarkers of inactive multifocal choroiditis with panuveitis and punctate inner choroidopathy (MFCPU/PIC) and to compare them with atrophic chorioretinal scars secondary to inflammatory and infectious mimickers. DESIGN: Cross-sectional observational study. SUBJECTS: Fifty-nine patients with inactive chorioretinal atrophic lesions, including 27 patients (57 lesions) with MFCPU/PIC and 32 patients (49 lesions) with non-MFCPU/PIC etiologies (sarcoidosis, tuberculosis, syphilis, serpiginous choroiditis, APMPPE, birdshot chorioretinopathy, and ocular toxoplasmosis), evaluated at Luigi Sacco Hospital (Milan, Italy). METHODS: All patients underwent multimodal imaging including color fundus photography, near-infrared reflectance, fundus autofluorescence, and spectral-domain OCT (SD-OCT), with additional high-resolution OCT (HR-OCT). Lesions were randomly sampled (maximum 3 per eye). Quantitative OCT measurements included retinal pigment epithelium atrophy size (RPE-AS), Bruch's membrane defect size (BrM-HS), and choroidal thickness coefficient (CTC). Structural alterations across retinal layers were graded. Regression models with cluster-robust standard errors were used to account for intrapatient clustering. MAIN OUTCOME MEASURES: Frequency of Bruch's membrane (BrM) disruption and inner retinal layer herniation; relationship between RPE-AS and BrM-HS; choroidal involvement; agreement between SD-OCT and HR-OCT. RESULTS: BrM disruption was observed in 94.7% of MFCPU/PIC lesions compared with 6.1% of controls (P < .001), remaining strongly associated with MFCPU/PIC independently from age and RPE-AS. Inner nuclear layer (INL) herniation was significantly more frequent in MFCPU/PIC lesions (57.9% vs 4.3%, P < .001). RPE atrophy was present in all lesions, while BrM defects were consistently smaller and concentrically localized within areas of RPE atrophy. RPE-AS and BrM-HS were positively correlated (β = 0.36, P = .002). MFCPU/PIC lesions demonstrated lower CTC values (P < .001) and more frequent focal choroidal excavation. Agreement between SD-OCT and HR-OCT was good (κ = 0.60), with no added diagnostic yield of HR-OCT. CONCLUSIONS: Bruch's membrane disruption and inner retinal layer herniation into focal choroidal excavation are highly characteristic OCT features of inactive MFCPU/PIC. These findings may facilitate diagnosis in the absence of active inflammation and support a distinctive lytic inflammatory mechanism involving the outer retina, BrM, and choroid.
Reply to Comment on: "Macular OCTA Biomarkers Predict Regional Retinal Nonperfusion Patterns on Ultra-Widefield Angiography in Diabetes".
Kakihara S, Fawzi AA
Am J Ophthalmol · 2026 May · PMID 42177935 · Publisher ↗
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Predictors of 1-Year Visual Outcome in Central-Involving Submacular Hemorrhage Secondary to Neovascular AMD.
Gilead N, Chong YJ, Cheng MFS … +9 more , Kikushima W, Sherif M, George L, Ong C, Sun C, Hong CH, Ibrahim FNI, Teo KYC, Cheung CMG
Am J Ophthalmol · 2026 May · PMID 42177934 · Publisher ↗
PURPOSE: To identify clinical and imaging predictors of 12-month visual outcome in patients with fovea-involving submacular hemorrhage (SMH) due to neovascular age-related macular degeneration (nAMD) and polypoidal choro...
PURPOSE: To identify clinical and imaging predictors of 12-month visual outcome in patients with fovea-involving submacular hemorrhage (SMH) due to neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV). DESIGN: Prospective observational clinical cohort study. SUBJECTS: Asian patients with nAMD or PCV presenting with fovea-involving SMH. METHODS: Between January 2016 and July 2024, eyes presenting with fovea-involving SMH ≥ 1 disc diameter with no evidence of blood organization were included. All patients received standard-of-care treatment. Clinical and multimodal imaging parameters were analyzed to identify predictors of visual outcome at 12 months. MAIN OUTCOME MEASURES: Good (≤0.3 logMAR) and poor (≥1.0 logMAR) visual outcomes at 12 months. RESULTS: Among 487 treatment-naïve eyes, 75 met inclusion criteria for fovea-involving SMH. Mean (SD) age was 71.40 (9.59) years, 74.4% were male, and 76.0% had PCV. Mean hemorrhage size was 19.45 (22.65) mm². All eyes received anti-VEGF therapy, 2.6% underwent additional pneumatic displacement, and 5.3% received photodynamic therapy. Best-corrected visual acuity (BCVA) improved from 1.04 (0.67) logMAR to 0.69 (0.62) at 12 months. 25 eyes (33.3%) achieved good visual outcome, while 22 eyes (29.3%) had poor visual outcome. On multivariable analysis, younger age (OR = 0.47 per decade, 95% CI: 0.26-0.86; P = .02), better baseline BCVA (OR = 0.87 per 0.1 logMAR, 95% CI: 0.79-0.97; P < .01), and thicker subfoveal choroid (OR = 1.50 per 50 µm, 95% CI: 1.07-2.10; P = .02) independently predicted good visual outcome. Conversely, larger hemorrhage size predicted poor visual outcome (OR = 1.04 per mm, 95% CI: 1.01-1.07; P = .02). CONCLUSION: One-third of eyes with SMH achieved 0.3 logMAR (Snellen equivalent 20/40) or better vision. In addition to age, baseline BCVA, and hemorrhage size, we identified choroidal thickness as a biomarker associated with visual outcome.
Accuracy of 8 Modern Intraocular Lens Power Calculation Formulas in Asian Eyes With Axial Length ≥ 32.00 mm.
Xiang J, He W, Qi J … +6 more , Meng J, Zhang K, Du Y, Cheng K, Lu Y, Zhu X
Am J Ophthalmol · 2026 May · PMID 42177933 · Publisher ↗
OBJECTIVE: To compare the accuracy of 8 modern intraocular lens (IOL) power calculation formulas in Asian eyes with axial length (AL) ≥32.00 mm. DESIGN: Retrospective observational study to compare IOL power calculation...
OBJECTIVE: To compare the accuracy of 8 modern intraocular lens (IOL) power calculation formulas in Asian eyes with axial length (AL) ≥32.00 mm. DESIGN: Retrospective observational study to compare IOL power calculation formulas. SUBJECTS: A total of 330 eyes from 330 Asian cataract patients with AL ≥ 32.00 mm were included. Eyes with previous ocular surgery, vision-threatening corneal disease, or surgical complications were excluded. METHODS: The accuracy of eight formulas was evaluated: Barrett Universal II, Cooke K6, EVO 2.0, Hill-RBF 3.0, Kane, Pearl-DGS, Hoffer QST, and Zhu-Lu. To minimize systematic refractive bias, prediction error (PE) values were arithmetically adjusted to zero the mean PE for each formula and each IOL model. Due to the 35.00 mm AL input limit of Hill-RBF and Kane, refractive outcomes were analyzed separately in the Main Group (32.00 mm ≤ AL < 35.00 mm, n = 307) and Ultra-Long Group (AL ≥ 35.00 mm, n = 23). The correlation between PE and AL was also assessed. MAIN OUTCOME MEASURES: Root mean square absolute error (RMSAE), median absolute error (MedAE), and percentages of eyes with prediction error within ±0.50 D. RESULTS: In the Main Group, Zhu-Lu showed the lowest RMSAE (0.562 D), with Cooke K6 ranking closely behind (0.563 D). Cooke K6 achieved the lowest MedAE (0.271 D), followed by EVO and Pearl-DGS (both 0.272 D). Pearl-DGS had the highest proportion of eyes within ±0.50 D (75.24%), whereas Zhu-Lu had the highest proportion within ±1.00 D (93.49%). Hoffer QST had the highest RMSAE (0.682 D), the highest MedAE (0.369 D), and the lowest proportion within ±0.50 D (61.89%). In the small Ultra-Long Group, Zhu-Lu yielded the lowest RMSAE (0.438 D) and the highest proportion within ±0.50 D (78.26%), whereas Cooke K6 had the lowest MedAE (0.281 D). Hoffer QST again showed the greatest hyperopic drift with increasing AL. CONCLUSIONS: In eyes with AL ≥ 32.00 mm, modern formulas showed distinct differences in predictive accuracy. Based on an integrated assessment across multiple accuracy metrics, Cooke K6, EVO, Pearl-DGS, and Zhu-Lu are clinically preferable options for this specific population, although their relative strengths differ across endpoints.
Comment on "RNFL Thickness in a Population-Based Cohort: The Canadian Longitudinal Study on Aging M2M (Machine-to-Machine) Study".
Aitha AR, Pamisetty V, Recharla M
Am J Ophthalmol · 2026 May · PMID 42177932 · Publisher ↗
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Asymmetric Peripheral Retinal Vascular Extension in Anti-Vascular Endothelial Growth Factor-Treated Type 1 Retinopathy of Prematurity: Disparity Between Nasal and Temporal Hemispheres.
Shah N, Chandler M, Sauer L … +1 more , Hartnett ME
Am J Ophthalmol · 2026 May · PMID 42177931 · Publisher ↗
PURPOSE: Anti-vascular endothelial growth factor (anti-VEGF) therapy is an important treatment for type 1 retinopathy of prematurity (T1ROP). We previously found that regulation of VEGF signaling increased developmental...
PURPOSE: Anti-vascular endothelial growth factor (anti-VEGF) therapy is an important treatment for type 1 retinopathy of prematurity (T1ROP). We previously found that regulation of VEGF signaling increased developmental vascularization into the temporal peripheral retina while reducing intravitreal neovascularization in T1ROP. To address our hypothesis that extension of retinal vascularization by early treatment with anti-VEGF could reduce T1ROP, we determined the effects of anti-VEGF therapy on retinal vascular extension in both retinal hemispheres. DESIGN: Retrospective, masked, nonrandomized, matched, comparative case series. SUBJECTS: Over 3 years, 34 of 382 screened infants developed bilateral T1ROP. Consent was obtained from parents of 21 infants for infants receiving bevacizumab 0.25 mg OU. Seven treated eyes (7 infants) had suitable imaging and were included in the treatment group. Seven untreated eyes (7 infants) without T1ROP were randomly selected after matching for birthweight and postmenstrual age from the 382 screened infants and assigned to the control group. METHODS: Infants had gradable 100° field-of-view fundus photographs of both retinal hemispheres at 2 time points: baseline before treatment, if administered, and follow-up, 12 to 35 days later. No eyes with vascularization to the ora at baseline or follow-up were included. Retinal vascular extent was measured in pixels from the optic disc margin to the temporal or nasal vascular borders and divided by the optic disc diameter in pixels to create disc diameter units (DD). Measurements were confirmed by a second masked analyst. The Mann-Whitney U test and Wilcoxon signed-rank test were used for statistical analysis. MAIN OUTCOME MEASURES: Temporal and nasal vascular extension in DD. RESULTS: Relative to control eyes, treated eyes had greater nasal (1.27 ± 0.59 vs 0.55 ± 0.44 DD; P = .038) and temporal (1.69 ± 1.16 vs 0.62 ± 0.49 DD; P = .04) extensions. There was greater disparity in vascular extension between nasal and temporal hemispheres in the treated group than in the control group (0.98 ± 0.64 vs 0.10 ± 0.10 DD; P = .005). Nasal extension was greater than temporal extension in 3 of 7 treated vs 1 of 7 control eyes. CONCLUSIONS: Treated eyes had significantly greater vascular extension in both hemispheres than control eyes, with greater nasal-temporal asymmetry. Although limited by sample size, our findings raise the question of uneven anti-VEGF diffusion in the infant vitreous. Further studies testing injection site, needle length, anti-VEGF agent, and molecular size differences and further follow-up periods are indicated.
Morphologic Staging of Photoreceptor Damage as a Predictor of Visual Recovery After PDT in Chronic Central Serous Chorioretinopathy.
Berni A, Scalabrin G, Neri G … +5 more , Introini U, Barresi C, Reibaldi M, Bandello F, Borrelli E
Am J Ophthalmol · 2026 May · PMID 42177930 · Publisher ↗
PURPOSE: To evaluate whether a morphologic staging system of photoreceptor integrity on spectral-domain optical coherence tomography (SD-OCT) predicts anatomical and functional outcomes after verteporfin photodynamic the...
PURPOSE: To evaluate whether a morphologic staging system of photoreceptor integrity on spectral-domain optical coherence tomography (SD-OCT) predicts anatomical and functional outcomes after verteporfin photodynamic therapy (PDT) in chronic central serous chorioretinopathy (CSC). DESIGN: Multicenter, retrospective observational cohort study. PARTICIPANTS: A total of 139 eyes from 126 patients with chronic CSC presenting with active subfoveal subretinal fluid (SRF) and treated with half-dose or half-fluence verteporfin PDT. METHODS: All eyes underwent standardized multimodal imaging and SD-OCT at baseline and during follow-up. Photoreceptor morphology within the central 1 mm was graded at baseline using a 6-stage OCT-based classification reflecting progressive disruption of the ellipsoid and interdigitation zones. Anatomical response was defined as complete foveal SRF resolution within 6 months. Functional outcome was the change in best-corrected visual acuity (ΔBCVA, logMAR) among eyes achieving SRF resolution. Cox regression models assessed predictors of SRF resolution, and multivariable linear and ANCOVA models evaluated determinants of visual improvement and final BCVA. MAIN OUTCOME MEASURES: Baseline photoreceptor stage, likelihood of SRF resolution, ΔBCVA among responders, and final BCVA within 6 months. RESULTS: SRF resolution occurred in 58% of eyes (81/139). The probability of SRF resolution decreased with worsening photoreceptor stage in univariable analysis, but in multivariable Cox regression, symptom duration (HR 0.97 per month, P = .023) was the only independent predictor of anatomical success. Among responders, visual recovery decreased stepwise across photoreceptor stages. Compared with Stage 1A, ΔBCVA declined progressively in Stage 3 (β = -0.117, P = .005), Stage 4 (β = -0.310, P < .001), and Stage 5 (β = -0.717, P < .001). For final BCVA, photoreceptor stage remained a strong independent predictor (Stage 3-5 all P ≤ .035) together with baseline BCVA (P < .001), while symptom duration was not significant. Responders showed significantly greater reduction in CST and SCT than nonresponders (both P < .001). CONCLUSIONS: In chronic CSC, symptom duration determines the likelihood of anatomical recovery after PDT, whereas photoreceptor integrity is the key determinant of visual acuity recovery. The proposed 6-stage OCT classification provides a reproducible structural biomarker that captures cumulative photoreceptor injury and robustly predicts visual prognosis, offering a clinically useful framework for treatment counseling, stratification in CSC trials, and future automated imaging analysis.
Cost Analysis of an Outpatient MRI Pathway for Optic Disc Edema: A Time-Driven Activity-Based Costing Approach.
Guillot FH, Davis J, Manikandan D … +7 more , Bai J, Carper MG, Carey AR, Saheed M, Nadgir R, Anaya J, Henderson AD
Am J Ophthalmol · 2026 May · PMID 42176834 · Publisher ↗
OBJECTIVE: To compare the costs and efficiency of an outpatient STAT neuroimaging pathway against traditional emergency department (ED)-based neuroimaging for patients with optic disc edema. DESIGN: Retrospective cost an...
OBJECTIVE: To compare the costs and efficiency of an outpatient STAT neuroimaging pathway against traditional emergency department (ED)-based neuroimaging for patients with optic disc edema. DESIGN: Retrospective cost analysis using time-driven activity-based costing (TDABC) methodology. SUBJECTS: One-hundred twenty-nine patients with optic disc edema, seen at the Wilmer Eye Institute, underwent expedited neuroimaging between November 2018 and February 2024. METHODS: We identified patients who received neuroimaging for optic disc edema either through the ED or a dedicated outpatient STAT neuroimaging pathway implemented in November 2020. Process maps were developed for each pathway. TDABC methodology was used to calculate the cost of personnel, equipment, facilities, and consumables based on resource-specific capacity cost rates and time utilization data extracted from the electronic medical record and staff interviews. MAIN OUTCOME MEASURES: The primary outcome was the total cost of neuroimaging via the STAT outpatient versus ED pathway. Secondary outcomes included total visit duration and the distribution of costs across different resource categories. RESULTS: The outpatient STAT pathway was significantly less costly than the ED pathway. The median total cost per patient was $285 for the STAT pathway compared with $355 for the combined ED pathway (P < .001), representing a 20% cost reduction. This savings was primarily driven by lower personnel ($154 vs $220; P < .001) and facilities costs ($1.30 vs $6.70; P < .001). The median imaging visit duration was 70% shorter in the STAT pathway (1.93 hours) compared with the ED (6.47 hours; P < .001). This time difference was largely attributable to the pre-MRI phase, which was over 20 times shorter in the outpatient setting (0.22 vs 4.80 hours; P < .001). CONCLUSIONS: An outpatient STAT neuroimaging pathway is a cost- and time-saving alternative to the ED for expedited neuroimaging in select patients presenting with optic disc edema. The novel use of TDABC methodology in this setting allowed for an unbiased assessment of healthcare costs, independent of local reimbursement structures or payor variability. Additionally, a detailed process map of the imaging workflow facilitated identification of inefficiencies. Together, these methods provide a reliable framework to optimize care pathways, substantially reduce healthcare costs, and alleviate burden on EDs.
Centripetal Retinal Degeneration Follows an Exponential Decay and May Be Reversed Following Gene Therapy.
Abdalla Elsayed MEA, Josan AS, Rehman S … +1 more , Maclaren RE
Am J Ophthalmol · 2026 May · PMID 42176833 · Publisher ↗
PURPOSE: To model the progression of the hyperautofluorescent ring in rod-cone dystrophies and to report a novel finding of its reversal following gene therapy. DESIGN: Retrospective analysis of a prospective cohort stud...
PURPOSE: To model the progression of the hyperautofluorescent ring in rod-cone dystrophies and to report a novel finding of its reversal following gene therapy. DESIGN: Retrospective analysis of a prospective cohort study. PARTICIPANTS: Fifty-eight individuals with genotyped rod-cone dystrophies and hyperautofluorescent rings on fundus autofluorescence (FAF). METHODS: Patients with a rod-cone dystrophy and hyperautofluorescent rings on FAF were identified and their rings categorized according to disease progression. Correlation between different FAF and optical coherence tomography (OCT) parameters in patients with early-mid stage disease were calculated. A retrospective, longitudinal analysis of FAF images was subsequently performed. A linear mixed model, with the dependent variable of total horizontal hyperautofluorescent ring width and independent variables of time, genotype and the interactions was used. MAIN OUTCOME MEASURES: Horizontal diameter of the hyperautofluorescent ring. RESULTS: A total of 58 rod-cone dystrophy patients were analyzed in this study. Twenty eyes of 20 patients presented with early to mid-stage disease. The internal ring diameter, external ring diameter and ring thickness, were strongly correlated with the ellipsoid zone width (r = 0.94), external limiting membrane width (r = 0.97) and loss of the ellipsoid zone (r = 0.92) respectively. Longitudinal analysis suggests that FAF changes decline very predictably in a logarithmic fashion (R = 0.958). Results indicated a significant reversal of the hyperautofluorescent ring following RPGR gene therapy (using Cotoretigene Toliparvovec), correlating with improvements in retinal sensitivity. CONCLUSIONS: Our findings suggest that centripetal retinal degeneration in rod-cone dystrophies follows an exponential decay and that gene therapy may reverse both structural and functional deficits.
Prevalence of Chronic Health Conditions by Vision Difficulty Status Among Middle-Aged and Older Adults, United States, 2020-2024.
Choi JHS, Carlson SA, Pavkov ME … +3 more , Pierce SL, Puckett M, Omura JD
Am J Ophthalmol · 2026 May · PMID 42176832 · Publisher ↗
OBJECTIVE: Examine the prevalence of select chronic health conditions by self-reported vision difficulty status among middle-aged and older adults in the United States. DESIGN: Cross-sectional, population-based analysis....
OBJECTIVE: Examine the prevalence of select chronic health conditions by self-reported vision difficulty status among middle-aged and older adults in the United States. DESIGN: Cross-sectional, population-based analysis. PARTICIPANTS: U.S. adults aged ≥45 years. METHODS: Self-reported data were from the 2020 to 2024 National Health Interview Survey (N = 85,026). Conditions included self-reported hypertension, heart disease, high cholesterol, stroke, arthritis, cancer, weak/failing kidneys, dementia, diabetes, depression, and obesity. Adjusted prevalence ratios (APRs) were estimated using multivariable logistic regression models for each condition by vision difficulty status (none, some, severe) stratified by age group (45-64, ≥65 years). MAIN OUTCOME MEASURES: Unadjusted and adjusted prevalence and APRs of 11 chronic health conditions by vision difficulty status. RESULTS: Overall, 20.2% of adults aged ≥45 years reported some vision difficulty and 2.1% reported severe vision difficulty. Among adults aged 45 to 64 years, the adjusted prevalences of most chronic conditions were higher among those with some or severe vision difficulty compared to those with no vision difficulty. For example, the adjusted prevalence of hypertension was 32.9% (95% confidence interval [CI]: 31.0-34.5) among those with no vision difficulty compared to 47.8% (95% CI: 42.4-53.2) among those with severe vision difficulty, with an APR of 1.45 (95% CI: 1.32-1.60). Similar patterns were observed among adults aged ≥65 years. CONCLUSIONS: Our findings highlight the importance of integrating vision health into chronic disease prevention and management strategies, considering the condition type, severity of vision difficulty and age when developing and tailoring these strategies.
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