Am. J. Ophthalmol. [JOURNAL]
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200 papers
Clinical Features of Corneal Adverse Events Associated With Trastuzumab Botidotin: Payload-Driven Epitheliopathy and Neuropathy.
Zhang Y, Tang G, Zhang J … +4 more , Fu Y, Zhang X, Qi Y, Zhou N
Am J Ophthalmol · 2026 May · PMID 42176831 · Publisher ↗
PURPOSE: HER2-targeted antibody-drug conjugates (ADCs) demonstrate significant efficacy in HER2-mutated or HER2-positive tumors but may cause ocular adverse events (AEs), particularly corneal epitheliopathy and blurred v...
PURPOSE: HER2-targeted antibody-drug conjugates (ADCs) demonstrate significant efficacy in HER2-mutated or HER2-positive tumors but may cause ocular adverse events (AEs), particularly corneal epitheliopathy and blurred vision. This study aimed to characterize the clinical features of trastuzumab botidotin (a HER2-targeted ADC)-related corneal AEs. DESIGN: Retrospective case series. SUBJECTS: Eight adult patients (15 eyes) with HER2-mutated or HER2-positive solid tumors treated with trastuzumab botidotin. METHODS: Assessments included best-corrected visual acuity, Ocular Surface Disease Index, Schirmer's test, tear break-up time, tear meniscus height, and corneal fluorescein staining. In vivo confocal microscopy (IVCM) was performed to evaluate cellular structures and confirm lesion characteristics. MAIN OUTCOME MEASURES: Corneal AEs associated with trastuzumab botidotin and their clinical features. RESULTS: Corneal AEs occurred in all eight patients. The mean time to visual impairment onset was 37.25 ± 5.90 days after trastuzumab botidotin initiation, with symptom severity peaking at 82.75 ± 14.26 days. Ocular Surface Disease Index scores increased from 5.73 ± 2.67 at baseline to 65.10 ± 13.26 at peak severity. Trastuzumab botidotin caused dry eye in all patients (n = 8), resulting in reduced Schirmer's test results (from 8.94 ± 1.66 mm to 4.20 ± 1.58 mm), shortened tear break-up time (from 9.63 ± 1.21 seconds to 3.37 ± 1.61 seconds), and decreased tear meniscus height (from 0.23 ± 0.04 mm to 0.14 ± 0.02 mm). Slit-lamp microscopy and fluorescein staining revealed that trastuzumab botidotin induced distinct corneal epitheliopathy, characterized by pseudomicrocysts, punctate epitheliopathy, diffuse punctate epitheliopathy, and vortex keratopathy. IVCM correlated these findings, showing cyst-like hyperreflective structures in the superficial epithelium, grape-like hyperreflective clusters in wing cells and basal cells, and associated cellular disorganization. IVCM demonstrated neurotoxic damage, characterized by thinning of subbasal nerves, decreased nerve density, and focal discontinuities in the subbasal nerve plexus. CONCLUSIONS: Trastuzumab botidotin was associated with visual impairment, corneal epitheliopathy, and nerve damage. Close collaboration between ophthalmologists and oncologists is crucial for early detection of corneal AEs related to ADC therapy, thereby improving clinical outcomes and patient quality of life.
Reply to Comment on "RNFL Thickness in a Population-Based Cohort: The Canadian Longitudinal Study on Aging M2M (Machine-to-Machine) Study".
Azizi A, da Costa DR, Scherer R … +3 more , Malek DA, Samico GA, Medeiros FA
Am J Ophthalmol · 2026 May · PMID 42176830 · Publisher ↗
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Ocular Hypertension Treatment Study: Effect of Time After Incident Glaucoma on OCT Optic Nerve Head and Macula Measurements.
Walker E, Bowd C, Jain S … +8 more , Huecker J, Dirkes KA, Vega S, Hunsicker M, Gordon MO, Kass MA, Weinreb RN, Zangwill LM
Am J Ophthalmol · 2026 May · PMID 42173190 · Publisher ↗
PURPOSE: The objectives of this report are to compare optical coherence tomography (OCT) based retinal nerve fiber layer (RNFL) and ganglion cell / inner plexiform layer (GCIPL) thickness in participants who developed pr...
PURPOSE: The objectives of this report are to compare optical coherence tomography (OCT) based retinal nerve fiber layer (RNFL) and ganglion cell / inner plexiform layer (GCIPL) thickness in participants who developed primary open-angle glaucoma (POAG) in the Ocular Hypertension Treatment Study (OHTS) to RNFL and GCIPL thickness in those who did not develop POAG (ie, a parallel control group) and to elucidate the relationship between duration after reaching an OHTS POAG endpoint and RNFL and GCIPL thickness. DESIGN: Clinical cohort study using OCT data. METHODS: Six hundred and forty six OHTS participants who completed OHTS 3 visit OCT imaging were included. Cirrus and Spectralis parapapillary RNFL and GCIPL thickness measurements were compared between 450 eyes that developed POAG and 723 eyes in the control group that did not develop POAG. RESULTS: In eyes that developed POAG compared to eyes that did not develop POAG, mean global RNFL thickness was between 11.1 and 12.7 µm thinner and mean global GCIPL was between 4.5 and 7.6 µm thinner using Spectralis and Cirrus OCT, respectively (all comparisons P < .001). The 10+ years after POAG diagnosis POAG eyes had ∼10% thinner mean global RNFL thickness and GCIPL thickness than eyes with shorter durations after POAG diagnosis. CONCLUSIONS: In the OHTS, the ocular hypertensive eyes that developed POAG had significantly thinner RNFL and GCIPL measurements compared with the ocular hypertensive eyes that did not develop glaucoma. In addition, longer duration of POAG was associated with thinner RNFL/GCIPL independent of POAG treatment status and IOP level. These results characterize the magnitude of RNFL and GCIPL thinning associated with increasing POAG duration and reinforce the role of OCT as a key tool for monitoring glaucomatous structural change in eyes with OH.
The Neovascular Ocular Hypertension Spectrum: A Novel Classification of Neovascular Glaucoma.
Swaminathan SS, Qiu M
Am J Ophthalmol · 2026 May · PMID 42173189 · Publisher ↗
PURPOSE: To propose a novel, anatomically based classification system for eyes traditionally labeled as neovascular glaucoma (NVG) that better reflects disease severity, guides contemporary management, and aligns with mo...
PURPOSE: To propose a novel, anatomically based classification system for eyes traditionally labeled as neovascular glaucoma (NVG) that better reflects disease severity, guides contemporary management, and aligns with modern anti-vascular endothelial growth factor (anti-VEGF) and angle-based surgical treatment paradigms. DESIGN: Perspective and conceptual framework. SUBJECTS, PARTICIPANTS, AND/OR CONTROLS: Not applicable. METHODS, INTERVENTION, OR TESTING: We synthesized contemporary clinical experience and published literature regarding the diagnosis and management of eyes with anterior segment neovascularization and elevated intraocular pressure (IOP). Emphasis was placed on iridocorneal angle anatomy, extent of peripheral anterior synechiae (PAS), disease activity in response to anti-VEGF therapy, and implications for medical and surgical management. Based on these considerations, we developed a staged classification system prioritizing angle status at the time of presentation. MAIN OUTCOME MEASURES: Development of a clinically intuitive, anatomically descriptive nomenclature to categorize disease severity, facilitate communication among clinicians, and support stage-specific treatment protocols. RESULTS: We propose the neovascular ocular hypertension (NVOH) spectrum, consisting of four stages arranged from least to most severe: NVOH suspect, NVOH, partial neovascular angle closure (NVAC), and total NVAC. Disease modifiers of active versus quiescent reflect the presence or regression of anterior segment neovascularization following anti-VEGF therapy. The framework also introduces the term acute neovascular crisis (ANC) to describe symptomatic, acutely elevated IOP associated with active partial or total NVAC. This classification emphasizes the extent of synechial angle closure as a key determinant of management, distinguishing eyes that may be candidates for angle-based microinvasive glaucoma surgery, after achieving quiescence, from those requiring urgent surgical IOP lowering. Limitations include the conceptual nature of the framework and the absence of prospective validation. CONCLUSIONS: The NVOH spectrum offers a modernized, anatomically grounded alternative to the ambiguous term "neovascular glaucoma." By prioritizing angle status and disease activity over optic nerve assessment, which is often unreliable in eyes with advanced retinal disease, this classification supports more precise diagnosis, tailored treatment selection, and improved interdisciplinary communication. Prospective studies are needed to validate this nomenclature, refine stage-specific treatment algorithms, and assess its impact on clinical outcomes.
Imaging Characteristics and Longitudinal Follow-Up of Inner Choroidal Fibrosis in Chronic Central Serous Chorioretinopathy.
Hansraj S, Chhablani J, Narayanan R … +1 more , Sahoo NK
Am J Ophthalmol · 2026 May · PMID 42173188 · Publisher ↗
PURPOSE: To study imaging characteristics of inner choroidal fibrosis (ICF) in eyes with chronic central serous chorioretinopathy (CSC) and report long term changes. DESIGN: Retrospective interventional case series. METH...
PURPOSE: To study imaging characteristics of inner choroidal fibrosis (ICF) in eyes with chronic central serous chorioretinopathy (CSC) and report long term changes. DESIGN: Retrospective interventional case series. METHODS: Records of chronic CSC patients between January 2004 and September 2024 were reviewed to identify and study longitudinal changes in eyes with ICF. ICF was divided into morphological types: type 1 and type 2. Type 1 ICF represented disorganized inner choroid without well-defined accumulations, while type 2 ICF represented accumulations with a demarcation line. RESULTS: Thirty-eight eyes of 23 patients were identified. All the eyes had complex CSC, with a mean of 1.7 lesions per eye. Patients were followed up for a median period of 36.5 months. The mean BCVA reduced from 0.67 ± 0.46 logMAR (20/95) to 0.78 ± 0.44 logMAR (20/121). Mean BCVA at time of presentation (0.83 logMAR, 20/135 vs 0.51 logMAR, 20/65; P = .1), as well as at last visit (0.88 logMAR, 20/152 vs 0.66 logMAR, 20/91; P = .7) was worse in eyes with Type 2 as compared to Type 1 ICF. Resolution of CSC was seen in 5 eyes (12.8%) at the last visit. There was a non-significant decrease in SFCT (456 vs 444 microns, P = .8) and significant increase in hypo-fluorescence area on indocyanine green angiography of 4.25 sq. mm (P < .00001). Higher duration of follow-up and persistent fluid were associated with increase of size in ICF on multivariate regression analysis. CONCLUSION: ICF in complex CSC was associated with persistent fluid and poor response to therapy. It was seen to increase in size with increasing chronicity.
Efficacy of En Face Optical Coherence Tomography Minimum Intensity Projection in Evaluating Inflammatory Retinal Vascular Changes.
Mizuno Y, Srivastava SK, Bellanda V … +6 more , Chen C, Barbosa GCS, Shin D, Sanchez E, Baynes K, Sharma S
Am J Ophthalmol · 2026 May · PMID 42173187 · Publisher ↗
PURPOSE: To evaluate the diagnostic performance of en face optical coherence tomography (OCT) using minimum intensity projection (MIP) to detect fluorescein angiography (FA)-defined inflammatory retinal vascular changes....
PURPOSE: To evaluate the diagnostic performance of en face optical coherence tomography (OCT) using minimum intensity projection (MIP) to detect fluorescein angiography (FA)-defined inflammatory retinal vascular changes. DESIGN: Prospective, single-center reliability and validity analysis. PARTICIPANTS: A total of 318 eyes from 177 patients with uveitis who underwent same-day ultra-widefield FA and macula-centered 12 × 12-mm spectral-domain OCT imaging. METHODS: Inflammatory retinal vascular changes were defined as vascular leakage and/or vascular wall staining on late-phase FA. En face OCT images were generated using MIP slabs spanning 10% to 70% of total retinal thickness. MIP images and retinal thickness maps were independently graded in a masked fashion and compared with FA as the reference standard. Diagnostic performance metrics were calculated. Inter-grader agreement was assessed using Cohen's κ coefficient. MAIN OUTCOME MEASURES: Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), F1 score, and inter-grader agreement for detecting FA-defined inflammatory retinal vascular changes. RESULTS: FA demonstrated inflammatory retinal vascular changes in 208 of 318 eyes (65%), including 94 with activity within the central 12 × 12-mm field and 114 with activity confined to the peripheral retina. Overall, MIP en face OCT achieved a sensitivity of 0.82, specificity of 0.55, PPV of 0.77, NPV of 0.62, and F1 score of 0.80 for detecting FA-defined inflammatory retinal vascular changes. Compared with retinal thickness maps, MIP demonstrated substantially higher sensitivity (0.82 vs 0.50) and F1 score (0.80 vs 0.57). MIP en face OCT identified FA-positive eyes with higher detection rates than retinal thickness maps for both central activity (98% vs 60%) and peripheral-only activity (68% vs 42%). Inter-grader agreement was higher for MIP images (κ = 0.75) than for thickness maps (κ = 0.37). In a subset of eyes with longitudinal follow-up, MIP positivity preceded or persisted beyond changes in FA leakage. CONCLUSIONS: En face OCT using MIP demonstrated high sensitivity for detecting FA-defined inflammatory retinal vascular changes. Although not a replacement for FA, this approach may provide a noninvasive adjunct for clinical assessment and longitudinal evaluation of uveitic disease.
Opacity Detection on Optical Coherence Tomography Based on an Incidence-Angle and Depth-Dependent Model of Corneal Reflectance.
Assaf JF, Yazbeck H, Sims D … +5 more , Hong J, Liu CF, Gunes I, Li Y, Huang D
Am J Ophthalmol · 2026 May · PMID 42167435 · Full text
PURPOSE: To develop and validate an automated corneal opacity detection algorithm for optical coherence tomography (OCT) images, utilizing an incidence-angle- and depth-dependent model of corneal reflectance. DESIGN: Ret...
PURPOSE: To develop and validate an automated corneal opacity detection algorithm for optical coherence tomography (OCT) images, utilizing an incidence-angle- and depth-dependent model of corneal reflectance. DESIGN: Retrospective, cross-sectional diagnostic accuracy study. SUBJECTS: Training used 95 healthy eyes from 49 volunteers. Testing included 50 eyes from 42 patients with corneal opacities and 35 healthy eyes from 35 volunteers. METHODS: Normal-eye OCT scans were used to model normative incidence-angle-dependent reflectance across corneal layers. The algorithm detected pixels above the normal reflectance range using model-based thresholds, binned percentile analysis, and morphological operations. Eye-level performance was evaluated against slit-lamp examination as clinical ground truth and compared with 5 trained physician annotators. Pixel-level agreement with consensus annotations (≥3 of 5 annotators) was assessed with Dice similarity coefficient. MAIN OUTCOME MEASURES: Eye-level accuracy, F1-score, sensitivity, and specificity; pixel-level Dice similarity coefficient and segmented-area agreement versus consensus annotations. RESULTS: At the eye level, the algorithm achieved accuracy of 0.93, F1-score of 0.94, sensitivity of 0.96, and specificity of 0.89. Human annotators had a mean accuracy of 0.83 ± 0.06, F1-score of 0.85 ± 0.04, sensitivity of 0.84 ± 0.09, and specificity of 0.80 ± 0.27. At the pixel level, mean Dice similarity coefficient versus consensus was 0.58 for the algorithm and 0.71 ± 0.05 for annotators. The algorithm's total segmented opacity area was close to the consensus pixel count (98% of consensus). CONCLUSION: An algorithm that incorporates incidence angle and depth-specific reflectance thresholds detects and segments corneal opacities. It demonstrated favorable accuracy at the eye level and produced quantitative opacity maps on OCT.
Incidence and Progression of Glaucoma Following Boston Type 1 Keratoprosthesis: A Systematic Review and Meta-Analysis.
Abu Osba A, Sawires K, Bondok M … +4 more , Abdelaal A, Harissi-Dagher M, Betsch D, Pollmann AS
Am J Ophthalmol · 2026 May · PMID 42167434 · Publisher ↗
TOPIC: Boston Type 1 Keratoprosthesis (KPro) implantation is an established surgery for severe corneal blindness when traditional keratoplasty is not feasible. This systematic review and meta-analysis aimed to quantify t...
TOPIC: Boston Type 1 Keratoprosthesis (KPro) implantation is an established surgery for severe corneal blindness when traditional keratoplasty is not feasible. This systematic review and meta-analysis aimed to quantify the incidence and progression of glaucoma following KPro implantation. CLINICAL RELEVANCE: Despite advances in device design and postoperative management, glaucoma remains a sight-threatening complication. Accurate estimates of glaucoma incidence and progression can inform treatment decisions and enhance long-term visual outcomes in this high-risk population. METHODS: MEDLINE, Embase, and CENTRAL were systematically searched from inception to June 2025. Two independent reviewers performed title/abstract screening, full-text screening, data extraction, and risk-of-bias assessment, with discrepancies resolved through discussion with a third reviewer. Studies reporting glaucoma-related outcomes following KPro implantation were included. Random-effects meta-analyses were performed to estimate pooled incidences of postoperative glaucoma. Risk of bias was assessed using Joanna Briggs Institute tools, and certainty of evidence was evaluated using GRADE. This review was prospectively registered on PROSPERO (ID: CRD420251036643). RESULTS: Twenty-three studies met inclusion criteria, encompassing 1,482 eyes with a mean follow-up of 39.4 months (±14.4). The mean patient age was 54.5 years (±8.9). Pre-existing glaucoma affected 45.9% of eyes. Overall, the pooled incidence of any form of postoperative glaucoma events was 25.6% (95% CI: 18.1-34.8%, I² = 87.3%) and an incidence rate of 0.09 events per eye-year (95% CI: 0.07-0.13; I² = 91.6%). Among studies explicitly reporting de novo glaucoma, the pooled incidence was 31.1% (95% CI: 20.6-43.9%, I² = 70.6%), while progression of pre-existing glaucoma occurred in 37.7% of eyes (95% CI: 17.9-62.6%, I² = 85.7%). Ocular hypertension without diagnostic confirmation of glaucoma was observed in 17.1% of eyes (95% CI: 5.6-41.9%, I² = 71.3%). Significant heterogeneity was observed across studies, stemming from variability in outcome definitions, indication for KPro, and reporting practices. CONCLUSIONS: Glaucoma represents a clinically important complication following KPro implantation, affecting approximately one-quarter to one-third of eyes postoperatively. Although the certainty of evidence is very low due to heterogeneity and variability in diagnostic definitions, the results underscore the need for vigilant perioperative monitoring and standardized diagnostic approaches.
Predictors of Good Visual Recovery in Patients With Spontaneously Resolved Acute CSCR - MICRoN Report Number Thirteen.
Hasan N, Sahoo N, Gidwani K … +37 more , Saju S, Cao J, Wykoff CC, Shah P, Singhanetr P, Rossin E, Ashfaq Y, Kroeger Z, Gregori G, Lupidi M, Trisolini CIV, Yiu G, Momanaei B, Ni R, Garg S, Imanaga N, Koizumi H, Checchin L, Pili L, Parodi MB, Khateb S, Piccoli G, Vujosevic S, Desideri LF, Munk MR, Winter H, Gill MK, Lima LH, Fernandez CAR, Barquet LA, Kim M, Lai TYY, Fung AT, Zhang M, Wu L, Chhablani J, MICRoN Study Group
Am J Ophthalmol · 2026 May · PMID 42167433 · Publisher ↗
PURPOSE: This study investigated factors that lead to failure to achieve 20/20 visual acuity (VA) in patients with spontaneously-resolved acute CSCR. DESIGN: Multicenter retrospective observational cohort study METHODS:...
PURPOSE: This study investigated factors that lead to failure to achieve 20/20 visual acuity (VA) in patients with spontaneously-resolved acute CSCR. DESIGN: Multicenter retrospective observational cohort study METHODS: In this study, data were collected from 189 patients with first episode, spontaneously resolved acute CSCR in collaboration with the Macula Society CSCR Study Group (MICRoN). Patients were categorized based on post-resolution best-recorded visual acuity (BRVA) as better or worse than 20/20. Demographic characteristics and multimodal imaging features were analyzed to identify pertinent baseline biomarkers. Multivariate logistic regression identified several factors that were associated with <20/20 VA after resolution. RESULTS: This study included 195 eyes (189 patients), of whom 108 eyes (55.38%) achieved ≥20/20 VA and 87 (44.62%) demonstrated <20/20 VA. The mean age of patients was 45.45 ± 10.84 years, and 139 (73.54%) were males. Multivariate logistic regression showed older age (OR = 1.07, 95% CI: 1.03-1.11; P = .001), poor baseline VA (OR = 1.37, 95% CI: 1.15-1.63; p < .001), absence of serous pigment epithelial detachment (PED) (OR = 0.30, 95% CI: 0.09-0.95; P = .040) and bilaterality (OR = 4.12, 95% CI: 1.33-12.74; P = .014) were independent predictors of <20/20 VA post-resolution. CONCLUSION: Resolution of SRF in acute CSCR does not uniformly translate into 20/20 vision. Older age, poorer baseline BRVA, absence of serous PED, and bilateral CSCR were independent predictors of failure to achieve 20/20 vision after resolution. These findings highlight the importance of careful prognostication and functional assessment in cases of acute, single-episode CSCR.
Artificial Intelligence in Ophthalmic Research and Patient Care-What Are We Really Afraid of?
Quarta A, Lee AY, Sadda SR
Am J Ophthalmol · 2026 May · PMID 42167432 · Publisher ↗
Abstract loading — click title to view on PubMed.
Limited Independent Impact of Maternal Age on Early Childhood Ophthalmic Morbidity: A Nationwide Population-Based Cohort Study.
Kang S, Lee S, Park GU … +3 more , Heo SJ, Choi EY, Seo Y
Am J Ophthalmol · 2026 May · PMID 42162815 · Publisher ↗
PURPOSE: To evaluate the independent effect of advanced maternal age (AMA) on pediatric ophthalmic morbidity, invasive interventions, and healthcare costs. DESIGN: Nationwide, population-based cohort study PARTICIPANTS:...
PURPOSE: To evaluate the independent effect of advanced maternal age (AMA) on pediatric ophthalmic morbidity, invasive interventions, and healthcare costs. DESIGN: Nationwide, population-based cohort study PARTICIPANTS: A total of 2,500,044 mother-infant pairs from a national health insurance database, followed from birth to 5 years of age. A health-screening subgroup of 365,494 pairs with detailed maternal metabolic and lifestyle data was analyzed to control for potential confounding. METHODS: Mother-infant pairs were categorized by maternal age (<35 vs ≥ 35 years) and birth status (term/normal birth weight [NBW] vs preterm or low birth weight [LBW]). Cox proportional hazards models and Poisson or negative binomial regression models were used to estimate adjusted hazard ratios (HRs) and incidence rate ratios (IRRs) for ophthalmic outcomes, invasive procedures, and healthcare utilization. Models were sequentially adjusted for neonatal factors, socioeconomic status, maternal comorbidities, and maternal metabolic and lifestyle variables. MAIN OUTCOMES MEASURES: Composite ophthalmic morbidity (amblyopia, strabismus, congenital cataract), retinopathy of prematurity (ROP), invasive ophthalmic procedures, ophthalmic outpatient visits, hospitalizations, and ophthalmology-related healthcare costs. RESULTS: Among Term/NBW infants, older maternal age was associated with a lower risk of composite ophthalmic morbidity (adjusted HR, 0.93; 95% CI, 0.92-0.94), primarily driven by a reduced hazard of strabismus. However, this did not translate into reductions in invasive procedures or hospitalization rates. In contrast, Preterm/LBW status was the primary driver of all ophthalmic risks (HRs 1.52-1.81) and procedures (IRRs 1.84-2.00) regardless of maternal age. Among term/NBW infants, higher ROP diagnosis rates observed in the AMA group (adjusted HR 1.331; 95% CI, 1.211-1.450) were not accompanied by increased ROP-related invasive treatment. Apparent differences in ophthalmology-related healthcare costs across maternal age groups were attenuated and no longer significant after adjustment for maternal metabolic health. CONCLUSIONS: Advanced maternal age is not an independent biological determinant of early pediatric ophthalmic disease or treatment-requiring morbidity. In the absence of prematurity or low birth weight, children born to older mothers are not at increased risk of early ophthalmic disorders. These findings provide evidence-based reassurance for older mothers and support counseling that emphasizes perinatal health status rather than maternal age itself.
Impact of Viewing Distance on the Occurrence Rate of Intermittent Exotropia Revealed by Ambulatory Eye Tracking.
Economides JR, Horton JC
Am J Ophthalmol · 2026 May · PMID 42162814 · Publisher ↗
PURPOSE: Eye tracking in ambulatory patients permits measurement of the occurrence rate of intermittent exotropia. This information is useful for deciding which patients need surgery. However, viewing distance can influe...
PURPOSE: Eye tracking in ambulatory patients permits measurement of the occurrence rate of intermittent exotropia. This information is useful for deciding which patients need surgery. However, viewing distance can influence the occurrence rate, creating a potential confound. To address this issue, an approach was devised to break down the overall occurrence rate into separate components, compiled during either near viewing or far viewing. DESIGN: Prospective cross-sectional study. SUBJECTS: This study included 35 patients with intermittent exotropia, ranging in age from 3 to 79 years, with a median of 10 years. METHODS: Eye-tracking glasses were used to record each eye's horizontal position while subjects engaged in their customary daily activities. Scene video was reviewed to parse the data into epochs of near viewing vs far viewing. MAIN OUTCOME MEASURES: Four exotropia occurrence rates were calculated: (1) overall rate before segmentation by viewing distance, (2) overall rate after segmentation by viewing distance, (3) rate during near viewing only, and (4) rate during far viewing only. In addition, eye positions during near viewing and far viewing were compared to assess convergence effort during exotropia. RESULTS: In participants with a low occurrence rate, exotropia occurred mostly during distance viewing. As the occurrence rate increased, exotropia became more common during near viewing. For 28 of 35 patients, segmentation of data into near vs far viewing had a negligible impact on the overall occurrence rate. However, in 7 patients, this process revealed a near exotropia peak partially hidden in the orthotropia far peak, which resulted in a higher overall exotropia occurrence rate after segmentation by viewing distance. Comparison of exotropia amplitude during near vs far viewing showed that convergence effort varied widely among deviated subjects and, surprisingly, bore no relationship to the overall rate of exotropia occurrence. CONCLUSIONS: Partitioning of data recorded with eye-tracking glasses into near viewing vs far viewing allows a more accurate assessment of the overall rate of exotropia occurrence. A major advantage is that the impact of viewing distance associated with various activities is neutralized because separate exotropia occurrence rates are provided for near vs far viewing. Incorporation of range-finding capability into currently available mobile eye trackers would enhance their utility for the evaluation of patients with exotropia.
En Face Optical Coherence Tomography Imaging as a Structural Surrogate for Posterior Pole Inflammatory Retinal Vascular Activity.
Mizuno Y, Srivastava SK, Barbosa GCS … +6 more , Bellanda V, Shin D, Sanchez E, Chen C, Baynes K, Sharma S
Am J Ophthalmol · 2026 May · PMID 42155876 · Publisher ↗
PURPOSE: To evaluate whether structural en face optical coherence tomography (OCT) can detect structural surrogates at the posterior pole associated with fluorescein angiography (FA)-defined inflammatory retinal vascular...
PURPOSE: To evaluate whether structural en face optical coherence tomography (OCT) can detect structural surrogates at the posterior pole associated with fluorescein angiography (FA)-defined inflammatory retinal vascular activity in uveitis. DESIGN: Prospective, single-center reliability and validity analysis. SUBJECTS: Twenty-four eyes from 12 patients with uveitis who underwent same-day ultra-widefield FA and macula-centered 12 × 12-mm spectral-domain OCT imaging. METHODS: FA-defined inflammatory retinal vascular activity was defined as vascular leakage and/or vascular wall staining on late-phase FA in the presence of intraocular inflammation. Structural en face OCT images were generated using a customized slab extending from 35 µm below the inner plexiform layer to 35 µm below the outer plexiform layer, corresponding to the outer plexiform layer-outer nuclear layer transition. Images were graded independently by 2 masked retinal specialists and compared with FA findings on an image-by-image basis. MAIN OUTCOME MEASURES: Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), F1 score, and intergrader agreement (Cohen's κ). RESULTS: Fifty-three images were analyzed, of which 32 demonstrated FA-defined activity. En face OCT showed a sensitivity of 0.94 (95% CI, 0.83-1.00), specificity of 0.38 (95% CI, 0.10-0.72), PPV of 0.70 (95% CI, 0.45-0.90), NPV of 0.80 (95% CI, 0.50-1.00), and an F1 score of 0.80. Intergrader agreement was moderate (κ = 0.65). CONCLUSIONS: Structural en face OCT demonstrated high sensitivity for detecting structural changes associated with FA-defined inflammatory vascular activity at the posterior pole, although specificity was limited. These findings support its potential role as a noninvasive adjunctive tool for identifying regions that may warrant further evaluation, rather than a standalone indicator of active disease.
Deconstructing White Dot Syndromes-Multimodal Imaging in Uveitis (MUV) Taskforce: Report 11.
Invernizzi A, Agarwal A, Jampol LM … +16 more , Sadda SR, Cimino L, Gangaputra S, Staurenghi G, Tugal-Tutkun I, El-Asrar AMA, Pavesio CE, Jabs DA, McCluskey P, Okada AA, Agrawal R, Accorinti M, DE Smet M, Sarraf D, Gupta V, Multimodal Imaging in Uveitis (MUV) Task Force
Am J Ophthalmol · 2026 May · PMID 42150663 · Publisher ↗
PURPOSE: The term white dot syndromes (WDS) has historically grouped multiple non-infectious posterior uveitis (NIPU) entities based on a similar funduscopic appearance of "white dots." Despite decades of use, the clinic...
PURPOSE: The term white dot syndromes (WDS) has historically grouped multiple non-infectious posterior uveitis (NIPU) entities based on a similar funduscopic appearance of "white dots." Despite decades of use, the clinical relevance of this umbrella terminology has been questioned. This perspective critically examines whether WDS remains a valid conceptual and diagnostic construct in the era of advanced retinal and choroidal imaging. DESIGN: Perspective review. METHODS: Critical interpretation of the available literature on imaging and current pathophysiological evidence, combined with observations collected using cutting edge imaging technology (structural high-resolution optical coherence tomography (OCT), OCT angiography, and indocyanine green [ICG] angiography [ICGA]) for 6 of the NIPU classically considered as WDS: multiple evanescent white dot syndrome (MEWDS), multifocal choroiditis with panuveitis (MFCPU), punctate inner choroiditis (PIC), acute posterior multifocal placoid pigment epitheliopathy (APMPPE), serpiginous choroiditis (SC), and birdshot chorioretinitis (BSCR). RESULTS: Although these diseases share some overlapping clinical features, multimodal imaging reveals profound differences, with each entity having distinct anatomic features on multimodal imaging. OCT angiography (OCTA) demonstrate distinct patterns of tissue involvement-from photoreceptor/retinal pigment epithelium (RPE) injury in MEWDS, to Bruch's membrane disruption in MFCPU and PIC, to profound choriocapillaris ischemia in APMPPE and SC, and deep stromal choroidal infiltration in BSCR. ICGA further differentiates these entities by choroidal perfusion characteristics, distinguishing true vascular non-perfusion from other inflammatory reactions leading to tissue damage. Imaging-based hypotheses of immunopathogenesis suggest that these entities may arise from different immunopathogenic pathways-transient outer retinal inflammation (MEWDS), possible antigenic exposure from structural disruptions (MFCPU/PIC), primary inflammatory inner choroidal vascular occlusive process (APMPPE), a possible autoimmune or autoinflammatory choroidal ischemic mechanism (SC), and a likely Human Leukocyte Antigen (HLA)-A29-associated autoimmune response affecting the inner retina and choroid (BSCR) CONCLUSIONS: The label WDS, originally based on appearance alone, does not take into consideration major biological and prognostic differences among these NIPU. Current imaging-guided hypotheses of immunopathogenesis suggest that these conditions should no longer be grouped under a single classification. A paradigm shift toward disease-specific terminology is warranted to improve diagnostic precision, guide management, and reflect presumed pathophysiological diversity.
Reply to Comment on: "Optical Coherence Tomography Radiomics and Machine Learning Enable Accurate Detection of Forme Fruste Keratoconus".
Luo S, Li X, Lin K … +4 more , Bao F, Chen S, Lu F, Wang J
Am J Ophthalmol · 2026 May · PMID 42144177 · Publisher ↗
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Anesthesia-Related Neurologic Risk in Patients of Venezuelan Descent: Implications for Ophthalmology.
Diehl T, Chang TCP, Bademci G … +2 more , Stein ALS, Masters NH
Am J Ophthalmol · 2026 May · PMID 42142861 · Publisher ↗
PURPOSE: To alert ophthalmologists to an emerging pattern of catastrophic neurologic injury following general anesthesia in patients of maternal Venezuelan descent, to describe the proposed genetic mechanism, and to prov...
PURPOSE: To alert ophthalmologists to an emerging pattern of catastrophic neurologic injury following general anesthesia in patients of maternal Venezuelan descent, to describe the proposed genetic mechanism, and to provide practical guidance for ophthalmologists regarding this high-risk population. DESIGN: Perspective SUBJECTS: Patients of maternal Venezuelan descent who experienced neurologic complications following elective surgical procedures under general anesthesia, including 1 pediatric patient undergoing strabismus surgery who had prior exposure to general anesthesia. Approximately 40 cases have been identified as of April 2026, spanning multiple countries, including the United States, Chile, Germany, Spain, and Guyana. METHODS: Narrative review of emerging case reports, genetic analyses, and evolving clinical guidance for ophthalmologists pertaining to anesthesia-related neurologic injury in patients carrying the m.11232T>C variant of the mitochondrial gene MT-ND4. Recommendations were synthesized and applied to the ophthalmologic clinical context. CONCLUSIONS: Emerging evidence in the past year has established a consistent clinical pattern and a biologically plausible mechanism for these cases of severe neurologic injury following general anesthesia in otherwise healthy patients of Venezuelan descent. By incorporating targeted screening, ensuring early anesthesiology consultation, and adapting perioperative management, ophthalmologists are in a unique position to help prevent devastating outcomes.
Comment on: "Optical Coherence Tomography Radiomics and Machine Learning Enable Accurate Detection of Forme Fruste Keratoconus".
Shanthi R, Kavitha K, K S
Am J Ophthalmol · 2026 May · PMID 42140466 · Publisher ↗
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The Effect of Peribulbar Block Volume on Intraocular Pressure Change: A Randomized Prospective Study.
Alam BER, Young SK, Kiyota Y … +8 more , Mullaly CM, Oh K, Agarwal K, Davies EC, Liu C, Lin MM, Lozada GA, Luo ZK
Am J Ophthalmol · 2026 May · PMID 42140465 · Publisher ↗
PURPOSE: Peribulbar block (PB) is a widely used anesthesia modality in ophthalmic surgical procedures globally. There are no evidence-based guidelines on PB best practices available. We studied the relationship between b...
PURPOSE: Peribulbar block (PB) is a widely used anesthesia modality in ophthalmic surgical procedures globally. There are no evidence-based guidelines on PB best practices available. We studied the relationship between block solution volume, the change in intraocular pressure (IOP) and anesthesia effect to guide practice. DESIGN: Prospective, controlled, 1:1 randomized, interventional study carried out at two ambulatory surgical centers. SUBJECTS: Ambulatory male and female patients between age 18 and 79 years of age undergoing planned intraocular surgery with PB as the designated anesthesia modality per surgeon's instruction prior to study enrollment. Eyes with any previous ocular procedure or surgery, or any orbital surgery were excluded. Eyes with corneal scars or cornea edema were also excluded. METHODS: Prior to the scheduled ophthalmic surgery, the enrolled eye was randomized to either 4 mL or 7 mL block volume immediately before PB administration by one of the five anesthesiologists. A regimented 2-minute manual massage was performed by the same research assistant after every block. IOPs were measured with a freshly calibrated tonopen before-block, immediate after-block, and after-manual massage, twice at each time point. Immediately after the completion of the intended surgery, the surgeon was asked to fill the anesthesia satisfaction sheet while staying masked to the block volume. MAIN OUTCOME MEASURES: IOP changes at each step and the surgeons' rating of the quality of anesthesia. RESULTS: There were 50 eyes completed the trial with 25 eyes in each group. There was no statistically significant difference between the two groups in terms of IOP change after the block or after the massage; both groups' IOP decreased significantly after the ocular massage. The 7-mL group achieved a significantly higher surgeon satisfaction score. CONCLUSION: 7-mL PB was shown to be a safe and more effective method for ocular surgical procedures.
Outcomes of Minimally Invasive Glaucoma Surgery, Trabeculectomy, and Tube Shunt Surgery in Secondary Glaucoma: IRIS® Registry Analysis.
Fujita A, Zebardast N, Lorch AC … +3 more , Miller JW, Friedman DS, IRIS® Registry Analytic Center Consortium
Am J Ophthalmol · 2026 May · PMID 42140464 · Publisher ↗
PURPOSE: To evaluate the outcomes of minimally invasive glaucoma surgery (MIGS), trabeculectomy, and tube shunt surgery among young patients with secondary glaucoma. DESIGN: Retrospective clinical cohort study SUBJECTS:...
PURPOSE: To evaluate the outcomes of minimally invasive glaucoma surgery (MIGS), trabeculectomy, and tube shunt surgery among young patients with secondary glaucoma. DESIGN: Retrospective clinical cohort study SUBJECTS: A total of 2483 eyes with secondary glaucoma aged 18 to 40 years who underwent MIGS, trabeculectomy, or tube shunt surgery (2013-2024) in the IRIS Registry (Intelligent Research in Sight). METHODS: The 2-year failure rates were calculated using the Kaplan-Meier estimator, with failure defined as having any of the following: (1) insufficient intraocular pressure (IOP) reduction, defined as either IOP > 21 mm Hg or IOP reduction < 20% from preoperative IOP, (2) hypotony, defined as IOP < 5 mm Hg, (3) any additional glaucoma procedures, or (4) development of no light perception. MAIN OUTCOME MEASURES: The 2-year failure rates per surgery type per glaucoma subtype. RESULTS: A total of 454 MIGS, 337 trabeculectomies, and 1692 tube shunt surgeries were analyzed. The overall failure rates at 2 years were 50.6% for trabeculectomy, 52.1% for tube shunt surgery, 53.3% for goniotomy, and 49.0% for canaloplasty. The failure rates among traumatic glaucoma were 39.2% for trabeculectomy, 44.2% for tube shunt surgery, 55.6% for goniotomy, and 50.0% for canaloplasty. Glaucoma due to "other eye disorders," mostly following prior ocular procedures, had the highest failure rates following trabeculectomy and tube shunt surgery (58.5% and 62.2%, respectively). The failure rate for trabeculectomy was the lowest in steroid-induced glaucoma (37.6%), but hypotony was observed in 10.0% of cases. In uveitic glaucoma, the failure rates were 56.0% for trabeculectomy, 45.6% for tube shunt surgery, 55.1% for goniotomy, and 35.9% for canaloplasty. CONCLUSIONS: MIGS accounted for nearly one in 5 of the glaucoma surgeries recorded in young patients with secondary glaucoma, with approximately half of cases remaining failure-free at 2 years. Surgical outcomes varied depending on the subtype of secondary glaucoma, with glaucoma due to other eye disorders being associated with higher failure rates. Trabeculectomy for steroid-induced glaucoma was successful in nearly two-thirds of the cases, but hypotony was more common in these individuals. The comparison between procedure types should be interpreted with caution as the results may be influenced by baseline disease severity.
Comment on: Big Data or Big Bias? Interpreting Large-Scale Ophthalmic Studies.
Vasu P, Dorairaj SK
Am J Ophthalmol · 2026 May · PMID 42140463 · Publisher ↗
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