Searches / Am. J. Ophthalmol. [JOURNAL]

Am. J. Ophthalmol. [JOURNAL]

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Cost Analysis of Outpatient Ophthalmic Procedures.

Moon EF, Meller LL, Korn BS … +1 more , Kikkawa DO

Am J Ophthalmol · 2026 Jun · PMID 42297201 · Publisher ↗

OBJECTIVE OR PURPOSE: To evaluate the financial feasibility of various ophthalmic procedures performed at outpatient facilities, including ambulatory surgical centers (ASCs) and hospital outpatient departments (HOPDs) re... OBJECTIVE OR PURPOSE: To evaluate the financial feasibility of various ophthalmic procedures performed at outpatient facilities, including ambulatory surgical centers (ASCs) and hospital outpatient departments (HOPDs) relative to Medicare facility reimbursement in 2025 and beyond. DESIGN: Cost efficiency analysis. SUBJECTS, PARTICIPANTS, AND/OR CONTROLS: Outpatient Facilities in San Diego, California. METHODS, INTERVENTION, OR TESTING: In this study, we propose a novel framework to analyze ASCs and HOPDs based on maximum intraoperative time to maintain financial neutrality. Common ophthalmic procedures were selected using insurance claims data. Total costs for each procedure were determined using a combination of internal financial records, defined operational frameworks, and publicly available data. These inputs were used to calculate the maximum intraoperative time for each procedure relative to publicly available Medicare facility reimbursement rates. MAIN OUTCOME MEASURES: The primary outcome was total intraoperative time to maintain financial neutrality for nine common ophthalmic surgical procedures. RESULTS: Common ophthalmic procedures included: cataract removal with insertion of intraocular lens, aqueous shunt to extraocular plate reservoir, upper eyelid blepharoplasty, dacryocystorhinostomy, trabeculectomy, penetrating keratoplasty, repair of blepharoptosis, strabismus repair, and mechanical pars plana vitrectomy. Maximum intraoperative time to maintain financial neutrality for ASCs ranged from 117.2 (aqueous shunt to extraocular equatorial plate reservoir) to 11.9 (vitrectomy) minutes and was driven by Medicare facility reimbursement and direct material cost per procedure. For HOPDs, maximum intraoperative time were approximately twice as high for most procedures and ranged from 160.8 (aqueous shunt to extraocular equatorial plate reservoir; CPT 66180) to 54.5 (blepharoplasty, upper eyelid; CPT 15823) minutes. CONCLUSIONS: In this analysis, the majority of ophthalmic procedures performed at ASCs analyzed had a maximum intraoperative time to maintain financial neutrality >30 minutes, indicating that ASCs are well-positioned to offer common ophthalmic surgical procedures in a financially-efficient manner. Our model finds that Medicare reimbursement relative to direct material cost per procedure was the main driver of maximum intraoperative time, highlighting the unique financial considerations ASCs may face due to limitations on reimbursement and lower Medicare facility fees compared to HOPDs. These findings support the utility of this framework in evaluating the cost-efficiency of ASCs to inform future decisions on procedures to adopt. Furthermore, our findings identify areas of discussion regarding the feasibility and utility of performing ophthalmic procedures at ASCs rather than in traditional hospital based operating rooms to promote equitable access to healthcare.

Application of a quantitative vascular severity score in retinopathy of prematurity in the United States and India: new insights into disease epidemiology and pathophysiology.

Campbell JP, Nayak S, Ostmo S … +6 more , Coyner AS, Singh P, Kalpathy-Cramer J, Shah P, Chan RP, Chiang MF

Am J Ophthalmol · 2026 Jun · PMID 42288327 · Publisher ↗

PURPOSE: To compare the epidemiology and phenotypic characteristics of two populations of patients with retinopathy of prematurity (ROP) using a quantitative artificial-intelligence (AI) derived vascular severity scale (... PURPOSE: To compare the epidemiology and phenotypic characteristics of two populations of patients with retinopathy of prematurity (ROP) using a quantitative artificial-intelligence (AI) derived vascular severity scale (VSS) METHODS: We retrospectively analyzed two datasets of ROP images: 1) The iROP dataset including 1019 babies and 6552 eye-level exams developed as part of a large US multicenter cohort study from 2012-2020. 2) 8281 consecutive ROP telemedicine examinations from 2363 babies in the Indian Aravind Eye Care System (AECS), from 2019-2020. We analyzed all eye exams using the iROP DL system that outputs a VSS from 1-9. The main outcome was the relationship between the VSS and the zone, stage, and extent of stage 3 in each dataset, assessed using generalized estimating equations to account for correlation from bilateral and repeated exams. RESULTS: In both datasets, higher VSS was associated with higher stage (P<.001 for all stages in both datasets), higher extent of stage 3 (i-ROP P=.004 and AECS P<.001), and more posterior zone for a given stage of ROP (i-ROP stage 1 P=0.04, 2 P<.001, and 3 P<.001 and AECS stage 1 P<.001 and 3 P<.001. For any given stage, the VSS was lower in the AECS dataset versus i-ROP (all P<.001). CONCLUSIONS: In both populations, the VSS was associated with more posterior zone and higher ROP stage/extent, though on average the VSS was lower in the AECS population. A correlation between measured VSS and intraocular vascular endothelial growth factor concentration might explain both findings.

Impact of Contact Lens Use on Clinical Profile and Outcomes of Fungal Keratitis: An 8-Year Retrospective Study.

Kate A, Wannapanich T, Mandell J … +2 more , Mammen A, Jhanji V

Am J Ophthalmol · 2026 Jun · PMID 42288326 · Publisher ↗

PURPOSE: To compare clinical characteristics, microbiological profiles, treatment strategies, and outcomes between contact lens-associated (CL) and non-contact lens-associated (non-CL) fungal keratitis. DESIGN: Retrospec... PURPOSE: To compare clinical characteristics, microbiological profiles, treatment strategies, and outcomes between contact lens-associated (CL) and non-contact lens-associated (non-CL) fungal keratitis. DESIGN: Retrospective, comparative clinical cohort study. METHODS: A review of culture-proven fungal keratitis treated at a tertiary referral center between 2018 and 2025 was conducted. Cases were categorized as CL or non-CL-associated. Demographic, clinical, microbiological, treatment, and outcome data were analyzed and compared between groups. RESULTS: Thirty-seven eyes were included, comprising 16 CL and 21 non-CL cases. CL users presented earlier than non-CL patients (median 7 vs. 14 days, p = 0.007) and had fewer associated ocular risk factors (31% vs. 81%, p = 0.001). Baseline visual acuity and infiltrate size did not differ significantly between groups. Candida species were isolated in 21% cases, Fusarium in 16% and Aspergillus in 8%. Fusarium (19% vs 13%) and Candida (24% vs 19%) infections were slightly more frequent in non-CL cases. Overall, filamentous fungi were the predominant organism group. Topical voriconazole was the most frequently used antifungal agent (78%). All CL-associated cases resolved with medical therapy alone, with a median time to resolution of 38 days (IQR 22-58). In contrast, 76% of non-CL cases resolved medically (median 42 days, IQR 32-76), while 23% required therapeutic keratoplasty (p = 0.04). Final visual acuity was comparable between groups (logMAR 0.2 vs. 0.5, p = 0.56). CONCLUSION: Contact lens-associated fungal keratitis is characterized by earlier presentation and fewer underlying ocular comorbidities, with favorable outcomes achieved through medical therapy alone. Despite similar microbiological profiles and treatment approaches, non-contact lens-associated fungal keratitis more frequently follows a complicated course requiring surgical intervention.

The American Journal of Ophthalmology reckons with "race" and "ethnicity".

Parrish RK

Am J Ophthalmol · 2026 Jun · PMID 42288325 · Publisher ↗

Abstract loading — click title to view on PubMed.

Noncombustible Nicotine or Tobacco Product Use after Smoking Cessation and Major Vision-Impairing Diseases: A Nationwide Cohort Study.

Cheon S, Kim Y, Kang ES … +2 more , Lee H, Jeong S

Am J Ophthalmol · 2026 Jun · PMID 42288324 · Publisher ↗

OBJECTIVE: We assessed the risk of major vision-impairing eye diseases among smokers who quit combustible cigarettes (CC) and switch to non-combustible nicotine or tobacco products (NNTPs) compared with those who complet... OBJECTIVE: We assessed the risk of major vision-impairing eye diseases among smokers who quit combustible cigarettes (CC) and switch to non-combustible nicotine or tobacco products (NNTPs) compared with those who completely quit using tobacco. DESIGN: Retrospective cohort study. PARTICIPANTS: 179,273 adults from the Korean National Health Insurance Service who smoked CC in 2011-2012 and reported cessation in 2018-2019, classified into complete quitters and NNTP switchers. METHODS: This nationwide longitudinal cohort study followed participants for up to 6 years and identified incident major vision-impairing eye diseases (cataract, glaucoma, age-related macular degeneration, diabetic retinopathy, and refractive and accommodation disorders) using standardized diagnostic codes. Propensity score matching was applied to emulate a pseudo-randomized comparison, balanced on key demographic, clinical, comorbidity, and lifestyle characteristics. Subdistribution hazard ratios (SHRs) were evaluated using the Fine-Gray subdistribution hazards model accounting for all-cause mortality as a competing risk. MAIN OUTCOME MEASURES: Adjusted SHRs for incident major vision-impairing eye diseases. RESULTS: Among 32,316 matched participants followed for a mean of 4.6 years, 6,328 incident major vision-impairing eye disease events occurred. The incidence was 41.1 and 44.0 per 1,000 person-years for complete quitters and NNTP switchers, respectively. Switching to NNTPs was associated with an increased risk of major vision-impairing eye disease (SHR, 1.07; 95% CI, 1.02-1.13). The risk elevation was most pronounced for diabetic retinopathy (SHR, 1.24; 95% CI, 1.00-1.53) and refractive and accommodation disorders (SHR, 1.07; 95% CI, 1.01-1.12). These findings were robust across inverse probability-weighted and Cox proportional hazards models. The association remained consistent in sensitivity analyses and across clinical subgroups. CONCLUSIONS: Transitioning from CC to NNTPs is associated with a modest but consistent increase in the risk of major vision-impairing eye diseases compared with complete nicotine abstinence. These findings challenge the assumption that substituting NNTPs for CCs is visually harmless and indicate that, from an ophthalmic perspective, complete cessation of all nicotine products should remain the preferred cessation goal.

Risk Factors and Predictive Model for Postoperative High Myopia in Children Undergoing Congenital Cataract Surgery With Intraocular Lens Implantation.

Liu E, Lin X, Zhu K … +7 more , Li J, Xie Q, Ma Y, Xiao Y, Yang J, Li J, Zhu D

Am J Ophthalmol · 2026 Jun · PMID 42288323 · Publisher ↗

PURPOSE: To identify risk factors associated with the development of high myopia following congenital cataract surgery and to establish a robust predictive model. DESIGN: Retrospective clinical cohort study. SUBJECTS: Th... PURPOSE: To identify risk factors associated with the development of high myopia following congenital cataract surgery and to establish a robust predictive model. DESIGN: Retrospective clinical cohort study. SUBJECTS: This retrospective study included 106 pediatric patients who underwent congenital cataract surgery with primary IOL implantation (mean follow-up 8.19 years). The model was externally validated in an independent cohort of 72 patients with a mean follow-up of 7.83 years. METHODS: Preoperative and postoperative ocular biometric parameters were collected. Risk factors for postoperative high myopia were analyzed using Cox proportional hazards regression, which served as the basis for model construction. The predictive performance of the model was rigorously evaluated for discrimination and calibration. Discriminative ability was quantified using Harrell's C-index and the area under the receiver operating characteristic curve (AUC). Model calibration was assessed via calibration plots by comparing predicted probabilities with actual observed outcomes. Internal validation was performed using a bootstrapping method (500 iterations) to ensure model stability and adjust for potential overfitting. RESULTS: An initial postoperative refraction of < +0.75D, and a higher IOL Power to Axial length Ratio (IOL/AL ratio) were identified as significant risk factors for the development of postoperative high myopia. Shorter preoperative axial length was associated with a greater magnitude of postoperative myopic shift. The predictive model demonstrated robust performance, achieving a C-index of 0.711 (internal validation C-index: 0.713). The area under the receiver operating characteristic curve (AUC) values for predicting high myopia at 5 and 10 years were 0.858 and 0.745, respectively. Furthermore, calibration curves demonstrated excellent agreement between the predicted and observed outcomes throughout the follow-up period. In external validation, the model achieved a C-index of 0.825, 5-year AUC of 0.833, and 10-year AUC of 0.713. CONCLUSIONS: Our analysis established that initial postoperative refraction < +0.75D, and an elevated IOL/AL ratio are key determinants of high myopia risk following surgery. Shorter preoperative axial length was associated with a greater magnitude of postoperative myopic shift. This predictive framework provides clinicians with a practical tool to optimize preoperative IOL selection and identify high-risk infants who require vigilant myopia prevention and balanced amblyopia management.

Current Practices, Evolving Techniques, and Immunologic Challenges in Living and Deceased Donor Limbal Stem Cell Transplantation.

Cheung AY, Auteri NJ, Holland EJ

Am J Ophthalmol · 2026 Jun · PMID 42285470 · Publisher ↗

This review focuses on allogeneic sources for restoring the ocular surface using limbal stem cell transplantation. We outline the current practices, evolving techniques, and immunologic challenges in living-related and d... This review focuses on allogeneic sources for restoring the ocular surface using limbal stem cell transplantation. We outline the current practices, evolving techniques, and immunologic challenges in living-related and deceased donor limbal stem cell transplantation. The diagnosis and staging guidelines for limbal stem cell deficiency are reviewed. We also explore the currently available treatment approaches, including the Cincinnati protocol for donor/recipient selection criteria and systemic immunosuppression (SI) regimen. Utilization of panel reactive antibody, HLA typing, ABO typing, and donor specific antibodies are highlighted. The traditional techniques as well as more novel variations are described. The importance of 3-agent SI protocols and patient adherence are emphasized to ensure excellent long-term outcomes. The primary immunologic challenge of allogeneic limbal stem cell transplantation, rejection, is also discussed in detail with recommended treatments, including a newer role for intravenous immunoglobulin. Other evolving practices have included a greater reliance on living-related conjunctival limbal allograft over deceased donor keratolimbal allograft due to improved outcomes, decreasing SI in older populations, and lengthening SI regimens due to the possibility of late acute rejection. Finally, we discuss the future of restoring the ocular surface via cell-based therapies, which may have the potential to decrease rejection.

Microperimetry as an Outcome Measure Improves Patient Eligibility and Efficacy Detection in RPGR Gene Therapy Trials.

Josan AS, Taylor LJ, Raji S … +2 more , Cehajic-Kapetanovic J, MacLaren RE

Am J Ophthalmol · 2026 Jun · PMID 42285469 · Publisher ↗

PURPOSE: To evaluate how primary endpoint selection influences patient eligibility, enrolment, and detection of treatment efficacy in RPGR gene therapy trials, comparing low luminance visual acuity (LLVA) with microperim... PURPOSE: To evaluate how primary endpoint selection influences patient eligibility, enrolment, and detection of treatment efficacy in RPGR gene therapy trials, comparing low luminance visual acuity (LLVA) with microperimetry-based outcome measures. DESIGN: Retrospective analysis of a phase 1/2-3 interventional clinical trial. SUBJECTS: Fifteen patients were included in this study. Each was administered with gene therapy in one with the other eye serving as control. METHODS: Month 12 data from patients with RPGR-associated retinopathy enrolled at a single centre in the XIRIUS trial (NCT03116113) were retrospectively analysed. FDA-aligned low-luminance visual acuity (LLVA) responder criteria (≥15-letter gain) and EMA-aligned significant change from baseline in microperimetry mean sensitivity, were applied. Microperimetry outcomes were evaluated across the full 68-point MAIA grid and within a central 16-point subset. Minimal baseline inclusion thresholds were used. The proportion of gene therapy-treated patients meeting FDA- and EMA-aligned (≥2.5 dB improvement in mean sensitivity) responder criteria was determined. MAIN OUTCOME MEASURES: Proportion of patients meeting the responder criteria in either microperimetry or LLVA. RESULTS: At baseline, LLVA excluded more patients from study inclusion due to floor effects than microperimetry. At month 12, 2 of 10 patients (20%) met LLVA responder criteria. In contrast, 5 of 11 patients (45%) met EMA-aligned whole-grid microperimetry responder criteria, including all LLVA responders and three additional patients with clear functional improvement not captured by LLVA. Restricting analysis to the central 16 microperimetry points further increased responder detection, identifying 7 of 11 patients (64%). Improvements in microperimetry mean sensitivity of at least 2.5 dB, exceeding expected test-retest variability. No responders were identified for any endpoint in untreated fellow eyes. CONCLUSIONS: Primary endpoint choice substantially affects efficacy detection and patient inclusion in RPGR gene therapy trials. LLVA demonstrated limited sensitivity and restricted eligibility to a narrow disease window, risking underestimation of treatment benefit. Microperimetry mean sensitivity, particularly when spatially aligned with the treated retinal area, detected functional improvement in a substantially larger proportion of patients and supports broader enrolment. Microperimetry-based endpoints provide a more sensitive and inclusive primary outcome measure for RPGR gene therapy trials.

Modeling of Lowe Patient-Derived Induced Pluripotent Stem Cells Into Trabecular Meshwork.

Sun Y, Kowal TJ, Shen Y … +4 more , Zhao J, Wang B, Lo CH, Lachman HM

Am J Ophthalmol · 2026 Jun · PMID 42285468 · Publisher ↗

PURPOSE: Congenital glaucoma is the leading cause of vision loss in patients with Lowe syndrome (LS), a rare X-linked disease caused by mutations in the OCRL gene. OCRL encodes an inositol polyphosphate 5-phosphatase. De... PURPOSE: Congenital glaucoma is the leading cause of vision loss in patients with Lowe syndrome (LS), a rare X-linked disease caused by mutations in the OCRL gene. OCRL encodes an inositol polyphosphate 5-phosphatase. Despite significant research efforts, the pathogenesis of glaucoma caused by OCRL deficiency remains unclear, partly due to the inaccessibility of patient-derived ocular cells. DESIGN: The study design is a comparative cell-based study focused on the functional characterization of induced human trabecular meshwork (iHTM) cell lines. METHODS: Two induced LS pluripotent stem cell (iPSC) lines, previously isolated and generated from an LS patient family, were differentiated into trabecular meshwork cells. LS100 is an affected LS patient; LS200 is an unaffected healthy sibling. Patient-based trabecular meshwork (iHTM) cell models were generated. Both stem cell and trabecular meshwork markers were evaluated by both immunoblot as well as immunostaining analysis. RESULTS: Induced trabecular meshwork cells expressed TM cell markers such as collagen IV, accompanied by the loss of pluripotency markers like OCT4. TM-like responses upon dexamethasone challenge included increased cross-linked actin network formation. The phagocytic function of TM cells was demonstrated by fluorescent labeling phagocytosis assay. Immunostaining revealed that compared to LS200-iHTM, LS100-iHTM had shortened primary cilia. This defect was further supported by reduced Gli1 protein expression in LS100-iHTM. Immunostaining of LAMP1, a lysosome marker, showed greater perinuclear lysosome clustering in LS100-iHTM than LS200-iHTM, indicating potentially dysfunctional nutrient sensing in the patient-derived iHTM cells. CONCLUSIONS: We established two iHTM cell lines derived from iPSCs of an LS patient and his healthy sibling. Functional characterization of both cell lines showed that OCRL deficiency in LS altered downstream pathways related to phagocytosis, primary ciliogenesis, and lysosome positioning. iHTM cells function like TM cells and retain LS-associated defects, highlighting their potential as in vitro models for future mechanistic and therapeutic studies.

Ciliochoroidal Effusion and Regional Scleral Thickening in Peripapillary Pachychoroid Syndrome.

Elifani M, Valsecchi N, Apa L … +4 more , Shhada S, Moramarco A, Fontana L, Mete M

Am J Ophthalmol · 2026 Jun · PMID 42285467 · Publisher ↗

PURPOSE: To assess anterior scleral thickness and the presence of ciliochoroidal effusion (CE) in eyes with peripapillary pachychoroid syndrome (PPS), and to compare the results with a cohort of healthy age-matched contr... PURPOSE: To assess anterior scleral thickness and the presence of ciliochoroidal effusion (CE) in eyes with peripapillary pachychoroid syndrome (PPS), and to compare the results with a cohort of healthy age-matched controls. DESIGN: Retrospective cross-sectional study METHODS: 20 eyes from 12 patients diagnosed with PPS and 30 eyes from 15 healthy control subjects. All participants underwent a comprehensive ophthalmic examination, including spectral-domain optical coherence tomography with enhanced depth imaging (EDI-OCT) and anterior segment OCT (AS-OCT). Choroidal thickness was measured at predefined macular and peripapillary locations, while anterior scleral thickness was assessed 6 mm posterior to the scleral spur in four quadrants. Ciliochoroidal effusion was evaluated qualitatively using AS-OCT. Comparisons between groups were performed using linear mixed models with Bonferroni correction (scleral thickness corrected p < 0.010) RESULTS: The mean age of PPS patients was 75.6 ± 9.8 years, and 16% were females. Anterior scleral thickness was significantly greater in the temporal quadrant in PPS eyes compared to controls (396.85 ± 74.97 μm vs 331.13 ± 62.65 μm: p = 0.007). Ciliochoroidal effusion was detected in 60% of PPS eyes, predominantly in the superior and temporal sectors, whereas no effusion was observed in healthy controls (p < 0.001). Eyes with CE exhibited a thicker mean scleral thickness and a thicker subfoveal choroidal thickness compared to eyes without effusion (p<0.05). CONCLUSION: Eyes with PPS demonstrated increased temporal scleral thickness and a high prevalence of CE. These findings suggest that scleral characteristics may represent a predisposing anatomical factor in PPS, although the precise pathophysiological mechanisms remain to be elucidated.

Current Concepts in Corneal Neurotization.

Ashton C, Borschel GH, Mireskandari K … +1 more , Ali A

Am J Ophthalmol · 2026 Jun · PMID 42285466 · Publisher ↗

Neurotrophic keratopathy (NK) results from loss of trigeminal innervation to the cornea, disrupting epithelial integrity, tear film regulation, and ocular surface homeostasis. Conventional treatments address the surface... Neurotrophic keratopathy (NK) results from loss of trigeminal innervation to the cornea, disrupting epithelial integrity, tear film regulation, and ocular surface homeostasis. Conventional treatments address the surface consequences of denervation but do not restore sensory input. Corneal neurotization (CN) directly addresses this biological deficit by transferring healthy donor axons to the anesthetic cornea, re-establishing afferent innervation and creating the conditions for epithelial maintenance and visual rehabilitation.

Clinical Outcomes and Genomic Epidemiology of Multidrug-Resistant Methicillin-Resistant Staphylococcus aureus Keratitis.

Cummings OW, Andre C, Ling J … +4 more , Yeung SN, Faggioni A, Iovieno A, Bispo PJM

Am J Ophthalmol · 2026 Jun · PMID 42276184 · Publisher ↗

PURPOSE: To characterize the clinical features, management, antimicrobial resistance patterns, and genomic epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) keratitis at two North American centers. DESIG... PURPOSE: To characterize the clinical features, management, antimicrobial resistance patterns, and genomic epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) keratitis at two North American centers. DESIGN: Retrospective interventional case series combined with laboratory investigation PARTICIPANTS: Seventy eyes of 67 patients presenting laboratory-confirmed MRSA keratitis were included METHODS: We performed a multicenter retrospective case series of patients with culture-proven MRSA keratitis treated between 2005 and 2022. Demographic and clinical data were collected. Antimicrobial susceptibility testing was conducted, and multidrug resistance (MDR) was defined as resistance to ≥3 antibiotic classes. A subset of isolates underwent whole-genome sequencing with core genome multilocus sequence typing. Vancomycin susceptibility, heteroresistance screening, and tolerance testing were performed on available isolates. MAIN OUTCOME MEASURES: Antimicrobial susceptibility and multidrug resistance rates, vancomycin phenotypic profiles, MRSA genotypic distribution, and final best-corrected visual acuity RESULTS: Median age was 63.5 years, and 61.4% were female. Ocular surface disease (67.7%) and prior ocular surgery (65.2%) were common. Only 25.4% had significant healthcare exposure in the preceding year. Most isolates (85.7%) were MDR. Fluoroquinolone susceptibility was low (moxifloxacin 19.7%). All isolates were susceptible to vancomycin (MIC₉₀ 2 µg/mL), and no vancomycin-intermediate, heteroresistant, or tolerant phenotypes were identified. Whole genome sequencing (n = 41) demonstrated predominance of clonal complexes 5 (68.3%) and 8 (29.2%). Visual outcomes were poor, with most patients (85.2%) having a final visual acuity worse than 20/60 among those with follow-up. CONCLUSIONS: MRSA keratitis is associated with high rates of multidrug resistance and poor visual outcomes despite guideline-based therapy. Infections were predominantly caused by CC5 MDR strains despite limited recent healthcare exposure. These findings highlight the persistence of highly resistant MRSA lineages in community-associated corneal infection and underscore the need for ongoing antimicrobial surveillance and optimized treatment strategies.

Optimized AAV5-RPGR ORF15 Gene Therapy Rescues Photoreceptor Structure and Function in XLRP Mouse Model.

Chen X, Xu X, Cao S … +4 more , Pan C, Wei S, Hou B, Zhou H

Am J Ophthalmol · 2026 Jun · PMID 42263801 · Publisher ↗

PURPOSE: To develop and evaluate an rAAV5-based gene therapy vector expressing an optimized human RPGR ORF15 transgene (rAAV5-RPGR) for the treatment of X-linked retinitis pigmentosa (XLRP) caused by RPGR mutations, addr... PURPOSE: To develop and evaluate an rAAV5-based gene therapy vector expressing an optimized human RPGR ORF15 transgene (rAAV5-RPGR) for the treatment of X-linked retinitis pigmentosa (XLRP) caused by RPGR mutations, addressing the challenges of cloning the unstable wild-type ORF15 sequence. DESIGN: This was a prospective experimental study. SUBJECTS: This was an animal study. METHODS: An optimized RPGR ORF15 sequence was designed to eliminate problematic secondary structures and cryptic splice sites. In vitro expression was validated in HEK 293T and photoreceptor-like 661W cells. A complete Rpgr knockout mouse model (Rpgr-KO) was generated and characterized phenotypically. Therapeutic efficacy was assessed in Rpgr-KO mice via subretinal injection of rAAV5-RPGR at low (1 × 10⁹ vg/eye), medium (3 × 10⁹ vg/eye), or high (1 × 10¹⁰ vg/eye) doses. Structural and functional outcomes were evaluated at 12- and 14-month post-injection. Short-term safety was assessed in rabbits 1 month after subretinal injection. MAIN OUTCOME MEASURES: Level of RPGR protein expression and Protein isoform profile (elimination of truncated isoforms), Cellular localization of transgene expression and Dose-dependence of expression, outer nuclear layer (ONL) thickness and electroretinography parameters. RESULTS: 1) The optimized vector increased RPGR protein expression 3.3-fold in vitro compared to wild-type and eliminated truncated isoforms. 2) Subretinal delivery of rAAV5-RPGR in mice demonstrated dose-dependent transgene expression localized correctly to photoreceptor inner segments. 3) In Rpgr-KO mice, high-dose treatment significantly preserved outer nuclear layer (ONL) thickness at the injection site (42% greater than controls at 14 months, P<0.01) and central retina (P<0.05), reduced aberrant rhodopsin mislocalization (P<0.01), and partially restored retinal function. ERG showed significantly improved scotopic a-wave (≥100 μV vs. <90 μV in controls at 10 cd·s/m²) and photopic b-wave amplitudes (49-66 μV vs. 31-46 μV at 30 cd·s/m²) in treated mice. 4) No vector-related toxicity was observed in rabbits. CONCLUSION: rAAV5-RPGR mediated efficiently, targeted expression of optimized RPGR-ORF15, significantly preserved photoreceptor structure and function in a severe XLRP mouse model, and demonstrated a favorable safety profile. This study provides preclinical proof-of-concept for RPGR-targeted gene replacement therapy.

Antiadalimumab Antibodies in Patients With Inflammatory Ocular Diseases: Incidence and Clinical Outcomes.

Liberman P, Yu SE, Mendez IJ … +5 more , Ramos EM, Berkenstock MK, Burkholder BM, Thorne JE, Jabs DA

Am J Ophthalmol · 2026 Jun · PMID 42263800 · Publisher ↗

PURPOSE: To determine the incidence, effect on adalimumab drug levels, and clinical consequences of antiadalimumab antibody formation, and to assess potential risk factors. DESIGN: Retrospective clinical cohort study. PA... PURPOSE: To determine the incidence, effect on adalimumab drug levels, and clinical consequences of antiadalimumab antibody formation, and to assess potential risk factors. DESIGN: Retrospective clinical cohort study. PARTICIPANTS: One hundred twenty-eight patients treated with adalimumab who underwent antiadalimumab antibody monitoring. METHODS: Beginning October 2023, regularly scheduled antiadalimumab antibody and adalimumab level testing was begun. Using staggered entry analysis, anchored observation to treatment initiation, incidence was calculated. Time-updated models evaluated risk factors for antiadalimumab antibody formation. MAIN OUTCOME: Incidence of antiadalimumab antibodies. RESULTS: Antiadalimumab antibodies developed in 37 of 128 patients for a rate of 0.077 per person-year (PY) (95% confidence interval [CI] 0.055/PY, 0.104/PY). Median serum adalimumab concentrations were significantly lower in antiadalimumab antibody-positive blood samples (2.6 µg/mL; interquartile range 0.8, 7.0) than in antibody-negative samples (10.2 µg/mL; interquartile range 6.9, 15.1), P < .00001. In time-updated analyses, there was a suggestion that concomitant immunosuppression was associated with a reduced risk of antiadalimumab antibodies (odds ratio [OR] 0.64; 95% CI 0.37, 1.10; P = .10) and weekly adalimumab dosing was associated with a reduced risk (OR 0.62; 95% CI 0.42, 0.91; P = .01). Antiadalimumab antibodies were associated with active ocular inflammation (OR 3.68; 95% CI 1.99, 6.82; P < .00001). CONCLUSIONS: Antiadalimumab antibodies occur commonly among patients treated with long-term adalimumab, with a cumulative incidence of nearly 50% by 8 years of therapy. Antibody formation was associated with lower serum adalimumab levels and active ocular inflammation.

Visual Outcomes and Associated Risk Factors for Blindness in Axenfeld-Rieger Syndrome.

Seresirikachorn K, Thiamthat W, Bitrian E … +1 more , Chang TCP

Am J Ophthalmol · 2026 Jun · PMID 42263799 · Publisher ↗

PURPOSE: To evaluate long-term visual outcomes in Axenfeld-Rieger syndrome (ARS), quantify blindness rates, and identify risk factors of blindness in ARS-related glaucoma. DESIGN: Retrospective cohort study. METHODS: Con... PURPOSE: To evaluate long-term visual outcomes in Axenfeld-Rieger syndrome (ARS), quantify blindness rates, and identify risk factors of blindness in ARS-related glaucoma. DESIGN: Retrospective cohort study. METHODS: Consecutive surgically naïve ARS patients diagnosed before age 18 at three tertiary hospitals in Thailand and the United States (2004-2023) were included. Visual status was classified per World Health Organization criteria. Outcomes were proportions of visual impairment/blindness at baseline and final follow-up, progression to blindness at 3, 5, and 10 years, and risk factors. RESULTS: Ninety-six patients (189 eyes; mean age 4.05 ± 5.35 years) were followed for 8.72 ± 5.76 years. Glaucoma developed in 55.5% of eyes. Among glaucomatous eyes, 17.4% were blind at presentation; blindness progressed to 19.2% at 3 years, 27.5% at 5 years, and 36.3% at 10 years. Bilateral blindness occurred in 23.5% of glaucoma patients. Pathogenic FOXC1 variants were identified in 2 of 5 families, all with at least moderate impairment. Risk factors of blindness included poor initial visual acuity (AoR = 9.72, P = .002), higher intraocular pressure (IOP) (AoR = 1.153, P = .020), number of glaucoma surgeries (AoR = 1.92, P < .001), cloudy cornea (AoR = 4.42, P = .001), female sex (AoR = 6.36, P = .017), and Asian ethnicity (AoR = 6.06, P = .027). CONCLUSIONS: Nearly 40% of ARS eyes with glaucoma develop blindness within 10 years. Risk factors include poor VA, elevated IOP, number of glaucoma surgeries, cloudy cornea, female sex, and Asian ethnicity. Early detection, aggressive IOP control, and close monitoring are critical to preserve vision.

Intraocular Pressure Changes Following Intraluminal Stent Removal from the Paul Glaucoma Implant: A Systematic Review and Meta-Analysis.

Lan CH, Pao SI, Tseng HL … +3 more , Yang WW, Lu DW, Yen WT

Am J Ophthalmol · 2026 Jun · PMID 42250672 · Publisher ↗

PURPOSE: This study aims to systematically review and perform a single-arm meta-analysis to comprehensively evaluate the effect of removal of intraluminal stent from the Paul glaucoma implant (PGI) on intraocular pressur... PURPOSE: This study aims to systematically review and perform a single-arm meta-analysis to comprehensively evaluate the effect of removal of intraluminal stent from the Paul glaucoma implant (PGI) on intraocular pressure (IOP) changes and to summarize its long-term efficacy and safety. CLINICAL RELEVANCE: Glaucoma remains one of the leading global causes of irreversible vision loss, necessitating effective surgical management for refractory cases. Glaucoma drainage devices (GDDs) are critical for these complex forms, and intraluminal stent removal from the PGI serves as a key strategy to titrate aqueous outflow and optimize long-term IOP control. METHODS: A systematic review was conducted by searching EMBASE, Medline, and CENTRAL. The meta-analysis ultimately included 5 observational studies. The Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) tool was used to assess the quality of the included studies. Continuous outcomes (e.g., post-removal stent IOP reduction) were analyzed using the mean difference (MD) with 95% confidence intervals (CI); dichotomous outcomes (e.g., hypotony incidence) were evaluated using pooled proportion with 95% CI. All meta-analyses employed a random-effects model. RESULTS: Our meta-analysis included 5 studies, involving a total of 283 eyes. The meta-analysis revealed that removal of the stent leads to a significant and immediate IOP reduction. The IOP reduction (immediate post-removal stent IOP minus pre-removal stent IOP) was significant, with a pooled mean difference of -9.09 mmHg IOP [mean difference (MD) = 9.09; 95% confidence interval (CI) = (-11.77, -6.41)]. In the pre-removal stent high-IOP (>21 mmHg) subgroup, the IOP reduction is -11.82 [95% CI = (-10.14, -13.51)]. This reduction was significantly greater than the pre-removal stent low-IOP (<21 mmHg) subgroup, whose reduction is -6.66 mmHg [95% CI = (-5.55, -7.77)]. Regarding safety, the pooled proportion of clinically hypotony was low and highly consistent (I² =0.00%) at only 0.03 [95% CI = (0.00, 0.15)]. CONCLUSION: Intraluminal stent removal from the PGI is an effective and safe IOP-lowering intervention. Its IOP reduction effect is significantly more pronounced in patients with pre-removal stent high IOP, providing crucial clinical guidance for managing persistently high IOP after PGI implantation.

Risk-Stratified Monitoring of Open Angle Glaucoma Suspects Based on Diagnostic Conversion Risk.

Yoo K, Wu L, James A … +4 more , Lung K, Camp A, Bolo K, Xu BY

Am J Ophthalmol · 2026 Jun · PMID 42242412 · Publisher ↗

OBJECTIVE: To assess annual rates and determinants of diagnostic conversion from open angle glaucoma suspects (OAGS) to primary open angle glaucoma (POAG) in the United States and develop a pragmatic, risk-stratified fra... OBJECTIVE: To assess annual rates and determinants of diagnostic conversion from open angle glaucoma suspects (OAGS) to primary open angle glaucoma (POAG) in the United States and develop a pragmatic, risk-stratified framework for tailoring follow-up frequency based on per-visit conversion risk. DESIGN: Retrospective cohort study. METHODS: Patients with newly diagnosed OAGS between 2007 and 2021 were identified in Optum's de-identified Clinformatics Data Mart Database based on International Classification of Diseases codes. Inclusion required (1) continuous enrollment during a 3-year lookback period and 5-year study period from index (first) date of OAGS diagnosis, (2) diagnosis by an ophthalmologist or optometrist with ≥1 optical coherence tomography (OCT) or visual field test, and (3) no prior glaucoma-specific treatment or POAG diagnosis. Cox proportional hazards modeling was performed to assess factors associated with diagnostic conversion to POAG. In a secondary analysis, subgroups were created based on age and treatment status and predicted probability of conversion was estimated for each group. MAIN OUTCOME(S) AND MEASURE(S): Diagnostic conversion of POAG. RESULTS: Among 83 305 OAGS patients (57.6% female; 5.4% Asian; 11.1% Black; 12.7% Hispanic; 70.8% non-Hispanic White), 17 134 (20.6%) converted to POAG, corresponding to an overall annual conversion rate of 6.1% (9.4% in year 1, 5.3% in years 2-5). On multivariable Cox regression, older age (HR ≥ 1.38), male sex (HR = 1.12), Black race (HR = 1.14), location outside the Northeast (HR ≥ 1.24), record of gonioscopy (HR = 1.90), and OAGS treatment (HR ≥ 1.31) were associated with greater hazard of conversion (P ≤ .02). Among the lowest-risk patients (<50 years; untreated), annual conversion was 2.0% with follow-up every 0.9 ± 0.6 years, whereas the highest-risk patients (>70 years; treated) had a 16.7% annual conversion rate with follow-up every 0.4 ± 0.4 years after year 1. When standardized to a 5.0% per-visit conversion threshold, corresponding monitoring intervals were 6.1 years and 0.6 years, respectively. CONCLUSIONS: The rate of conversion from OAGS to POAG is <6.0% per year beyond the first year after diagnosis. Estimating per-visit conversion risk enables risk-stratified surveillance strategies that may safely reduce visit frequency for very low-risk patients while preserving timely detection in higher-risk groups, thereby improving clinical efficiency and resource allocation.

Intralenticular Vacuole Mimicking a Posterior Polar Cataract With Posterior Capsule Dehiscence.

Fidha Shirin PK, Jothi Balaji J, Sudharshan S

Am J Ophthalmol · 2026 Jun · PMID 42242411 · Publisher ↗

Abstract loading — click title to view on PubMed.

Subclinical Peripheral Vascular Leakage in Demyelinating Disease-Associated Uveitis.

Levant SD, Ray H, Venkat AG

Am J Ophthalmol · 2026 Jun · PMID 42235728 · Publisher ↗

PURPOSE: To evaluate the cross-sectional association between clinical examination findings and angiographic disease activity in demyelinating disease-associated uveitis, and to describe longitudinal trends in clinical, u... PURPOSE: To evaluate the cross-sectional association between clinical examination findings and angiographic disease activity in demyelinating disease-associated uveitis, and to describe longitudinal trends in clinical, ultrawidefield fluorescein angiography (UWF-FA) leakage, and optical coherence tomography (OCT) markers. DESIGN: Retrospective cohort study with cross-sectional and longitudinal components. PARTICIPANTS: A total of 58 eyes from 30 patients with confirmed demyelinating disease (predominantly multiple sclerosis) and concurrent uveitis evaluated at a tertiary referral center. METHODS: Eyes were evaluated at three timepoints: initial presentation, acute uveitis flare, and most recent encounter. Clinical inflammation, graded per Standardization of Uveitis Nomenclature criteria, was compared with OCT parameters and UWF-FA leakage (scored by anatomic Zones 1-3). Linear mixed models and generalized estimating equations were used, accounting for intereye correlation and repeated measures. MAIN OUTCOME MEASURES: Clinical measures (logMAR visual acuity, anterior chamber [AC] and vitreous cell grades); macular fluid dynamics (central subfield thickness, intraretinal fluid [IRF], and subretinal fluid); and UWF-FA leakage. RESULTS: AC and vitreous inflammation significantly improved following acute flare (P < .001 and P = .01, respectively), as did macular IRF (P = .001) and subretinal fluid (P < .001). Total anatomic burden of angiographic leakage was highest at initial presentation and did not change significantly between acute flare and most recent encounter (P = .78). Among 48 paired clinical-angiographic encounters, 68.8% of eyes classified as clinically inactive (0 AC cells, 0 vitreous cells, no active retinal/choroidal lesions) demonstrated ongoing vascular leakage on UWF-FA. In a multivariable generalized estimating equations model, far-peripheral (Zone 3) leakage did not significantly predict concurrent IRF (OR = 2.33, 95% CI 0.62-8.73, P = .21). Cumulative structural damage, including epiretinal membrane and macular atrophy, increased significantly over time (P < .05 and P = .04, respectively). CONCLUSIONS: The high prevalence of subclinical peripheral vascular leakage on UWF-FA in clinically inactive eyes demonstrates clinical examination and OCT may not capture the full spectrum of angiographic abnormalities in demyelinating disease-associated uveitis. This observational clinical-angiographic discordance suggests that UWF-FA may provide complementary information for disease staging and monitoring. Prospective studies are needed to determine whether angiographic findings should influence therapeutic endpoints.
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