JAMA ophthalmology最新文献

Importance: Understanding of intraocular pressure (IOP) as a continuous risk factor for glaucoma has evolved over time, and IOP reduction is widely acknowledged as the mainstay of treatment. However, the impact of specific IOP levels on clinical decision-making remains an underexplored topic.

Objective: To assess how IOP levels influence the decision to initiate or escalate glaucoma therapy in clinical practice.

Design, setting, and participants: In this retrospective, multicenter cohort study, the Sight Outcomes Research Collaborative (SOURCE) ophthalmology data repository was used to identify clinic encounters between October 2009 and January 2022 for patients with glaucoma with IOPs ranging from 12 mm Hg to 25 mm Hg. Data analysis was performed from July 2024 to September 2025.

Main outcomes and measures: The primary outcome was whether IOP-lowering therapy was initiated or escalated after each clinic encounter, defined as a new prescription for IOP-lowering medication within 1 week of the encounter, laser treatment within 4 weeks, or glaucoma surgery within 8 weeks. The rate of treatment initiation at different IOP levels was measured, and then mixed-effects logistic regression was used to model the odds of treatment initiation at specific indicator IOP levels.

Results: This analysis included 1 866 801 clinic encounters from 184 504 eyes of 94 232 unique patients across 7 sites in SOURCE. Mean (SD) patient age was 69.5 (10.8) years, and of the total clinic encounters, 1 084 827 (58.1%) included female patients. The rate of IOP-lowering treatment increased with higher IOP levels, with the largest acceleration in treatment rate at IOPs of 22 mm Hg or higher. With mixed-effects logistic regression modeling, an indicator IOP of 22 mm Hg had a greater effect on treatment initiation (odds ratio, 1.11; 95% CI, 1.08-1.14) compared with lower indicator IOPs.

Conclusions and relevance: In this cohort study, while clinicians seem to generally use IOP as a continuous risk factor in their treatment patterns, with higher rates of glaucoma therapy at increasing IOP levels, these findings suggest that the historical IOP cutoff of 22 mm Hg may still influence clinician decision-making in glaucoma management. Improved clinical decision support may be useful to assist clinicians with using IOP as a continuous risk factor in their decision-making.

Importance: Voretigene neparvovec (VN) marketed as Luxturna (Novartis Europharm Ltd) is the first approved gene therapy for severe RPE65-related retinal dystrophy, showing low-luminance vision improvement in adult trials. Low-luminance tests pose challenges for children, but pattern visual evoked potentials (VEPs) need minimal cooperation and provide objective measures of visual activation of the striate cortex. In this study, VN outcomes in young children were assessed using pattern VEPs in addition to standard measures.

Objective: To evaluate vision outcomes and complications after VN treatment in children.

Design, setting, and participants: This was a retrospective case series of children receiving VN from February 2020 to December 2023. Children with biallelic pathogenic variants in RPE65 were recruited from Great Ormond Street Hospital, a single-center, UK specialist pediatric hospital.

Exposure: Treatment with VN, a recombinant adeno-associated virus vector-based gene therapy.

Main outcomes and measures: Pretreatment and posttreatment pattern VEPs, visual acuity (VA), full-field stimulus test (FST), optical coherence tomography (OCT) measures, and ocular complications.

Results: A total of 14 pediatric patients (27 eyes) were included in this analysis. Median (IQR) age at treatment of 9 female (64.3%) and 5 male (35.7%) patients was 6.88 (3.27-8.83) years, with a median (IQR) follow-up of 3.42 (2.65-4.08) years. VA improved from logMAR 1.00 to 0.76 (difference, -0.24). When 4 off-chart VA conversions were excluded, the change was less than 1 line, -0.03 (pretreatment, logMAR 0.74 [20/100] to posttreatment, 0.71 [20/100]). Only 3 eyes of 14 children (11%) completed a reliable full-field stimulus test, showing a mean (SD) 20.6 (14.8) dB. All 10 tested patients completed pattern VEPs; 7 showed clinically meaningful improvement, 2 worsened with chorioretinal atrophy, and 1 remained unchanged. Complications included transient inflammation (5 of 14 patients [35.7%]) and localized atrophy (6 of 14 patients [42.9%]).

Conclusions and relevance: This case series study reports VN-treated patients as young as 15 months, confirming visual improvements, although not necessarily VA when off-chart VA conversions were excluded, consistent with previously reported outcomes. Pattern VEPs provided an objective measure of retinogeniculostriate recovery, supporting their use as an outcome measure in future trials for young children with inherited retinal diseases.

Importance: Recent insights into impaired glutamylation caused by distal truncating variants in RPGR ORF15 and its association with the cone-dominated phenotype have provided the first molecular evidence of a genotype-phenotype correlation in male individuals with X-linked RPGR-related retinal dystrophy, though this correlation remains unexplored in female carriers.

Objective: To characterize the clinical phenotype in female carriers of RPGR variants causing X-linked cone dystrophy in hemizygous male individuals.

Design, setting, and participants: This case-control study was conducted at a specialist genetics clinic from May to December 2024. A total of 11 patients were examined, including female carriers with RPGR variants causing cone dystrophy (n = 7) and age-similar female carriers of RPGR variants causing rod-cone dystrophy as controls (n = 4).

Exposures: RPGR variants associated with X-linked cone dystrophy in hemizygous male individuals.

Main outcomes and measures: Results of ophthalmic examination, multimodal retinal imaging, and functional testing.

Results: Seven female carriers aged 11 to 71 years were identified from RPGR cone dystrophy pedigrees. Visual acuity ranged from 6/4.8 to 6/7.5 (Snellen, 20/16 to 20/25), and 4 of the 7 participants experienced photophobia. Myopia and high cylindrical powers were common (6/7 [86%]), with myopia greater than -6.00 D in 2 patients. Fundus autofluorescence imaging revealed a diffuse, granular hyperautofluorescence pattern limited to the posterior pole, compared with the typical spoke pattern that extended into the far periphery in female carriers from RPGR rod-cone pedigrees. Green reflectance imaging most sensitively detected an abnormality in the form of an en face tapetallike sheen, which colocalized with a hyperreflective outer retinal band observed on optical coherence tomography. Ultra-widefield retinal imaging demonstrated no peripheral abnormalities. A mosaic pattern of reduced retinal sensitivity was found within the central 20° on microperimetry, which did not correlate with features observed on retinal imaging. Normal rod responses were measured on electroretinography, but average cone responses were 60.1% of the lower normal limit compared with 36% in male probands.

Conclusions and relevance: This study identified a distinct phenotype in female carriers of RPGR variants causing X-linked cone dystrophy. In this cohort, the phenotype was consistent with mild cone dysfunction and anatomical macular changes. Depending on X-inactivation skew and rate of disease progression, some female carriers may be suitable for emerging gene therapies currently in clinical trials for affected male individuals.