Importance:The highly myopic eye remodels in 3 dimensions, but the longitudinal trajectories of globe shape and their associations with sight-threatening outcomes remain poorly defined. Objective:To characterize 15-year 3-dimensional (3D) remodeling trajectories of highly myopic globes and examine their associations with baseline features and ocular outcomes. Design, Setting, and Participants:This 15-year 3D magnetic resonance imaging (MRI) cohort substudy was nested within the Zhongshan High Myopia Cohort. Thirty participants (60 eyes) with bilateral high myopia (spherical equivalent refraction, -6.00 D or worse) randomly drawn from 95 participants imaged in September 2011 were rescanned in September 2025. Exposures:Orbital 3D MRI reconstructions were classified into 6 globe-shape categories. Paired classifications, global enlargement, and staphyloma status defined 5 remodeling patterns: quiescence, proportional expansion, focal emergence, focal progression, and shape transition. Main Outcomes and Measures:Distribution of remodeling patterns and their associations with myopic macular degeneration (MMD), myopic traction maculopathy (MTM), posterior staphyloma (PS), visual acuity, and visual field indices. Results:Among the 30 included participants, the mean (SD) age was 37.30 (15.89) years, and 16 (53.3%) participants were women. The 60 eyes were classified as quiescent (21 [35.0%]), proportional expansion (12 [20.0%]), focal emergence (14 [23.3%]), focal progression (6 [10.0%]), or shape transition (7 [11.7%]). No deformed eye reverted to spheroidal. Pattern distribution was associated with baseline age and contour: 10 of 12 eyes (83.3%) of individuals younger than 20 years underwent proportional expansion, whereas 13 of 24 eyes (54.2%) of individuals aged 40 years and older followed focal progression or shape transition. Eyes with focal emergence had the largest best-corrected visual acuity decline (0.26 logMAR) and mean deviation worsening (-3.50 dB), and eyes with shape transition had the largest pattern standard deviation increasing (1.95 dB). At similar axial elongation, eyes developing focal deformation had higher frequencies of MMD progression (91.7%; 95% CI, 74.2-97.7 vs 58.8%; 95% CI, 36.0-78.4; P = .02), incident or progressive PS (91.7%; 95% CI, 74.2-97.7 vs 17.6%; 95% CI, 6.2-41.0; P < .001), and MTM (58.3%; 95% CI, 38.8-75.5 vs 11.8%; 95% CI, 3.3-34.3; P = .003). Conclusions and Relevance:Highly myopic globes followed age- and geometry-associated trajectories linked to outcomes beyond axial elongation. These 2-time-point findings potentially support 3D shape analysis as a candidate framework for individualized surveillance, pending prospective validation.
Importance:Stargardt disease (STGD) is the most common macular dystrophy, resulting in profound loss of vision. There is no approved treatment. Objective:To evaluate the safety and effects of oral gildeuretinol acetate on the growth of retinal atrophic lesions in individuals with STGD. Design, Setting, and Participants:TEASE-1 was a 2-year, multicenter, double-masked, placebo-controlled randomized clinical trial incorporating a crossover group and additional natural history (NH) cases selected prior to drafting the statistical analysis plan. The trial was conducted at 7 outpatient clinics in the US. Participants were aged 12 years or older, clinically diagnosed with STGD, with well-demarcated area(s) of significantly reduced autofluorescence, and supported with at least 1 ABCA4 disease-causing or likely disease-causing variant. The study was conducted between August 2015 and October 2019; data were analyzed between July and December 2020. Interventions:Participants were randomized 1.5:1.5:1:1 to daily oral gildeuretinol acetate, 14 mg; gildeuretinol acetate, 24 mg; or placebo for 24 months; or placebo for 12 months followed by gildeuretinol for 12 months. Main Outcomes and Measures:The primary efficacy end point was the growth rate of well-delineated and homogeneous areas of retinal atrophic lesions over 24 months of treatment on fundus autofluorescence imaging. Safety end points included treatment-emergent adverse events (AEs), serious AEs, and clinical laboratory assessments. Results:A total of 50 participants were randomized, and 54 NH cases included. The mean (range) age of randomized participants was 44.3 (18-60) years. Overall, 58 of 104 participants or cases (55.8%) were female. The growth rate of retinal atrophic lesions was 0.182 mm/y with gildeuretinol and 0.232 mm/y in the untreated group (placebo and NH), representing a mean difference of -0.050 mm/y (95% CI, -0.072 to -0.027; P < .001) and a 21.6% relative reduction. In a prespecified sensitivity analysis restricted to randomized participants, the growth rate was 0.206 mm/y with gildeuretinol and 0.242 mm/y with placebo, representing a mean difference of -0.036 mm/y (95% CI, -0.062 to -0.009; P = .008) and a 14.9% relative reduction. The majority of AEs were mild or moderate and equally distributed between groups. No treatment-related serious AEs, clinically significant liver function abnormalities, or participant-reported night blindness or dark adaption difficulties occurred. Conclusions and Relevance:In the TEASE-1 randomized clinical trial, the primary efficacy end point of retinal atrophic lesion growth from 6 to 24 months was 0.05 mm/y greater on average in the untreated group (placebo and NH) than the gildeuretinol acetate group. Further research is needed to determine the clinical relevance of this end point. Trial Registration:ClinicalTrials.gov Identifier: NCT02402660.
Importance:Early detection of glaucoma progression is essential. Optical coherence tomography angiography (OCTA) vascular metrics may identify progression before structural OCT or visual field changes. Objective:To evaluate timing and agreement of event-based progression detection among OCT, OCTA, and visual field testing in glaucoma. Design, Setting, and Participants:This was a retrospective cohort study designed in August 2024. Included were patients from the Diagnostic Innovations in Glaucoma Study (DIGS) who underwent OCT and OCTA imaging and visual field testing from January 2015 to April 2023. Inclusion required 2 or more years of follow-up and 4 or more visits with each modality. Exposures:OCT, OCTA, and visual field testing. Main Outcomes and Measures:OCT and OCTA progression were defined as change exceeding test-retest variability thresholds at 2 consecutive visits; visual field progression was assessed with guided progression analysis. Progression rates and lead times were compared. Results:A total of 180 eyes (111 perimetric, 69 preperimetric) from 116 patients (mean [SD] age, 67.6 [13.7] years; 61 female [52.6%]) were included in this analysis. During mean (SD) follow-up of 5.1 (1.4) years, 107 eyes (59.4%) had progression detected by at least 1 modality as follows: 58 eyes (32.2%) by OCTA vessel density, 45 eyes (25.0%) by OCT circumpapillary retinal nerve fiber layer (CPRNFL) thickness, and 59 eyes (32.8%) by visual field testing. Among eyes with progression, the earliest detection occurred with OCTA vessel density in 40 eyes (37.4%), OCT CPRNFL thickness in 32 eyes (29.9%), and visual field testing in 26 eyes (24.3%). Among 45 stable eyes, specificity was 75.6% for OCT CPRNFL thickness and 68.9% for OCTA vessel density. Mean lead times were 2.3 years for OCTA vessel density before visual field progression (95% CI, 1.3-3.2 years), 1.5 years for OCT CPRNFL thickness before visual field progression (95% CI, 0.6-2.4 years), and 0.2 years for OCT CPRNFL thickness vs OCTA vessel density (95% CI, -0.6 to 0.9 years). Conclusions and Relevance:Results of this cohort study suggest that OCTA vessel density may detect event-based glaucoma progression earlier than OCT or visual field testing at the cost of a slight decrease in specificity compared with OCT. These findings support a potential complementary role for OCTA in glaucoma monitoring, although the cost-benefit of additional testing requires further evaluation.
Importance:Myopia prevalence is rising in the US. Spectacle lenses with highly aspherical lenslets (HAL) are effective in Asian populations but unproven in US children. Objective:To evaluate the 24-month safety and effectiveness of HAL spectacle lenses compared with single-vision spectacle lenses (SVL) in US children with myopia. Design, Setting, and Participants:This double-masked randomized clinical trial took place at 9 investigational sites in the US and included children aged 6 to 12 years with a manifest spherical equivalent refraction (SER) of -0.75 to -4.50 diopters (D). Key exclusion criteria included a history of prior myopia control intervention, strabismus, amblyopia, or any ocular or systemic conditions and medications affecting refractive status. Enrollment was from December 2021 to July 2022, and the 24-month follow-up reported here was completed in October 2024. Interventions:Participants were randomized (1:1) to HAL or SVL. Main Outcomes and Measures:Primary outcomes were 24-month changes in cycloplegic SER (cSER) and axial length. Results:Of 159 randomized participants (80 [50.3%] male; mean [SD] age, 9.7 [1.6] years), 135 (84.9%) completed the 24-month assessment. The baseline mean (SD) cSER was -2.21 (1.07) D in the HAL group and -2.05 (1.22) D in the SVL group. At 24 months, adjusted mean (SE) myopia progression was -0.25 (0.05) D in the HAL group and -0.90 (0.05) D in the SVL group (difference, 0.64 D; 95% CI, 0.50 to 0.79; P < .001), a 71% relative reduction. The baseline mean (SD) axial length was 24.26 (0.92) mm in the HAL group and 24.32 (0.83) mm in the SVL group. Adjusted mean (SE) axial elongation was 0.21 (0.02) mm in the HAL group and 0.45 (0.02) mm in the SVL group (difference, -0.24 mm; 95% CI, -0.29 to -0.19; P < .001), a 53% relative reduction. Best-corrected visual acuity was equivalent between groups (mean difference, -0.01 logMAR; 95% CI, -0.02 to 0.00; P = .23). Ocular adverse events occurred in 9 of 77 participants the HAL group (11.7%) vs 12 of 82 in the SVL group (14.6%); none were serious or lens related. The total number of subjective symptom reports were 19 (HAL) and 25 (SVL). Conclusions and Relevance:In this randomized clinical trial of US children, spectacle lenses with HAL provided a reduction in myopia progression and axial elongation over 24 months. While longer-term data are needed to evaluate sustained treatment efficacy, these findings support HAL as a safe and effective myopia control intervention and underlie US Food and Drug Administration authorization of the study device. Trial Registration:ClinicalTrials.gov Identifier: NCT05174780.
This case report discusses bilateral central retinal artery occlusion (CRAO) in a young adult with no cardiovascular history who presented with bilateral vision loss 3 days after recreational cocaine use.
A 60-year-old man presented with progressive vision loss over several weeks in his right eye, noting a dark spot in his central vision and metamorphopsia. What would you do next?
Importance:Congenital nasolacrimal duct obstruction (CNLDO) is a common condition in infants. While observation and surgical probing are commonly used in clinical practice, evidence to guide the choice between these approaches is lacking, and the efficacy of lacrimal sac massage remains controversial. Objective:To assess whether lacrimal sac massage is noninferior to lacrimal duct probing for treating CNLDO in infants. Design, Setting, and Participants:This noninferiority randomized clinical trial took place at an outpatient clinic in Guangzhou, China, from April to September 2025 and included 160 infants younger than 1 year with CNLDO, presenting with epiphora or discharge in 1 or both eyes since birth. Children with bilateral eye disease were only analyzed for the right eye. Patients were excluded if they had previously undergone surgery for CNLDO or had another systemic disease or ocular infection. Interventions:Patients were randomly assigned to receive lacrimal duct probing in the consultation room (n = 80) or standardized, regular lacrimal sac massage performed by parents (n = 80). Main Outcomes and Measures:The primary outcome was the resolution rate at 3 months, defined as complete or substantial resolution of epiphora, alongside the complete resolution of purulent discharge. The prespecified noninferiority margin was -10 percentage points. Results:The mean (SD) age of the participants was 6.2 (2.5) months, and 98 (61.3%) were male. Resolution occurred in 69 of 80 participants (86.2%) in the massage group compared with 67 of 80 (83.7%) in the probe group (difference, 2.5 percentage points; 95% CI, -8.78 to 13.76). No serious complications occurred. The mean (SD) symptom resolution time was 1.1 (0.5) weeks in the probe group and 3.8 (2.8) weeks in the massage group (difference, 2.7 weeks; 95% CI, 1.96 to 3.38; P < .001). Conclusions and Relevance:For infants younger than 1 year with CNLDO, lacrimal sac massage for 3 months was noninferior to lacrimal duct probing in efficacy, with no serious complications in either group. These findings support lacrimal sac massage as an alternative to surgical probing for CNLDO in infants younger than 1 year similar to those enrolled in this trial. Trial Registration:ClinicalTrials.gov Identifier: NCT06924723.
