Current Issue

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In this week’s issue

• Epigenetic aging alone, as established by DNA methylation studies, correlates with faster glaucoma progression independent of IOP. 
• Repeated low-level red light (RLRL) therapy can delay myopia progression and axial elongation in children, but new research shows it can lead to ganglion cell damage and cone photoreceptor loss.
• Pegcetocoplan treatment reduces vision loss in the fovea and junctional zone in patients with geographic atrophy, per microperimetry analysis.
• Myopic children in the high-add contact lens group (BLINK trial) showed choroidal thickening and slower axial elongation, but choroidal changes accounted for only a portion of the treatment effect

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Ophthalmology
Accelerated epigenetic aging & faster glaucoma progression

Age is just a number, but methylation patterns aren't. Biological age, as measured by epigenetic methylation patterns, may drive glaucoma progression. In a retrospective cohort study of 200 patients with primary open-angle glaucoma, researchers compared those with fast (n=100) versus slow (n=100) visual field and OCT progression. Epigenetic age and acceleration were determined using the Horvath, Hannum, PhenoAge, and GrimAge clocks from DNA methylation profiles obtained from blood samples. Fast glaucoma progressors showed a 2.93-year higher biological age (P<0.001); each additional year of acceleration increased the odds of glaucoma progression by 15% (OR=1.15, 95% CI 1.07–1.23). The association was especially strong in patients with normal IOP, suggesting pressure-independent damage susceptibility to the optic nerve. The findings in this study provide the first evidence of epigenetic aging as a prognostic biomarker for glaucoma progression.

American Journal of Ophthalmology
Pegcetacoplan slows vision loss in GA: Microperimetry analysis

Pegcetacoplan is the newest scotoma stopper! Geographic atrophy (GA), an advanced form of age-related macular degeneration (AMD), was previously untreatable until FDA approval of pegcetacoplan, a C3 and C3b complement inhibitor. The two phase 3 OAKS and DERBY trials evaluated monthly (PM) and every-other-month (PEOM) intravitreal pegcetacoplan treatment in 1,258 eyes with subfoveal or non-subfoveal GA. Given the fovea’s critical role in detailed central vision, this study aimed to assess microperimetry points within the central macula and junctional zone. This was a post hoc analysis of phase 3 randomized controlled trial data that analyzed time to absolute scotoma development and retinal sensitivity via microperimetry endpoints. After 24 months of treatment, PM treatment delayed the development of absolute scotomas of all 4 central macular points (HR=0.66). PM and PEOM treatment delayed the development of absolute scotomas of all 16 central points (HR=0.57, 0.52). Microperimetry assessment shows that pegcetocoplan treatment reduces vision loss in the foveal region and junctional zone for patients with GA secondary to AMD.

Investigative Ophthalmology & Visual Science (IOVS)

Effect of contact lens wear on the choroid: Results from the BLINK study

Don’t BLINK: The (choroid) plot thickens! The Bifocal Lenses in Nearsighted Kids (BLINK) randomized controlled trial showed that high-add power multifocal contact lenses significantly slowed myopia progression and axial elongation in children compared to medium-add and single-vision lenses. This post hoc study examined whether structural changes in the choroid could explain this. OCT imaging was performed at baseline, 2 weeks after lens wear, and annually for 3 years in 281 participants. Only myopic children in the high-add group showed choroidal thickening at 2 weeks (P = 0.003), and this thickening was maintained throughout the study. However, choroidal changes explained only 20–29% of the treatment effect, and the variability within each group suggests individual responses (both choroidal thickening and thinning) were highly inconsistent. While not predictive at the individual level, short-term choroidal changes may still offer value as population-level biomarkers in clinical trials assessing the efficacy of myopia control interventions.

JAAPOS

Childhood vision loss leaves a lifelong mark on economic opportunity?

Amblyopia may blur more than vision, but early detection could clear the path ahead. This retrospective, case-control study used data from the NIH’s All of Us Research Program to explore socioeconomic associations of amblyopia among working-age adults (18-64 years). After identifying 601 amblyopic participants with complete socioeconomic data and comparing them to 2,404 matched controls, the study examined income, employment, insurance status, and homeownership. Amblyopia was significantly associated with higher unemployment (OR 1.56) and greater reliance on Medicaid insurance (OR 1.43) compared to controls, even after adjusting for multiple socioeconomic factors. Other disparities, such as lower homeownership and income under $35,000, were observed on univariate analysis but did not remain significant in multivariable models. Limitations included reliance on diagnostic codes and the absence of visual acuity data. These findings underscore the potential long-term social and economic consequences of amblyopia, especially considering inequities in screening and treatment based on race and income.

Can deep learning models create screening tools for diabetic macular edema?

Computer, do you see what I see? Generalizability of screening models for diabetic macular edema (DME) is critical for machine learning solutions that aim to be used in wide contexts. This study used a deep learning model (convolutional neural network) to examine color fundus images across multiple datasets and locations and analyzed those images on multiple levels (single image, single eye, both eyes), thereby addressing prior research limitations. Training and validation were conducted with the EyePACS dataset (32,049 images from 15,892 patients, with 49% of all images being DME positive), and additional validation was conducted with the Messidor-2, IDRiD, and Lahey datasets for ‘real-world’ experience. At the patient level, the model demonstrated an accuracy of 0.90, sensitivity of 0.90, a specificity of 0.90, and an area under the curve of 0.96. Its performance at the image and eye levels were similar. This study demonstrates that the machine learning model employed can achieve high accuracy and performance using readily-available color fundus photographs across a variety of contexts for screening.

Wisconsin Epidemiologic Study of Diabetic Retinopathy - 1984

To develop or not to develop… a study on diabetic retinopathy. Diabetic retinopathy is the second leading cause of blindness in the United States. This population-based epidemiological study over 25 years aimed to determine the incidence, prevalence, and severity of diabetic retinopathy and visual impairment and associated risk factors in diabetic patients. The original study was 1980-1982 and there have been six patient follow-ups 1984-86, 1990-92, 1995-96, 2000-01, 2006-07, and 2012-14. There were 996 type 1 diabetic patients and 1370 type 2 diabetic patients who were analyzed for the incidence rate and severity of diabetic retinopathy using stereoscopic color fundus photographs.

Key Points:

• Diabetic retinopathy was found to be related to longer duration with the disease, high levels of glycosylated hemoglobin, proteinuria, increased diastolic BP, and male sex.
• Incidence and progression of diabetic retinopathy was greatest in those who were younger at the time of diagnosis
• After 20 years of diabetes mellitus, nearly 99% of patients with type 1 and 60% with type 2 disease demonstrated some degree of diabetic retinopathy.

Overall, after 25 years there have been over 230 reports from the WESDR study to show glycemic control is associated with a decreased risk of diabetic retinopathy and other diabetic complications. It furthermore identified additional risk factors for diabetic retinopathy in those with diabetes.