Audio link: 

https://open.spotify.com/episode/5oAdDy8eWldXuLzetm88tL?si=bb926d634f604242

In this week’s issue

• Despite a substantial burden of diabetic retinopathy outside metropolitan areas, nearly all diagnostic and treatment services are delivered in urban practices. 
• RAFT-OS transplantation improved ocular surface disease in advanced aniridia-related keratopathy with an acceptable safety profile in a first-in-human clinical trial.
• Women, Black patients, and patients with socioeconomic challenges were significantly less likely to receive timely surgery for rhegmatogenous retinal detachment in a large US retrospective study.
• A novel prediction model combining placental and early neonatal factors accurately identified infants at risk for retinopathy of prematurity before routine screening begins.

Ophthalmology

Diabetic retinopathy care in urban vs. rural U.S.

We have made incredible strides in diabetic retinopathy (DR) care, but we may be leaving our rural neighbors in the rearview mirror.  Even though effective treatments for DR are available, protecting patients from irreversible vision loss requires consistent, long-term care. To identify where access gaps persist, researchers analyzed 12 years of clinical data from the IRIS® Registry to quantify the geographic distribution of therapeutic and diagnostic DR procedures across the U.S. Across the 12 year period, urban practices performed 95-99% of the overall procedural volume, remaining disproportionately high even after factoring in population differences (67-80%) and disease burden (65-90%), with >93% of rural patients receiving therapeutic interventions in urban practices. In non-urban settings, comprehensive ophthalmologists performed >35% of intravitreal injections and panretinal photocoagulation (compared to just 5-7% in urban areas), yet rural residents still experienced a higher rate of proliferative disease and greater lapses in longitudinal monitoring. These findings support an urgent need for strategies to improve access to specialty retinal care in non-urban communities.

JAMA Ophthalmology 

Tissue-engineered transplant for aniridia-related keratopathy

Could lab-grown tissues be the solution? Aniridia-related keratopathy (ARK) is a disorder characterized by progressive instability of the ocular surface, leading to impaired vision. Treatment options are limited due to the recurrence of disease in donor transplant tissue. Real Architecture for 3D Tissues-Ocular Surface (RAFT-OS) is a tissue-engineered collagen scaffold developed for adults with advanced ARK. This open-label, nonrandomized phase 1 clinical trial included 9 participants. Ocular surface normalization was assessed after participants underwent RAFT-OS transplant in one eye, and the results were compared to their untreated eye. Treated eyes had a mean Ocular Surface Score (OSS) reduction of 3.6 points at 3 months, which was partially maintained at 12 months, whereas untreated eyes showed no statistically significant change. These results indicate that RAFT-OS is a feasible treatment for adults with ARK and may lead to early ocular surface improvement without substantial safety concerns. 

American Journal of Ophthalmology 

Who gets timely retinal detachment surgery?

For a detached retina, time is vision, but who gets surgery first? Rhegmatogenous retinal detachment (RRD), the most common form of retinal detachment, is characterized by a full-thickness retinal break allowing liquefied vitreous humor to infiltrate the subretinal space, precipitating detachment of the neurosensory retina from the underlying retinal pigment epithelium. Prompt surgical repair has been associated with improved visual outcomes. Researchers sought to identify disparities in rates of RRD intervention through a large-scale US-based retrospective cohort study using a database of 66 healthcare organizations (TriNetX). Patients with RRD between 08/2015 and 01/2026 were propensity-matched by sex, race, ethnicity, and psychosocial factors. The primary outcome was RRD intervention assessed at 1 day, 1 week, 1 month, and 3 months following diagnosis. The following cohorts were more likely to receive surgical repair within 1 day: male patients (RR 1.20), White compared to Black patients (RR 1.47), and patients without socioeconomic or psychosocial conditions (RR 3.35). Disparities persisted through 3 months after diagnosis. These findings add to the growing literature on inequity in ophthalmology, suggesting further exploration to address this complex, multifactorial problem.

Investigative Ophthalmology and Visual Science 

Can the placenta help predict retinopathy of prematurity?

The placenta may offer a glimpse of ROP risk before it comes into view. Retinopathy of prematurity (ROP) can lead to lifelong visual impairment in premature infants, making early identification of those at highest risk especially important. Current screening relies heavily on gestational age and birth weight, while existing prediction models depend on postnatal changes that emerge weeks later. The authors examined whether combining placental pathology with early neonatal factors improves prediction before routine screening. In a retrospective cohort of 591 premature neonates, researchers developed and internally validated the PAPROP (Placenta as an Additional Predictor for ROP) model and compared its performance with a model based on gestational age and birth weight alone. PAPROP modestly improved discrimination compared with gestational age and birth weight alone, with an AUC of 0.81 versus 0.78. At clinically selected risk thresholds, the model could reduce unnecessary screenings by 13% to 25% without missing any stage 2 or severe ROP cases. PAPROP offers promising early ROP risk stratification, though its reliance on historical data and a limited severe disease sample necessitate external validation before clinical adoption.

American Journal of Ophthalmology

A new lens on global ROP

How can artificial intelligence help us better understand ROP? Low- to middle-income countries (LMICs) are currently facing a “third wave” of ROP, marked by greater survival rates among premature infants and a higher incidence of ROP at larger birthweights and gestational ages compared to high-income countries. Telemedicine ROP screening using digital retinal images can leverage artificial intelligence to quantify disease severity using vascular severity scores (VSS). This retrospective study compared VSS and ICROP classifications of ROP retinal images from the i-ROP cohort (n=6552 eye-level examinations) and the Aravind Eye Care System (AECS) (n=8281 eye-level examinations). In both cohorts, higher VSS was associated with more severe disease, including higher ROP stage, greater extent of Stage 3 disease, and more posterior disease involvement within comparable stages. Overall, VSS was significantly lower in the AECS cohort, suggesting possible differences in disease phenotype between the two populations. Key limitations of this study include the use of a different camera for half of the AECS dataset and potential variation in disease classification.

JAMA Ophthalmology

Sound advice: voice-based AI for patient education

Can voice-based generative AI serve as a tool for patient education? Age-related macular degeneration (AMD) is a leading cause of vision loss, but it can be managed with intravitreal therapy (IVT). Low first-year adherence rates to IVT necessitate the help of patient education tools. Polaris is a voice-based generative AI system that was implemented to guide patients in education about IVT. 26 patients were included and administered pre- and post-interaction surveys about their experience with AI-assisted care. The post-survey found a 28 percentage point increase in patients who believed AI would positively impact healthcare. 96% of participants rated the tool organized and understandable, 85% deemed it useful for newly diagnosed AMD patients, and 81% reported increased confidence in AI's role in health care. Additionally, 19 retinal specialists and 5 practice managers (PMs) participated, with 63% of HCPs and 80% of PMs having increased confidence in AI's potential in the post-survey. Overall, this study indicates the strong potential for use of AI in supporting patient education.

Sometimes the best intervention is none at all. The DRCR.net Protocol V study sought to determine the optimal management of center-involving diabetic macular edema. In this randomized controlled trial, 702 individuals (n=702 study eyes) with type 1 or type 2 diabetic with baseline visual acuity of 20/25 or better were enrolled. Participants were placed into 3 study groups: initial observation (n=236), initial laser photocoagulation (n=240), and initial aflibercept (n=226). Aflibercept was initiated in the observation and laser groups as needed based on reduced vision and worsened macular edema.

Key Points: 

• At 2 years, there was no significant difference in the rate of vision loss (5-letter reduction) between the observation (19%), laser photocoagulation (17%), and aflibercept group (16%)
• There was a small increase in the proportion of patients that were 20/20 at year 2 for the Aflibercept group (77%) compared to initial observation (66%) (P = 0.03); this was not true for Aflibercept versus laser

Overall, the DRCR V is a landmark study because it was the first large RCT to evaluate management outcomes in diabetic macular edema after the development of anti-VEGF treatments. Anti-VEGF treatments provided ophthalmologists with a new option for diabetic macular edema; however, there was no evidence prior to this study to demonstrate that early treatment initiation improved visual acuity outcomes for these patients. This study demonstrated that individuals with good baseline visual acuity did not require initiation of treatment with anti-VEGF intravitreal injections or laser photocoagulation.