Current Issue

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In this week’s issue

• Antiviral therapy can significantly reduce the high recurrence rates of CMV-associated anterior uveitis
• Rates of undiagnosed age-related eye diseases are relatively high among the elderly population in Singapore and associated with poorer outcomes
• A new study shows that antidepressants are associated with a decreased risk of AMD onset and progression
• SPP1+ cells’ interaction with macrophages may reveal a key to understanding uveal melanoma metastasis
• Social determinants of health impact the likelihood of obtaining a yearly eye examination in the United States 

https://open.spotify.com/episode/2IV8G6qk3rQw9JbWRjClNk?si=H3k-O3pMQuShQ9-Pq2cKXw 

Ophthalmology

Antiviral therapy in CMV-associated anterior uveitis

CMV strikes again, can antivirals break the cycle? Cytomegalovirus-associated anterior uveitis (CMV-AU) is notably associated with high rates of recurrence, high intraocular pressure, and progressive corneal endothelial cell loss that can lead to irreversible vision loss. Investigators aimed to evaluate the risk of anterior uveitis recurrence with positive PCR results for CMV-AU before and after initiation of antiviral therapy, and compare the efficacy of oral valganciclovir followed by 0.15% ganciclovir ointment vs. continuous 2% topical ganciclovir. This multicenter retrospective cohort study included 136 PCR-confirmed CMV-AU patients, with 113 receiving oral valganciclovir treatment and 23 receiving 2% topical ganciclovir treatment for 6 weeks. The primary outcomes were uveitis recurrence rate, and severe EC loss. After a median follow-up of 27 months, post-treatment recurrence occurred in 98 patients (72.0%) after treatment, and the recurrence rate dropped by 59.6% overall, from 2.87 to 1.16 per person-year. Overall, there was a greater reduction in the 2% topical ganciclovir group (-78.8%) than the oral valganciclovir group (-54.3%). However, severe EC loss was significantly more frequent in the topical ganciclovir group (70.0%) than in the oral valganciclovir group (34.4%). Thus, antiviral therapy can significantly reduce the high recurrence rates of CMV-AU. While oral valganciclovir may preserve corneal EC better than topical ganciclovir, stepping down to 0.15% ganciclovir could lead to increased recurrence.

JAMA Ophthalmology

Silent sight-stealers in Singapore’s seniors

Out of sight, out of mind takes on a new meaning with undetected eye disease. Age-related eye diseases remain a leading cause of visual impairment worldwide, yet many older adults unknowingly live with them particularly in aging Asian populations. This cross-sectional cohort study used PIONEER-1 data from 1,878 Singaporean adults ≥60 years to assess the contemporary prevalence, risk patterns, and impact of undiagnosed age-related macular degeneration (AMD), diabetic retinopathy (DR), cataract, and glaucoma. Researchers found that 35.8% had ≥1 undiagnosed eye disease, including nearly 90% of AMD and DR cases, 40.8% of cataracts, and 48.1% of glaucoma. Undiagnosed patients reported worse quality-of-life scores (-1.97% to -4.57%), a 2.46-fold greater likelihood of visual impairment, and 1.73-fold higher healthcare expenditure compared with diagnosed individuals. These findings underscore the urgent need for culturally-targeted screening, education, and early detection programs to protect vision in Asia’s rapidly aging population.

American Journal of Ophthalmology (AJO)

Can antidepressants protect against AMD?

Antidepressants for peace of mind and vision? Age-related macular degeneration (AMD) is a leading cause of blindness in older adults, affecting 20 million people in the US and 196 million worldwide, with prevalence projected to rise to 288 million by 2040. Antidepressants have been previously hypothesized to reduce the risk of AMD, but this has not been well proven in the literature. This study is a comprehensive (1.9 million patients), large-scale comparison of three major classes of antidepressants (SSRIs, SNRIs, and TCAs) and their associated risk with both onset and progression of AMD. The use of all three antidepressant classes were associated with a significantly reduced risk of onset and progression of nonexudative and exudative AMD. SNRI users exhibited the strongest protective association against new nonexudative AMD incidence (Risk Ratio (RR) 0.141) and exudative AMD incidence (RR 0.161) compared to matched controls. The benefits may stem from the medications’ potential to reduce inflammation and oxidative stress, as well as provide neuroprotection. This study highlights an understudied relationship between widely prescribed antidepressants and their potential to mitigate AMD development and progression.

Investigative Ophthalmology & Visual Science (IOVS) 

Can SPP1+ cells predict which uveal melanomas will metastasize?

What do osteopontin-expressing tumor cells and macrophages have in common? Possibly a deadly alliance. Uveal melanoma (UM) is known for its early metastasis, especially to the liver, but little is known about the cells that seed this spread. Identifying early metastatic subpopulations could open new doors for therapy and surveillance. One emerging suspect is SPP1+ tumor cells, which express osteopontin, a protein associated with immune modulation and invasion in other cancers. This study used single-cell RNA sequencing to profile 16 primary and metastatic UM samples, analyzing cell-type composition, SPP1 expression, and intercellular interactions with macrophages. SPP1+ tumor cells were enriched in early metastases and showed distinct transcriptional features compared to their primary tumor counterparts. SPP1+ cells demonstrated a strong predicted ligand-receptor interaction with tumor-associated macrophages, suggesting a collaborative role in immune evasion and dissemination. Importantly, SPP1+ cells were not abundant in primary tumors without metastasis. SPP1+ tumor cells may represent an early metastatic subpopulation that works in tandem with macrophages to drive UM progression. Targeting this cell-cell axis could help intercept metastasis before it takes hold.

AJO International
Sociodemographic disparities in eye examinationsWhy do some people make it to their yearly eye exam, while others don’t? Routine eye care is critical for detecting glaucoma, diabetic retinopathy, and other silent causes of vision loss, and access remains uneven across the United States. This cross-sectional study analyzed 27,246 U.S. adults from the 2022 National Health Interview Survey to identify which sociodemographic factors influence eye exam utilization. Just over half of adults (54.4%) reported seeing an eye specialist in the past year. Several groups were more likely to have had an exam, including women, Hispanic adults, Asian adults, and older individuals, with the likelihood increasing significantly after age 50. Adults who were uninsured, non-citizens, lower income, lower education, single/cohabiting, or living in the Western United States had significantly lower odds of receiving an eye exam. Insurance status and socioeconomic measures were particularly strong predictors. Even after adjusting for age and general health status, structural factors such as insurance coverage, financial stability, citizenship, and geographic region influenced whether someone obtained routine vision care. These findings highlight the powerful role of social determinants of health in shaping access to preventive eye care.

Translational Vision Science & Technology

AI prediction of toric ICL rotation and visual outcomes

Rotation impacts refraction! Accurate prediction of postoperative rotation after toric implantable collamer lens (TICL) implantation is critical to achieving optimal astigmatism correction and visual outcomes. This study developed and compared machine learning models to predict both the quantitative degree of TICL rotation and the qualitative impact on residual astigmatism, vision, and the need for realignment surgery. Data from 642 eyes of 371 patients were used to train regression and classification models incorporating 24 preoperative and anatomical variables, including anterior chamber parameters and sulcus-to-sulcus distance. The transformer-based Tabular Prior-Data Fitted Network (TabPFN) achieved the highest accuracy, with a mean absolute error of 5.64° ± 2.33° and root mean square error of 10.67° ± 5.88°, outperforming traditional models. For classifying rotation-related outcomes, TabPFN reached accuracies between 0.906 and 0.981, with near-perfect precision (0.99 ± 0.01) and an AUC of 0.90 for predicting cases requiring realignment surgery. Critical postoperative rotation thresholds were identified as 7.5°, 4.5°, and 2.5° for inducing >0.5 D of residual astigmatism, and 9.5°, 7.5°, and 4.5° for causing vision loss across low, medium, and high astigmatism groups, respectively. These results demonstrate that AI can accurately estimate TICL rotation and stratify risk for vision-affecting misalignment, offering a clinically useful decision-support tool to improve postoperative predictability in refractive surgery.

Early Treatment for ROP (ET-ROP)

Is patience still a virtue when managing ROP? The most common cause of pediatric blindness in the United States is retinopathy of prematurity (ROP), a condition characterized by abnormal angiogenesis following incomplete retinal vascularization in premature infants. Surgical management of ROP involves cryotherapy or laser therapy to avascular retina – however prior to the ETROP study, standard of care involved waiting to intervene until risk of retinal detachment or macular folds reached ≥ 50% (“threshold” ROP). ETROP was a randomized control trial to determine whether early ablation for “prethreshold” ROP (risk ≥ 15%) would improve visual acuity and structural outcomes compared to conventional management.

Key Points

• At 9 months of age, early peripheral retinal ablation significantly reduced unfavorable visual (from 19.5% to 14.5%, p=.01) and structural outcomes (from 15.6% to 9.1%, P < 0.001). 
• Further analysis revealed a new clinical algorithm for early prethreshold ROP treatment: Type 1 ROP (Zone I, any stage ROP with plus disease; Zone I, stage 3 ROP without plus disease; or Zone II, stage 2 or 3 with plus disease) should be managed with immediate intervention, while Type 2 ROP (zone I, stage I or 2 ROP without plus disease or zone II, stage 3 ROP without plus disease) should be closely monitored. 
• Patients were followed until 6 years of age and the structural benefits of early treatment persisted for eyes with high-risk prethreshold ROP; however, visual acuity benefits were only present for eyes with type 1 ROP.

ETROP was a landmark study that established the current treatment guidelines for ROP, demonstrating the structural and visual benefits of early intervention for eyes with type 1 ROP. However even with early treatment, 65.4% of eyes still developed visual acuity worse than 20/40, indicating the fundamental limitations in ROP management.