Current Issue

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In this week’s issue

• A new study found that children of lower socioeconomic status will benefit most from in school vision screening programs.
• Selenium supplementation shows no QOL improvement at 6 months in Graves ophthalmopathy patients from selenium-sufficient regions.
• In a mouse model evaluating Fuchs endothelial corneal dystrophy, heterozygous Tcf4 loss seems to confer protection against disease progression.
• A meta-analysis pooling data from five major randomized trials of ranibizumab for DME found that vision outcomes between black and white patients were similar with this medication.
• A Generative Adversarial Network-powered OCT model achieved 99% accuracy in detecting diabetic retinopathy, indicating continued improvement in AI medical learning.

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Ophthalmology
School-based vision program outcomes associated with school characteristics

Putting school vision programs under the lens. Schools play an important role in childhood vision health and development, as prevention and early treatment of vision problems early in life can significantly affect quality of life in adulthood. Disparities in health care come into play with access to pediatric eye care and those of lower socioeconomic status are more likely to face these barriers. School-based vision programs (SBVPs) are on the rise throughout the country, and this study aims to investigate the outcomes of SBVPs and ascertain which schools would benefit from them most. This is a retrospective cross-sectional study that analyzed the association between school characteristics and SBVP outcomes such as vision screening failure, eyeglass prescriptions, and referral to community eye care using fractional regression models. Increased proportion of students qualifying for free-and-reduced meals was weakly correlated with rates of screening failure, eyeglasses prescription, and referral for eye care with Pearson Correlation coefficients of 0.22 (95% CI, 0.12-0.31), 0.11 (95% CI, 0.01-0.20), and 0.22 (95% CI, 0.12-0.31), respectively. There was a 2.6% increase in screening failure rate (change rate, 2.60; 95% CI, 1.54-3.65) with each 10% increase in proportion of students qualifying for free-and-reduced meals. Students from communities of lower socioeconomic status contribute significantly to vision care demand in public schools, and dedicating resources to schools in these corresponding areas may have the greatest impact and benefit.

JAMA Ophthalmology
Selenium's limited role in selenium-sufficient Graves ophthalmopathy

A challenge to prior assumptions... The SeGOSS trial investigated selenium supplementation (100μg twice daily with vitamin B complex) for mild to moderate Graves ophthalmopathy (GO) in selenium-sufficient regions. While earlier studies in selenium-deficient areas showed promising results, this randomized, open-label study of 70 patients found no improvement in quality of life at the 6-month primary endpoint compared to vitamin B complex alone. Interestingly, at 3 months, the selenium group showed transient benefits with higher QOL improvement rates (78.4% vs 48.5%) and better proptosis reduction that disappeared by 6 months. In patients with more active disease (CAS ≥2), selenium demonstrated sustained proptosis improvement through 6 months, suggesting potential targeted applications. No adverse events were reported, with plasma selenium levels remaining within safe ranges throughout the trial. These findings may necessitate reconsideration of routine selenium supplementation for GO patients in selenium-sufficient regions like North America.

IVOS

Tcf4 acts as a modulator of disease in FECD mouse model

Two wrongs don’t make a right, but two mutations may offer protection. Fuchs endothelial corneal dystrophy (FECD) is characterized by abnormal extracellular matrix (ECM) deposits within the cornea that cause progressive vision impairment. Several genetic variants are thought to contribute to FECD pathogenesis, including mutations in COL8A2 and a trinucleotide repeat in TCF4. In this study, to investigate TCF4’s role in the disease, Tcf4 heterozygous knockout mice were crossed with the established FECD mouse model, Col8a2Q455K, to generate Col8aQ455K/Tcf4± mice. Corneal endothelial cells were analyzed via RNA sequencing and visualized via contact specular microscopy. Compared with Col8a2Q455K mice, Col8aQ455K/Tcf4± mice had enriched expression of ion transport and muscle fiber genes, as well as decreased TNF-associated signaling. Morphologically, the Col8aQ455K/Tcf4± mice showed reduced guttae and enhanced corneal endothelial cell survival over time, and expression of ECM genes like Fn1 were lower. Overall, this study demonstrates that heterozygous Tcf4 mutation confers protection against guttae formation and disease progression in the FECD mouse model. This highlights the potential utility of TCF4 as a drug target, though more studies are needed to fully understand its mechanism of action in FECD.

 JAMA Ophthalmology

Does race have an impact on vision outcomes in treatment of DME?

When it comes to treating diabetic eye disease, does everyone really see the same results? Diabetic macular edema (DME) has a higher prevalence in Black and Hispanic patients in the US, yet clinical trial data has historically underrepresented these populations. This meta-analysis pooled data from five major randomized trials of ranibizumab (including RIDE, RISE, Protocols I, S, and T) to evaluate whether vision outcomes differ by race among patients treated for DME. Only Black and White participants were analyzed due to low enrollment of other racial groups. Black participants had better baseline visual acuity (66.7 [95% CI, 65.0-68.4] vs 62.0 [95% CI, 61.1-62.8] ETDRS letter score) but gained fewer letters at 24 months (6.1 ETDRS letters [95% CI, 3.6-8.6] vs 10.2 ETDRS letters [95% CI, 9.3-11.1]). After adjusting for baseline vision, this difference narrowed (7.7 ETDRS letters [95% CI, 5.8-9.7] vs 9.9 ETDRS letters [95% CI, 9.0-10.7]). In a propensity-matched analysis from RIDE/RISE, mean visual gains were similar (10.6 ETDRS letters [95% CI, 7.1-14.1] vs 10.1 ETDRS letters[95% CI, 7.3-12.9]; P = .83). While initial differences suggest a potential disparity, adjusted and matched analyses point toward comparable efficacy of ranibizumab across races. This study emphasizes the importance of improving diversity in clinical trial enrollment and collecting more detailed demographic information to ensure results reflect real-world populations.

JAMA Ophthalmology

Photodiagnosis and Photodynamic Therapy

Can GANs help level the playing field in DR diagnosis?

Sometimes the best way to fix your dataset… is to create more of it. Diabetic retinopathy (DR) is a global cause of preventable blindness, but training AI models to detect it from OCT images is often hindered by limited data and class imbalance. Generative Adversarial Networks (GANs) offer a promising solution by creating realistic synthetic images that enhance model training, especially when true cases are scarce. This study introduced a novel pipeline that paired GAN-based data augmentation with denoising autoencoders and EfficientNetB0 to build a robust DR classifier. GANs were used to generate high-quality synthetic OCT images, balancing the dataset and improving generalizability. Autoencoders removed noise and artifacts, and EfficientNetB0 was fine-tuned on this enhanced dataset. The final model achieved 99% accuracy, recall, and specificity, outperforming comparable methods. By leveraging GANs to overcome class imbalance, a persistent obstacle in medical AI, this study demonstrates how synthetic data can boost real-world diagnostic performance. Future directions include interpretability tools and adaptation to additional imaging modalities to support broader clinical deployment.

International Optic Nerve Trauma Study (IONT) - 1999

Maybe nothing is usually better than something in neuro-ophthalmology. Prior to the 1999 IONT study, there were a variety of management options used for patients with traumatic optic neuropathy, but there was no clear formula for success. The 1999 IONT treated patients with traumatic optic neuropathy with corticosteroids (n = 85), surgery (n = 33), or no treatment (n=9) with the primary outcome of visual acuity.

Key Points:

• After adjusting for baseline visual acuity, there were no significant differences in outcomes between the treatment groups and the observation group 
• The dosage or timing of corticosteroid therapy did not affect visual acuity outcome

The IONT study is a landmark study because it determined that the method of treatment did not affect visual outcome in traumatic optic neuropathy. As a result, and due to potential adverse effects of treatment, neither corticosteroid therapy nor surgery should be considered the standard of care. Instead, observation as the standard and further treatment based on the individual patient are most appropriate.