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In this week’s issue

• Long-term, repeated intravitreal anti-VEGF injections were associated with a significantly increased risk of cataract surgery in the treated eye, with risk increasing in a dose-dependent manner.
• Prespecified OCT interpretation rules, particularly assessment of the TSNIT curve, accurately distinguished glaucomatous damage from myopic structural changes with high sensitivity and specificity.
• Delaying the initial retinopathy of prematurity screening examination until 34 weeks postmenstrual age in selected medium-risk infants safely reduced unnecessary examinations without missing treatment-requiring ROP.
• Subretinal AAV8-mediated PD-L1 gene therapy reduced retinal inflammation and preserved retinal structure and function in a rat model of autoimmune uveitis, suggesting a potential future immune-modulating treatment strategy.

Ophthalmology

Does anti-VEGF therapy increase your risk of cataract surgery?

Turns out the injected eye keeps a running tab. Intravitreal anti-VEGF therapy transformed the management of neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), and retinal vein occlusion (RVO), with short-term trial data suggesting a reassuring cataract safety profile. Long-term evidence, however, has been sparse, and prior reports of cataract development following anti-VEGF exposure were largely attributed to iatrogenic needle injury rather than the biological effects of repeated dosing. In this retrospective cohort study from a single tertiary center in South Korea, 603 phakic patients who received ≥12 unilateral anti-VEGF injections were followed over a median of 74 months. Incident cataract surgery was compared between the injected eye and the untreated fellow eye using Cox regression. The 10-year cumulative incidence of cataract surgery was 40.7% in injected eyes vs 7.2% in fellow eyes, with an adjusted hazard ratio of 8.17 for the injected eye and a clear dose-response across injection quartiles. Injected eyes also showed a higher rate of complete posterior vitreous detachment at the time of surgery. Long-term, repeated intravitreal anti-VEGF injections were independently associated with a substantially increased risk of surgery-requiring cataracts – a finding the authors frame as a reason to monitor lens status closely, not to hold back therapy.

JAMA Ophthalmology 

OCT rules sharpen glaucoma diagnosis in myopic eyes

Can OCT help distinguish glaucoma from myopic changes? Diagnosing glaucoma in myopic eyes is challenging because optic disc tilt, torsion, and retinal nerve fiber layer shifts can mimic glaucomatous changes. In this multicenter diagnostic study, investigators evaluated 5 prespecified OCT rules in 1,525 eyes from 943 adults with nonpathologic moderate or high myopia across China, Hong Kong, Taiwan, the US, and India. The strongest rule was qualitative assessment of the TSNIT curve for a dip or depression, which achieved 96% sensitivity and 95% specificity in the internal cohort and 93% sensitivity and 93% specificity in the external cohort. A combined rule using inferior peripapillary RNFL or inferotemporal mGC-IPL thinning also performed well externally, with 90% sensitivity and 93% specificity. These findings suggest that prespecified OCT rules may provide practical decision support for detecting glaucomatous optic neuropathy in myopic eyes while reducing false positives from physiologic myopic variation.

American Journal of Ophthalmology 

Can retinopathy of prematurity screening be safely delayed in selected infants?

A risk-stratified approach may safely reduce unnecessary ROP examinations in selected medium-risk infants. Retinopathy of prematurity (ROP) screening is essential for preventing childhood blindness but requires frequent retinal examinations that can burden infants and healthcare systems. In this retrospective diagnostic comparison study, researchers validated the FIRST-ROP algorithm, which delays the initial ROP examination to 34 weeks postmenstrual age (PMA) in medium-risk preterm infants. The study evaluated 3,641 infants born at ≥27 weeks' gestational age and weighing ≥800 g over a 30-year period. Overall, 604 infants (17%) developed ROP, and 15 required treatment, with a median PMA at first treatment of 40.0 weeks. Delaying screening to 34 weeks PMA would have reduced examinations by 17% without missing any cases of treatment-warranted ROP, and no infant required treatment before 34 weeks PMA. These findings suggest that the FIRST-ROP algorithm may safely reduce unnecessary examinations while maintaining sensitivity for vision-threatening ROP, supporting a more risk-stratified approach to screening.

Investigative Ophthalmology & Visual Science

Can gene therapy restore immune tolerance in autoimmune uveitis?

Sometimes we need to teach the immune system when to stop. Autoimmune uveitis is a T cell–mediated inflammatory eye disease that can lead to irreversible vision loss, and current treatments often require long-term systemic immunosuppression. In this preclinical study, researchers tested whether adeno-associated virus serotype 8 (AAV8) could deliver the immune checkpoint protein PD-L1 directly to the retina to restore local immune tolerance. Using a rat model of experimental autoimmune uveitis, they evaluated retinal inflammation, structure, function, immune cell infiltration, and gene expression following subretinal AAV8/PD-L1 administration. Eyes treated with AAV8/PD-L1 demonstrated significantly less intraocular inflammation, reduced T-cell and leukocyte infiltration, lower IL-17 expression, preserved retinal structure and electroretinographic function, and no detectable structural or functional toxicity in normal eyes. Transcriptomic analysis further showed suppression of inflammatory pathways involved in T-cell receptor signaling and Th17 differentiation, supporting restoration of a more tolerant retinal immune environment. While these findings remain limited to an animal model, they suggest that local PD-L1 gene therapy may represent a promising future strategy for treating autoimmune uveitis by modulating immune responses within the eye rather than suppressing systemic immunity.

Cornea

When the cornea loses its nerve

Restoring corneal sensation may be the key to reversing the damage caused by neurotrophic keratopathy. Corneal innervation is essential for preserving epithelial integrity and supporting normal wound healing. Injury to the trigeminal nerve can reduce or eliminate corneal sensation, impair epithelial repair, and ultimately result in neurotrophic keratopathy (NK). Treatment is guided by disease severity, ranging from conservative medical management in early stages to surgical or regenerative approaches, including amniotic membrane transplantation, recombinant nerve growth factor, and corneal neurotization (CN). CN is a restorative procedure that reestablishes corneal sensation by transferring a healthy sensory nerve to the anesthetic cornea through either direct nerve transfer or an indirect nerve graft. This prospective multicenter interventional study evaluated indirect CN using a sural nerve graft in 14 patients with severe NK following neurosurgical injury. Corneal sensitivity improved substantially, with corneal esthesiometry increasing from a baseline of 0.2 cm to 2.83 cm at final follow-up, while uncorrected distance visual acuity also improved over the study period. Clinical improvement was typically observed within 6 months and was accompanied by enhanced ocular surface health, including improved tear film stability, healing of persistent epithelial defects, reduced corneal vascularization and scarring, and increased subjective corneal sensation. These findings suggest that indirect CN can restore functional corneal innervation while promoting recovery of the ocular surface in patients with advanced NK.

British Journal of Ophthalmology

Calling all eye care allies! Annual diabetic retinopathy (DR) screening remains underutilized. Outpatient endocrinology clinics provide an opportunity to close that gap. In this real-world implementation study, investigators integrated the autonomous AI system AEYE-DS with the Topcon NW500 non-mydriatic camera in an endocrinology outpatient clinic. Fundus photos were captured by a novice non-ophthalmic operator and automatically analyzed for more-than-mild DR (mtmDR). The system produced a definitive result in 95.7% of patients without dilation, and 29.6% screened positive for mtmDR. Among the 34 AI-positive patients who completed confirmatory examination, 20 (59%) had confirmed mtmDR and 4 (12%) required treatment with anti-VEGF or panretinal photocoagulation. Patient satisfaction was high, with more than 80% reporting the screening was easy, efficient, and worth recommending. The study’s findings suggest that autonomous AI can be integrated smoothly into endocrinology workflow and may support a scalable stepped-referral model. Downstream follow-up remains a key challenge. 

Some risks are worth taking…but not cardiovascular risk. The Eye Disease Case-Control Study looked to describe potential risk factors associated with central retinal vein occlusion in this prospective, case-control study.

Key Points:

• Multivariate analysis revealed an associated increased risk of CRVO in individuals with systemic hypertension, diabetes mellitus requiring treatment, and decreased physical exercise
• Risk for ischemic CRVO risk was significantly increased in patients with cardiovascular disease, history of diabetes mellitus, and hemoglobin A1C greater than 6.3%
• Postmenopausal women had a decreased risk of CRVO when using exogenous estrogen replacement  

In short, individuals with cardiovascular risk factors such as systemic HTN, increased blood sugar levels, and less physical exercise are more at risk of CRVO, especially the ischemic type. Of note, women who used postmenopausal estrogens were at a decreased risk of CRVO, suggesting a potential protective role of exogenous estrogen in this population.