In this week’s issue

• Retinal vein occlusions are a strong predictor of long-term mortality
• Cannabis use is linked to reduced PVR risk after retinal detachment repair
• Chlorhexidine is a less painful alternative to povidone-iodine for intravitreal injection-related infection prophylaxis 
• Efferocytosis contributes to corneal immune homeostasis after UVB-induced apoptosis
• New AI tool boosts quality control for FAF-based inherited retinal disease diagnosis

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Ophthalmology

Retinal vein occlusion is associated with increased mortality

RVO is a warning we can’t ignore. Retinal vein occlusion (RVO) is the second most common blinding retinal vascular disease after diabetic retinopathy and can be classified as affecting the branch (BRVO) or central (CRVO) retinal veins. RVO has been linked to metabolic risk factors, but there are few studies that quantify the mortality risk of RVO. In this prospective cohort study, serial fundus photos from 12,954 adults were taken over 10 years to identify new BRVO and CRVO events and analyze potential associations with ocular and systemic factors as well as with mortality. Overall, this study found that the five year cumulative incidence was 0.35% for BRVO and 0.043% for CRVO, increasing to 0.64% and 0.14% at ten years. An increased mortality risk was noted in patients with RVO (BRVO HR 2.27; CRVO HR 3.83) even after adjusting for metabolic risk factors. While rare, RVO in this large cohort was a strong and independent predictor of mortality, and this study emphasizes the importance for regular risk assessment in affected patients.

JAMA Ophthalmology

Can cannabis curb PVR after retinal detachment repair?

High times, low risks? Proliferative vitreoretinopathy (PVR) is a major cause of retinal detachment (RD) repair failure with limited preventive options. Cannabis is a recreational psychoactive drug with possible anti-inflammatory and neuroprotective effects and has shown promise as an adjunct therapy for various ophthalmic diseases. This retrospective multicenter cohort study analyzed data from 68 U.S. health systems (2005–2025) and compared 1,193 patients with documented cannabis use to 1,193 matched non-users after primary RD repair. Exclusion criteria included proliferative diabetic retinopathy and follow up limited to six months or less. At both six months and one year, cannabis users with RD repair by any method had about half the relative risk of developing PVR (RR ~0.48) or of requiring complex re-repair (RR ~0.62) compared to non-users, although the absolute risk reduction was small (~2%). Adjusted analyses confirmed the association between cannabis and reduced PVR risk, even after controlling for myopia, vitreous hemorrhage, and ocular trauma. However, cannabis users had higher rates of systemic adverse effects such as pulmonary disease. These findings indicate a potential protective role of cannabis in PVR prevention, but prospective trials are needed to confirm causality and evaluate dosing.

American Journal of Ophthalmology (AJO)

Povidone iodine vs chlorhexidine in preventing post-injection endophthalmitis

Don’t touch me, I'm sterile! Intravitreal injections (IVIs) are a common treatment for retinal vascular disorders, including wet age-related macular degeneration, proliferative diabetic retinopathy, and retinal vein occlusion. They carry a small but feared risk of postinjection endophthalmitis (PIE), a severe vision-threatening complication with an incidence of approximately 0.05%. Povidone-iodine (PI) is conventionally used for PIE prophylaxis, but chlorhexidine (CHX) is being explored as an alternative due to potentially better patient tolerance due to less ocular surface irritation. This meta-analysis aimed to compare the efficacy and safety of CHX and PI for PIE prevention. The study revealed no difference in the rates of culture-positive PIE (0.016% CHX vs 0.009%) and culture-negative PIE (0.016% CHX vs 0.017% PI) between the CHX and PI groups. However, the study also found that patients who received CHX PIE prophylaxis had lower pain levels and reduced rates of corneal epitheliopathy. This study highlights a potential improvement in patient comfort that can be offered to patients receiving IVIs that does not compromise patient safety. 

Investigative Ophthalmology & Visual Science (IOVS)

Can cleaning up dead cells help calm UV damaged eyes?

Macrophages - the unsung janitors keeping your cornea inflammation-free. Ultraviolet B (UVB) radiation induces apoptosis in corneal stromal cells, triggering inflammation and tissue damage. While macrophages are known to engulf dead cells, it is unclear whether macrophage activity helps resolve corneal inflammation in photodamaged corneas. This study used a mouse model of UVB-induced corneal damage to track apoptotic cell clearance and macrophage activity as well as in vitro assays to understand how macrophage activity influences corneal inflammatory signaling. UVB exposure caused apoptosis of corneal stromal cells and recruitment of macrophages to the injury site, and macrophages actively engulfed apoptotic cells and suppressed the production of pro-inflammatory cytokines like IL-1β and TNF-α. Inhibition of macrocyte activity led to greater inflammation, suggesting this class of innate immune cells plays a protective role in resolving inflammation in the UVB-injured cornea. Enhancing macrophage activity could be a promising strategy to mitigate UVB-related corneal inflammation.

Clinical Therapeutics
Socioeconomic disparities influence access to and choice of anti-VEGF therapy
Who gets the best shots? This study analyzed over 3,000 patients with diabetic macular edema, proliferative diabetic retinopathy, retinal vein occlusion, or wet age-related macular degeneration using the NIH All of Us database to uncover how socioeconomic status affects intravitreal injection (IVI) access. Only 25.9% of included patients received IVI, and those earning over $150,000/year were more likely to receive treatment. Among the 652 treated patients, annual income over $150,000, college education, Asian race, Hispanic ethnicity, and older age were significantly more likely to receive aflibercept or ranibizumab, the more expensive anti-VEGF agents, compared to bevacizumab. These findings reveal inequities in both access to anti-VEGF treatment and medication choice, underscoring the need for health systems to address disparities and promote equitable retinal care.

Journal: Ophthalmology

Retinograd-AI: Automating image quality assessment for IRD imaging

Inherited retinal diseases (IRDs) often require high-quality fundus autofluorescence (FAF) imaging for diagnosis and monitoring, but manual image quality grading is time-consuming and subjective. This study introduces Retinograd-AI, an open-source AI model trained to assess image gradability in FAF scans from IRD patients, an essential preprocessing step for clinical and research AI pipelines like Eye2Gene. Trained on 2,445 expert-graded FAF images and validated on a held-out test set, Retinograd-AI achieved 91% accuracy and AUC of 0.94 for distinguishing gradable vs. ungradable images, performance that matched human grader agreement. Applied to a broader dataset of 136,631 images, the model uncovered trends in gradability by age, sex, ethnicity, and genotype. Notably, filtering images using Retinograd-AI boosted a gene prediction model’s accuracy from 33.8% to 68.9%. By automating image quality control, Retinograd-AI enables large-scale, reliable image analysis in IRD research and clinical AI development, setting a foundation for expansion into other retinal diseases.

Idiopathic Intracranial Hypertension Trial (IIHT) - 2014

What feels like a brain tumor, acts like a brain tumor, but isn’t a brain tumor? Pseudotumor cerebri! The Idiopathic Intracranial Hypertension Trial (IIHT) sought to determine the benefit of acetazolamide in reducing visual loss symptoms after 6 months of treatment in conjunction with weight loss. Patients with a new diagnosis of IIH by modified Dandy criteria (aged 18-60 years), excluding those with previous IIH or IIH for more than 2 weeks, were randomized to two groups: placebo (n = 79) or acetazolamide (n = 86) for 6 months.

Key Points

• The acetazolamide group had greater improvement in perimetric mean deviation (+1.24) versus placebo (+0.71), with P = 0.050
• Both the acetazolamide group and placebo group displayed improved intracranial pressures and papilledema grade, but the acetazolamide group improved more ( -1.31 versus -0.61, P < 0.001)
• The acetazolamide group had a higher incidence of adverse effects, most notably paresthesia and nausea, but no permanent side effects

The IIHT showed that acetazolamide is effective for both lowering intracranial pressure and treating visual field defects associated with idiopathic intracranial hypertension. Limitations to high doses of acetazolamide are side effects, some of which include paresthesia of the extremities, metallic taste in the mouth, fatigue, and frequent urination.