In this week’s issue

• Ophthalmic herpes showed no overall malignancy risk, though increased risk emerged in immunologically vulnerable patients.
• Anti-VEGF therapy with brolucizumab outperformed laser in visual outcomes for PDR at one year.
• Vitamin B may have a protective association with glaucoma, pointing to a potential role for nutrition in eye health.
• Specific metabolomic changes distinguish PVR from RD, pointing to pathways involved in fibrosis and inflammation.

Ophthalmology

Does ophthalmic herpes signal hidden cancer risk?

Sometimes infections raise concern for something deeper, but not always. Herpes zoster ophthalmicus (HZO) has long been debated as a potential marker of malignancy risk. However, existing data has been inconsistent. Additionally, it remains unclear whether ophthalmic herpes simplex virus (HSV) infections are associated with malignancy risk. In this large retrospective cohort study, investigators compared patients with incident HZO or ophthalmic HSV with propensity score-matched controls to assess incident malignancy risk over both short- and long-term follow-up. Neither HZO nor ophthalmic HSV was associated with an increased risk of cancer in the overall population. However, among patients with underlying immune dysregulation (i.e. autoimmune disease, immunodeficiency), HZO was linked to ~3-fold higher risk of subsequent malignancy. Overall, ophthalmic herpes infections alone may not justify expanded malignancy workup, though HZO in the setting of immune dysfunction may warrant closer oncologic vigilance.

JAMA Ophthalmology 

Brolucizumab as an alternative for proliferative diabetic retinopathy

Injections vs. lasers: Which is more effective at treating PDR? In its advanced stage, diabetic retinopathy can lead to proliferative diabetic retinopathy (PDR), characterized by neovascularization in the retina. Panretinal laser photocoagulation (PRP), first-line therapy for PDR, has been associated with many side effects and has since been replaced or used in combination with anti-VEGF injections. Brolucizumab has a high affinity for VEGF and a low molecular weight, allowing a higher volume of the drug to be delivered per injection. The CONDOR study is a randomized clinical trial of 689 participants comparing the efficacy of brolucizumab to PRP. Results demonstrated that brolucizumab was noninferior and superior to PRP in best-corrected visual acuity (BCVA). Brolucizumab had a mean change in letter score of 0.2, while PRP showed a mean change of -4.2. The results demonstrated that brolucizumab is a feasible alternative to PRP monotherapy in the treatment of PDR. The findings also suggest that brolucizumab may help reverse disease progression and maintain visual function. 

American Journal of Ophthalmology 

Vitamin B intake and open angle glaucoma risk

B‑lieve It or not. Open angle glaucoma is a leading cause of irreversible blindness worldwide. However, management is largely limited to lowering intraocular pressure (IOP) after disease onset. Currently, there are no widely accepted preventative measures for glaucoma. With an aging population, the prevalence of glaucoma is increasing, and subsequently so is the interest in lifestyle factors that may modify glaucoma risk. B‑vitamins have been hypothesized to play a role in glaucoma pathophysiology due to their involvement in mitochondrial function, neuroprotection, and homocysteine metabolism. This prospective, population-based cohort study used data from the long-running Rotterdam Study in the Netherlands. The study included 6,742 individuals without open angle glaucoma at baseline. Dietary intake and the development of open angle glaucoma were tracked for over 10 years. Glaucoma-associated parameters (e.g., IOP, nerve fiber layer, and ganglion cell layer thickness) were also measured. Higher daily dietary intake of niacin (vitamin B3) and cobalamin (vitamin B12) were significantly associated with a lower risk of open-angle glaucoma. Higher intake of niacin and cobalamin were also associated with lower IOP. Higher cobalamin intake was associated with increased ganglion cell layer thickness. Associations of other B vitamins (B1, B2, and B6) with open-angle glaucoma, IOP, RNFL, and GCL thickness were not observed. While these results are observational, the findings support further investigation into whether targeted nutritional strategies could benefit people at risk of developing glaucoma or its progression.  

Investigative Ophthalmology & Visual Science  

A metabolic fingerprint for proliferative vitreoretinopathy

Sometimes, the hardest part of retinal detachment repair is not closing the break but stopping the scar. Rhegmatogenous retinal detachment (RRD) can often be repaired surgically, but proliferative vitreoretinopathy (PVR) remains a major cause of repair failure. In PVR, retinal pigment epithelial cells and other cells form contractile membranes that pull on the retina, causing recurrent detachment and limited visual recovery. Because current treatment is mainly surgical, identifying pathways that distinguish PVR from lower-grade RRD may reveal future therapeutic targets. Researchers performed untargeted metabolomic profiling of vitreous samples from 38 surgical eyes: controls undergoing IOL scleral fixation (n=10), RRD with grade A/B PVR changes (n=18), and grade C PVR (n=10). Lower-grade RRD showed no significant metabolite differences from controls, suggesting that retinal detachment alone did not drive the metabolomic signal. Grade C PVR showed a distinct vitreous metabolic profile compared with both controls and lower-grade RRD, with upregulation of purine, amino acid, nitrogen-handling, fibrosis-related, and stress-response pathways. Overall, these findings suggest that PVR has a distinct vitreous metabolic signature that may help explain its fibroproliferative behavior and identify future therapeutic targets beyond inflammation alone.

Journal of Glaucoma

Under pressure: How does preservative-free latanoprost compare?

Reducing irritation with preservative-free latanoprost (PFL) could be key to improving treatment adherence among glaucoma patients. Latanoprost drops are a first-line treatment for ocular hypertension and glaucoma, but contain preservatives that often cause ocular surface disorders and irritation. This meta-analysis included 10 randomized controlled trials conducted between 2013 and 2025 across the United States, India, South Korea, and Europe, comparing intraocular pressure (IOP) reduction and safety profiles of PFL and preserved latanoprost (PL) in patients with glaucoma and ocular hypertension. While patients using PL experienced a significantly greater mean IOP reduction at the two-week follow-up visit (mean difference = 0.43 mmHg, 95% CI: 0.05-0.81), no differences were found at the 4-, 6-, or 12-week follow-ups. Also, patients using PFL had a significantly lower risk of surface hyperemia (RR=0.66, 95% CI: 0.51-0.85). Overall, PFL is an alternative to effectively manage IOP in sensitive patients.

Nature Biomedical Engineering

Measure twice, cut once: AI-guided navigation to improve surgical accuracy

Can an AI system close the gap between novice and experienced surgeons? AI has been applied to screening and diagnosis, but a gap remains for intraoperative applications. Using 11,426 microscopic surgical videos from 8 medical centers, the authors developed an Ophthalmic Video Foundation Model (OVFM) that provides surgeons with real-time, step-by-step navigation guidance during eye surgery. Ten ophthalmologists, five novices and five experts, performed cataract surgeries on pig eyes guided by real-time overlays projected directly into the surgical microscope by OVFM. The study measured improvements in incision angle accuracy and in shape and centering of the capsulorhexis, the opening of the anterior lens capsule during cataract surgery. OVFM significantly improved surgical accuracy across four measures: incision angle error reduction (main and secondary), second incision angle error reduction, capsulorhexis centration error reduction, and capsulorhexis shape matching improvement. Notably, novice surgeons benefited more than expert surgeons, with significantly larger improvements on capsulorhexis centration and shape matching with OVFM. This study represents a major step toward using AI during surgery to standardize surgical technique and potentially improve patient outcomes.

PIVOT (Pneumatic Retinopexy vs. Vitrectomy) - 2018

When things seem blurry, a PIVOT in your vision can bring them back into focus. The aim of this study was to evaluate and compare the results of pneumatic retinopexy (PnR, n=77) and pars plana vitrectomy (PPV=73) as treatment options for primary rhegmatogenous retinal detachment (RRD) involving the superior retina. 

Key Points

• ETDRS scores for PnR were better than PPV by 4.9 letters at 12 months (79.9 ±10.4 letters vs. 75.0 ±15.2 letters; P=0.024).
• Vertical metamorphopsia scores were superior for the PnR group compared with the PPV group at 12 months (0.14±0.29 vs.0.28±0.42; P=0.026). 
• Primary anatomic success at 12 months was achieved by 80.8% of patients undergoing PnR versus 93.2% undergoing PPV (P=0.045), with 98.7% and 98.6%, respectively, achieving secondary anatomic success.

Overall, the PIVOT landmark study demonstrated that pneumatic retinopexy is recommended as the initial treatment for eligible superior RRDs, as it offers superior visual acuity, fewer metamorphopsias, and a lower complication rate compared to vitrectomy.