Current Issue

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In this week’s issue

• GLP-1 receptor agonists may significantly reduce the risk of AMD and glaucoma, suggesting a promising new approach to protecting vision.
• Pathogenic mismatch repair gene variants commonly linked to Lynch syndrome were found in a subset of uveal melanoma patients.
• Glaucoma is linked with circadian rhythm sleep disorders and other sleep-wake disturbances.
• Physical activity acutely increases IOP in glaucoma patients, returning near baseline during recovery, with IOP closely tracking blood pressure and heart rate changes.
• Undergoing intraocular surgery after ptosis repair more than doubles the long-term risk of ptosis recurrence requiring reoperation.

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Ophthalmology
Can GLP-1RAs protect the aging eye?

What’s good for the pancreas might also be good for the retina. Age-related macular degeneration (AMD) and primary open-angle glaucoma (POAG) are leading causes of irreversible vision loss. While current treatments focus on late stages, identifying protective strategies for early intervention is an ongoing challenge. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), already used for diabetes and obesity, have shown neuroprotective and anti-inflammatory properties—making them promising candidates for ocular disease prevention. In this large retrospective cohort study, over 9,600 patients aged 60+ on GLP-1RAs were compared to matched cohorts on metformin, insulin, statins, or aspirin, using electronic health records with 5 years of follow-up. GLP-1RA use was associated with a significantly reduced risk of nonexudative AMD (HR 0.68–0.72) and POAG (HR 0.58) compared to metformin (HR 0.68, 95% CI 0.56–0.84), insulin (HR 0.72, 95% CI 0.58–0.89), and statins (HR 0.70, 95% CI 0.57–0.87). Risk of POAG was also significantly lower compared to insulin (HR 0.58, 95% CI 0.45–0.76). Risk reduction was observed as early as 3 years into treatment and results were validated across multiple independent cohorts. No meaningful impact was observed on cataract or ocular hypertension risk. This study supports the potential repurposing of GLP-1RAs for ophthalmic protection, highlighting a novel therapeutic pathway for slowing age-related vision loss. Future prospective studies are needed to confirm these findings and explore potential mechanisms.

JAMA Ophthalmology

Uveal melanoma: A rare tumor manifestation of Lynch syndrome

A potential genetic match, no swiping right needed. Uveal melanoma is a rare intraocular tumor affecting about 5 in 1 million people annually across the U.S. and Europe. While high-penetrance variants like BAP1 and MBD4 are already known—and MBD4 responds well to immune checkpoint inhibitors—this study investigated whether mismatch repair (MMR) genes, commonly mutated in Lynch syndrome, may also play a role. In a prospective cohort of 381 patients diagnosed with uveal melanoma (July 2021–Feb 2023), whole-exome sequencing of a 122-gene panel was performed. Results revealed 79 pathogenic variants in 70 individuals, with 21 variants located in clinically relevant genes, significantly enriched for MMR genes. Notably, one case with an MLH1 germline variant showed tumor monosomy 3 with loss of the wild-type MLH1 allele and mutational signatures SBS6/ID1/ID2, supporting a pathogenic role. Many patients also reported Lynch-associated family cancers, such as colorectal and endometrial cancer. These findings support a previously unrecognized association between MMR gene mutations and uveal melanoma, suggesting a new avenue for targeted immunotherapy given the high response rates of MMR-mutant tumors to checkpoint inhibitors.

American Journal of Ophthalmology (AJO)

Is glaucoma associated with circadian rhythm sleep disorders?

Could glaucoma be keeping patients up at night? Glaucoma damages melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) and axons in the optic nerve. These cells play a role in processing the photic input transmitted to the suprachiasmatic nucleus in the hypothalamus, which in turn stimulates the pineal gland and modulates sleep-wake functions. Given this pathway, a mechanistic link between glaucoma and sleep disorders has been proposed. This cross-sectional study analyzed data from 2.7 million California Medicare beneficiaries aged ≥65. Diagnoses of glaucoma and circadian rhythm sleep disorders (CRSD) were identified using ICD-10 codes. A total of 8.1% of beneficiaries had glaucoma, 13.1% had a sleep-wake disorder, and 0.1% had CRSD. Among those with glaucoma, 15.7% had concurrent sleep-wake disorders, and 0.2% had a diagnosis of CRSD. Adjusted logistic regression models showed that beneficiaries with glaucoma were 12% more likely than those without glaucoma to have any sleep-wake disorder (OR 1.12), and 20% more likely to have CRSD (OR 1.20), after controlling for age, sex, race and ethnicity, systemic disease burden defined by Charlson Comorbidity Index (CCI) score, age-related macular degeneration, diabetic retinopathy, presence of cataracts, and pseudophakia. Glaucoma severity was not associated with a greater likelihood of CRSD, suggesting a threshold effect where any glaucomatous damage increases the risk of CRSD. A limitation of the study is the lack of stratification by glaucoma subtypes, which may have different associations with sleep-wake disorders and should be explored in future research. Nonetheless, early screening for CRSD in those with glaucoma may improve overall patient health.

British Journal of Ophthalmology

Continuous IOPs highlight exercise-induced pressure fluctuations

Who would’ve thought that IOP hits the gym too? Intraocular pressure (IOP) is a key clinical surrogate used to assess glaucoma risk, monitor disease progression, and guide treatment decisions. While exercise has been associated with reduced IOP when measured after activity, its real-time effects during exertion have remained unclear, largely due to the limitations of conventional tonometry. This study employed an implanted IOP sensor (eyemate-IO) to continuously monitor IOP in ten patients with open-angle glaucoma during a cycling exercise protocol. Researchers recorded IOP, heart rate, and blood pressure as exercise intensity increased, and then tracked changes during recovery. IOP increased progressively with exertion, from a baseline average of 15.4 mmHg to a peak average of 18.0 mmHg, before falling to an average of 14.4 mmHg post-exercise. Notably, IOP was strongly correlated with heart rate and systolic blood pressure during activity, but these associations dissipated upon return to rest. These findings suggest that IOP rises transiently with physical effort before ultimately decreasing below baseline following exercise. This pattern, revealed only through continuous monitoring, underscores the potential of implanted IOP sensors to capture real-time pressure dynamics in everyday contexts and inform glaucoma management.

Eye 

When surgeries collide: Recurrent ptosis after intraocular surgery

Looks like repaired eyelids may not appreciate going back into the OR! New onset ptosis (drooping of the upper eyelid) is a known complication of intraocular surgery in healthy patients. However, few studies have evaluated the incidence of ptosis following intraocular surgery on patients who have previously undergone ptosis repair, and thus have compromised eyelid integrity. As such, this retrospective cohort study matched 1,598 patients who had previously undergone ptosis repair and underwent an intraocular surgery within 10 years of the repair (PRIOS group) against 1,598 patients with a history of ptosis repair who did not have any intraocular surgery within 10 years of the repair (PRO group) for ptosis recurrence requiring reoperation. Patients in the PRIOS group were twice as likely to need a second surgery for recurrent ptosis (HR: 2.16 at 2 years, 1.98 at 5 years, 1.67 at 10 years). The risk persisted over time with early separation of Kaplan–Meier curves, and reoperation rates were notably higher by 3 months post-intraocular surgery. This study highlights the importance of considering ptosis recurrence during preoperative counseling and surgical planning of intraocular procedures. 

Journal of Neuro-Ophthalmology

Seeing is believing: MRI metric use in genetic optic atrophy

If a picture is worth a thousand words, then an MRI may speak volumes about the progression of genetic optic atrophy. While T2-hyperintensity and optic nerve atrophy are well-known MRI markers of several chronic optic neuropathies, their roles in genetic optic atrophy are less defined. In this study, 15 patients diagnosed with non-glaucomatous optic atrophy of genetic origin with available magnetic resonance (MR) images of the orbits and/or brain were analyzed. T2 short Tau inversion recovery (STIR) signal and optic nerve caliber were quantified using a standardized protocol and compared between cases and controls, with inter-rater reliability calculated. Clinical features, including visual acuity, cup-to-disc ratio, and visual field testing, were analyzed and correlated with these quantitative measures. Compared to controls, a significant increase in T2 STIR signal (1.6-fold) and reduction in optic nerve caliber (0.72-fold) were demonstrated in those with genetic optic nerve atrophy. Inter-rater reliability was strong for both measures with correlation coefficients of 0.98 and 0.74, respectively. These MRI metrics demonstrated a significant correlation with clinical parameters. Based on these findings, a standardized assessment of optic nerve signal intensity and caliber on MRI may be useful in providing an objective approach to diagnosing and characterizing genetic optic atrophy conditions: decreasing diagnostic ambiguity, assessing disease progression, and facilitating earlier diagnosis.

Cell Reports Medicine

Multi-disease AI screening with ultra-wide fundus photography

With retinal diseases often requiring specialized care and early detection, scalable screening solutions are critical. This study developed an AI-based platform trained on ultra-wide-field fundus photographs to simultaneously detect and provide referral suggestions for multiple fundus diseases, including diabetic retinopathy, glaucoma suspect, and AMD. The model was trained on 329,927 images and validated on three external datasets. It achieved AUCs of 0.982 for DR, 0.970 for glaucoma suspect, and 0.990 for AMD in internal testing, with similarly high performance on external datasets. Referral recommendation accuracy also exceeded an AUC of 0.97. Additionally, the system generates heatmaps for interpretability and includes a data quality assessment module to flag ungradable images. This multi-task AI system shows promise for real-world screening of multiple retinal diseases simultaneously, potentially streamlining referrals in urban and resource-limited settings. Prospective validation and clinical implementation will be the key next steps.

Endophthalmitis Vitrectomy Study (EVS) - 1995

When a storm is brewing inside of the vitreous, how do you get to the destination safely? Before the 1995 EVS study, there was no clear consensus on how to utilize vitrectomy and IV antibiotics for patients with post-op endophthalmitis. Therefore, the EVS study sought to define a treatment protocol for these scary cases. In the study, 420 patients with clinical evidence of endophthalmitis within 6 weeks after cataract surgery or secondary intraocular lens implantation were randomly assigned to four groups with combinations of pars plana vitrectomy PPV or no PPV, and treatment with or without systemic antibiotics.

Key Points

• Systemic antibiotics may not be necessary and increase cost, length of stay, and toxic side effects
• Routine PPV is not necessary for patients with better than light perception (LP) vision at presentation
• PPV is beneficial for patients presenting with LP or worse vision, leading to better visual outcomes and reduced adverse outcomes

Overall, EVS established an LP cutoff for routine PPV in post-op endophthalmitis. If a patient can see HM, you can wave them goodbye instead of taking straight to the OR.