Current review of glucagon-like peptide 1 receptor agonists and risk of nonarteritic anterior ischemic optic neuropathy.

Mini-review synthesizing clinical, epidemiologic, and mechanistic data from multiple study designs including cohorts, registries, and pharmacovigilance analyses.

“This mini-review synthesizes the current clinical, epidemiologic, and possible mechanism between GLP-1RA–based therapies and NAION risk factors, informing balanced risk assessment and interdisciplinary clinical decision-making.”

Adults with type 2 diabetes or obesity, including those with specific risk factors such as disc-at-risk anatomy, hypertension, hyperlipidemia, and obstructive sleep apnea.

“Risk factors include disc-at-risk, type 2 diabetes, OSA, HTN, HLD, renal disease, and ischemic heart disease.”

Variable across synthesized studies, ranging from 69 randomized controlled trials to cohorts exceeding 100 million patients in EHR databases.

“The evidence now spans multiple study types: large claims/electronic health record (EHR) cohorts, national registry analyses, retrospective reviews, pharmacovigilance disproportionality analyses, and narrative reviews that synthesize mechanistic plausibility and clinical implications.”

Variable across synthesized studies, with some reporting cumulative incidence over 3 years or 5 years.

“Hathaway et al noted cumulative incidence rates as high as 8.9% over 3 years for GLP-1 users”

A small cup-to-disc ratio ('disc-at-risk') is the most robust anatomical predictor of NAION, present in 60% to 80% of patients.

“A small cup-to-disc ratio ('disc-at-risk') was found to be the most robust anatomical predictor of NAION.”

Use of GLP-1RAs demonstrates a statistically significant association with NAION development, with relative risk estimates ranging between 1.2 and 4.3.

“Although data across electronic health records, national registries, and pharmacovigilance analyses suggest a very low absolute incidence of NAION, the use of GLP-1RAs demonstrates a statistically significant association with NAION development, yielding relative risk estimates between 1.2 and 4.3.”

Systemic microvascular diseases and conditions like obstructive sleep apnea and end-stage renal disease are linked to increased susceptibility to optic nerve head ischemia.

“Systemic microvascular disease (diabetes, hypertension, hyperlipidemia) and conditions such as obstructive sleep apnea and end-stage renal disease were also linked to increased susceptibility to optic nerve head ischemia.”

Findings are limited by residual confounding, reliance on code-based NAION definitions, potential surveillance bias, and the rarity of the event leading to uncertainty in randomized controlled trials.

“Across these study designs, findings are limited by residual confounding factors, generalization of the optic disc anatomy, and incomplete clinical data.”