This retrospective, multi-center case-control study evaluated whether cup-to-disc ratio (CDR) differs between NAION patients with and without GLP-1 RA exposure, and quantified NAION odds by CDR category, using 1,812 unaffected fellow eyes from 2,169 NAION patients (2018–2024) across 16 neuro-ophthalmology centers, compared to 465 controls.
CDR did not differ across GLP-1 RA groups (mean CDR ~0.13). Eyes with photo-measured CDR ≤0.20 had 46× greater NAION odds (OR=46.3; 95% CI 23.0–93.4) vs. eyes with CDR >0.40; 54% of NAION fellow eyes had CDR ≤0.20 vs. only 9% of controls (p<0.001).
- Study does not assess whether GLP-1 RA medications are an independent risk factor for NAION — causality cannot be inferred. - CDR was provider-estimated in most cases, with photo-measured CDR available only for a subset, introducing measurement variability. - Retrospective design and reliance on medical records may introduce selection and ascertainment bias.
Crowded optic discs (CDR ≤0.20) carry a 46-fold increased odds of NAION regardless of GLP-1 RA use — clinicians can use photo-measured CDR to better counsel patients on their baseline NAION risk. GLP-1 RA exposure does not appear to change the disc anatomy risk profile, but this study cannot determine whether these drugs independently raise NAION risk.
