Cup-to-disc ratio in GLP-1 RA Associated Non-Arteritic Anterior Ischemic Optic Neuropathy.
case_control · Level III
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- Record sourced from PubMed, PMID 42556433.
- Also identified by DOI 10.1016/j.ophtha.2026.07.036.
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Abstract
First: to determine whether the cup-to-disc ratio (CDR) of patients with GLP-1 RA associated nonarteritic anterior ischemic optic neuropathy (NAION) is similar to the CDR of NAION patients without GLP-1 RA exposure. Second: to stratify the odds of developing NAION based on CDR. A retrospective, multi-center, case control study of the CDR of NAION cases diagnosed between 2018-2024 SUBJECTS AND CONTROLS: The Disc-at-Risk Study Group included 16 neuro-ophthalmology centers that reviewed medical records of 1,812 unaffected fellow eyes from 2,169 consecutive patients with NAION. The control group included both eyes of 465 patients. The study compared the unaffected fellow eyes of three groups of NAION patients: semaglutide users (117 eyes), non-semaglutide GLP-1 RA users (83 eyes) and no GLP-1 RA medications (1,612 eyes). Control eyes defined the distribution of CDR in the general population. CDR of unaffected fellow eyes of NAION patients with and without exposure to GLP-1 RA medications RESULTS: The average provider-estimated CDR in unaffected fellow eyes of NAION patients was 0.13 with no significant difference among the three groups. A measured CDR ≤ 0.40 was found in 94% of fellow eyes but only 56% of controls (p<0.001). A measured CDR ≤ 0.20 was found in 54% of fellow eye photographs but only 9% of controls (p<0.001). Eyes with a measured CDR ≤ 0.20 have the highest NAION odds (OR=46.3; 95% CI 23.0-93.4), and eyes with a CDR >0.20 and ≤ 0.40 had more modest odds (OR=6.8; 95% CI 3.5-13.2) compared with eyes with a measured CDR >0.40. NAION patients with and without exposure to GLP-1 RA medications have the same high prevalence of crowded optic discs. The odds of NAION are inversely proportional to CDR. Irrespective of GLP-1 RA exposure, eyes with a photo-measured CDR ≤ 0.20 have 46 times greater odds of NAION than eyes with a CDR > 0.40. Although the absolute risk of NAION is low, this quantification of NAION risk may help better inform patients concerned about NAION risk. This study does not assess whether GLP-1 RA medications are an independent risk factor for NAION.