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Updated: Aug 7, 2026
The Rodent Model of Nonarteritic Anterior Ischemic Optic Neuropathy (rNAION)
Published on: November 20, 2016
Cup-To-Disc Ratio in Glucagon-Like Peptide 1 Receptor Agonist-Associated Nonarteritic Anterior Ischemic Optic
Christian M Robertson1, Derrick S Fung1, Kyle H Smith1
1Baylor Scott & White Eye Institute, Department of Ophthalmology, Baylor Scott & White Medical Center, Temple, Texas.
Purpose:
To determine whether the cup-to-disc ratio (CDR) of patients with glucagon-like peptide 1 receptor agonist (GLP-1 RA) -associated nonarteritic anterior ischemic optic neuropathy (NAION) is similar to the CDR of patients with NAION without GLP-1 RA exposure and to stratify the odds of developing NAION based on CDR.
Design:
A retrospective, multicenter, case-control study of the CDR of NAION cases diagnosed between 2018 and 2024.
Subjects And Controls:
The Disc-at-Risk Study Group included 16 neuro-ophthalmology centers that reviewed medical records of 1812 unaffected fellow eyes from 2169 consecutive patients with NAION. The control group included both eyes of 465 patients.
Methods:
The study compared the unaffected fellow eyes of 3 groups of patients with NAION: semaglutide users (117 eyes), nonsemaglutide GLP-1 RA users (83 eyes), and No GLP-1 RA medications (1612 eyes). Control eyes defined the distribution of CDR in the general population.
Main Outcome Measures:
The CDR of unaffected fellow eyes of patients with NAION with and without exposure to GLP-1 RA medications.
Results:
The average provider-estimated CDR in unaffected fellow eyes of patients with NAION was 0.13, with no significant difference among the 3 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 (odds ratio = 46.3; 95% confidence interval, 22.9-93.4), and eyes with a CDR > 0.20 and ≤0.40 had more modest odds (odds ratio = 6.8; 95% confidence interval, 3.5-13.2) compared with eyes with a measured CDR > 0.40.
Conclusions:
Patients with NAION 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.
Financial Disclosure(S):
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
