SAT-593 - A Case of Bilateral NAION in the Setting of Tirzepatide Use and Glycemic Variability

Background: Non-arteritic anterior ischemic optic neuropathy (NAION) is the most common acute optic neuropathy in adults over 50, characterized by sudden, painless vision loss with optic disc edema. Recent studies have reported a possible association between tirzepatide or semaglutide use and NAION.

Case Presentation: We report a man in his sixties with type 2 diabetes, hypertension, obstructive sleep apnea, hyperlipidemia, and tobacco use who developed bilateral NAION while receiving tirzepatide. His A1c decreased from 7.2% to 6.4% following tirzepatide initiation. Approximately three months later, he developed painless right eye vision loss with optic disc edema and peripapillary hemorrhage consistent with NAION. Workup for alternative etiologies including inflammatory markers, MRI, lumbar puncture, PET scan, and infectious studies was unrevealing.
Tirzepatide was subsequently interrupted due to medication unavailability, during which blood glucose ranged 300–400 mg/dL and A1c rose to 8.4%. During this period of poor glycemic control, he developed visual decline in the left eye with new optic disc edema on examination. After resuming tirzepatide, he presented several weeks later with worsening peripheral vision in the right eye. He denied eye pain, headaches, jaw claudication, or neurologic deficits. Repeat evaluation showed no evidence of acute intracranial or inflammatory pathology. Given bilateral optic nerve involvement and emerging safety concerns regarding GLP-1-based therapies, tirzepatide was discontinued and alternative glycemic management was pursued.

Discussion: NAION risk factors such as diabetes, hypertension, hyperlipidemia, OSA, and tobacco use were all present in this patient. Optic neuropathy developed after tirzepatide initiation, with bilateral progression during marked glycemic instability. Observational studies report a small but significant association between GLP-1-based therapies and NAION, though absolute risk is low and may reflect baseline vascular burden. Rapid glycemic improvement may transiently alter optic nerve head perfusion in susceptible individuals, analogous to early worsening seen in diabetic retinopathy. Here, both initial glycemic improvement and subsequent severe hyperglycemia coincided with visual decline, implicating glycemic variability rather than drug exposure alone.

Conclusion: This case illustrates a temporal association between tirzepatide use, significant glycemic fluctuations, and bilateral NAION in a patient with multiple vascular risk factors. The clinical course underscores the importance of careful glycemic titration and ophthalmic monitoring in high-risk individuals treated with GLP-1 receptor agonists.

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