Gulf War Illness (GWI) is a multisystem disease with variable presentations, making diagnosis difficult. Non-invasive biomarkers would aid in disease diagnosis. We hypothesized that the eye could serve as a biomarker for GWI. We performed a retrospective case-control study using a sample of 1246 patients seen during a 5-month period in an optometry clinic. We identified veterans who were active duty during the Gulf War Era and either had a questionnaire-based diagnosis of GWI (cases) or did not (controls). Medical records were reviewed for eye and medical co-morbidities, medication use, and retinal macular and nerve fiber layer (NFL) thicknesses based on optical coherence tomography (OCT) images. Compared to controls (n = 85), individuals with GWI (n = 60) had a higher frequency of dry eye symptoms (50% vs 32.9%, p = 0.039). Multivariable analysis revealed average retinal NFL thickness (odds ratio; OR = 0.95), cup-to-disc ratio (OR = 0.005), age (OR = 0.82), and PTSD (OR = 20.5) were predictors of a GWI diagnosis. We conclude that GWI is associated with dry eye symptoms and RNFL thinning may serve as a biomarker for disease.

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