Background/Aims: Glutamate is the primary excitatory neurotransmitter in the central nervous system, and elevated levels have been implicated in neurotoxicity. Corneal nerves are integral to ocular surface health and abnormalities can contribute to dry eye disease (DED). This study evaluates the relationship between serum glutamate levels, DED signs and symptoms, and corneal nerve parameters. Methods: A total of 124 veterans evaluated at the Miami Veterans Affairs Eye Clinic were included. Participants completed standardized questionnaires assessing ocular surface symptoms and pain, underwent comprehensive ocular surface examination and in vivo confocal microscopy, and provided blood samples for serum glutamate analysis. Results: Mean age was 55.67 ± 4.59 years; 90.3% were male, 55.6% White, and 35.5% Hispanic. Serum glutamate ranged from 0.26 to 3.16 µM/µL (mean 1.22 ± 0.57 µM/µL). Glutamate levels were not associated with DED symptoms as assessed by standardized questionnaires. Higher glutamate levels were linked with DED signs including reduced tear production (right eye: r = −0.05, p = 0.55; left eye: r = −0.25, p = 0.01) and increased corneal staining (right eye: r = 0.10, p = 0.29; left eye: r = 0.20, p = 0.03). Most notable were associations between elevated glutamate and corneal nerve health, including reduced corneal sensation (right eye: r = −0.20, p = 0.03; left eye: r = −0.18, p = 0.047) and decreased corneal nerve fiber width (r = −0.23, p = 0.01). Conclusions: Our findings support an association between systemic neurochemical status, specifically circulating glutamate, and ocular surface and corneal nerve health.

Gulf War Illness (GWI) is a chronic multi-symptom condition affecting veterans of the 1990–1991 Gulf War, with ocular discomfort increasingly recognized among its manifestations. This pilot study evaluated whether lipid alterations in tears and plasma could serve as potential biomarkers of GWI. Participants included Gulf War-era veterans seen in the Miami Veterans Affairs Hospital eye clinic from 2018–2022. Cases met GWI criteria, while controls were non-deployed, age- and gender-matched veterans without GWI. Participants completed systemic and ocular symptom questionnaires, and lipidomic profiling of tears and plasma quantified sphingolipids and eicosanoids. Compared to controls (n = 21), GWI cases (n = 19) reported greater ocular symptom burden, while ocular signs were similar between groups. Lipidomic analyses revealed increased tear eicosanoids ((±)14(15)-EET and (±)8(9)-EET), elevated plasma sphingomyelins (SM C16:0 DH, SM C20:0, SM C22:0), and reduced plasma monohexosylceramide (MHC C16:0) and sphingomyelin (SM C14:0) in cases. Logistic regression and random forest models identified plasma SM C16:0 DH and SM C20:0 as top predictors distinguishing GWI cases from controls, with an area under the receiver operating characteristic curve (AUC) of 0.89. These findings suggest lipid dysregulation in ocular and systemic compartments and support further investigation of tears as a minimally invasive source for biomarker discovery.