Investigating the Eye as a Biomarker of Gulf War Illness: Sphingolipid and Eicosanoid Composition in Tears and Plasma.

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.