Longitudinal Assessment of Ocular Biomarkers in Individuals With Gulf War Illness Symptoms

Gulf War illness (GWI) is characterized by a constellation of symptoms, including, but not limited to, diarrhea, fatigue, and memory problems that affect Gulf War veterans. Currently, there are no objective biomarkers for GWI. Previous studies have identified differences in optical coherence tomography (OCT) metrics between individuals with GWI symptoms and those without. However, there are limited data on how these metrics change over time. Therefore, in this current study, we conducted a prospective case-control investigation to determine if OCT metrics show longitudinal changes in those affected by GWI. We conducted a prospective study with 100 Gulf War-era veterans at the Miami Veterans Affairs Hospital from November 2018 to February 2022. Inclusion criteria required service during 1990-1991, with both deployed and nondeployed veterans included. Exclusions were based on factors like active infection, unmanaged psychotic disorders, significant head injuries, severe neurological disorders, and eye pathologies affecting OCT imaging. All participants provided informed consent, and the study was institutional review board-approved and conducted per the Declaration of Helsinki and Health Insurance Portability and Accountability Act guidelines. GWI symptoms were assessed using the modified Kansas questionnaire, categorizing veterans into groups based on GWI symptoms presence and deployment status. Data on demographics, comorbidities, medications, and medical and ocular diagnoses were collected. Participants underwent OCT imaging at 2 time points, 1 year apart, with macular, retinal nerve fiber layer, and ganglion cell layer-inner plexiform layer (GCL-IPL) thicknesses measured. Additionally, blood samples were collected and cytokine levels measured at baseline. Data analysis involved descriptive statistics, t-tests, and multivariable regression models. Statistical analyses were performed using SPSS 28.0. Logistic regression demonstrated that post-traumatic stress disorder (odds ratio [OR]: 8.18, 95% confidence interval [CI]: 2.327-28.851, P = .001) and a lower baseline macular thickness in the outer nasal segment (OR: 0.959, 95% CI: 0.924-0.994, P = .023) remained significantly associated with GWI symptoms. The model also found that individuals with GWI symptoms were more likely to have an increase in inner temporal GCL-IPL layer thickness over a 1-year period (OR: 1.187, 95% CI: 0.974-1.447, P = .089). When analysis was conducted only among those deployed, on