Ocular Symptoms and Biomarkers of Gulf War Illness

Abstract

Purpose : Gulf War Illness (GWI) is a chronic multisystem disease thought to be driven by neuroinflammatory and neurodegenerative mechanisms. We examined potential ocular biomarkers of GWI symptoms, including ocular symptoms, ocular coherence tomography (OCT) characteristics, and serum proteins.

Methods : Prospective case-control study of 108 GW Era veterans, split into 2 groups based on the presence of GWI symptoms. Information on demographics, deployment history, and co-morbidities were captured. All individuals underwent dry eye testing. 101 individuals underwent OCT imaging, and 105 provided a blood sample which was analyzed for inflammatory cytokines using an enzyme-linked immunosorbent assay. The main outcome measure was to determine ocular metrics associated with GWI symptoms, examined with multivariable forward stepwise logistic regression followed by receiver operating characteristic analysis.

Results : The mean age of the population was 55±4, 90.7% self-identified as male, 53.3% as White, and 54.3% as Hispanic. Demographics were similar between those with vs. without GWI symptoms. Individuals with GWI symptoms reported higher intensities of ocular pain (assessed via Numeric Rating Scale, range 0-10: 2.70±3.31 vs. 0.84±1.49, p<0.01) and sensations of dryness (5-item Dry Eye Questionnaire, range 0-22, 10.83±4.09 vs. 7.38±4.52, p<0.01). Individuals with GWI symptoms had higher temporal retinal nerve fiber layer (RNFL) thickness (61.33±11.52 vs. 55.80±10.23 µm, p=0.02). Across all multivariable models, temporal RNFL thickening (odds ratio (OR)=1.09-1.17), inferior ganglion cell layer-inner plexiform layer (GCL-IPL) thinning (OR=0.35-0.85), and ocular symptoms assessed via different questionnaires (OR=1.04-3.06) remained significantly associated with GWI symptoms. Inflammatory cytokines were less consistent as the serum proteins across models varied. The best predictive model included temporal RNFL thickening, inferior GCL-IPL thinning, higher dry eye symptoms via the Ocular Surface Disease Index, higher interleukin-17 (IL-17) levels, lower IL-2 levels, and lower tumor necrosis factor receptor I levels, and demonstrated an area under the curve of 0.88 with 90% sensitivity and 76% specificity.

Conclusions : Several ocular biomarkers, including ocular surface symptoms and temporal NFL and inferior GCL-IPL thickness, in conjunction with a number of inflammatory cytokines, had a reasonable sensitivity for the presence of GWI symptoms in our population.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.