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Ocular manifestations and biomarkers of Gulf War Illness in US veterans.

ABSTRACT: 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.

SUBMITTER: Baksh BS

PROVIDER: S-EPMC7985482 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Ocular manifestations and biomarkers of Gulf War Illness in US veterans.

Baksh Brandon S BS Zayan Kristen L KL Goldhardt Raquel R Felix Elizabeth R ER Klimas Nancy N Galor Anat A

Scientific reports 20210322 1

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 ...[more]

PMID: 33753811

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Project description:Gulf War Illness (GWI) is a chronic disorder affecting approximately 30% of the veterans who served in the 1991 Gulf War. It is characterised by a constellation of symptoms including musculoskeletal pain, cognitive problems and fatigue. The cause of GWI is not definitively known but exposure to neurotoxicants, the prophylactic use of pyridostigmine bromide (PB) pills, and/or stressors during deployment have all been suspected to play some pathogenic role. Recent animal models of GWI have suggested that neuroinflammatory mechanisms may be implicated, including a dysregulated activation of microglia and astrocytes. However, neuroinflammation has not previously been directly observed in veterans with GWI. To measure GWI-related neuroinflammation in GW veterans, we conducted a Positron Emission Tomography (PET) study using [11C]PBR28, which binds to the 18 kDa translocator protein (TSPO), a protein upregulated in activated microglia/macrophages and astrocytes. Veterans with GWI (n = 15) and healthy controls (HC, n = 33, including a subgroup of healthy GW veterans, HCVET, n = 8), were examined using integrated [11C]PBR28 PET/MRI. Standardized uptake values normalized by occipital cortex signal (SUVR) were compared across groups and against clinical variables and circulating inflammatory cytokines (TNF-α, IL-6 and IL-1β). SUVR were validated against volume of distribution ratio (n = 13). Whether compared to the whole HC group, or only the HCVET subgroup, veterans with GWI demonstrated widespread cortical elevations in [11C]PBR28 PET signal, in areas including precuneus, prefrontal, primary motor and somatosensory cortices. There were no significant group differences in the plasma levels of the inflammatory cytokines evaluated. There were also no significant correlations between [11C]PBR28 PET signal and clinical variables or circulating inflammatory cytokines. Our study provides the first direct evidence of brain upregulation of the neuroinflammatory marker TSPO in veterans with GWI and supports the exploration of neuroinflammation as a therapeutic target for this disorder.

Project description:The Boston University-based Gulf War Illness Consortium (GWIC) is a multidisciplinary initiative developed to provide detailed understanding of brain and immune alterations that underlie Gulf War illness (GWI), the persistent multisymptom disorder associated with military service in the 1990-1991 Gulf War. The core GWIC case-control clinical study conducted in-depth brain and immune evaluation of 269 Gulf War veterans (223 GWI cases, 46 controls) at three U.S. sites that included clinical assessments, brain imaging, neuropsychological testing, and analyses of a broad range of immune and immunogenetic parameters. GWI cases were similar to controls on most demographic, military, and deployment characteristics although on average were two years younger, with a higher proportion of enlisted personnel vs. officers. Results of physical evaluation and routine clinical lab tests were largely normal, with few differences between GWI cases and healthy controls. However, veterans with GWI scored significantly worse than controls on standardized assessments of general health, pain, fatigue, and sleep quality and had higher rates of diagnosed conditions that included hypertension, respiratory and sinus conditions, gastrointestinal conditions, and current or lifetime depression and post-traumatic stress disorder. Among multiple deployment experiences/exposures reported by veterans, multivariable logistic regression identified just two significant GWI risk factors: extended use of skin pesticides in theater (adjusted OR = 3.25, p = 0.005) and experiencing mild traumatic brain injury during deployment (OR = 7.39, p = 0.009). Gulf War experiences associated with intense stress or trauma (e.g., participation in ground combat) were not associated with GWI. Data and samples from the GWIC project are now stored in a repository for use by GWI researchers. Future reports will present detailed findings on brain structure and function, immune function, and association of neuroimmune measures with characteristics of GWI and Gulf War service.

Dataset Information

Ocular manifestations and biomarkers of Gulf War Illness in US veterans.

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Ocular manifestations and biomarkers of Gulf War Illness in US veterans.

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