Dry eye symptoms and signs in United States Gulf War era veterans with myalgic encephalomyelitis/chronic fatigue syndrome.

BACKGROUND: To examine ocular symptoms and signs of veterans with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) diagnosis, ME/CFS symptoms, and controls. METHODS: This was a prospective, cross-sectional study of 124 South Florida veterans in active duty during the Gulf War era. Participants were recruited at an ophthalmology clinic at the Miami Veterans Affairs Hospital and evaluated for a diagnosis of ME/CFS, or symptoms of ME/CFS (intermediate fatigue, IF) using the Canadian Consensus criteria. Ocular symptoms were assessed via standardised questionnaires and signs via comprehensive slit lamp examination. Inflammatory blood markers were analysed and compared across groups. RESULTS: Mean age was 55.1 ± 4.7 years, 88.7% identified as male, 58.1% as White, and 39.5% as Hispanic. Ocular symptoms were more severe in the ME/CFS (n = 32) and IF (n = 48) groups compared to controls (n = 44) across dry eye (DE; Ocular Surface Disease Index [OSDI]: 48.9 ± 22.3 vs. 38.8 ± 23.3 vs. 19.1 ± 17.8, p < 0.001; 5 item Dry Eye Questionnaire [DEQ-5]: 10.8 ± 3.9 vs. 10.0 ± 4.6 vs. 6.6 ± 4.2, p < 0.001) and pain-specific questionnaires (Numerical Rating Scale 1-10 [NRS] right now: 2.4 ± 2.8 vs. 2.4 ± 2.9 vs 0.9 ± 1.5; p = 0.007; Neuropathic Pain Symptom Inventory modified for the Eye [NPSI-E]: 23.0 ± 18.6 vs. 19.8 ± 19.1 vs. 6.5 ± 9.0, p < 0.001). Ocular surface parameters and blood markers of inflammation were generally similar across groups. CONCLUSION: Individuals with ME/CFS report increased ocular pain but similar DE signs, suggesting that mechanisms beyond the ocular surface contribute to symptoms.

Validation of an automatically generated screening score for frailty: the care assessment need (CAN) score.

BACKGROUND: Frailty is a state of vulnerability to stressors that is prevalent in older adults and is associated with higher morbidity, mortality and healthcare utilization. Multiple instruments are used to measure frailty; most are time-consuming. The Care Assessment Need (CAN) score is automatically generated from electronic health record data using a statistical model. The methodology for calculation of the CAN score is consistent with the deficit accumulation model of frailty. At a 95 percentile, the CAN score is a predictor of hospitalization and mortality in Veteran populations. The purpose of this study was to validate the CAN score as a screening tool for frailty in primary care. METHODS: This is a cross-sectional, validation study compared the CAN score with a 40-item Frailty Index reference standard based on a comprehensive geriatric assessment. We included community-dwelling male patients over age 65 from an outpatient geriatric medicine clinic. We calculated the sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of the CAN score. RESULTS: 184 patients over age 65 were included in the study: 97.3% male, 64.2% White, 80.9% non-Hispanic. The CGA-based Frailty Index defined 14.1% as robust, 53.3% as prefrail and 32.6% as frail. For the frail, statistical analysis demonstrated that a CAN score of 55 provides sensitivity, specificity, PPV and NPV of 91.67, 40.32, 42.64 and 90.91% respectively whereas at a score of 95 the sensitivity, specificity, PPV and NPV were 43.33, 88.81, 63.41, 77.78% respectively. Area under the receiver operating characteristics curve was 0.736 (95% CI = .661-.811). CONCLUSION: CAN score is a potential screening tool for frailty among older adults; it is generated automatically and provides acceptable diagnostic accuracy. Hence, the CAN score may be a useful tool to primary care providers for detection of frailty in their patient panels.

Associations between dry eye disease and sleep quality: a cross-sectional analysis.

BACKGROUND/AIMS: To investigate relationships between dry eye (DE) disease and sleep quality, with a focus on which aspects of sleep most closely relate to DE. METHODS: 141 veterans (mean age: 56±5) seen at the Miami Veterans Affairs eye clinic filled out questionnaires to quantify the severity of DE symptoms (5-Item Dry Eye Questionnaire (DEQ-5) and Ocular Surface Disease Index (OSDI)) and ocular pain (Numerical Rating Scale (NRS) and Neuropathic Pain Symptom Inventory modified for the Eye (NPSI-E)). All individuals also underwent an ocular surface examination. Aspects of sleep quality were assessed using the Pittsburgh Sleep Quality Index (PSQI). DE metrics were examined by PSQI scores and subscores. RESULTS: Most participants (76%) reported mild or greater DE symptoms (DEQ-5 ≥6). Overall, ocular symptoms were more related to sleep metrics than signs. The strongest DE symptom association was between the OSDI and sleep disturbances (PSQI subscore 5, r=0.49, p<0.0005). For DE signs, ocular surface inflammation and meibum quality were related to subjective sleep quality (PSQI subscore 1, r=0.29, p=0.03, for both). On linear regression analyses, most ocular symptom questionnaires remained associated with sleep disturbances (PSQI subscore 5: NRS (r=0.52, p<0.0005), DEQ-5 (r=0.36, p<0.0005), and OSDI (r=0.31, p<0.0005)). For DE signs, ocular surface inflammation and meibum quality remained associated with subjective sleep quality (r=0.26, p=0.01; r=0.46, p<0.0005, respectively). CONCLUSION: DE symptom and ocular pain intensity were closely related to sleep metrics, most strongly to sleep disturbances. Relationships were weaker for DE signs, with subjective sleep quality relating to inflammation and meibum quality.

Associations between Corneal Nerve Structure and Function in a Veteran Population.

Background: We evaluate the relationship between corneal nerve structure and function in a veteran population. Methods: 83 veterans (mean age: 55 ± 5 years) seen at the Miami Veterans Affairs (VA) eye clinic were included in this study. Each individual filled out questionnaires to evaluate ocular symptoms (5-Item Dry Eye Questionnaire, DEQ5; Ocular Surface Disease Index, OSDI) and ocular pain (Numerical Rating Scale, NRS; Neuropathic Pain Symptom Inventory modified for the Eye, NPSI-Eye). The individuals also underwent an ocular surface examination that captured functional nerve tests including corneal sensation, corneal staining, and the Schirmer test for tear production. Corneal sub-basal nerve analysis was conducted using in vivo confocal microscopy (IVCM) images with corneal nerve density, length, area, width, and fractal dimension captured. IVCM and functional corneal metrics from the right eye were examined using correlational and linear regression analysis. Results: Most corneal structural metrics were not related to functional metrics, except for weak correlations between various IVCM metrics and tear production. In addition, corneal nerve fiber area was positively related to corneal sensation (r = 0.3, p = 0.01). On linear regression analyses, only the corneal fractal dimension remained significantly related to tear production (ß = -0.26, p = 0.02) and only the corneal nerve fiber area remained significantly related to corneal sensation (ß = 0.3, p = 0.01). Conclusions: Most corneal nerve structural metrics did not relate to functional metrics in our veteran population, apart from a few weak correlations between structural metrics and tear production. This suggests that using corneal nerve anatomy alone may be insufficient for predicting corneal function.

Is Meibomian Gland Dysfunction One Disease? Heterogeneity Among Phenotypes.

PURPOSE: The purpose of this study was to examine ocular surface symptoms, tear metrics, and tear cytokines by Meibomian gland dysfunction (MGD) features. METHODS: Symptom questionnaires and an ocular surface evaluation were performed on 40 individuals with varied MGD signs [Meibomian gland (MG) plugging, eyelid vascularity, meibum quality, and MG dropout]. Tear proteins were extracted off Schirmer strips and analyzed for 23 human inflammation-related proteins. Statistical analysis was performed to examine associations between dry eye metrics inflammatory proteins and MGD features. RESULTS: The study involved 40 South Florida veterans with a mean age of 61 ± 13 years; most individuals were male (95%), White (31%), and non-Hispanic (85%). MGD features differentially related to dry eye signs. Eyelid vascularity, meibum quality, and MG dropout, but not MG plugging, correlated with higher corneal staining and lower tear production. MGD features also differentially related to tear cytokines. Eyelid vascularity most closely related to inflammation with significant correlations for interferon-gamma-γ (r = 0.36, P = 0.02), interleukin-4 (IL-4) (r = 0.43, P = 0.006), IL-17A (r = 0.42, P = 0.007), matrix metalloproteinase-2 (r = 0.39, P = 0.01), C-X-C motif chemokine ligand 5 (Regulated upon Activation, Normal T-Cell Expressed and presumably Secreted [RANTES]) (r = 0.32, P = 0.04), and tumor necrosis factor α (r = 0.36, P = 0.02). The other 3 MGD signs were less related to inflammation. Multivariable models revealed IL-4 to be most closely related to eyelid vascularity (standardized ß = 0.39, P < 0.0001). CONCLUSIONS: Eyelid vascularity was the MGD sign most closely related to inflammatory cytokines, suggesting that different MGD features may be driven by different pathophysiological mechanisms.

Ocular and inflammatory markers associated with Gulf War illness symptoms.

To examine the utility of ocular coherence tomography (OCT) metrics, in conjunction with systemic markers of inflammation, in identifying individuals with Gulf War Illness (GWI) symptoms. Prospective case-control study of 108 Gulf War Era veterans, split into 2 groups based on the presence of GWI symptoms, defined by the Kansas criteria. Information on demographics, deployment history, and co-morbidities were captured. 101 individuals underwent OCT imaging and 105 individuals provided a blood sample which was analyzed for inflammatory cytokines using an enzyme-linked immunosorbent assay-based chemiluminescent assay. The main outcome measure was predictors of GWI symptoms, examined with multivariable forward stepwise logistic regression analysis followed by receiver operating characteristic (ROC) analysis. The mean age of the population was 55 ± 4, 90.7% self-identified as male, 53.3% as White, and 54.3% as Hispanic. A multivariable model that considered demographics and co-morbidities found that a lower inferior temporal ganglion cell layer-inner plexiform layer (GCL‒IPL) thickness, higher temporal nerve fiber layer (NFL) thickness, lower interleukin (IL)-1ß levels, higher IL-1α levels, and lower tumor necrosis factor-receptor I levels correlated with GWI symptoms. ROC analysis demonstrated an area under the curve of 0.78 with the best cut-off value for the prediction model having a sensitivity of 83% and specificity of 58%. RNFL and GCL‒IPL measures, namely increased temporal thickness and decreased inferior temporal thickness, respectively, in conjunction with a number of inflammatory cytokines, had a reasonable sensitivity for the diagnosis of GWI symptoms in our population.

Automated identification and quantification of activated dendritic cells in central cornea using artificial intelligence.

PURPOSE: To validate an algorithm quantifying activated dendritic cells (aDCs) using in-vivo confocal microscopy (IVCM) images. METHODS: IVCM images obtained at the Miami Veterans Affairs Hospital were retrospectively analyzed. ADCs were quantified both with an automated algorithm and manually. Intra-class-correlation (ICC) and a Bland-Altman plot were used to compare automated and manual counts. As a secondary analysis, individuals were grouped by Dry Eye (DE) subtype: 1) aqueous-tear deficiency (ATD; Schirmer's test ≤5 mm); 2) evaporative DE (EDE; TBUT≤5s); or 3) control (Schirmer's test>5 mm; TBUT>5s) and ICCs were re-examined. RESULTS: 173 non-overlapping images from 86 individuals were included in this study. The mean age was 55.2 ± 16.7 years; 77.9% were male; 20 had ATD; 18 EDE and 37 were controls. The mean number of aDCs in the central cornea quantified automatically was 0.83 ± 1.33 cells/image and manually was 1.03 ± 1.65 cells/image. A total of 143 aDCs were identified by the automated algorithm and 178 aDCs were identified manually. While a Bland-Altman plot indicated a small difference between the two methods (0.19, p < 0.01), the ICC of 0.80 (p = 0.01) demonstrated excellent agreement. Secondarily, similar results were found by DE type with an ICC of 0.75 (p = 0.01) for the ATD group, 0.80 (p = 0.01) for EDE, and 0.82 (p = 0.01) for controls. CONCLUSIONS: Quantification of aDCs within the central cornea may be successfully estimated using an automated machine learning based algorithm. While this study suggests that analysis using artificial intelligence has comparable results with manual quantification, further longitudinal research to validate our findings in more diverse populations may be warranted.

Pyridostigmine Bromide Pills and Pesticides Exposure as Risk Factors for Eye Disease in Gulf War Veterans.

To examine associations between the pyridostigmine bromide (PB) pill and/or pesticide exposure during the 1990-1991 Gulf War (GW) and eye findings years after deployment. A cross-sectional study of South Florida veterans who were deployed on active duty during the GW Era (GWE). Information on GW exposures and ocular surface symptoms were collected via standardized questionnaires and an ocular surface examination was performed. Participants underwent spectral domain-ocular coherence tomography (SD-OCT) imaging that included retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), and macular maps. We examined for differences in eye findings between individuals exposed versus not exposed to PB pills or pesticides during service. A total of 40.7% (n = 44) of individuals reported exposure to PB pills and 41.7% (n = 45) to pesticides; additionally, 24 reported exposure to both in the GW arena. Demographics were comparable across groups. Individuals exposed to PB pills reported higher dry eye (DE) symptoms scores (the 5-Item Dry Eye Questionnaire, DEQ-5: 9.3 ± 5.3 vs. 7.3 ± 4.7, p = 0.04) and more intense ocular pain (average over the last week: 2.4 ± 2.6 vs. 1.5 ± 1.8, p = 0.03; Neuropathic Pain Symptom Inventory modified for the Eye (NPSI-E): 18.2 ± 20.0 vs. 10.8 ± 13.8, p = 0.03) compared to their non-exposed counterparts. DE signs were comparable between the groups. Individuals exposed to PB pills also had thicker OCT measurements, with the largest difference in the outer temporal segment of the macula (268.5 ± 22.2 µm vs. 260.6 ± 14.5 µm, p = 0.03) compared to non-exposed individuals. These differences remained significant when examined in multivariable models that included demographics and deployment history. Individuals exposed to pesticides had higher neuropathic ocular pain scores (NPSI-E: 17.1 ± 21.1 vs. 11.6 ± 12.9, p = 0.049), but this difference did not remain significant in a multivariable model. Individuals exposed to PB pills during the GWE reported more severe ocular surface symptoms and had thicker OCT measures years after deployment compared to their non-exposed counterparts.

Dry Eye Symptoms and Signs in US Veterans With Gulf War Illness.

PURPOSE: To examine dry eye (DE) symptoms and signs in individuals with vs without Gulf War illness (GWI). DESIGN: Prospective cross-sectional study. METHODS: We performed a prospective, cross-sectional study of South Florida veterans who were active duty during the Gulf War era (GWE; 1990-1991) and seen at an eye clinic between October 1, 2020, and March 13, 2021. Veterans were split into 2 groups: those who met Kansas criteria for GWI (cases, n = 30) and those who did not (controls, n = 41). DE symptoms were assessed via standardized questionnaires whereas DE signs were assessed using a series of ocular surface parameters. Differences between groups were assessed via Mann-Whitney U test. Linear regression analyses were used to examine which GWI symptoms most closely aligned with DE symptoms. RESULTS: Veterans with GWI had higher DE symptoms scores compared to controls (Ocular Surface Disease Index [OSDI] scores: mean 41.20±22.92 vs 27.99±24.03, P = .01). In addition, veterans with GWI had higher eye pain scores compared with controls (average eye pain over past week: 2.63±2.72 vs 1.22±1.50, P = .03), including on neuropathic ocular pain questionnaires (Neuropathic Pain Symptom Inventory modified for the Eye [NPSI-E]: 17.33±17.20 vs 9.63±12.64, P = .03). DE signs were mostly similar between the groups. GWI symptoms "nausea or upset stomach" (ß=14.58, SE = 3.02, P < .001) and "headache" (ß=7.90, SE = 2.91, P = .011) correlated with higher OSDI scores. CONCLUSION: Individuals with GWI have more severe DE symptoms and ocular pain scores but similar tear and ocular surface parameters compared to controls without GWI. This finding suggests that mechanisms beyond tear dysfunction drive eye symptoms in GWI.

How Should Corneal Nerves be Incorporated Into the Diagnosis and Management of Dry Eye?

PURPOSE: a)Confocal microscopy and aethesiometry have allowed clinicians to assess the structural and functional integrity of corneal nerves in health and disease. This review summarizes literature on nerves in dry eye disease (DED) and discusses how this data can be applied to DED diagnosis and treatment. RECENT FINDINGS: b)Subjects with DED have a heterogenous symptom and sign profile along with variability in nerve structure and function. Most studies have reported lower nerve density and sensitivity in aqueous tear deficiency, while findings are more inconsistent for other DED subtypes. Examining nerve status, along with profiling symptoms and signs of disease, can help categorize subjects into disease phenotypes (structural and functional patterns) that exist under the umbrella of DED. This, in turn, can guide therapeutic decision-making. SUMMARY: c)Due to the heterogeneity in symptoms and signs of DED, corneal nerve evaluations can be valuable for categorizing individuals into disease sub-types and for guiding clinical decision making.