Assessment of Somatosensory Function in Patients With Idiopathic Dry Eye Symptoms

Abstract

IMPORTANCE Somatosensory dysfunction likely underlies dry eye (DE) symptoms in many individuals yet remains an understudied component of the disease. Its presence has important diagnostic and therapeutic implications. OBJECTIVE To assess the integrity of nociceptive system processes in persons with DE and ocular pain using quantitative sensory testing (QST) techniques applied at a site remote from the eye. DESIGN, SETTING, AND PARTICIPANTS A cross-sectional study conducted at Miami Veterans Affairs Hospital included 118 individuals with a wide variety of DE symptoms and signs. The study was conducted from October 31, 2013, to January 28, 2016. INTERVENTIONS Individuals completed questionnaires regarding ocular symptoms (5-Item Dry Eye Questionnaire [DEQ5], Ocular Surface Disease Index [OSDI], and Neuropathic Pain Symptom Inventory modified for the eye [NPSI-E]), psychological status, and medication use and underwent an ocular surface examination. The QST metrics included measures of vibratory and thermal thresholds and cold and hot pain temporal summation (surrogate measures of central sensitization) on the forearm. MAIN OUTCOMES AND MEASURES Correlations among DE and ocular pain symptom severity with QST metrics measured on the forearm. The OSDI score ranges from 0 to 100, with 100 indicating the most severe DE symptoms. The DEQ5 score ranges from 0 to 22, with the highest score indicating the most severe symptoms, and the NPSI-E score ranges from 0 to 100, with the highest score indicating the most severe symptoms. Psychological state was measured with the 9-item Patient Health Questionnaire, the PTSD Checklist-Military Version for PTSD, and the Symptom Checklist-90 for anxiety. RESULTS Of the 118 patients who participated in the study, 105 (88.9%) were men (mean [SD] age, 60 [10] years), and a mean of 41% had PTSD, 10% depression, and 0.93% anxiety. Using stepwise linear regression analyses, significant associations were identified between overall DE symptom severity and posttraumatic stress disorder scores and tear breakup time (DEQ5 model: R = 0.54; OSDI model: R = 0.61, P < .001). All other variables (ie, demographics, comorbidities, medications, tear film factors, and QST metrics) dropped out of these models. When specifically considering neuropathic-like qualities of DE pain, however, anxiety and hot pain temporal summation at the forearm explained 17% of the variability in ocular burning (R = 0.41; P < .001), and PTSD score, tear breakup time, and hot pain temporal summation at the forearm explained 25% of the variability in sensitivity to wind (R = 0.50; P < .001) and 30% of the variability in total NPSI-E scores (R = 0.55; P < .001). CONCLUSIONS AND RELEVANCE Our findings demonstrate that neuropathic-like DE pain symptom severity correlates with quantitative measures of pain sensitivity at a site remote from the eye. This result provides additional evidence that DE symptoms are not only manifestations of a local disorder but also involve somatosensory dysfunction beyond the trigeminal system.

Sex Disparity in How Pain Sensitivity Influences Dry Eye Symptoms

“…12,14 The higher proportion of women to men found in this study reflects the general recruitment pool that subjects were drawn upon. The only study that examined this in men was by Galor et al, 13 who found that increased pain sensitivity was associated with greater symptoms of dry eye. It should be noted that their cohort was significantly older (mean age of 60 years), with a majority of subjects having a mental illness and taking psychiatric medications, whereas our study consisted of a younger and healthy cohort.…”

“…[9][10][11] The sex difference in pain sensitivity is of particular interest because of the results of recent studies, which have shown that greater pain sensitivity is associated with higher levels of dry eye symptoms and ocular surface discomfort. [12][13][14] It should be noted that the cohorts in these studies primarily consisted of women, and it is unknown whether there is a sexspecific difference in how pain sensitivity influences symptoms. 12,14 To answer this question, a prospective cross-sectional study was conducted that included a thorough assessment of the ocular surface and used the Pain Sensitivity Questionnaire (PSQ) to quantify pain sensitivity.…”

The Growing Need for Validated Biomarkers and Endpoints for Dry Eye Clinical Research

“…148,155,161–163 However, the relationship between DED and corneal nerve changes is not clear. One study has reported that improvement in corneal fluorescein staining score and symptomatology following treatment was evident only in the patient group showing near normal corneal sub-basal nerve fiber length.…”

Comparative Evaluation of 5 Validated Symptom Questionnaires as Screening Instruments for Dry Eye Disease

“…1,4,5 However, the C statistic, sensitivity, and specificity values of the 5 questionnaires were all relatively modest and potentially reflect the heterogeneous nature and complex interrelationships between ocular surface homeostatic disturbances, somatosensory pathways, and symptomatic experiences of dry eye disease. 6,7…”