Objective The purpose of this study was to examine the severity and quality of ocular pain complaints in patients with dry eye symptoms. Methods Subjects with clinically-relevant dry eye symptoms (dryness, discomfort, tearing) of unknown origin seen in the Miami Veterans Affairs eye clinic were administered questionnaires for dry eye symptoms and ocular pain and underwent a standardized ocular examination. Qualities and severity ratings of ocular pain in subjects with idiopathic dry eye were compared to similar measures from published data in other chronic pain populations. Results The study sample consisted of 154 subjects, of which 91% were male and ranged in age from 27 to 89 (mean age = 61). Fifty-three percent of participants reported an average ocular pain of at least moderate intensity (numerical rating scale (NRS) ≥ 4), with specific characteristics (i.e., “burning” spontaneous pain) reported at frequencies comparable to prevalent chronic neuropathic pain syndromes as reported in the literature. Significant correlations were found between ocular pain metrics and dry eye symptom severity scores (r=0.57 to 0.66). Dry eye signs, however, did not generally correlate with ocular pain severity. Conclusions A significant proportion of subjects with idiopathic dry eye symptoms reported moderate or greater ocular pain intensity, with the majority endorsing descriptors commonly used by patients with non-ocular neuropathic pain conditions. Identifying sub-groups of dry eye patients based on the presence and characteristics of ocular pain complaints may improve dry eye sub classification and better individualize treatment strategies.

Recent data demonstrate that dry eye (DE) susceptibility and other chronic pain syndromes (CPS) such as chronic widespread pain, irritable bowel syndrome and pelvic pain, may share common heritable factors. Previously, we showed that DE patients describing more severe symptoms tended to report features of neuropathic ocular pain (NOP). We hypothesize that patients with a greater number of CPS would have a different DE phenotype compared to those with fewer CPS. We recruited a cohort of 154 DE patients from the Miami Veterans Affairs Hospital and defined high and low CPS groups by cluster analysis. In addition to worse non-ocular pain complaints and higher PTSD and depression scores (P<0.01), we found that the high CPS group reported more severe neuropathic-type DE symptoms compared to the low CPS group, including worse ocular pain assessed via 3 different pain scales (P<0.05), with similar objective corneal DE signs. This is the first study to demonstrate DE patients who manifest a greater number of comorbid CPS report more severe DE symptoms and features of NOP. These findings provide further evidence that NOP may represent a central pain disorder, and that shared mechanistic factors may underlie vulnerability to some forms of DE and other comorbid CPS.

Dry eye is becoming a major health concern due to its increasing incidence, significant morbidity, and economic burden. Recent evidence suggests that a subset of dry eye may be better represented as a chronic neuropathic pain disorder due to its features of dysesthesia, spontaneous pain, allodynia, and hyperalgesia. Future therapies targeted at the underlying neuroplasticity may yield improved efficacy for patients with this subset of dry eye, which we term "burning eye syndrome."

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.

Current management goals of allergic conjunctivitis aim to minimize the inflammatory cascade associated with allergic response in the initial stages of the pathological mechanism. Based on the mechanistic data reviewed herein, the recognition that neuronal inflammation explains many of the symptoms in allergic conjunctivitis opens new frontiers for drug discovery.