Persistent, Severe Dry Eye Linked to Pain, Nonocular Factors

Laurie Barclay, MD

December 22, 2016

Researchers identified factors predicting severe dry eye symptoms 1 year after presentation in a longitudinal study published online December 22 in JAMA Ophthalmology. Although findings may not be generalizable to nonveteran populations, the investigators emphasize the importance of pain perception and severity to 1-year prognosis.

"[M]ost patients with severe baseline dry eye symptoms reported persistent severe symptoms at 1 year," write Erin S. Ong, BS, BA, from the Ophthalmology Department, Bruce W. Carter Department of Veteran Affairs, Miami Veterans Administration Medical Center, Florida, and colleagues. "Baseline nociceptive and neuropathic ocular pain, in addition to sleep disturbances, mental health status, nonocular pain, and medications were also risk factors."

Dry eye syndrome is highly prevalent, affecting millions of people. Although previous cross-sectional studies examined risk factors for dry eye severity, few looked at risk factors or symptom progression over time.

"This study highlights the important role of pain severity and perception on severity and persistence of dry eye," the authors write. They recommend that dry eye questionnaires include the time course of dry eye symptoms, pain severity, and neuropathic qualities.

Front desk staff or technicians could easily and inexpensively record answers to these questions, along with short, standardized questionnaires for depression and anxiety to identify patients who may benefit from mental health care consultation.

"Additional longitudinal studies are needed to characterize dry eye findings beyond 1 year and evaluate which pain management strategies, whether systemic or local, will be most beneficial in patients with dry eye," the study authors conclude.

Biologically Plausible Findings

From October 1, 2013, to April 30, 2015 at the Miami Veterans Affairs Hospital, 120 patients with a broad range of idiopathic dry eye symptoms and signs but no overt eyelid or corneal abnormalities were prospectively recruited and followed for changes in symptom severity over the course of 1 year. Participants (mean age, 64 ± 11 years; 109 men) underwent ocular surface examination including tear film assessment and baseline risk factor analysis, as well as Dry Eye Questionnaire 5 at their first and 1-year follow-up visit.

Exclusion criteria were contact lenses, refractive surgery, ocular medications except for artificial tears, active external ocular process, cataract surgery within the last 6 months, any history of glaucoma or retinal surgery, HIV, sarcoidosis, graft-versus-host disease, or collagen vascular disease.

At 1 year, 26 (44.8%) of 58 participants with no, mild, or moderate baseline symptoms developed more severe symptoms, whereas 46 (74.2%) of 62 patients with severe baseline symptoms continued to have severe symptoms (Dry Eye Questionnaire 5 score, ≥12).

Factors predicting severe dry eye symptoms at 1 year were more severe dry eye symptoms, ocular pain, and neuropathic pain–like ocular symptoms at baseline. Other risk factors were sleep disturbances, including sleep apnea and insomnia; psychiatric conditions, including posttraumatic stress disorder and depression; nonocular pain; and medications (anxiolytics and analgesics). In previous cross-sectional studies, these nonocular risk factors were also linked to dry eye.

The most significant risk factors for severe dry eye symptoms at 1 year, according to multivariable analysis, were sleep apnea (odds ratio [OR], 3.80; 95% confidence interval [CI], 1.00 - 14.49; P = .05), Dry Eye Questionnaire 5 score (OR, 1.15; 95% CI, 1.02 - 1.30; P = .02), and posttraumatic stress disorder score (OR, 1.04; 95% CI, 1.01 - 1.08; P = .02).

"Although this cohort was limited to US veterans, which may not be generalizable to other populations, our results suggest that pain perception and severity are important when evaluating and managing dry eye," the study authors conclude.

Other study limitations include loss to follow-up, ocular surface examination only at initial visit, and lack of interim assessments between baseline and 1 year.

Despite these limitations, the investigators suggest that the findings are biologically plausible. Regarding neuropathic pain within the eye, the corneal nociceptors are near the ocular surface, where they can be damaged by trauma, environmental stress, or tear film abnormalities.

"Repeated stress can lead to peripheral sensitization, which may subsequently lead to changes in the central nervous system," the study authors write.

"Sleep apnea is associated with eyelid laxity, which has been found to be a risk factor for severe ocular surface symptoms, perhaps owing to disruption of the healthy tear film dynamic. Mental health conditions may either predispose individuals to pain or be a result of pain."

The Department of Veterans Affairs, National Institutes of Health, and Research to Prevent Blindness supported this study. The authors have disclosed no relevant financial relationships.

JAMA Ophthalmol. Published online December 22, 2016.

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