Disconnect between dry eye signs, symptoms may point to age, underlying comorbid conditions

Comorbidities related to clinical pain and chronic underlying conditions may be at play in patients in whom self-reported symptoms of dry eye do not correspond to any measurable signs of ocular surface disease, according to a recent study published in the British Journal of Ophthalmology.

“Overall, our idea of dry eye has shifted over the past few years. It used to be a disease where we only considered what is happening on the ocular surface—tear production, tear evaporation. We were driven by abnormal ocular surface findings,” explained senior author Anat Galor, MD, staff physician, Miami VA Medical Center, and associate professor of clinical ophthalmology, Bascom Palmer Eye Institute, University of Miami, FL.

“What we found, and what other investigators found, was that there was a disconnect between dry eye symptoms and signs. Patients would come in and tell you how their eyes felt, and then you would look at the eye, and sometimes the findings were aligned, but many times they weren’t. In fact, in a previous study, we found that only 8% of variability in symptoms were explained by signs, which is a very poor correlation,” she added.

Dr. Galor explained why a shift is occurring in the knowledge and subsequently, the management of dry eye disease.

“If you look at epidemiologic studies, people have really focused the population-based studies on symptoms, because it’s very difficult to study signs in a large population. A lot of what we know about the epidemiology of dry eye really is really the epidemiology of dry eye symptoms. So, there have been few studies that have looked at the epidemiology of signs,” she said.

“We wanted to revisit the epidemiology of dry eye and look specifically at discordance between symptoms and signs, and then try to understand what is driving the discordance,” she added.

Dr. Galor and colleagues enrolled 326 subjects (mean age: 62 years; mean symptom duration: 10 years; 92% men). All patients underwent ocular surface exams in which signs of disease were evaluated, and they completed questionnaires to assess for ocular symptoms, psychological status, and medication use.
Researchers also used quantitative sensory testing (QST) to assess the integrity of patients’ nociceptive systems, which included vibratory and thermal threshold measures and temporal summation of pain obtained at the forearm and forehead.

They then analyzed correlations between dry eye discordance score, which they defined as the degree of discrepancy between symptom severity and dry eye signs, and patient characteristics. Higher discordance scores were indicative of more symptoms than signs.

Dr. Galor and fellow researchers found a negative correlation with age and dry eye discordance score (Pearson r= -0.30; P < 0.0005), but positive correlations with mental health indices, and with chronic pain elsewhere in the body and intensity rating of prolonged aftersensations of pain evoked by hot and cold stimuli.

Upon performing multiple linear regression, they found that post-traumatic stress disorder and non-ocular pain intensity were important predictors of dry eye discordance score, Dry Eye Questionnaire-5, and Ocular Surface Disease Index. DE discordance was also sensitive to QST.

“What we found was that patients who had anxiety and pain outside the eye were more likely have a disconnect between symptoms and signs to the positive degree, that is, more symptoms than signs. And conversely, aging was associated with more signs than symptoms,” said Dr. Galor. “This isn’t surprising because dry eye is not one disease. It’s a group of diseases, and within that group, there are different profiles.”

So how can clinicians use this information to manage the varied patients who present with dry eye?

“The take-away is that dry eye is not one disease. It’s important to categorize patients into categories that are defined by the underlying pathophysiology or by response to treatment. So, in a 45-year-old with dry eye symptoms, anxiety and chronic pain conditions, but with minimal signs of dry eye, artificial tears may not be the answer. Instead, working with the PCP and the mental health provider to try to look at the dry eye as part of a chronic pain disorder probably makes more sense,” explained Dr. Galor.

“Whereas in an older individual, where the lacrimal and meibomian glands are not working as well as they were when the individual was young, trying to optimize the ocular surface with artificial tears and other therapies makes more sense. To summarize, it is important to have a classification system and use different tools in the toolbox for the different subtypes of dry eye,” she concluded.

This study was supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Clinical Sciences Research EPID-006-15S (Dr AG), NIH Center Core Grant P30EY014801 and Research to Prevent Blindness Unrestricted Grant. The above sponsors provided financial support to cover the researchers' time but were not involved in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; or decision to submit the manuscript for publication. The authors noted that the contents of this study do not represent the views of the Department of Veterans Affairs or the United States Government.