Neuropathic Ocular Pain: An Important Yet Underevaluated Feature of Dry Eye

A Galor; RC Levitt; ER Felix; ER Martin; CD Sarantopoulos


Eye. 2015;29(3):301-312. 

In This Article

Genetic Predisposition may Affect the Dry Eye Phenotype by Influencing Ocular Sensory Apparatus Function and/or the Inflammatory Cascade

Genetic polymorphisms are well known to affect neuronal function and inflammation, and are therefore likely to modulate the clinical presentation of dry eye and affect its severity. Although there are only a few reports on genetic polymorphisms and symptoms of dry eye, substantial research supports the fact that relatively common inherited genetic polymorphisms underlie individual differences in pain perception,[85] pain-related behaviors, and the development of persistent pain syndromes.[86,87] For example, COMT (catechol-O-methyl transferase) is an important gene whose functional variants have been described in over 100 publications and 30 reviews. COMT variants are associated with various forms of pain including neuropathic pain, musculoskeletal pain, fibromyalgia, temporomandibular disorder (TMD), headache, and postsurgical pain.[88–93] Importantly, COMT alleles also predict pain severity.[94] Furthermore, individuals homozygous for the COMT Val158Met variant consistently demonstrate psychological dysfunction associated with their chronic pain.[95]

Given the role of inflammation and dry eye, it is interesting that polymorphisms in the proinflammatory cytokine genes IL-1β (rs1143634) and IL-6R (rs8192284) were recently reported to be associated with non-Sjogren's dry eye symptoms in a Korean population.[96] This finding makes intuitive sense, as having a genetic propensity for inflammation can profoundly influence neuroplasticity and contribute to neuronal dysfunction and neuropathic pain.[97–99] With only limited information available, more research is needed on genetic susceptibility to dry eye and the acute-to-chronic pain transition as well as epigenetic alterations that may be associated with the severity and persistence of symptoms.