Tear Fluid Biomarkers for Ocular Pain.

There is a growing interest in identifying potential biomarkers that can objectively serve as tools for diagnosis, monitoring, and treatment of ocular chronic pain. Although pain is a biological warning signal absolutely necessary for our survival, when it lasts for 3 or more months it becomes chronic and then it is considered a disease by itself. Chronic pain is a very disabling condition/disease which highly impairs the quality of life of patients. Development of ocular chronic pain, persistent and of high intensity, is present in some patients with dry eye disease (DED), or it can be triggered by some pathological events or after surgical procedures. However, in many of these cases the ocular clinical examination is apparently normal, and the explanation of that pain is not obvious. This type of pain is also difficult to treat because its pathophysiological mechanisms are not completely understood yet, and there are no standard criteria for its diagnosis. Several tear fluid biomarkers have been presented for different ocular diseases, and also for non-ocular, systemic diseases. Different studies have addressed the analysis of tear molecular profiles, including proteins, cytokines and neuromediators such as IL-9, MIP-1α, IL-10, IL-8, TNF-α, IL-6, Fractalkine, IL-1RA, Substance P, CGRP, NPY, and NGF levels associated with the presence of chronic ocular pain. Additionally, the preoperative tear levels of CGRP have been shown as predictive risk factor for ocular pain development after refractive surgery. These specific molecular profiles might help to explain the differences in symptomatology and clinical parameters in patients suffering from ocular pain and to identify those subjects more prone to develop it. Understanding the molecular bases underlying ocular pain will help in the search for effective, selective, and personalized therapies.