Abstract
Dry eye is a common clinical condition diagnosed by cumulative evidence of symptoms and signs. Many new treatments in dry eye are either expensive, invasive, have potential for side effects, or are not easily accessible. In severe dry eye, the ideal modality of treatment to begin with is often not clear as specific molecular disturbances are not evident from just examination of clinical manifestations. Assessing the effects of ongoing treatment is not straight forward since there is lack of agreement between clinical signs and symptoms. There is a need to have more objective methods of selecting treatment for dry eye and monitoring the effect of treatment.Recently, there are many new technologies applied to the discovery of tear biomarkers, for e.g., mass spectrometry based proteomics techniques and multiplex assays such as the bead-based sandwich indirect immunofluorescent assays. Tear proteins assays have even been made available as point-of-care devices. This review focuses on the evidence for the involvements of tear proteins in dry eye, possible changes in tear concentrations with therapy and the strength of evidence regarding dry eye pathology. Much remains to be done in terms of developing office-based assays and ascertaining their reliability, but current evidence suggests that tear proteins have a role in the clinical practice of dry eye.
Highlights
Diagnosis of dry eye According to the International Dry Eye Workshop, “dry eye is a multifactorial disease of the tear and ocular surface that results in symptoms of discomfort, visual disturbance, and tear instability with potential damage to the ocular surface
In this article we consider a tear protein to be potentially suitable as a clinical biomarker if it fulfils the following three criteria in the literature available: Firstly, the tear proteins which have been studied in dry eye disease in humans and found to be consistently deranged with a clearly defined normal range may be considered to be more relevant for clinical use
There is no published review which focused on these 3 criteria for determining the clinical relevance of the tear proteins in dry eye, we aim to provide a concise guide to enumerate these factors for the common tear proteins
Summary
Diagnosis of dry eye According to the International Dry Eye Workshop, “dry eye is a multifactorial disease of the tear and ocular surface that results in symptoms of discomfort, visual disturbance, and tear instability with potential damage to the ocular surface. A similar panel has been advocated for the diagnosis of primary Sjogren syndrome [6] The importance of this discovery lies in the fact that most of the diagnostic tests need to be used in combination to reliably diagnose dry eye. It may be possible to have a higher index of suspicion for a systemic cause of dry eye based on the levels of specific tear glycoproteins in addition to relevant history and clinical findings Conditions such as pemphigoid may affect the glycoproteins differently from age-related dry eye [20]. In this article we consider a tear protein to be potentially suitable as a clinical biomarker if it fulfils the following three criteria in the literature available: Firstly, the tear proteins which have been studied in dry eye disease in humans and found to be consistently deranged with a clearly defined normal range may be considered to be more relevant for clinical use. For the analysis of a dozen or more cytokines and chemokines in a few microliter of tears, it seems the best technology is the multiplex beadbased immunofluorescent sandwich assay, and the sensitivity for detection of some cytokines are in the order of several picogram/milliliter concentrations, surpassing even the minimum detection limits of mass spectrometry based methods [90]
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