Corneal Confocal Microscopy in Dry Eye Treated with Corticosteroids

Garoli, Elena; Termine, Vittoria; Pichi, Francesco; Ratiglia, Roberto; Nucci, Paolo

doi:10.1097/opx.0000000000000600

Cited by 67 publications

(63 citation statements)

References 34 publications

(65 reference statements)

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“…149 In contrast another study showed that corneal sub-basal nerve fiber length was similar in the patient group that showed clinical improvement and the patient group with no clinical improvement following treatment. 151 Notably, though nerve length was similar, sub-basal dendritic cell density was decreased in the patient group that responded positively to treatment. 151 Nonetheless, including corneal nerve changes in DED clinical trials, would require extensive instruction for each site and support of automated analysis.…”

Section: Point Of Care Biomarkersmentioning

confidence: 89%

“…148–155 This has been studied using in vivo confocal microscopy, which allows visualization of the layers of the cornea. 156 Some effort has been made to identify potential predictive anatomic biomarkers on the corneal surface and the MGs, primarily using confocal microscopy.…”

Section: Point Of Care Biomarkersmentioning

confidence: 99%

“…156 Some effort has been made to identify potential predictive anatomic biomarkers on the corneal surface and the MGs, primarily using confocal microscopy. 149,151 Several groups also are investigating the potential applications of MultiPhoton microscopy for studying ocular surface anatomy. 157 …”

Section: Point Of Care Biomarkersmentioning

confidence: 99%

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The Growing Need for Validated Biomarkers and Endpoints for Dry Eye Clinical Research

Roy

Wei

Kuklinski

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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PurposeBiomarkers with minimally invasive and reproducible objective metrics provide the key to future paradigm shifts in understanding of the underlying causes of dry eye disease (DED) and approaches to treatment of DED. We review biomarkers and their validity in providing objective metrics for DED clinical research and patient care.MethodsThe English-language literature in PubMed primarily over the last decade was surveyed for studies related to identification of biomarkers of DED: (1) inflammation, (2) point-of-care, (3) ocular imaging, and (4) genetics. Relevant studies in each group were individually evaluated for (1) methodological and analytical details, (2) data and concordance with other similar studies, and (3) potential to serve as validated biomarkers with objective metrics.ResultsSignificant work has been done to identify biomarkers for DED clinical trials and for patient care. Interstudy variation among studies dealing with the same biomarker type was high. This could be attributed to biologic variations and/or differences in processing, and data analysis. Correlation with other signs and symptoms of DED was not always clear or present.ConclusionsMany of the biomarkers reviewed show the potential to serve as validated and objective metrics for clinical research and patient care in DED. Interstudy variation for a given biomarker emphasizes the need for detailed reporting of study methodology, including information on subject characteristics, quality control, processing, and analysis methods to optimize development of nonsubjective metrics. Biomarker development offers a rich opportunity to significantly move forward clinical research and patient care in DED.OverviewDED is an unmet medical need — a chronic pain syndrome associated with variable vision that affects quality of life, is common with advancing age, interferes with the comfortable use of contact lenses, and can diminish results of eye surgeries, such as cataract extraction, LASIK, and glaucoma procedures. It is a worldwide medical challenge with a prevalence rate ranging from 8% to 50%. Many clinicians and researchers across the globe are searching for better answers to understand the mechanisms related to the development and chronicity of DED. Though there have been many clinical trials for DED, few new treatments have emerged over the last decade. Biomarkers may provide the needed breakthrough to propel our understanding of DED to the next level and the potential to realize our goal of truly personalized medicine based on scientific evidence. Clinical trials and research on DED have suffered from the lack of validated biomarkers and less than objective and reproducible endpoints. Current work on biomarkers has provided the groundwork to move forward. This review highlights primarily ocular biomarkers that have been investigated for use in DED, discusses the methodologic outcomes in providing objective metrics for clinical research, and suggests recommendations for further work.

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Section: Point Of Care Biomarkersmentioning

confidence: 89%

Section: Point Of Care Biomarkersmentioning

confidence: 99%

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The Growing Need for Validated Biomarkers and Endpoints for Dry Eye Clinical Research

Roy

Wei

Kuklinski

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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“…[10][11][12][13][14][15][16][17] Supporting the role of inflammation in the pathogenesis of DED is a body of clinical evidence that antiinflammatory therapies, including corticosteroids and cyclosporine, reduce inflammatory markers, and provide symptomatic improvement. [18][19][20][21] The aim of the study was to characterize tear composition in humans having hyperosmolar tears, to determine whether tear hyperosmolarity is associated with specific changes to tear cytokines that could be useful as a diagnostic clinical marker for DED.…”

mentioning

confidence: 99%

Tear Interferon-Gamma as a Biomarker for Evaporative Dry Eye Disease

Jackson

Zeng

Wong

et al. 2016

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. To assess whether tear hyperosmolarity, being diagnostic of dry eye disease (DED), is associated with specific alterations to the cytokine content of human tears that may provide a biomarker for DED. METHODS.In this prospective, cross-sectional, clinical study, participants (n ¼ 77) were recruited from a single clinical site and categorized into groups based upon tear osmolarity status (n ¼ 62 hyperosmolar, n ¼ 15 normo-osmolar). Comprehensive anterior eye clinical assessments were undertaken. Concentrations of seven cytokines (IL-2, IL-4, IL-6, IL-10, IL-17A, IFN-c, and TNF-a) in basal tears were assayed using multiplex cytometric bead array. The main outcome measure was difference in cytokine concentration between groups. Group comparisons were undertaken using 2-tailed t-tests. Cohen's effect size was calculated for each finding. Spearman correlations between cytokine concentrations, clinical symptoms, and clinical parameters of DED were calculated. RESULTS.Tear hyperosmolarity was specifically associated with increased tear IFN-c levels (13.3 6 2.0 vs. 4.4 6 1.4 pg/mL, P ¼ 0.03). Cohen's effect size was large (0.8) for changes to tear IFN-c levels. Significant correlations were observed between IFN-c concentration and each of: tear osmolarity (r ¼ 0.34; P ¼ 0.007), total ocular surface staining (r ¼ 0.56, P < 0.0001), and Schirmer test score (r ¼ À0.33, P ¼ 0.003).CONCLUSIONS. Tear hyperosmolarity is specifically associated with higher levels of the proinflammatory cytokine IFN-c, which correlate with key clinical parameters of DED. The calculated effect size (0.8) suggests that this assay has diagnostic power as a biomarker for evaporative DED.Keywords: dry eye, diagnosis, cytokine, inflammation, osmolarity, tear, interferon-gamma T ear hyperosmolarity is a consequence of reduced lacrimal secretion and/or excessive tear evaporation, and is recognized to be a key pathogenic mechanism in dry eye disease (DED). [1][2][3][4] While historically the clinical assessment of tear osmolarity has been hindered by difficulties associated with tear collection methods and access to laboratory facilities, technological advancements have enabled tear osmolar determinations to become clinically viable. Measurement of tear osmolarity has been suggested to be the single best objective indicator of DED severity.5 A diagnostic cut-off value of 316 mOsmol/L has been described to be highly specific for diagnosing clinically significant DED, yielding a sensitivity of 73% and a specificity of 90%. 6 In DED, abnormal elevation of the osmolarity of the tear fluid is proposed to induce epithelial injury through the activation of inflammatory events at the ocular surface, resulting in the liberation of inflammatory mediators that can induce epithelial cell apoptosis. 1,7 Short-term exposure of cultured human corneal epithelial cells to an hyperosmolar medium can induce IL-6 expression.8 In an animal model of ocular surface disease, tear hyperosmolarity resulted in conjunctival goblet cell death and tear film instability. 9 Fur...

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“…Topical corticosteroids bind and activate the cytosolic glucocorticoid receptor and promote anti-inflammatory gene expression in leukocytes and lymphocyte apoptosis [84-85]. New biomarkers, such dendritic cell density, assessed via confocal microscopy, have been shown to correlate with treatment-related inflammation changes and may help predict response to topical corticosteroids [86]. Although the long-term use of corticosteroids has complications, a brief course has proven effective in DE [84, 87].…”

Section: Therapeutic Interventionsmentioning

confidence: 99%

Therapeutic Strategies to Treat Dry Eye in an Aging Population

Ezuddin

Alawa

2015

Drugs Aging

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Dry eye (DE) is a prevalent ocular disease that primarily affects the elderly. Affecting up to 30% of adults aged 50 years and older, dry eye affects both visual function and quality of life. Symptoms of dry eye which include ocular pain (aching, burning), visual disturbances, and tearing can be addressed with therapeutic agents that target dysfunction of the meibomian glands, lacrimal glands, goblet cells, ocular surface and/or neural network. This review provides an overview of the efficacy, use, and limitations of current therapeutic interventions being used to treat DE.

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Corneal Confocal Microscopy in Dry Eye Treated with Corticosteroids

Cited by 67 publications

References 34 publications

The Growing Need for Validated Biomarkers and Endpoints for Dry Eye Clinical Research

The Growing Need for Validated Biomarkers and Endpoints for Dry Eye Clinical Research

Tear Interferon-Gamma as a Biomarker for Evaporative Dry Eye Disease

Therapeutic Strategies to Treat Dry Eye in an Aging Population

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