Corneal Involvement in Graves' Orbitopathy: An In Vivo Confocal Study

PURPOSE: To study the clinical involvement of the ocular surface and the in vivo morphology of corneal cells and nerves, in patients affected by active and inactive Graves' orbitopathy (GO). METHODS: The study included 26 consecutive GO patients and 20 age- and sex-matched healthy control subjects. GO was diagnosed on the basis of the criteria of the European Group on Graves' Orbitopathy, and disease activity was evaluated by the Clinical Activity Score (CAS). Each participant underwent a full eye examination, including an evaluation of symptoms (Ocular Surface Disease Index score), tear break-up time, fluorescein and lissamine green staining, corneal apex sensitivity, and Schirmer's test. The corneal apex was examined by means of confocal microscopy to investigate the number and morphology of epithelial and stromal corneal cells and subbasal nerves. RESULTS: Eleven (43%) of the 26 patients had active GO. One-way ANOVA with the least-significant difference (LSD) post hoc test revealed statistically significant differences between patients and controls in all the evaluated parameters, except corneal sensitivity and nerve reflectivity. Among the GO patients, the only significant difference observed in active compared with inactive disease was in the number of hyperreflective (activated) keratocytes (P<0.001, LSD). Corneal sensitivity correlated inversely with proptosis (P<0.001, Spearman's test). CONCLUSIONS: GO patients show clinical and confocal corneal alterations and signs and symptoms partially related to dry eye disease. The ocular surface inflammation in GO seems to be due to both the dry eye and the autoimmune orbitopathy.