Subclinical corneal endothelial alterations in Familial Mediterranean Fever patients during clinical remission

Abstract

Purpose: Although ocular involvement in Familial Mediterranean Fever (FMF) has been described, the corneal endothelium has not been systematically evaluated in these patients. This study aimed to compare corneal endothelial and anterior segment parameters between FMF patients in clinical remission and healthy controls, and to explore whether these parameters differ according to MEFV M694V genotype. Methods: In this prospective, observational case–control study, 90 genetically confirmed FMF patients in clinical remission and 60 age- and sex-matched healthy controls were evaluated. Only the right eye of each participant was analyzed. Corneal endothelial parameters were assessed by non-contact specular microscopy, and corneal structural parameters by Scheimpflug-based tomography. Measured parameters included endothelial cell density (ECD), central corneal thickness (CCT), coefficient of variation of cell area (CV), and percentage of hexagonal cells (HEX). MEFV mutation analysis was performed by Sanger sequencing. Results: Compared with controls, FMF patients showed a lower ECD (median 2154.5 vs. 2348 cells/mm2, p < 0.001; approximately 8.2% lower), a higher CCT (556.5 vs. 543 μm, p < 0.001), a higher CV (42 vs. 39.5, p = 0.003), and a lower HEX (44.5% vs. 48%, p < 0.001). Intraocular pressure was modestly higher (18 vs. 15 mmHg, p < 0.001) and the iridocorneal angle was narrower (42° vs. 47°, p < 0.001) in the FMF group, with both groups remaining within normal physiological ranges. Within the FMF group, patients homozygous for M694V (n = 14) showed a higher mean CCT (540.93 ± 39.14 vs. 510.93 ± 36.21 μm, p = 0.020) and a lower median ECD (2071 vs. 2218.5 cells/mm2, p = 0.006) than heterozygotes (n = 29). In an exploratory multivariable logistic regression within this subgroup, CCT and ECD were jointly associated with M694V homozygous versus heterozygous status (correct classification 69.8%). Conclusion: FMF patients in clinical remission show measurable differences in corneal endothelial parameters compared with healthy controls, and these differences appear more pronounced in M694V homozygous patients. Because the study is cross-sectional, it is not possible to conclude that these parameters reflect ongoing disease activity; prospective, longitudinal studies are needed to determine whether corneal endothelial assessment has a role in the ophthalmologic follow-up of patients with FMF.