The Association between Meibomian Gland Atrophy and Corneal Subbasal Nerve Loss in Patients with Chronic Ocular Graft-versus-host Disease

Abstract

Purpose: To investigate the association between meibomian gland (MG) loss and corneal subbasal nerve plexus density in patients with chronic graft-versus-host disease (GVHD) related dry eye disease (DED).Materials and Methods: This cross-sectional study included 22 adult patients with severe DED secondary to chronic GVHD. Control group comprised age- and sex-matched 28 healthy subjects with no evidence of ocular disease. All subjects underwent tear breakup time (TBUT), corneal staining, Schirmer I test without anesthesia, quantitative MG drop-out assessment using infrared meibography and corneal subbasal nerve density measurements with in vivo confocal microscopy (IVCM) (ConfoScan4, Nidek, Japan). One eye per patient was included for statistical purposes. Mann-Whitney U test and one-way multivariate ANOVA test were used for comparative analyses.Results: Compared to healthy subjects (mean age = 26.9 ± 13.5 years (range = 20-44 years)), patients with chronic GVHD (mean age = 29.6 ± 12.6 years (range = 19-45 years)) had worse meibography scores (p < .001), reduced corneal subbasal nerve plexus densities (p < .001), lower TBUT scores (p = .012), lower Schirmer I values (p = .001) and higher corneal staining scores (p = 003). Meiboscores in the GVHD and control groups were 2.9 ± 1.1 (range = 1-4) vs. 0.7 ± 0.4 (range = 0-2) for the superior (p < .001), and 3.2 ± 1.2 (range = 2-4) vs. 0.5 ± 0.3 (range = 0-2) for inferior (p < .001) eyelids, respectively. Corneal subbasal nerve densities of patients with GVHD did not reveal a correlation with meiboscores (r = 0.030; p = .709 for the inferior and r = 0.268; p = .075 for the superior eyelids) but showed a weak correlation with Schirmer I test values (r = 0.268; p = .014).Conclusions: Patients with chronic GVHD are at high risk for developing DED and MG dysfunction. In the setting of chronic GVHD-related DED, MG loss does not appear to be a significant factor for corneal subbasal nerve damage.

Keywords: Graft-versus-host disease; dry eye disease; in vivo confocal microscopy; meibography; meibomian gland dysfunction; ocular surface.