Patients With Dry Eye Disease and Low Subbasal Nerve Density Are at High Risk for Accelerated Corneal Endothelial Cell Loss

Abstract

Purpose: To evaluate changes in corneal endothelial cell density over time in patients with dry eye disease (DED) and to correlate endothelial cell loss with corneal subbasal nerve density.

Methods: This retrospective study included 40 eyes of 20 patients with DED. Laser in vivo confocal microscopy had been performed in the central cornea of both eyes at an initial visit and repeated after a mean follow-up of 33.2 ± 10.2 months. The densities of corneal endothelial cells and subbasal nerves were measured in both visits and compared with 13 eyes of 13 normal age-matched controls.

Results: At the initial visit, the DED group had lower densities of corneal endothelial cells (2620 ± 386 cells/mm) and subbasal nerves (17.8 ± 7.5 mm/mm) compared with the control group (2861 ± 292 cells/mm and 22.8 ± 3.0 mm/mm, with P = 0.08 and P = 0.01, respectively). At the end of follow-up, although there was no significant change in subbasal nerve density (16.7 ± 7.2 mm/mm, P = 0.43), the mean corneal endothelial cell density significantly decreased to 2465 ± 391 cells/mm (P = 0.01), with a mean corneal endothelial cell loss of 2.1 ± 3.6% per year. The endothelial cell loss showed a statistically significant negative correlation with the initial subbasal nerve density (Rs = -0.55, P = 0.02).

Conclusions: Patients with DED have an accelerated corneal endothelial cell loss compared with that reported in the literature for normal aging. Those with lower subbasal nerve density, in particular, are at a higher risk for endothelial cell loss over time.

Fig. 1

Corneal subbasal nerve density and corneal endothelial cell density in initial and follow-up visits of patients with dry eye disease as well as in the age-matched control group. The data presented as mean ± standard error of the mean.

Fig. 2

Corneal subbasal nerves (A) and corneal endothelial cells, as their borders were marked by the variable-frame method, (B) in a normal control. A patient with dry eye disease shows reduced densities of corneal subbasal nerves (C) and corneal endothelial cells (D) compared with the controls. After a follow-up of more than 3 years, there was no substantial change in corneal subbasal nerve density (E). However, corneal endothelial cell density showed a significant reduction (F). Please note that not all cases demonstrated such a dramatic decrease in endothelial cell density.