Cellular and subbasal nerve alterations in early stage Fuchs’ endothelial corneal dystrophy: an in vivo confocal microscopy study

Abstract

Purpose To analyze the morphology and density of corneal epithelial cells, keratocytes, and subbasal nerves, in patients with early stage Fuchs' endothelial corneal dystrophy (FECD) by in vivo confocal microscopy (IVCM). Methods IVCM (Confoscan 4, Nidek, Inc.) of the central cornea was performed in 30 corneas of 30 patients with early stage FECD and 13 corneas of 13 normal controls. Images were analyzed for morphology and density of the superficial and basal epithelial cells, keratocyte density, endothelial cell density (ECD), as well as subbasal corneal nerve parameters. Central corneal thickness (CCT) was measured in all patients and normals by ultrasound pachymetry. Results The ECD was significantly lower ( À 45.5%, Po0.001) in FECD patients as compared with controls. Total number of nerves and main nerve trunks were significantly reduced ( À 46.3%, Po0.001; À 39.7%, Po0.001) in patients with FECD. Posterior keratocyte density was significantly higher in FECD patients (Po0.001). Significant inverse correlations were found between CCT and total number of nerves (r ¼ À 0.69, Po0.001), CCT and main nerve trunks ( À 0.47, P ¼ 0.016), as well as CCT and total nerve length (r ¼ À 0.62, P ¼ 0.006). Significant correlation was found between ECD and total number of nerves (r ¼ 0.44, P ¼ 0.012) as well as between ECD and main nerve trunks (r ¼ 0.65, Po0.001). Conclusions IVCM demonstrates alterations in corneal innervation in patients with early stage FECD, suggesting a potential role of corneal nerves in the pathogenesis of FECD. Additional studies are required to investigate whether subbasal nerve alterations are caused by nonspecific corneal edema, from FECDinduced decrease in ECD, or potentially leading to loss of endothelial cells.

The pathophysiology of Fuchs' endothelial dystrophy – A review of molecular and cellular insights

“…However, there was no significant difference in posterior stromal keratocyte density (Hecker et al, 2011). In contrast, examination of mild cases of FECD (stage 1 and 2) using IVCM revealed a significantly higher posterior keratocyte density compared to healthy controls, however, there was no significant difference in anterior keratocyte density (Schrems-Hoesl et al, 2013).…”

“…Mild cases of FECD (stage 1 and 2) imaged by IVCM were observed to have significantly lower sub-basal nerve density compared to healthy controls (Schrems-Hoesl et al, 2013). Additionally, the thicker the central cornea in FECD patients, the fewer the number of nerves and main nerve trunks and the shorter the total length of sub-basal nerves (Schrems-Hoesl et al, 2013).…”

“…Additionally, the thicker the central cornea in FECD patients, the fewer the number of nerves and main nerve trunks and the shorter the total length of sub-basal nerves (Schrems-Hoesl et al, 2013). In late stage FECD, sub-basal nerves may be completely absent (0%e40% of cases) (Ahuja et al, 2012;Alomar et al, 2011;Park et al, 2012).…”

“…IVCM studies have demonstrated 45%e59% lower endothelial cell density in FECD compared to healthy corneas (Mustonen et al, 1998;Schrems-Hoesl et al, 2013).…”

Elevated Cytokine Levels in the Aqueous Humor of Eyes With Bullous Keratopathy and Low Endothelial Cell Density

“…Moreover, recent clinical studies have shown that decreases in the corneal nerve are associated with ECD loss. 52,53 We previously reported that corneal denervation resulted in a decreased ECD, which could be rescued by the administration of neuropeptide in animal experiments. (Yamaguchi T, et al IOVS 2014;55:AR-VO E-Abstract 2077).…”