In Vivo Confocal Microscopy Shows Alterations in Nerve Density and Dendritiform Cell Density in Fuchs' Endothelial Corneal Dystrophy

Abstract

Purpose: To evaluate corneal nerve and immune cell alterations in Fuchs' endothelial corneal dystrophy (FECD) and pseudophakic bullous keratopathy (PBK) by laser in vivo confocal microscopy (IVCM) as correlated to corneal sensation and endothelial cell loss.

Design: Prospective, cross-sectional, controlled study.

Methods: Thirty-three eyes with FECD were compared to 13 eyes with PBK and 17 normal age-matched control eyes at a tertiary referral center. FECD was classified into early (without edema) and late stage (with edema). Corneal IVCM and esthesiometry were performed. Corneal nerve and immune dendritiform cell (DC) alterations were evaluated and correlated to clinical parameters.

Results: FECD and PBK eyes showed significantly (P = .001) diminished total nerve length (11.5 ± 1.3 and 2.9 ± 0.7 mm/mm²) and number (8.8 ± 1.1 and 2.2 ± 0.4 n/frame), compared to controls (23.3 ± 8.1 mm/mm² and 25.9 ± 1.3 n/frame). Decreased nerves corresponded to diminished sensation in FECD (4.9 ± 0.2 cm; R = 0.32; P = .045), compared to controls (5.9 ± 0.04 cm). Early- and late-stage FECD showed significantly reduced total nerve length (13.1 ± 1.4 and 9.9 ± 1.2 mm/mm², respectively) and number (8.2 ± 2.5 and 6.5 ± 2.1 n/frame), compared to controls (P < .001). DC density was significantly increased in FECD (57.8 ± 10.4 cells/mm²; P = .01), but not in PBK (47.7 ± 11.6 cells/mm²; P = .60) compared to controls (22.5 ± 4.5 cells/mm²). A subset of early FECD patients (7/22) demonstrated very high DC density (>100/mm²).

Conclusion: IVCM demonstrates profound diminishment of subbasal corneal nerves in early- and late-stage FECD and in PBK, correlating to decreased sensation. Increased DC density in early FECD demonstrates potential subclinical inflammation. The data suggest that reduction in subbasal nerves and increased immune activation may play a role in the pathophysiology of FECD.

Figure 1.. In vivo confocal microscopy images

Central corneal in vivo confocal microscopy images showing the epithelium (Row 1) in normal controls (Column 1); Early stage Fuchs’ endothelial corneal dystrophy (FECD) (Column 2); Late stage FECD (Column 3); pseudophakic bullous keratopathy (PBK) (Column 4); subbasal layer (Row 2) in normal controls (Column 1); Early stage FECD (Column 2); Late stage FECD (Column 3); PBK (Column 4); and endothelium (Row 3) in normal controls (Column 1); Early stage FECD (Column 2); Late stage FECD (Column 3); and PBK (Column 4). Patients with early stage FECD show decreased nerves and increased immune dendritic cells (arrow) in the subbasal layer (Row 2, Column 2) and guttae (arrow) in the endothelium (Row 3, Column 2). Patients with late stage FECD show epithelial edema (arrow) (Row 1, Column 3), decreased subbasal nerves (Row 2, Column 3) and reduced endothelial density (Row 3, Column 3). Patients with PBK show epithelial edema (Row 1, Column 4), reduced subbasal nerve density (Row 2, Column 4) and reduced endothelial cell density without guttae (Row 3, Column 4). Size bar = 100μm.

Figure 2.. Confocal microscopy parameters in Fuchs’ endothelial corneal dystrophy (FECD) and pseudophakic bullous keratopathy (PBK)

Comparison of number of total nerves (top left), total nerve length (top tight); immune dendritic cell density (middle left), and corneal sensation (middle right) in normal controls, Fuchs’ endothelial corneal dystrophy (FECD) and pseudophakic bullous keratopathy (PBK). *indicates statistical significance compared to normal controls; p<0.05. Correlation of total nerves with endothelial cell density (bottom left) R=0.66; p<0.001 and with central corneal sensation (bottom right) R=0.32; p=0.045.

Figure 3.. Confocal parameters in early and late stage Fuchs’ endothelial corneal dystrophy

Reduced corneal subbasal nerve numbers (top left) and length (top right), as well as increased epithelial immune dendritic cell density (bottom left) are shown in early stage Fuchs’ endothelial corneal dystrophy (FECD) and late stage FECD. Reduced corneal sensation (bottom right) was also observed in both groups, although no statistical difference was found. *indicates statistical significance compared with normal controls; p<0.05.