Fuchs Endothelial Corneal Dystrophy: A Systematic Immunofluorescence Study of Collagen Type VIII Suggests Heterogeneous Pathophysiology.

PURPOSE:The purpose of this study was to investigate the pathophysiologic heterogeneity of Fuchs endothelial corneal dystrophy (FECD). METHODS:We conducted a systematic immunofluorescence study on 39 Descemet membrane samples from FECD patients and compared these with 10 Descemet membrane samples from patients with pseudophakic bullous keratopathy (PBK) and 7 normal corneas. Samples were analyzed with immunofluorescence using antibodies to the α1-chain [collagen VIII α1-chain (COL8A1)] and α2-chain (COL8A2). Intensity of staining was assessed using a subjective grading scale from 0 to 3. The presence of specific staining patterns was noted. RESULTS:The overall distribution of COL8A1 staining intensity between groups was significantly different (P = 0.002). There was marked/intense staining in 85% (33/39) of the FECD samples, 40% (4/10) of the PBK samples (P = 0.034), and 29% (2/7) of normal samples (P = 0.004). The overall distribution of COL8A2 staining intensity was not significantly different between groups (P = 0.39). There was marked/intense staining in 33% (13/39) of the FECD samples, 10% (1/10) of PBK samples, and 14% (1/7) of the normal samples. There was substantial variation in staining intensity in the FECD group, a phenomenon that was especially pronounced for the COL8A2 antibody. CONCLUSIONS:We found increased staining for COL8A1, but not COL8A2 in FECD samples. Further, there was striking variation of staining intensity in FECD patients, indicating pathophysiological heterogeneity.