Morphological Distinction of Descemet's Membrane Protrusions in Bullous Keratopathy and Guttae in Fuchs Endothelial Corneal Dystrophy

Purpose: To characterize dome-shaped protrusions (DSPs), a previously unrecognized alteration of Descemet's membrane (DM) in bullous keratopathy (BK), and to determine how DSPs differ from classic guttae in Fuchs endothelial corneal dystrophy (FECD). Methods: DM specimens were collected from 75 eyes with BK during endothelial keratoplasty. A subset of eyes with sufficiently dense protrusions (≥50 per field at ×200 magnification) was selected for detailed analyses. Flat-mounted DMs were examined by phase-contrast microscopy, scanning electron microscopy, and immunofluorescence staining. Quantitative analyses included measurements of protrusion area, centroid spacing, and density. Texture characteristics were assessed using fast Fourier transform, gray-level co-occurrence matrix metrics, and local binary pattern profiling. Results: DSPs appeared as small, blurred-edge elevations lacking the halo and fusion typical of guttae. Compared with guttae, DSPs showed smaller areas (mean of 69.5 µm² vs. 148.7 µm²), greater centroid spacing (21.8 µm vs. 15.3 µm), and lower density (161 protrusions/mm² vs. 359 protrusions/mm²) (P < 0.01 for all). Scanning electron microscopy demonstrated smooth, nodular excrescences in FECD, whereas DSPs displayed fine fibrillar surfaces. Immunohistochemistry revealed strong periguttae fibronectin and collagen I deposition in FECD, whereas DSPs were negative for both markers and were instead surrounded by diffuse staining across the DM surface. The fast Fourier transform, gray-level co-occurrence matrix, and local binary pattern analyses showed that DSPs exhibited smoother, more homogeneous, and less anisotropic microtexture signatures than were observed for FECD guttae. Conclusions: DSPs may represent a previously unrecognized pattern of DM remodeling in BK. Their discovery provides new insight into endothelial stress responses.