Purpose: To identify structural alterations of Descemet's membrane (DM) in bullous keratopathy (BK) and to explore their association with intracellular dark endothelial spots (IDESs) observed by specular microscopy. Methods: This multicenter, retrospective, observational study included 75 eyes that underwent endothelial keratoplasty for corneal endothelial dysfunction. Based on preoperative clinical diagnosis, eyes were classified as having Fuchs endothelial corneal dystrophy (FECD)-related or non-FECD BK. DM specimens were collected during endothelial keratoplasty and analyzed as flat-mounted preparations using phase-contrast microscopy. IDESs were evaluated preoperatively by masked assessment using specular microscopy. Results: Among the 75 eyes, 25 were clinically diagnosed with FECD. Of the remaining 50 eyes with BK, 15 showed no characteristic histological abnormalities, 11 exhibited guttae-like changes, and 24 demonstrated a distinct and previously unrecognized DM alteration, termed dome-shaped protrusions (DSPs). Specular microscopy images suitable for IDES evaluation were available in a subset of cases. IDESs were detected in 10 of 18 DSP-positive eyes and in 1 of 10 DSP-negative eyes, indicating a significant association between DSPs and IDESs (odds ratio 11.25; P < 0.05). Conclusions: DSPs represent a distinct structural alteration of the DM in non-FECD BK and are significantly associated with IDESs observed by specular microscopy. These findings provide insight into the heterogeneity of endothelial failure in BK and suggest a link between clinical imaging findings and underlying DM morphology. Translational Relevance: Dome-shaped protrusions provide a histopathological correlate for intracellular dark endothelial spots observed by specular microscopy and may support improved phenotyping of endothelial dysfunction in non-Fuchs endothelial corneal dystrophy bullous keratopathy.
Shimizu et al. (2026) studied this question.