Purpose: Corneas with advanced Fuchs' endothelial dystrophy that require endothelial keratoplasty manifest anterior corneal structural and cellular abnormalities that have been associated with visual deficits before and after endothelial keratoplasty. In this study, we determined the onset of these abnormalities in the course of the disease. Design: Cross-sectional study. Participants: Sixty-three eyes (39 subjects) with a range of severity of Fuchs' dystrophy and 25 eyes (13 subjects) with normal corneas. Methods: All corneas were examined using slit-lamp biomicroscopy, ultrasonic pachymetry, and confocal microscopy. The clinical grade of Fuchs' dystrophy was assessed according to the presence and extent of guttae and clinically evident edema and was categorized as mild (grades 1 and 2), moderate (grades 3 and 4), or advanced (grades 5 and 6). Normal corneas were devoid of any central guttae (grade 0). Corneal backscatter (haze) was measured from the confocal image light intensity profile. Stromal cell density and number and the presence of abnormal subepithelial cells were determined from confocal images. Comparisons between groups were made by using generalized estimating equation models. Main Outcome Measures: Anterior corneal backscatter, stromal cell density and number, presence of subepithelial cells, and central corneal thickness. Results: Anterior corneal backscatter was 18% to 67% higher in eyes with moderate and advanced Fuchs' dystrophy compared with normal eyes (P ≤ 0.003); a similar trend was noted in mild Fuchs' dystrophy eyes compared with normal eyes (P = 0.08). Stromal cell density and the absolute number of stromal cells in the anterior 10% of the stroma were approximately 20% and 27% lower, respectively, in Fuchs' dystrophy (regardless of severity) compared with normal (P < 0.001). Abnormal subepithelial cells were visible in 9%, 19%, and 30% of corneas with mild, moderate, and advanced Fuchs' dystrophy, respectively. Only corneas with advanced Fuchs' dystrophy were thicker than normal (P < 0.001). Conclusions: Anterior corneal cellular and structural abnormalities begin early in the course of Fuchs' dystrophy, before the onset of clinically evident edema. The chronicity of these changes can explain their incomplete resolution after endothelial keratoplasty, and understanding the onset of these may help to determine the optimal time to intervene to achieve best outcomes.
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