Purpose: To assess interobserver agreement between 2 corneal specialists grading Fuchs' dystrophy clinically and to determine if the corneal central-to-peripheral thickness ratio (CPTR) may be an alternative and objective metric of disease severity. Design: Cross-sectional study. Participants: Forty-five eyes (26 subjects) with mild and moderate Fuchs' dystrophy, 73 eyes (60 subjects) with advanced Fuchs' dystrophy, and 267 eyes (142 subjects) with normal corneas. Methods: Corneas with Fuchs' dystrophy were graded by 2 corneal specialists based on the confluence and area of guttae and the presence or absence of edema. Central corneal thickness (CCT) and peripheral corneal thickness at 4 mm from the center (PCT4) were measured by using scanning-slit pachymetry. The value of CPTR4 was the quotient of CCT and PCT4. Main Outcome Measures: Interobserver agreement for clinical grade and CPTR4. Results: Interobserver agreement for clinical grading of Fuchs' dystrophy was moderate (κ = 0.32; 95% confidence interval, 0.19-0.45). In normal corneas, CCT was not correlated with age (r = -0.10; P = 0.28; n = 267), PCT4 decreased with age (r = -0.33; P<0.001; n = 254), and CPTR4 increased with age (r = 0.59; P<0.001; n = 254). Central corneal thickness was higher in Fuchs' dystrophy (652±61 μm; n = 118) than in normal corneas (559±31 μm; n = 267; P<0.001). Also, PCT4 was higher in Fuchs' dystrophy (650±51 μm; n = 107) than in normal corneas (643±43 μm; n = 254; P<0.001 after adjusting thickness for age). Furthermore, CPTR 4 was higher in advanced Fuchs' dystrophy (1.03±0.07; n = 65) than in mild and moderate Fuchs' dystrophy (0.95±0.07; n = 42; age-adjusted P<0.001), which in turn was higher than in normal corneas (0.87±0.05; n = 254; age-adjusted P<0.001). Finally, CPTR4 was highly correlated with clinical grade of Fuchs' dystrophy (r = 0.77; P<0.001; n = 361), was repeatable (median coefficient of variation, 1.3%), and provided excellent discrimination between Fuchs' dystrophy and normal corneas (area under the receiver operator characteristic curve, 0.93). Conclusions: Agreement between corneal specialists for the subjective and morphologic clinical grading of Fuchs' dystrophy is only moderate. The corneal CPTR is an objective, repeatable, and possibly functional, metric of severity of Fuchs' dystrophy that warrants further investigation to determine its role in monitoring disease progression and predicting the need for keratoplasty. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
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