Fuchs' Endothelial Corneal Dystrophy

Abstract

Purpose To assess inter-observer agreement between two corneal specialists grading Fuchs dystrophy clinically, and to determine if the corneal central to peripheral thickness ratio (CPTR) might 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 two 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. CPTR4 was the quotient of CCT and PCT4. Main Outcome Measures Inter-observer agreement for clinical grade; CPTR4. Results Inter-observer 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). CCT was higher in Fuchs dystrophy (652 ± 61 μm, n=118) than in normal corneas (559 ± 31 μm, n=267, p<0.001). 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). CPTR4 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). CPTR4 was highly correlated with clinical grade of Fuchs dystrophy (r=0.77, p<0.001, n=361). CPTR4 was repeatable (median coefficient of variation, 1.3%), and provided excellent discrimination between Fuchs dystrophy and normal (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.

Corneal High-Order Aberrations and Backscatter in Fuchs' Endothelial Corneal Dystrophy

“…The associations between the optical changes (posterior HOAs and corneal backscatter) and disease severity (ECD e and CCT 14,16 ) can be attributed to increasing area and confluence of guttae. However, we were unable to establish a similar relationship between anterior corneal HOAs and disease severity.…”

“…FECD severity was graded clinically based on the area and confluence of guttae, and the presence of edema,as described previously. 15,16 Corneas with 1-12 or ≥12 non-confluent central guttae (grades 1 and 2) were considered to have mild FECD; corneas with confluent guttae of 1-2-mm and 2-5-mm diameter (grades 3 and 4) were considered to have moderate FECD; and corneas with > 5-mm diameter of confluent guttae or any visible stromal or epithelial edema (grades 5 and 6) were considered to have advanced FECD. Corneas without guttae were considered normal (grade 0); control subjects were only enrolled if over age 40 years to match the age distribution of the disease group.…”

Corneal Abnormalities Early in the Course of Fuchs' Endothelial Dystrophy

“…Nevertheless, corneas in the early stages of Fuchs dystrophy appear to be thicker than normal, 7,31 suggesting that subclinical edema is present early in the disease because of early endothelial dysfunction. Thus, the anterior corneal abnormalities may be secondary to chronic subclinical corneal edema.…”

“…Corneas with central or paracentral guttae were considered to have Fuchs dystrophy and were graded according to the confluence of guttae and presence of corneal epithelial or stromal edema. 7,14 Corneas with grades 1 or 2 were considered to have mild Fuchs dystrophy, with grades 3 or 4 were considered to have moderate Fuchs dystrophy, and with grades 5 or 6 were considered to have advanced Fuchs dystrophy. If corneas had clinically detectable corneal edema, they were assigned to grade 6 irrespective of the distribution of guttae.…”

“…However, with the advances in corneal transplantation techniques enabling earlier surgical intervention 4 and the future promise of non-surgical treatments, 5,6 staging Fuchs dystrophy based on the presence or absence of clinical edema may no longer be adequate. 7 Ideally, we would identify patients who would benefit from intervention before any changes in the host tissue that affect outcomes become irreversible.…”