Onset of corneal abnormalities in Fuchs' dystrophy begins early in the course of the disease

Fuchs' dystrophy is a bilateral, progressive, inherited disease of the corneal endothelium characterized by cornea guttata and corneal edema and resulting in decreased vision. Advanced and untreated cases result in corneal scarring and vascularization.

Due to advances in corneal transplantation techniques that enable earlier surgical intervention and the potential of nonsurgical treatments, staging Fuchs' dystrophy based on the presence or absence of clinical edema may no longer be adequate.

"The ideal is to identify patients who will benefit from intervention before any changes in the host tissue that affect outcomes become irreversible," says Sanjay V. Patel, M.D., chair of Ophthalmology at Mayo Clinic's campus in Rochester, Minnesota. "Improving our understanding of the onset of corneal changes that affect outcomes may help to determine the optimal time for intervention."

Dr. Patel and a research team at Mayo Clinic in Rochester, Minnesota, conducted a cross-sectional study to determine when corneal abnormalities become evident in the course of Fuchs' dystrophy. "Specifically, we examined corneas with a range of severity of Fuchs' dystrophy by using confocal microscopy in vivo to measure corneal backscatter, stromal cell populations and the presence of abnormal subepithelial cells," says Dr. Patel.

The research team recruited 39 subjects (63 eyes) with a range of severity of Fuchs' dystrophy and 13 subjects (25 eyes) with normal corneas from patients at Mayo Clinic in Rochester, Minnesota. 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.

Anterior corneal backscatter

"The primary outcome of this study was anterior corneal backscatter," says Dr. Patel. The research team assessed differences in corneal backscatter between severities of disease using generalized estimating equation models to account for any correlation between fellow eyes of the same subject.

Relationships between backscatter, number of stromal cells, clinical grade, effective endothelial cell density and central corneal thickness were illustrated by using Pearson correlation coefficients, and significances of the correlations were determined by using generalized estimating equation models.

Analysis showed that:

  • Anterior corneal backscatter was 18 to 67 percent higher in eyes with moderate and advanced Fuchs' dystrophy compared with normal eyes. A similar trend was noted in mild Fuchs' dystrophy eyes compared with normal eyes.
  • Stromal cell density and the absolute number of stromal cells in the anterior 10 percent of the stroma were approximately 20 percent and 27 percent lower, respectively, in Fuchs' dystrophy, regardless of severity, when compared with normal.
  • Abnormal subepithelial cells were visible in 9 percent, 19 percent and 30 percent of corneas with mild, moderate and advanced Fuchs' dystrophy, respectively.
  • Only corneas with advanced Fuchs' dystrophy were thicker than normal, although the small sample sizes might have prevented finding a significant difference between mild and moderate Fuchs' dystrophy and normal.
  • In all eyes, anterior corneal backscatter and the number of cells in the anterior 10 percent of the stroma were correlated with clinical grade.

"Although Fuchs' dystrophy clinically manifests as corneal guttae and edema, the anterior cornea also changes in other ways subtly and subclinically, possibly before the onset of a clinically detectable increase in corneal thickness," says Dr. Patel. "Nevertheless, corneas in the early stages of Fuchs' dystrophy appear to be thicker than normal, 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."

Results of the team's research were published in Ophthalmology in 2014. "To summarize, we found that the anterior cornea manifests abnormalities early in the course of Fuchs' dystrophy, at stages where changes previously were considered insignificant," says Dr. Patel. "Improving our understanding of the onset of corneal changes in Fuchs' dystrophy may help to determine the optimal time to intervene, especially as newer treatments are developed.

"In addition, quantitative analyses of corneas with Fuchs' dystrophy could lead to objective methods of assessing disease severity and to a better understanding of the optical performance of these corneas before and after keratoplasty."

For more information

Amin SR, et al. Corneal abnormalities early in the course of Fuchs' endothelial dystrophy. Ophthalmology. 2014;121:2325.