Corneal backscatter as a biomarker for edema severity in Fuchs endothelial corneal dystrophy: a cross-sectional study

Fuchs endothelial corneal dystrophy (FECD) is characterized by progressive endothelial dysfunction and corneal edema. Reliable objective biomarkers for grading disease severity are currently evolving. Corneal backscatter may reflect edema-related changes in corneal transparency and could serve as an additional objective measure of FECD severity across different edema stages. The purpose of this study was to evaluate the potential of corneal backscatter as a biomarker for severity of FECD.

In this retrospective, observational, single-center cross-sectional study, 99 eyes of 67 patients with FECD were divided into three groups depending on the presence of clinical, subclinical or no corneal edema. The corrected distance visual acuity (CDVA) was obtained and Scheimpflug tomography was performed. Subclinical corneal edema was diagnosed if more than one of the following criteria were present in Scheimpflug tomography: loss of regular isopachs, displacement of the thinnest point of the cornea, and focal posterior corneal surface depression. Clinical corneal edema was diagnosed by slit-lamp biomicroscopy. The primary outcome was the difference in total corneal backscatter in the central 2-mm zone. Secondary analyses were the correlation of corneal backscatter to CDVA, tomographic parameters such as central corneal thickness (CCT) and thinnest corneal thickness (TCT), as well as their diagnostic accuracy and predictive potential to differentiate between edema severity.

The total central corneal backscatter was significantly higher among eyes with high edema severity (P < 0.05). Differences in corneal backscatter between subgroups diminished with increasing depth of corneal layer and towards the periphery. The anterior (Marginal R² = 0.260; P < 0.001) and total (Marginal R² = 0.208; P < 0.001) corneal backscatter in the central 2-mm zone correlated well with CDVA. Corneal backscatter showed a higher correlation with CDVA than CCT (Marginal R² = 0.198; P < 0.001) and TCT (Marginal R² = 0.096; P = 0.004). Central corneal backscatter in the anterior 120 µm demonstrated moderate diagnostic accuracy for distinguishing subclinical corneal edema from no edema (threshold = 31.2 GSU; AUC = 0.73) or clinical edema (threshold = 34.9 GSU; AUC = 0.76).

Our study corroborates that corneal backscatter values increase with increasing corneal edema stage and therefore present a potential adjunctive biomarker to assess FECD severity in addition to edema status and clinical gradings.