Corneal Epithelial Wavefront Error as a Novel Diagnostic Marker for Epithelial Basement Membrane Dystrophy

Abstract

Synopsis: Corneal epithelial wavefront error and epithelial thickness variance qualify as highly sensitive and specific biomarkers for epithelial basement membrane dystrophy (EBMD). The biomarkers show a normalization after treatment of EBMD with phototherapeutic keratectomy. Purpose: To gauge the diagnostic value of epithelial basement membrane dystrophy (EBMD), a novel spectral-domain optical coherence tomography (SD-OCT)-based imaging modality for simultaneous morphological (thickness profile) and refractive (optical wavefront) assessment of the corneal epithelial layer in one of the most common but often underdiagnosed corneal dystrophies. Methods: In this prospective observational study, a total of 32 eyes of 32 patients diagnosed with EBMD and 32 eyes of 32 healthy control subjects were examined with high-resolution anterior segment SD-OCT (MS-39; CSO, Florence, Italy). Various epithelial thickness and epithelial wavefront-derived terms were compared between groups and receiver operating characteristic (ROC) curves were computed to analyze the diagnostic capacity of the respective parameters. A total of 17 of 32 EBMD patients underwent treatment with phototherapeutic keratectomy (PTK) and were followed up for 3 months. Results: Epithelial thickness variance (60.4 ± 56.7 µm versus 7.6 ± 6.1 µm) and interquartile range (11.0 ± 6.9 versus 3.3 ± 1.9 µm) were markedly elevated in EBMD patients as compared with healthy controls (both with p < 0.001). Epithelial wavefront analysis showed a highly statistically significant excess in all examined aberration terms in EBMD patients (all with p < 0.001). Significantly greater areas under the curve (AUCs) were yielded by the epithelial wavefront-derived parameters (e.g., total epithelial wavefront error: AUC = 0.966; 95% confidence interval (CI) 0.932-1) than by the epithelial thickness-derived parameters (e.g., variance: AUC = 0.919; 95% CI 0.848-0.990). Conclusions: Corneal epithelial wavefront aberrometry proved valuable as an objective biomarker for EBMD, with high sensitivity and specificity. PTK resulted in a reduction of morphological and refractive epithelial irregularities in EBMD.

Keywords: cornea; dystrophy; ocular surface; treatment lasers.

Figure 1

Terms of mean (A), minimum (B) and maximum (C) epithelial thickness as well as interquartile range (D) and variance (E) of epithelial thickness. The reduction of IQR after PTK showed the highest significance, followed by variance, mean thickness, and minimum thickness. The maximum epithelial thickness did not show a statistically significant decrease after PTK. * p < 0.05; ** p < 0.01; EBMD, epithelial basement membrane dystrophy; PTK, phototherapeutic keratectomy.

Figure 2

ROC analyses of (A) the variance of epithelial thickness and (B) the IQR show a high capacity for discrimination between healthy and EBMD corneas. AUC, area under the curve; EBMD, epithelial basement membrane dystrophy; IQR, interquartile range; ROC, receiver operating characteristic.

Figure 3

ROC analyses of the wavefront errors between healthy individuals and EBMD patients prove an even higher discriminatory power compared to Figure 2. The highest AUC was achieved for analysis of the total WFE RMS (A), followed by the residual WFE RMS (B) and total HOA RMS (C). ROC, receiver operating characteristic; WFE, wave front error; EBMD, epithelial basement membrane dystrophy; HOA, higher order aberrations.

Figure 4

Corneal epithelial aberrometry. Displayed are lower-order aberrations spherical WFE (A) und cylindrical WFE (B) and higher-order aberrations spherical aberration (C), coma (D), trefoil (E) and total HOA (F) in EBMD patients before and after PTK, as well as in a healthy control group. * p < 0.05; ** p < 0.01; *** p < 0.001; WFE, wavefront error; EBMD, epithelial basement membrane dystrophy; PTK, phototherapeutic keratectomy; RMS, root mean square.

Figure 5

Corneal epithelial aberrometry—summative terms. Displayed are the total WFE (A), as well as residual WFE (B), in EBMD patients before and after PTK as well as in a healthy control group. * p < 0.05; ** p < 0.01; *** p < 0.001; WFE, wavefront error; EBMD, epithelial basement membrane dystrophy; PTK, phototherapeutic keratectomy; RMS, root mean square.