We appreciate the opportunity to further clarify details from our recent article “Epithelial Mapping Efficacy for Subclinical Keratoconus Identification.”
Toprak’s comments regarding our the subclinical keratoconus definition that we used highlight the core message from our study: in the absence of demonstrable topographic abnormalities (ie, the earliest subclinical phases), epithelial thickness was indistinguishable from normal corneas. We fully agree that current definitions and criteria for subclinical keratoconus are heterogenous and confusing. We recently performed an extensive literature review on the “subclinical” study populations in an evaluation of the Global Consensus statements regarding subclinical keratoconus diagnosis. In this paper, we cited the paper by Henriquez and colleagues in the Methods section: “For the SKC cohort, we used the term subclinical despite the known lack of consensus regarding terminology or inclusion criteria in the literature.” To date, there are no established standards, and no clear distinctions between subclinical and forme fruste keratoconus terminology or disease manifestations.
We reported details regarding keratoconus stages in the Results: “Pentacam topographical keratoconus classification (TKC) … all eyes in the KC group were classified as KC 1, 1-2, or 2.” Including advanced stages would not have served our study purpose, as in those cases the diagnosis was evident based on corneal curvature, without the need for additional diagnostic modalities. Thus, by evaluating early-stage KC, we aimed to better assess the discriminative capacity of epithelial mapping for subclinical and early disease detection.
Multiple authors have recently demonstrated that it is reasonable and accurate to consider asymmetric keratoconic eyes as independent variables due to the characteristic asymmetry of the disease. The natural inter-eye variability in these cases supports the approach of analyzing each eye separately rather than assuming correlation between them.
We agree that eyes with abnormal topographic features are more likely to demonstrate recognizable epithelial remodeling patterns than eyes without distinct topographic abnormalities. Once those surfaces co-localize, the patient’s diagnosis is obvious, and no additional imaging is needed to improve diagnostic accuracy. However, in subclinical eyes with indistinct topographic features, epithelial thickness patterns did not differ in any identifiable way from normal corneal epithelial patterns. In fact, we found examples of patients with distinct morphologic abnormalities, yet without recognizable epithelial remodeling patterns ( Figure ).
