Despite most of the studies have analyzed the diagnostic efficiency of the included parameters for the disease, we are still not sure whether there is a big deviation in the diagnostic efficiency of the parameters obtained in the existing studies, and which parameters are really considered as more meaningful parameters. Therefore, the main purpose of this study was to re-analyze the diagnostic parameters of keratoconus presented in published articles based on Pentacam, a typical morphological device, or Corvis ST, a device reflecting corneal biomechanical characteristics, to screen out the better sensitive diagnostic parameters for CKC and FFKC respectively, and to provide a further reference for the early diagnosis of keratoconus.
In this study, the 20 sensitive diagnostic parameters obtained by partial dependence analysis of important diagnostic parameters could be divided into the following 7 categories: mixed parameters (TBI, BAD-D), thickness progression parameters (ARTavg, ARTmax, PPIavg, PPImax and PPImin), typical thickness parameters (Thinnest point of the cornea, TP), surface morphological parameters (IVA, ISV, IHD, KI), corneal volume parameters (CV 3), height parameters (F.Ele.Th, B.Ele.Th, AED_TP, PED_TP and PEmax), dynamic response parameters (CBI, SPA1).
In general, most of the 20 sensitive diagnostic parameters screened out in this study were related to the thinnest point of the cornea, such as thickness progression parameters, height parameters based on the thinnest cornea (F.Ele.Th, B.Ele.Th, AED_TP and PED_TP), and even TP itself was also selected as the sensitive diagnostic parameters of FFKC. It is well known that pachymetric progression index (PPI) is calculated as the progression value at different pachymetric rings, and Ambrósio’s Relational Thickness (ART) expresses the ratio of the thinnest pachymetry and the respective pachymetric progression[12, 13]. Moreover, AED_TP and PED_TP were the relative difference between the best fit sphere (BFS) elevation map and the enhanced elevation map at the thinnest point on the front and back surface of the cornea, in which the enhanced BFS has been modified to accentuate ectatic or conical regions (with exclusion of a 3.5 mm optical zone in the thinnest portion of the cornea) [5, 12]. In summary, all these further indicated that various morphological parameters based on the typical position of the thinnest point of corneal thickness might have special significance for the diagnosis of keratoconus.
SPA1, as a stiffness parameter to resist corneal deformation under the action of air puff , was found to be the only Corvis ST output parameter that was sensitive to forme fruste keratoconus but not sensitive to clinical keratoconus. Clinically, the morphology of FFKC is generally considered to be normal, so the function of the parameter SPA1 reflecting the overall corneal stiffness is easier to show. For CKC, in view of the obvious changes in its morphology, the parameters describing corneal morphology given by Pentacam play a major role in the diagnosis . This suggested that the parameters related to corneal biomechanics properties might indeed had potential importance in the diagnosis of forme fruste keratoconus.
In addition, the diagnostic test meta-analysis of SPA1 not only verified the diagnostic performance of SPA1 again, but also verified effectiveness and credibility of secondary screening of sensitive parameters by random forest regression to a certain extent. Furthermore, despite both the secondary parameter screening method and diagnostic test meta-analysis can comprehensively evaluate the diagnostic performance of an parameter, the latter is not convenient for the situation with a large number of parameters, while the former can analyze multiple parameters at one time, therefore, the secondary parameter screening method used in this study is also worthy of affirmation and application.
Of course, our study also had certain limitations. First of all, the number of morphological parameters and biomechanical parameters contained in the same database was quite different, that is, the former was often two or three times higher than the latter, mainly because the development of Corvis ST was several years later than Pentacam. Also, the purpose of this study was to obtain particularly sensitive parameters that could be used to diagnose CKC and FFKC respectively based on the information in the literature, rather than merely to analyze the consistency of the diagnostic performance of the same parameter in literatures. Therefore, those parameters with relatively common diagnostic performance had not been screened out.
In a word, the sensitive diagnostic parameters of keratoconus mainly include the following 7 categories: mixing parameters, thickness progression parameters, surface morphological parameters, corneal volume parameters, height parameters, typical thickness parameters and dynamic response parameters. Among them, the diagnostic value of SPA1, which represents the biomechanical properties of cornea, is worthy of further attention in the diagnosis of keratoconus in forme fruste keratoconus. Moreover, the morphological parameters based on the typical position of the thinnest point of corneal thickness have potential special significance for the diagnosis of disease.