The prevalence of corneal abnormalities in first-degree relatives of patients with keratoconus: a prospective case-control study

Abstract

Purpose: Although there is a high prevalence of keratoconus in the Middle East including Israel, limited data is available describing first-degree relatives of patients with sporadic keratoconus (KC) using Scheimpflug imaging. The purpose of this study is to accurately phenotype first-degree relatives of patients with sporadic KC in Israel using corneal tomography, which may help determine the genetic aetiology of KC.

Methods: First-degree relatives (N = 56) of 16 KC probands participated in this prospective case-control study. Healthy controls (N = 96) were from a previous study. Autorefraction, visual acuity, slit lamp biomicroscopy, retinoscopy, subjective refraction and Scheimpflug imaging (CSO Sirius Topographer) of keratoconus patients and their first-degree relatives were evaluated. The worse eye was used for KC and KC suspects. The main outcome measure was prevalence of abnormal corneal topography and tomography parameters, which was compared between first-degree relatives vs controls. p values < 0.05 were considered significant.

Results: KC (N = 2) or KC suspect (N = 8) was diagnosed in 18% (95% CI 8-28%) of the first-degree relatives. At least one abnormal corneal parameter was evident in 34% of first-degree relatives, while this was significantly lower for controls (14%, χ²_{(1,N = 152)} = 8.8, p = 0.01). Qualitative analysis showed KC first-degree relatives had significantly more abnormal anterior corneal topography patterns than controls (34% vs 17%, χ²_{(1,N = 152)} = 5.9, p = 0.02). For first-degree relatives, sex was not a factor influencing prevalence of corneal abnormalities (18% for both men and women, χ²_{(1,N = 56)} = 0.0, p = 1.0). A significant correlation was found for first-degree relatives between age and most corneal parameters, while this was not evident for the control group.

Conclusions and relevance: Eye care practitioners should consider first-degree relatives of patients with KC at moderate risk for the disease and/or corneal abnormalities.

Keywords: genetics; keratoconus.

Figure 1

Quantitative analysis of corneal abnormalities. Blue bars represent normal healthy control subjects and orange bars represent First‐degree relatives of keratoconus subjects. Abbreviations: TCT, Thinnest corneal thickness; Sif, symmetry index front; Sib, symmetry index back; RMSf, root mean square front; RMSb, root mean square back; BCVf, Baiocchi Calossi Versaci front; BCVb, Baiocchi Calossi Versaci front. Any elevation defect represents a defect at least one of the following parameters: BCVf, BCVb, RMSf and RMSb. Any defect represents indicates subjects with at least one of the other abnormalities in the figure. Asterisk represents a significant difference between first‐degree relatives and healthy controls (Chi‐square or Fisher’s exact test, see Table  S2 for details).

Figure 2

Prevalence of topography patterns in family members and normal controls. Abbreviations: SB, symmetric bowtie; AB, asymmetric bowtie; SRAX, with skewed radial axes; IS, inferior steepening; SS, superior steepening.