Prevalence And Heritability Of Keratoconus In First-Degree Relatives Of Patients With Keratoconus

Part Ⅰ The prevalence of keratoconus in first-degree relatives of patients with keratoconus(KC).Background: KC is a progressive disease characterized by gradual corneal thinning and ectasia.The exact pathogenesis of KC is still unknown.A positive family history of 6-10% in KC cases,and the higher concordance rate in monozygotic twins suggest that genetic factors play a role in the development of KC.Researchers in many countries and regions have studied the first-degree relatives of KC patients,reporting that the prevalence of KC among first-degree relatives ranges from 3.3% to 27.9%.In China,DU et al.included 48 parents of 26 patients and reported a prevalence of 2.08% in parents.However,the prevalence of KC in first-degree relatives of KC patients remains unclear.Purpose: The present study investigated the prevalence of KC among first-degree relatives of KC patients.Methods: From July 2018 to March 2022,661 first-degree relatives of 384 KC patients were included in the present study.Corneal tomography,uncorrected distance visual acuity,manifest refraction with corrected distance visual acuity,intraocular pressure,slit-lamp microscopy,and fundus examination were performed.The diagnosis of KC was based on Belin/Ambrosio enhanced ectasia total deviation value(BADD value)on the Pentacam(Oculus,Lynnwood,WA,USA).BADD value <1.6 was diagnosed as healthy,and 1.6≤ BADD value < 2.6 was diagnosed as suspected KC,and 2.6≤ BADD value was diagnosed as KC.Results: The present study included 337(50.98%)female and 324(49.02%)male subjects.The prevalence of KC and suspected KC in first-degree relatives was 8.77%(n=58)and 29.05%(n=192),respectively.The prevalence of KC was 9.29% among parents-offspring and 7.23% among siblings.Conclusions: The higher prevalence of KC among first-degree relatives of patients with KC suggests that first-degree relatives of KC are at high risk of developing KC.Part Ⅱ Heritability of corneal parameters in nuclear families with keratoconus(KC).Background: KC is a progressive disease characterized by gradual corneal thinning and ectasia.The high prevalence of first-degree relatives of KC indicates that KC has familial aggregation and genetic factors play a role in the development of KC.Genome-wide association analysis,linkage analysis,and candidate gene analysis revealed KC susceptibility genes and associated loci,as well as changes in mitochondrial genome and epigenetics,but how these sites and changes affect the disease remains unclear.Based on the background,we introduced heritability to explain the role of genetic factors in the clinical traits of KC.Heritability provides a clear answer of what percentage of variation in observed traits is due to genetic factors.The greater the heritability,the greater the contribution of genetic factors to the cause.Investigation of heritability of corneal parameters in nuclear families with KC is helpful to determine the endophenotype and related genes of KC and further understand the potential genetic mechanism of KC.To date,heritability of corneal parameters in nuclear families with KC has not been reported.Purpose: This study investigated the heritability of corneal parameters obtained by Pentacam in nuclear families with KC.Methods: This study recruited KC nuclear families,including patients with KC and their parents.All subjects underwent corneal imaging with Pentacam HR(Oculus,Lynnwood,WA,USA).Family units were analyzed to calculate the heritability of corneal parameters by linear mixed-effects model using the R statistical software.Results: 82 nuclear families including 82 probands and their 164 parents were included in the analysis.The pachymetry at apex,pupil and thinnest point were all significantly heritable at 43.26%,42.63%,and43.09%,respectively.Posterior radius of curvature(PRC)had higher heritability in comparison with anterior radius of curvature(ARC)(19.16% vs 14.37%).Moreover,the heritability of index of vertical asymmetry(IVA)was the highest(19.49%),and that of central keratoconus index(CKI)was the lowest(6.64%)among combined topometric indices.Conclusions: The present study is the first heritability assessment in nuclear families with KC and demonstrates a substantial heritability in corneal parameters obtained by Pentacam.The pachymetric indices is heritable and may be suitable as KC endophenotypes.This study highlights the necessity of further genetic and molecular studies to discover the genes associated with KC and understand the causes.