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Annual Review of Vision Science

Volume 6, 2020

Genetic and Environmental Risk Factors for Keratoconus

Abstract

Keratoconus, a progressive corneal ectasia, is a complex disease with both genetic and environmental risk factors. The exact etiology is not known and is likely variable between individuals. Conditions such as hay fever and allergy are associated with increased risk, while diabetes may be protective. Behaviors such as eye rubbing are also implicated, but direct causality has not been proven. Genetics plays a major role in risk for some individuals, with many large pedigrees showing autosomal inheritance patterns. Several genes have been implicated using linkage and follow-up sequencing in these families. Genome-wide association studies for keratoconus and for quantitative traits such as central corneal thickness have identified several genetic loci that contribute to a cumulative risk for keratoconus, even in people without a family history of the disease. Identification of risk genes for keratoconus is improving our understanding of the biology of this complex disease.

Keyword(s): complex disease, corneal ectasia, genetics, inherited eye disease, keratoconus
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/content/journals/10.1146/annurev-vision-121219-081723
2020-09-15
2024-05-04
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Literature Cited

  1. Abu-Amero KK, Helwa I, Al-Muammar A, Strickland S, Hauser MA et al. 2015a. Case-control association between CCT-associated variants and keratoconus in a Saudi Arabian population. J. Negat. Results Biomed. 14:10
     [Google Scholar]
  2. Abu-Amero KK, Helwa I, Al-Muammar A, Strickland S, Hauser MA et al. 2015b. Screening of the seed region of MIR184 in keratoconus patients from Saudi Arabia. Biomed. Res. Int. 2015:604508
     [Google Scholar]
  3. Akpek EK, Jun AS, Goodman DF, Green WR, Gottsch JD 2002. Clinical and ultrastructural features of a novel hereditary anterior segment dysgenesis. Ophthalmology 109:513–19
     [Google Scholar]
  4. Al-Muammar AM, Kalantan H, Azad TA, Sultan T, Abu-Amero KK 2015. Analysis of the SOD1 gene in keratoconus patients from Saudi Arabia. Ophthalmic Genet 36:373–75
     [Google Scholar]
  5. Aldave AJ, Yellore VS, Principe AH, Abedi G, Merrill K et al. 2005. Candidate gene screening for posterior polymorphous dystrophy. Cornea 24:151–55
     [Google Scholar]
  6. Aldave AJ, Yellore VS, Salem AK, Yoo GL, Rayner SA et al. 2006. No VSX1 gene mutations associated with keratoconus. Investig. Ophthalmol. Vis. Sci. 47:2820–22
     [Google Scholar]
  7. Alio JL, Vega-Estrada A, Sanz P, Osman AA, Kamal AM et al. 2018. Corneal morphologic characteristics in patients with Down syndrome. JAMA Ophthalmol 136:971–78
     [Google Scholar]
  8. Alsbirk PH. 1978. Corneal thickness. II. Environmental and genetic factors. Acta Ophthalmol 56:105–13
     [Google Scholar]
  9. Bae HA, Mills RA, Lindsay RG, Phillips T, Coster DJ et al. 2013. Replication and meta-analysis of candidate loci identified variation at RAB3GAP1 associated with keratoconus. Investig. Ophthalmol. Vis. Sci. 54:5132–35
     [Google Scholar]
  10. Bak-Nielsen S, Ramlau-Hansen CH, Ivarsen A, Plana-Ripoll O, Hjortdal J 2018. A nationwide population-based study of social demographic factors, associated diseases and mortality of keratoconus patients in Denmark from 1977 to 2015. Acta Ophthalmol 97:497–504
     [Google Scholar]
  11. Barbaro V, Di Iorio E, Ferrari S, Bisceglia L, Ruzza A et al. 2006. Expression of VSX1 in human corneal keratocytes during differentiation into myofibroblasts in response to wound healing. Investig. Ophthalmol. Vis. Sci. 47:5243–50
     [Google Scholar]
  12. Bawazeer AM, Hodge WG, Lorimer B 2000. Atopy and keratoconus: a multivariate analysis. Br. J. Ophthalmol. 84:834–36
     [Google Scholar]
  13. Bisceglia L, Ciaschetti M, De Bonis P, Campo PA, Pizzicoli C et al. 2005. VSX1 mutational analysis in a series of Italian patients affected by keratoconus: detection of a novel mutation. Investig. Ophthalmol. Vis. Sci. 46:39–45
     [Google Scholar]
  14. Bisceglia L, De Bonis P, Pizzicoli C, Fischetti L, Laborante A et al. 2009. Linkage analysis in keratoconus: replication of locus 5q21.2 and identification of other suggestive loci. Investig. Ophthalmol. Vis. Sci. 50:1081–86
     [Google Scholar]
  15. Brancati F, Valente EM, Sarkozy A, Feher J, Castori M et al. 2004. A locus for autosomal dominant keratoconus maps to human chromosome 3p14-q13. J. Med. Genet. 41:188–92
     [Google Scholar]
  16. Burdon KP, Coster DJ, Charlesworth JC, Mills RA, Laurie KJ et al. 2008. Apparent autosomal dominant keratoconus in a large Australian pedigree accounted for by digenic inheritance of two novel loci. Hum. Genet. 124:379–86
     [Google Scholar]
  17. Burdon KP, Macgregor S, Bykhovskaya Y, Javadiyan S, Li X et al. 2011. Association of polymorphisms in the hepatocyte growth factor gene promoter with keratoconus. Investig. Ophthalmol. Vis. Sci. 52:8514–19
     [Google Scholar]
  18. Bykhovskaya Y, Caiado Canedo AL, Wright KW, Rabinowitz YS 2015a. C.57 C>T mutation in MIR 184 is responsible for congenital cataracts and corneal abnormalities in a five-generation family from Galicia, Spain. Ophthalmic Genet 36:244–47
     [Google Scholar]
  19. Bykhovskaya Y, Li X, Epifantseva I, Haritunians T, Siscovick D et al. 2012. Variation in the lysyl oxidase (LOX) gene is associated with keratoconus in family-based and case-control studies. Investig. Ophthalmol. Vis. Sci. 53:4152–57
     [Google Scholar]
  20. Bykhovskaya Y, Li X, Taylor KD, Haritunians T, Rotter JI, Rabinowitz YS 2014. Linkage analysis of high-density SNPs confirms keratoconus locus at 5q chromosomal region. Ophthalmic Genet 37:109–10
     [Google Scholar]
  21. Bykhovskaya Y, Seldin MF, Liu Y, Ransom M, Li X, Rabinowitz YS 2015b. Independent origin of c.57C>T mutation in MIR184 associated with inherited corneal and lens abnormalities. Ophthalmic Genet 36:95–97
     [Google Scholar]
  22. Cagil N, Ugurlu N, Sahan CY, Sevli S 2017. Lack of MIR143, MIR145, MIR184, MIR1224, and MIR29b1 mutations in keratoconus pathogenesis. Turk. J. Med. Sci. 47:1669–71
     [Google Scholar]
  23. Chao CC, Butala SM, Herp A 1988. Studies on the isolation and composition of human ocular mucin. Exp. Eye Res. 47:185–96
     [Google Scholar]
  24. Charlesworth J, Kramer PL, Dyer T, Diego V, Samples JR et al. 2010. The path to open-angle glaucoma gene discovery: endophenotypic status of intraocular pressure, cup-to-disc ratio, and central corneal thickness. Investig. Ophthalmol. Vis. Sci. 51:3509–14
     [Google Scholar]
  25. Chow RL, Volgyi B, Szilard RK, Ng D, McKerlie C et al. 2004. Control of late off-center cone bipolar cell differentiation and visual signaling by the homeobox gene Vsx1. PNAS 101:1754–59
     [Google Scholar]
  26. Colin J, Sale Y, Malet F, Cochener B 1996. Inferior steepening is associated with thinning of the inferotemporal cornea. J. Refract. Surg. 12:697–99
     [Google Scholar]
  27. Cote JF, Motoyama AB, Bush JA, Vuori K 2005. A novel and evolutionarily conserved PtdIns(3,4,5)P3-binding domain is necessary for DOCK180 signalling. Nat. Cell Biol. 7:797–807
     [Google Scholar]
  28. Cote JF, Vuori K. 2006. In vitro guanine nucleotide exchange activity of DHR-2/DOCKER/CZH2 domains. Methods Enzymol 406:41–57
     [Google Scholar]
  29. Cozma I, Atherley C, James NJ 2005. Influence of ethnic origin on the incidence of keratoconus and associated atopic disease in Asian and white patients. Eye 19:924–25; author reply 925–26
     [Google Scholar]
  30. Czugala M, Karolak JA, Nowak DM, Polakowski P, Pitarque J et al. 2012. Novel mutation and three other sequence variants segregating with phenotype at keratoconus 13q32 susceptibility locus. Eur. J. Hum. Genet. 20:389–97
     [Google Scholar]
  31. Dash DP, Silvestri G, Hughes AE 2006. Fine mapping of the keratoconus with cataract locus on chromosome 15q and candidate gene analysis. Mol. Vis. 12:499–505
     [Google Scholar]
  32. Davidson AE, Borasio E, Liskova P, Khan AO, Hassan H et al. 2015. Brittle cornea syndrome ZNF469 mutation carrier phenotype and segregation analysis of rare ZNF469 variants in familial keratoconus. Investig. Ophthalmol. Vis. Sci. 56:578–86
     [Google Scholar]
  33. De Bonis P, Laborante A, Pizzicoli C, Stallone R, Barbano R et al. 2011. Mutational screening of VSX1, SPARC, SOD1, LOX, and TIMP3 in keratoconus. Mol. Vis. 17:2482–94
     [Google Scholar]
  34. Dharmaraj S, Leroy BP, Sohocki MM, Koenekoop RK, Perrault I et al. 2004. The phenotype of Leber congenital amaurosis in patients with AIPL1 mutations. Arch. Ophthalmol. 122:1029–37
     [Google Scholar]
  35. Dimasi DP, Hewitt AW, Kagame K, Ruvama S, Tindyebwa L et al. 2011. Ethnic and mouse strain differences in central corneal thickness and association with pigmentation phenotype. PLOS ONE 6:e22103
     [Google Scholar]
  36. Doughty MJ, Zaman ML. 2000. Human corneal thickness and its impact on intraocular pressure measures: a review and meta-analysis approach. Surv. Ophthalmol. 44:367–408
     [Google Scholar]
  37. Dudakova L, Palos M, Jirsova K, Stranecky V, Krepelova A et al. 2015. Validation of rs2956540:G>C and rs3735520:G>A association with keratoconus in a population of European descent. Eur. J. Hum. Genet. 23:1581–83
     [Google Scholar]
  38. Durst R, Sauls K, Peal DS, deVlaming A, Toomer K et al. 2015. Mutations in DCHS1 cause mitral valve prolapse. Nature 525:109–13
     [Google Scholar]
  39. Farzadfard A, Nassiri N, Moghadam TN, Paylakhi SH, Elahi E 2016. Screening for MIR184 mutations in Iranian patients with keratoconus. J. Ophthalmic Vis. Res. 11:3–7
     [Google Scholar]
  40. Froukh T, Hawwari A. 2019. Autosomal recessive non-syndromic keratoconus: homozygous frameshift variant in the candidate novel gene GALNT14. Curr. Mol. Med. 19:683–87
     [Google Scholar]
  41. Gajecka M, Radhakrishna U, Winters D, Nath SK, Rydzanicz M et al. 2009. Localization of a gene for keratoconus to a 5.6-Mb interval on 13q32. Investig. Ophthalmol. Vis. Sci. 50:1531–39
     [Google Scholar]
  42. Gordon-Shaag A, Millodot M, Essa M, Garth J, Ghara M, Shneor E 2013. Is consanguinity a risk factor for keratoconus. Optom. Vis. Sci. 90:448–54
     [Google Scholar]
  43. Gordon-Shaag A, Millodot M, Kaiserman I, Sela T, Barnett Itzhaki G et al. 2015a. Risk factors for keratoconus in Israel: a case-control study. Ophthalmic Physiol. Opt. 35:673–81
     [Google Scholar]
  44. Gordon-Shaag A, Millodot M, Shneor E, Liu Y 2015b. The genetic and environmental factors for keratoconus. Biomed. Res. Int. 2015:795738
     [Google Scholar]
  45. Gorskova EN, Sevost'ianov EN. 1998. Epidemiology of keratoconus in the Urals. Vestn. Oftalmol. 114:38–40
     [Google Scholar]
  46. Gottesman II, Gould TD. 2003. The endophenotype concept in psychiatry: etymology and strategic intentions. Am. J. Psychiatry 160:636–45
     [Google Scholar]
  47. Gwilliam R, Liskova P, Filipec M, Kmoch S, Jirsova K et al. 2005. Posterior polymorphous corneal dystrophy in Czech families maps to chromosome 20 and excludes the VSX1 gene. Investig. Ophthalmol. Vis. Sci. 46:4480–84
     [Google Scholar]
  48. Hameed A, Khaliq S, Ismail M, Anwar K, Ebenezer ND et al. 2000. A novel locus for Leber congenital amaurosis (LCA4) with anterior keratoconus mapping to chromosome 17p13. Investig. Ophthalmol. Vis. Sci. 41:629–33
     [Google Scholar]
  49. Hao XD, Chen P, Chen ZL, Li SX, Wang Y 2015. Evaluating the association between keratoconus and reported genetic loci in a Han Chinese population. Ophthalmic Genet 36:132–36
     [Google Scholar]
  50. Hashemi H, Heydarian S, Hooshmand E, Saatchi M, Yekta A et al. 2019. The prevalence and risk factors for keratoconus: a systematic review and meta-analysis. Cornea 39:263–70
     [Google Scholar]
  51. Heon E, Greenberg A, Kopp KK, Rootman D, Vincent AL et al. 2002. VSX1: a gene for posterior polymorphous dystrophy and keratoconus. Hum. Mol. Genet. 11:1029–36
     [Google Scholar]
  52. Hughes AE, Bradley DT, Campbell M, Lechner J, Dash DP et al. 2011. Mutation altering the miR-184 seed region causes familial keratoconus with cataract. Am. J. Hum. Genet. 89:628–33
     [Google Scholar]
  53. Hughes AE, Dash DP, Jackson AJ, Frazer DG, Silvestri G 2003. Familial keratoconus with cataract: linkage to the long arm of chromosome 15 and exclusion of candidate genes. Investig. Ophthalmol. Vis. Sci. 44:5063–66
     [Google Scholar]
  54. Ihalainen A. 1986. Clinical and epidemiological features of keratoconus genetic and external factors in the pathogenesis of the disease. Acta Ophthalmol. Suppl. 178:1–64
     [Google Scholar]
  55. Iliff BW, Riazuddin SA, Gottsch JD 2012. A single-base substitution in the seed region of miR-184 causes EDICT syndrome. Investig. Ophthalmol. Vis. Sci. 53:348–53
     [Google Scholar]
  56. Jun AS, Broman KW, Do DV, Akpek EK, Stark WJ, Gottsch JD 2002. Endothelial dystrophy, iris hypoplasia, congenital cataract, and stromal thinning (edict) syndrome maps to chromosome 15q22.1-q25.3. Am. J. Ophthalmol. 134:172–76
     [Google Scholar]
  57. Kalkan Akcay E, Akcay M, Uysal BS, Kosekahya P, Aslan AN et al. 2014. Impaired corneal biomechanical properties and the prevalence of keratoconus in mitral valve prolapse. J. Ophthalmol. 2014:402193
     [Google Scholar]
  58. Karolak JA, Gambin T, Rydzanicz M, Szaflik JP, Polakowski P et al. 2016. Evidence against ZNF469 being causative for keratoconus in Polish patients. Acta Ophthalmol 94:289–94
     [Google Scholar]
  59. Karolak JA, Rydzanicz M, Ginter-Matuszewska B, Pitarque JA, Molinari A et al. 2015. Variant c.2262A>C in DOCK9 leads to exon skipping in keratoconus family. Investig. Ophthalmol. Vis. Sci. 56:7687–90
     [Google Scholar]
  60. Khawaja AP, Rojas Lopez KE, Hardcastle AJ, Hammond CJ, Liskova P et al. 2019. Genetic variants associated with corneal biomechanical properties and potentially conferring susceptibility to keratoconus in a genome-wide association study. JAMA Ophthalmol. 137:1005–12
     [Google Scholar]
  61. Klyce SD. 1984. Computer-assisted corneal topography: high-resolution graphic presentation and analysis of keratoscopy. Investig. Ophthalmol. Vis. Sci. 25:1426–35
     [Google Scholar]
  62. Klyce SD. 2009. Chasing the suspect: keratoconus. Br. J. Ophthalmol. 93:845–47
     [Google Scholar]
  63. Kokolakis NS, Gazouli M, Chatziralli IP, Koutsandrea C, Gatzioufas Z et al. 2014. Polymorphism analysis of COL4A3 and COL4A4 genes in Greek patients with keratoconus. Ophthalmic Genet 35:226–28
     [Google Scholar]
  64. Kosker M, Suri K, Hammersmith KM, Nassef AH, Nagra PK, Rapuano CJ 2014. Another look at the association between diabetes and keratoconus. Cornea 33:774–79
     [Google Scholar]
  65. Kriszt A, Losonczy G, Berta A, Vereb G, Takacs L 2014. Segregation analysis suggests that keratoconus is a complex non-Mendelian disease. Acta Ophthalmol 92:e562–68
     [Google Scholar]
  66. Kulkarni K, Yang J, Zhang Z, Barford D 2011. Multiple factors confer specific Cdc42 and Rac protein activation by dedicator of cytokinesis (DOCK) nucleotide exchange factors. J. Biol. Chem. 286:25341–51
     [Google Scholar]
  67. Kuo IC, Broman A, Pirouzmanesh A, Melia M 2006. Is there an association between diabetes and keratoconus. Ophthalmology 113:184–90
     [Google Scholar]
  68. Landers JA, Hewitt AW, Dimasi DP, Charlesworth JC, Straga T et al. 2009. Heritability of central corneal thickness in nuclear families. Investig. Ophthalmol. Vis. Sci. 50:4087–90
     [Google Scholar]
  69. Le Tourneau T, Merot J, Rimbert A, Le Scouarnec S, Probst V et al. 2018. Genetics of syndromic and non-syndromic mitral valve prolapse. Heart 104:978–84
     [Google Scholar]
  70. Lechner J, Bae HA, Guduric-Fuchs J, Rice A, Govindarajan G et al. 2013. Mutational analysis of MIR184 in sporadic keratoconus and myopia. Investig. Ophthalmol. Vis. Sci. 54:5266–72
     [Google Scholar]
  71. Lechner J, Porter LF, Rice A, Vitart V, Armstrong DJ et al. 2014. Enrichment of pathogenic alleles in the brittle cornea gene, ZNF469, in keratoconus. Hum. Mol. Genet. 23:5527–35
     [Google Scholar]
  72. Lek M, Karczewski KJ, Minikel EV, Samocha KE, Banks E et al. 2016. Analysis of protein-coding genetic variation in 60,706 humans. Nature 536:285–91
     [Google Scholar]
  73. Li X, Bykhovskaya Y, Canedo AL, Haritunians T, Siscovick D et al. 2013. Genetic association of COL5A1 variants in keratoconus patients suggests a complex connection between corneal thinning and keratoconus. Investig. Ophthalmol. Vis. Sci. 54:2696–704
     [Google Scholar]
  74. Li X, Bykhovskaya Y, Haritunians T, Siscovick D, Aldave A et al. 2012. A genome-wide association study identifies a potential novel gene locus for keratoconus, one of the commonest causes for corneal transplantation in developed countries. Hum. Mol. Genet. 21:421–29
     [Google Scholar]
  75. Li X, Rabinowitz YS, Tang YG, Picornell Y, Taylor KD et al. 2006. Two-stage genome-wide linkage scan in keratoconus sib pair families. Investig. Ophthalmol. Vis. Sci. 47:3791–95
     [Google Scholar]
  76. Liskova P, Dudakova L, Krepelova A, Klema J, Hysi PG 2017. Replication of SNP associations with keratoconus in a Czech cohort. PLOS ONE 12:e0172365
     [Google Scholar]
  77. Liskova P, Ebenezer ND, Hysi PG, Gwilliam R, El-Ashry MF et al. 2007. Molecular analysis of the VSX1 gene in familial keratoconus. Mol. Vis. 13:1887–91
     [Google Scholar]
  78. Liskova P, Hysi PG, Waseem N, Ebenezer ND, Bhattacharya SS, Tuft SJ 2010. Evidence for keratoconus susceptibility locus on chromosome 14: a genome-wide linkage screen using single-nucleotide polymorphism markers. Arch. Ophthalmol. 128:1191–95
     [Google Scholar]
  79. Litke AM, Samuelson S, Delaney KR, Sauve Y, Chow RL 2018. Investigating the pathogenicity of VSX1 missense mutations and their association with corneal disease. Investig. Ophthalmol. Vis. Sci. 59:5824–35
     [Google Scholar]
  80. Lu Y, Vitart V, Burdon KP, Khor CC, Bykhovskaya Y et al. 2013. Genome-wide association analyses identify multiple loci associated with central corneal thickness and keratoconus. Nat. Genet. 45:155–63
     [Google Scholar]
  81. Lucas SEM, Zhou T, Blackburn NB, Mills RA, Ellis J et al. 2017. Rare, potentially pathogenic variants in ZNF469 are not enriched in keratoconus in a large Australian cohort of European descent. Investig. Ophthalmol. Vis. Sci. 58:6248–56
     [Google Scholar]
  82. Lucas SEM, Zhou T, Blackburn NB, Mills RA, Ellis J et al. 2018. Rare, potentially pathogenic variants in 21 keratoconus candidate genes are not enriched in cases in a large Australian cohort of European descent. PLOS ONE 13:e0199178
     [Google Scholar]
  83. Maeda N, Klyce SD, Smolek MK, Thompson HW 1994. Automated keratoconus screening with corneal topography analysis. Investig. Ophthalmol. Vis. Sci. 35:2749–57
     [Google Scholar]
  84. Maharana PK, Sharma N, Vajpayee RB 2013. Acute corneal hydrops in keratoconus. Indian J. Ophthalmol. 61:461–64
     [Google Scholar]
  85. Mantelli F, Argueso P. 2008. Functions of ocular surface mucins in health and disease. Curr. Opin. Allergy Clin. Immunol. 8:477–83
     [Google Scholar]
  86. McComish B, Sahebjada S, Bykhovskaya Y, Willoughby C, Richardson A et al. 2019. Association of genetic variation with keratoconus. JAMA Ophthalmol. 138:174–81
     [Google Scholar]
  87. McMahon TT, Kim LS, Fishman GA, Stone EM, Zhao XC et al. 2009. CRB1 gene mutations are associated with keratoconus in patients with Leber congenital amaurosis. Investig. Ophthalmol. Vis. Sci. 50:3185–87
     [Google Scholar]
  88. McMonnies CW. 2009. Mechanisms of rubbing-related corneal trauma in keratoconus. Cornea 28:607–15
     [Google Scholar]
  89. McMonnies CW, Boneham GC. 2003. Keratoconus, allergy, itch, eye-rubbing and hand-dominance. Clin. Exp. Optom. 86:376–84
     [Google Scholar]
  90. Meller N, Irani-Tehrani M, Kiosses WB, Del Pozo MA, Schwartz MA 2002. Zizimin1, a novel Cdc42 activator, reveals a new GEF domain for Rho proteins. Nat. Cell Biol. 4:639–47
     [Google Scholar]
  91. Merdler I, Hassidim A, Sorkin N, Shapira S, Gronovich Y, Korach Z 2015. Keratoconus and allergic diseases among Israeli adolescents between 2005 and 2013. Cornea 34:525–29
     [Google Scholar]
  92. Moschos MM, Kokolakis N, Gazouli M, Chatziralli IP, Droutsas D et al. 2013. Polymorphism analysis of VSX1 and SOD1 genes in Greek patients with keratoconus. Ophthalmic Genet 36:13–17
     [Google Scholar]
  93. Naderan M, Naderan M, Rezagholizadeh F, Zolfaghari M, Pahlevani R, Rajabi MT 2014. Association between diabetes and keratoconus: a case-control study. Cornea 33:1271–73
     [Google Scholar]
  94. Naderan M, Rajabi MT, Zarrinbakhsh P, Bakhshi A 2017. Effect of allergic diseases on keratoconus severity. Ocul. Immunol. Inflamm. 25:418–23
     [Google Scholar]
  95. Naderan M, Shoar S, Rezagholizadeh F, Zolfaghari M, Naderan M 2015. Characteristics and associations of keratoconus patients. Cont. Lens Anterior Eye 38:199–205
     [Google Scholar]
  96. Nemet AY, Vinker S, Bahar I, Kaiserman I 2010. The association of keratoconus with immune disorders. Cornea 29:1261–64
     [Google Scholar]
  97. Nielsen K, Birkenkamp-Demtroder K, Ehlers N, Orntoft TF 2003. Identification of differentially expressed genes in keratoconus epithelium analyzed on microarrays. Investig. Ophthalmol. Vis. Sci. 44:2466–76
     [Google Scholar]
  98. Nielsen K, Hjortdal J, Aagaard Nohr E, Ehlers N 2007. Incidence and prevalence of keratoconus in Denmark. Acta Ophthalmol. Scand. 85:890–92
     [Google Scholar]
  99. Nowak DM, Karolak JA, Kubiak J, Gut M, Pitarque JA et al. 2013. Substitution at IL1RN and deletion at SLC4A11 segregating with phenotype in familial keratoconus. Investig. Ophthalmol. Vis. Sci. 54:2207–15
     [Google Scholar]
  100. Owens H, Gamble G. 2003. A profile of keratoconus in New Zealand. Cornea 22:122–25
     [Google Scholar]
  101. Rabinowitz YS. 1998. Keratoconus. Surv. Ophthalmol. 42:297–319
     [Google Scholar]
  102. Rabinowitz YS. 2003. The genetics of keratoconus. Ophthalmol. Clin. North Am. 16:607–20
     [Google Scholar]
  103. Rabinowitz YS, Rasheed K. 1999. KISA% index: a quantitative videokeratography algorithm embodying minimal topographic criteria for diagnosing keratoconus. J. Cataract Refract. Surg. 25:1327–35
     [Google Scholar]
  104. Romero-Jimenez M, Santodomingo-Rubido J, Wolffsohn JS 2010. Keratoconus: a review. Cont. Lens Anterior Eye 33:157–66; quiz 205
    [Google Scholar]
  105. Rong SS, Ma STU, Yu XT, Ma L, Chu WK et al. 2017. Genetic associations for keratoconus: a systematic review and meta-analysis. Sci. Rep. 7:4620
     [Google Scholar]
  106. Ryan DG, Oliveira-Fernandes M, Lavker RM 2006. MicroRNAs of the mammalian eye display distinct and overlapping tissue specificity. Mol. Vis. 12:1175–84
     [Google Scholar]
  107. Saad A, Gatinel D. 2010. Topographic and tomographic properties of forme fruste keratoconus corneas. Investig. Ophthalmol. Vis. Sci. 51:5546–55
     [Google Scholar]
  108. Saee-Rad S, Hashemi H, Miraftab M, Noori-Daloii MR, Chaleshtori MH et al. 2011. Mutation analysis of VSX1 and SOD1 in Iranian patients with keratoconus. Mol. Vis. 17:3128–36
     [Google Scholar]
  109. Sahebjada S, Schache M, Richardson AJ, Snibson G, MacGregor S et al. 2013. Evaluating the association between keratoconus and the corneal thickness genes in an independent Australian population. Investig. Ophthalmol. Vis. Sci. 54:8224–28
     [Google Scholar]
  110. Seiler T, Huhle S, Spoerl E, Kunath H 2000. Manifest diabetes and keratoconus: a retrospective case-control study. Graefe's Arch. Clin. Exp. Ophthalmol. 238:822–25
     [Google Scholar]
  111. Shneor E, Millodot M, Blumberg S, Ortenberg I, Behrman S, Gordon-Shaag A 2013. Characteristics of 244 patients with keratoconus seen in an optometric contact lens practice. Clin. Exp. Optom. 96:219–24
     [Google Scholar]
  112. Sohocki MM, Bowne SJ, Sullivan LS, Blackshaw S, Cepko CL et al. 2000. Mutations in a new photoreceptor-pineal gene on 17p cause Leber congenital amaurosis. Nat. Genet. 24:79–83
     [Google Scholar]
  113. Stabuc-Silih M, Ravnik-Glavac M, Glavac D, Hawlina M, Strazisar M 2009. Polymorphisms in COL4A3 and COL4A4 genes associated with keratoconus. Mol. Vis. 15:2848–60
     [Google Scholar]
  114. Stabuc-Silih M, Strazisar M, Ravnik-Glavac M, Hawlina M, Glavac D 2010. Genetics and clinical characteristics of keratoconus. Acta Dermatovenerol. Alp. Pannonica Adriat. 19:3–10
     [Google Scholar]
  115. Steele TM, Fabinyi DC, Couper TA, Loughnan MS 2008. Prevalence of Orbscan II corneal abnormalities in relatives of patients with keratoconus. Clin. Exp. Ophthalmol. 36:824–30
     [Google Scholar]
  116. Tang YG, Rabinowitz YS, Taylor KD, Li X, Hu M et al. 2005. Genomewide linkage scan in a multigeneration Caucasian pedigree identifies a novel locus for keratoconus on chromosome 5q14.3-q21.1. Genet. Med. 7:397–405
     [Google Scholar]
  117. Toh T, Liew SH, MacKinnon JR, Hewitt AW, Poulsen JL et al. 2005. Central corneal thickness is highly heritable: the twin eye studies. Investig. Ophthalmol. Vis. Sci. 46:3718–22
     [Google Scholar]
  118. Torres Netto EA, Al-Otaibi WM, Hafezi NL, Kling S, Al-Farhan HM et al. 2018. Prevalence of keratoconus in paediatric patients in Riyadh, Saudi Arabia. Br. J. Ophthalmol. 102:1436–41
     [Google Scholar]
  119. Tyynismaa H, Sistonen P, Tuupanen S, Tervo T, Dammert A et al. 2002. A locus for autosomal dominant keratoconus: linkage to 16q22.3-q23.1 in Finnish families. Investig. Ophthalmol. Vis. Sci. 43:3160–64
     [Google Scholar]
  120. Udar N, Atilano SR, Brown DJ, Holguin B, Small K et al. 2006. SOD1: a candidate gene for keratoconus. Investig. Ophthalmol. Vis. Sci. 47:3345–51
     [Google Scholar]
  121. Vazirani J, Basu S. 2013. Keratoconus: current perspectives. Clin. Ophthalmol. 7:2019–30
     [Google Scholar]
  122. Vincent AL, Jordan CA, Cadzow MJ, Merriman TR, McGhee CN 2014. Mutations in the zinc finger protein gene, ZNF469, contribute to the pathogenesis of keratoconus. Investig. Ophthalmol. Vis. Sci. 55:5629–35
     [Google Scholar]
  123. Wang Y, Jin T, Zhang X, Wei W, Cui Y et al. 2013. Common single nucleotide polymorphisms and keratoconus in the Han Chinese population. Ophthalmic Genet 34:160–66
     [Google Scholar]
  124. Wang Y, Rabinowitz YS, Rotter JI, Yang H 2000. Genetic epidemiological study of keratoconus: evidence for major gene determination. Am. J. Med. Genet. 93:403–9
     [Google Scholar]
  125. Wang YM, Ma L, Lu SY, Chan TCY, Yam JCS et al. 2018. Analysis of multiple genetic loci reveals MPDZ-NF1B rs1324183 as a putative genetic marker for keratoconus. Br. J. Ophthalmol. 102:1736–41
     [Google Scholar]
  126. Weed KH, MacEwen CJ, Giles T, Low J, McGhee CN 2008. The Dundee University Scottish Keratoconus study: demographics, corneal signs, associated diseases, and eye rubbing. Eye 22:534–41
     [Google Scholar]
  127. Woodward MA, Blachley TS, Stein JD 2016. The association between sociodemographic factors, common systemic diseases, and keratoconus: an analysis of a nationwide health care claims database. Ophthalmology 123:457–65.e2
     [Google Scholar]
  128. Ye C, Ng PK, Jhanji V 2014. Optical quality assessment in normal and forme fruste keratoconus eyes with a double-pass system: a comparison and variability study. Br. J. Ophthalmol. 98:1478–83
     [Google Scholar]
  129. Zadnik K, Barr JT, Edrington TB, Everett DF, Jameson M et al. 1998. Baseline findings in the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) study. Investig. Ophthalmol. Vis. Sci. 39:2537–46
     [Google Scholar]
  130. Zhang J, Zhang L, Hong J, Wu D, Xu J 2015. Association of common variants in LOX with keratoconus: a meta-analysis. PLOS ONE 10:e0145815
     [Google Scholar]
  131. Zheng Y, Ge J, Huang G, Zhang J, Liu B et al. 2008. Heritability of central corneal thickness in Chinese: the Guangzhou Twin Eye study. Investig. Ophthalmol. Vis. Sci. 49:4303–7
     [Google Scholar]
/content/journals/10.1146/annurev-vision-121219-081723
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Genetic and Environmental Risk Factors for Keratoconus
Annual Review of Vision Science 6, 25 (2020); https://doi.org/10.1146/annurev-vision-121219-081723
/content/journals/10.1146/annurev-vision-121219-081723
/content/journals/10.1146/annurev-vision-121219-081723
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