Skip to main content
Top
Published in: Ophthalmology and Therapy 2/2018

Open Access 01-12-2018 | Review

Genetic Aspects of Keratoconus: A Literature Review Exploring Potential Genetic Contributions and Possible Genetic Relationships with Comorbidities

Authors: Eleftherios Loukovitis, Konstantinos Sfakianakis, Panagiota Syrmakesi, Eleni Tsotridou, Myrsini Orfanidou, Dimitra Rafailia Bakaloudi, Maria Stoila, Athina Kozei, Spyridon Koronis, Zachos Zachariadis, Paris Tranos, Nikos Kozeis, Miltos Balidis, Zisis Gatzioufas, Aliki Fiska, George Anogeianakis

Published in: Ophthalmology and Therapy | Issue 2/2018

Login to get access

Abstract

Introduction

Keratoconus (KC) is a complex, genetically heterogeneous, multifactorial degenerative disorder that is accompanied by corneal ectasia which usually progresses asymmetrically. With an incidence of approximately 1 per 2000 and 2 cases per 100,000 population presenting annually, KC follows an autosomal recessive or dominant pattern of inheritance and is, apparently, associated with genes that interact with environmental, genetic, and/or other factors. This is an important consideration in refractive surgery in the case of familial KC, given the association of KC with other genetic disorders and the imbalance between dizygotic twins. The present review attempts to identify the genetic loci contributing to the different KC clinical presentations and relate them to the common genetically determined comorbidities associated with KC.

Methods

The PubMed, MEDLINE, Google Scholar, and GeneCards databases were screened for KC-related articles published in English between January 2006 and November 2017. Keyword combinations of “keratoconus,” “risk factor(s),” “genetics,” “genes,” “genetic association(s),” and “cornea” were used. In total, 217 articles were retrieved and analyzed, with greater weight placed on the more recent literature. Further bibliographic research based on the 217 articles revealed another 124 relevant articles that were included in this review. Using the reviewed literature, an attempt was made to correlate genes and genetic risk factors with KC characteristics and genetically related comorbidities associated with KC based on genome-wide association studies, family-based linkage analysis, and candidate-gene approaches.

Results

An association matrix between known KC-related genes and KC symptoms and/or clinical signs together with an association matrix between identified KC genes and genetically related KC comorbidities/syndromes were constructed.

Conclusion

Twenty-four genes were identified as potential contributors to KC and 49 KC-related comorbidities/syndromes were found. More than 85% of the known KC-related genes are involved in glaucoma, Down syndrome, connective tissue disorders, endothelial dystrophy, posterior polymorphous corneal dystrophy, and cataract.
Literature
2.
go back to reference Kennedy RH, Bourne WM, Dyer JA. A 48-year clinical and epidemiologic study of keratoconus. Am J Ophthalmol. 1986;101(3):267–73.PubMedCrossRef Kennedy RH, Bourne WM, Dyer JA. A 48-year clinical and epidemiologic study of keratoconus. Am J Ophthalmol. 1986;101(3):267–73.PubMedCrossRef
3.
go back to reference Ertan A, Kamburoglu G. Intacs implantation using a femtosecond laser for management of keratoconus: comparison of 306 cases in different stages. J Cataract Refract Surg. 2008;34(9):1521–6.PubMedCrossRef Ertan A, Kamburoglu G. Intacs implantation using a femtosecond laser for management of keratoconus: comparison of 306 cases in different stages. J Cataract Refract Surg. 2008;34(9):1521–6.PubMedCrossRef
4.
go back to reference Krachmer JH, Feder RS, Belin MW. Keratoconus and related noninflammatory corneal thinning disorders. Surv Ophthalmol. 1984;28(4):293–322.PubMedCrossRef Krachmer JH, Feder RS, Belin MW. Keratoconus and related noninflammatory corneal thinning disorders. Surv Ophthalmol. 1984;28(4):293–322.PubMedCrossRef
6.
go back to reference Romero-Jiménez M, Santodomingo-Rubido J, Wolffsohn JS. Keratoconus: a review. Cont Lens Anterior Eye. 2010;33(4):157–66.PubMedCrossRef Romero-Jiménez M, Santodomingo-Rubido J, Wolffsohn JS. Keratoconus: a review. Cont Lens Anterior Eye. 2010;33(4):157–66.PubMedCrossRef
7.
go back to reference Jhanji V, Sharma N, Vajpayee RB. Management of keratoconus: current scenario. Br J Ophthalmol. 2010;95(8):1044–50.PubMedCrossRef Jhanji V, Sharma N, Vajpayee RB. Management of keratoconus: current scenario. Br J Ophthalmol. 2010;95(8):1044–50.PubMedCrossRef
8.
go back to reference Kumar NL, Rootman DS. Newer surgical techniques in the management of keratoconus. Int Ophthalmol Clin. 2010;50(3):77–88.PubMedCrossRef Kumar NL, Rootman DS. Newer surgical techniques in the management of keratoconus. Int Ophthalmol Clin. 2010;50(3):77–88.PubMedCrossRef
9.
go back to reference Orucoglu F, Toker E. A novel scoring system for distinguishing keratoconus from normal eyes. Cont Lens Anterior Eye. 2016;39(5):369–74.PubMedCrossRef Orucoglu F, Toker E. A novel scoring system for distinguishing keratoconus from normal eyes. Cont Lens Anterior Eye. 2016;39(5):369–74.PubMedCrossRef
10.
go back to reference Moreira LB, Bardal RA, Crisigiovanni LR. Contact lenses fitting after intracorneal ring segments implantation in keratoconus. Arq Bras Oftalmol. 2013;76(4):215–7.PubMedCrossRef Moreira LB, Bardal RA, Crisigiovanni LR. Contact lenses fitting after intracorneal ring segments implantation in keratoconus. Arq Bras Oftalmol. 2013;76(4):215–7.PubMedCrossRef
11.
go back to reference Zadnik K, Steger-May K, Fink BA, Joslin CE, Nichols JJ, Rosenstiel CE, et al. Between-eye asymmetry in keratoconus. Cornea. 2002;21(7):671–9.PubMedCrossRef Zadnik K, Steger-May K, Fink BA, Joslin CE, Nichols JJ, Rosenstiel CE, et al. Between-eye asymmetry in keratoconus. Cornea. 2002;21(7):671–9.PubMedCrossRef
12.
go back to reference Nichols JJ, Steger-May K, Edrington TB, Zadnik K. The relation between disease asymmetry and severity in keratoconus. Br J Ophthalmol. 2004;88(6):788–91.PubMedPubMedCentralCrossRef Nichols JJ, Steger-May K, Edrington TB, Zadnik K. The relation between disease asymmetry and severity in keratoconus. Br J Ophthalmol. 2004;88(6):788–91.PubMedPubMedCentralCrossRef
13.
go back to reference Belin MW, Duncan J, Ambrosio R Jr, et al. A new tomographic method of grading keratoconus: the ABCD grading system. Int J Keratoconus Ectatic Corneal Dis. 2015;4(3):85–93.CrossRef Belin MW, Duncan J, Ambrosio R Jr, et al. A new tomographic method of grading keratoconus: the ABCD grading system. Int J Keratoconus Ectatic Corneal Dis. 2015;4(3):85–93.CrossRef
14.
go back to reference Cannon DJ, Foster CS. Collagen cross linking in keratoconus. Investig Ophthalmol Vis Sci. 1978;17:63–5. Cannon DJ, Foster CS. Collagen cross linking in keratoconus. Investig Ophthalmol Vis Sci. 1978;17:63–5.
15.
go back to reference Duncan JK, Belin MW, Borgstrom M. Assessing progression of keratoconus: novel tomographic determinants. Eye Vis Lond. 2016;11:3–6. Duncan JK, Belin MW, Borgstrom M. Assessing progression of keratoconus: novel tomographic determinants. Eye Vis Lond. 2016;11:3–6.
16.
go back to reference Lema I, Sobrino T, Duran JA, et al. Subclinical keratoconus and inflammatory molecules from tears. Br J Ophthalmol. 2009;93(6):820–4.PubMedCrossRef Lema I, Sobrino T, Duran JA, et al. Subclinical keratoconus and inflammatory molecules from tears. Br J Ophthalmol. 2009;93(6):820–4.PubMedCrossRef
17.
go back to reference Lopes BT, Lopes T, Ramos IC, Faria-Correia F, Luz A, Valbon BDF, et al. Correlation of topometric and topographic indices with visual acuity in patients with KCN. Int J Keratoconus Ectatic Corneal Dis. 2012;1(3):167–72.CrossRef Lopes BT, Lopes T, Ramos IC, Faria-Correia F, Luz A, Valbon BDF, et al. Correlation of topometric and topographic indices with visual acuity in patients with KCN. Int J Keratoconus Ectatic Corneal Dis. 2012;1(3):167–72.CrossRef
18.
go back to reference Mahmoud AM, Nuñez MX, Blanco C, Koch DD, Wang L, Weikert MP, et al. Expanding the cone location and magnitude index to include corneal thickness and posterior surface information for the detection of keratoconus. Am J Ophthalmol. 2013;156(6):1102–11.PubMedCrossRef Mahmoud AM, Nuñez MX, Blanco C, Koch DD, Wang L, Weikert MP, et al. Expanding the cone location and magnitude index to include corneal thickness and posterior surface information for the detection of keratoconus. Am J Ophthalmol. 2013;156(6):1102–11.PubMedCrossRef
19.
go back to reference Mannion LS, Tromans C, O’Donnell C. Reduction in corneal volume with severity of keratoconus. Curr Eye Res. 2011;36(6):522–7.PubMedCrossRef Mannion LS, Tromans C, O’Donnell C. Reduction in corneal volume with severity of keratoconus. Curr Eye Res. 2011;36(6):522–7.PubMedCrossRef
20.
go back to reference Pramanik S, Musch D, Sutphin J, Farjo A. Extended long-term outcomes of penetrating keratoplasty for keratoconus. Ophthalmology. 2006;113(9):1633–8.PubMedCrossRef Pramanik S, Musch D, Sutphin J, Farjo A. Extended long-term outcomes of penetrating keratoplasty for keratoconus. Ophthalmology. 2006;113(9):1633–8.PubMedCrossRef
21.
go back to reference Shah S, Laiquzzaman M, Bhoiwani R, et al. Assessment of the biomechanical properties of the cornea with the ocular response analyzer in normal and keratoconic eyes. Investig Ophthalmol Vis Sci. 2007;48(7):3026–31.CrossRef Shah S, Laiquzzaman M, Bhoiwani R, et al. Assessment of the biomechanical properties of the cornea with the ocular response analyzer in normal and keratoconic eyes. Investig Ophthalmol Vis Sci. 2007;48(7):3026–31.CrossRef
22.
go back to reference Wojcik K, Blasiak J, Szaflik J, Szaflik J. Role of biochemical factors in the pathogenesis of keratoconus. Acta Biochim Pol. 2014;1:55–62. Wojcik K, Blasiak J, Szaflik J, Szaflik J. Role of biochemical factors in the pathogenesis of keratoconus. Acta Biochim Pol. 2014;1:55–62.
23.
go back to reference Ghosheh FR, Cremona FA, Rapuano CJ, Cohen EJ, Ayres BD, Hammersmith KM, et al. Trends in penetrating keratoplasty in the United States 1980–2005. Int Ophthalmol. 2008;28(3):147–53.PubMedCrossRef Ghosheh FR, Cremona FA, Rapuano CJ, Cohen EJ, Ayres BD, Hammersmith KM, et al. Trends in penetrating keratoplasty in the United States 1980–2005. Int Ophthalmol. 2008;28(3):147–53.PubMedCrossRef
24.
go back to reference Wheeler J, Hauser MA, Afshari NA, Allingham RR, Liu Y. The genetics of keratoconus: a review. Reprod Syst Sex Disord. 2012;(Suppl 6). Wheeler J, Hauser MA, Afshari NA, Allingham RR, Liu Y. The genetics of keratoconus: a review. Reprod Syst Sex Disord. 2012;(Suppl 6).
25.
go back to reference Alió JL, Piñero DP, Alesón A, Teus MA, Barraquer RI, Murta J, et al. Keratoconus-integrated characterization considering anterior corneal aberrations, internal astigmatism, and corneal biomechanics. J Cataract Refract Surg. 2011;37(3):552–68.PubMedCrossRef Alió JL, Piñero DP, Alesón A, Teus MA, Barraquer RI, Murta J, et al. Keratoconus-integrated characterization considering anterior corneal aberrations, internal astigmatism, and corneal biomechanics. J Cataract Refract Surg. 2011;37(3):552–68.PubMedCrossRef
26.
go back to reference Ambrósio R, Alonso RS, Luz A, Velarde LGC. Corneal-thickness spatial profile and corneal-volume distribution: tomographic indices to detect keratoconus. J Cataract Refract Surg. 2006;32(11):1851–9.PubMedCrossRef Ambrósio R, Alonso RS, Luz A, Velarde LGC. Corneal-thickness spatial profile and corneal-volume distribution: tomographic indices to detect keratoconus. J Cataract Refract Surg. 2006;32(11):1851–9.PubMedCrossRef
27.
go back to reference Barsam A, Petrushkin H, Brennan N, Bunce C, Xing W, Foot B, et al. Acute corneal hydrops in keratoconus: a national prospective study of incidence and management. Eye. 2015;29(4):469–74.PubMedPubMedCentralCrossRef Barsam A, Petrushkin H, Brennan N, Bunce C, Xing W, Foot B, et al. Acute corneal hydrops in keratoconus: a national prospective study of incidence and management. Eye. 2015;29(4):469–74.PubMedPubMedCentralCrossRef
28.
go back to reference Bourges JL, Savoldelli M, Dighiero P, et al. Recurrence of keratoconus characteristics: a clinical and histological follow-up analysis of donor grafts. Ophthalmology. 2003;110(10):1920–5.PubMedCrossRef Bourges JL, Savoldelli M, Dighiero P, et al. Recurrence of keratoconus characteristics: a clinical and histological follow-up analysis of donor grafts. Ophthalmology. 2003;110(10):1920–5.PubMedCrossRef
29.
go back to reference Droitcourt C, Touboul D, Ged C, et al. A prospective study of filaggrin null mutations in keratoconus patients with or without atopic disorders. Dermatology. 2011;4:336–41.CrossRef Droitcourt C, Touboul D, Ged C, et al. A prospective study of filaggrin null mutations in keratoconus patients with or without atopic disorders. Dermatology. 2011;4:336–41.CrossRef
30.
go back to reference Fontes BM, Ambrosio R Jr, Jardim D, Velarde GC, Nosé W. Corneal biomechanical metrics and anterior segment parameters in mild keratoconus. Ophthalmology. 2010;117(4):673–9.PubMedCrossRef Fontes BM, Ambrosio R Jr, Jardim D, Velarde GC, Nosé W. Corneal biomechanical metrics and anterior segment parameters in mild keratoconus. Ophthalmology. 2010;117(4):673–9.PubMedCrossRef
31.
go back to reference Karolak JA, Kulinska K, Nowak DM, et al. Sequence variants in COL4A1 and COL4A2 genes in Ecuadorian families with keratoconus. Mol Vis. 2011;17:827–43.PubMedPubMedCentral Karolak JA, Kulinska K, Nowak DM, et al. Sequence variants in COL4A1 and COL4A2 genes in Ecuadorian families with keratoconus. Mol Vis. 2011;17:827–43.PubMedPubMedCentral
32.
go back to reference Kenney MC, Chwa M, Atilano SR, Tran A, Carballo M, Saghizadeh M, et al. Increased levels of catalase and cathepsin V/L2 but decreased TIMP-1 in keratoconus corneas: evidence that oxidative stress plays a role in this disorder. Investig Opthalmol Vis Sci. 2005;46(3):823–32.CrossRef Kenney MC, Chwa M, Atilano SR, Tran A, Carballo M, Saghizadeh M, et al. Increased levels of catalase and cathepsin V/L2 but decreased TIMP-1 in keratoconus corneas: evidence that oxidative stress plays a role in this disorder. Investig Opthalmol Vis Sci. 2005;46(3):823–32.CrossRef
33.
go back to reference Lema I, Durán JA, Ruiz C, Díez-Feijoo E, Acera A, Merayo J. Inflammatory response to contact lenses in patients with keratoconus compared with myopic subjects. Cornea. 2008;27(7):758–63.PubMedCrossRef Lema I, Durán JA, Ruiz C, Díez-Feijoo E, Acera A, Merayo J. Inflammatory response to contact lenses in patients with keratoconus compared with myopic subjects. Cornea. 2008;27(7):758–63.PubMedCrossRef
34.
go back to reference Li X, Bykhovskaya Y, Canedo ALC, Haritunians T, Siscovick D, Aldave AJ, et al. Genetic association of COL5A1 variants in keratoconus patients suggests a complex connection between corneal thinning and keratoconus. Investig Opthalmol Vis Sci. 2013;54(4):2696–704.CrossRef Li X, Bykhovskaya Y, Canedo ALC, Haritunians T, Siscovick D, Aldave AJ, et al. Genetic association of COL5A1 variants in keratoconus patients suggests a complex connection between corneal thinning and keratoconus. Investig Opthalmol Vis Sci. 2013;54(4):2696–704.CrossRef
35.
go back to reference Li X, Bykhovskaya Y, Tang YG, Picornell Y, Haritunians T, Aldave AJ, et al. An association between the calpastatin (CAST) gene and keratoconus. Cornea. 2013;32(5):696–701.PubMedPubMedCentralCrossRef Li X, Bykhovskaya Y, Tang YG, Picornell Y, Haritunians T, Aldave AJ, et al. An association between the calpastatin (CAST) gene and keratoconus. Cornea. 2013;32(5):696–701.PubMedPubMedCentralCrossRef
36.
go back to reference Li X, Yang H, Rabinowitz YS. Keratoconus: classification scheme based on videokeratography and clinical signs. J Cataract Refract Surg. 2009;35(9):1597–603.PubMedPubMedCentralCrossRef Li X, Yang H, Rabinowitz YS. Keratoconus: classification scheme based on videokeratography and clinical signs. J Cataract Refract Surg. 2009;35(9):1597–603.PubMedPubMedCentralCrossRef
37.
go back to reference Maeda N, Klyce SD, Smolek MK, et al. Automated keratoconus screening with corneal topography analysis. Invest Ophthalmol Vis Sci. 1994;35(6):2749–57.PubMed Maeda N, Klyce SD, Smolek MK, et al. Automated keratoconus screening with corneal topography analysis. Invest Ophthalmol Vis Sci. 1994;35(6):2749–57.PubMed
38.
go back to reference Matthews FJ, Cook SD, Majid MA, Dick AD, Smith VA. Changes in the balance of the tissue inhibitor of matrix metalloproteinases (TIMPs)-1 and -3 may promote keratocyte apoptosis in keratoconus. Exp Eye Res. 2007;84(6):1125–34.PubMedCrossRef Matthews FJ, Cook SD, Majid MA, Dick AD, Smith VA. Changes in the balance of the tissue inhibitor of matrix metalloproteinases (TIMPs)-1 and -3 may promote keratocyte apoptosis in keratoconus. Exp Eye Res. 2007;84(6):1125–34.PubMedCrossRef
39.
40.
go back to reference Piñero DP, Alió JL, Alesón A, Vergara ME, Miranda M. Corneal volume, pachymetry, and correlation of anterior and posterior corneal shape in subclinical and different stages of clinical keratoconus. J Cataract Refract Surg. 2010;36(5):814–25.PubMedCrossRef Piñero DP, Alió JL, Alesón A, Vergara ME, Miranda M. Corneal volume, pachymetry, and correlation of anterior and posterior corneal shape in subclinical and different stages of clinical keratoconus. J Cataract Refract Surg. 2010;36(5):814–25.PubMedCrossRef
42.
go back to reference Shah S, Laiquzzaman M. Comparison of corneal biomechanics in pre and post-refractive surgery and keratoconic eyes by ocular response analyser. Cont Lens Anterior Eye. 2009;32(3):129–32.PubMedCrossRef Shah S, Laiquzzaman M. Comparison of corneal biomechanics in pre and post-refractive surgery and keratoconic eyes by ocular response analyser. Cont Lens Anterior Eye. 2009;32(3):129–32.PubMedCrossRef
43.
go back to reference Sherwin T, Brookes NH, Loh IP, et al. Cellular incursion into Bowman’s membrane in the peripheral cone of the keratoconic cornea. Exp Eye Res. 2002;74(4):473–82.PubMedCrossRef Sherwin T, Brookes NH, Loh IP, et al. Cellular incursion into Bowman’s membrane in the peripheral cone of the keratoconic cornea. Exp Eye Res. 2002;74(4):473–82.PubMedCrossRef
44.
go back to reference Sutton G, Madigan M, Roufas A, Mcavoy J. Secreted frizzled-related protein 1 (SFRP1) is highly upregulated in keratoconus epithelium: a novel finding highlighting a new potential focus for keratoconus research and treatment. Clin Exp Ophthalmol. 2010;38(1):43–8.PubMedCrossRef Sutton G, Madigan M, Roufas A, Mcavoy J. Secreted frizzled-related protein 1 (SFRP1) is highly upregulated in keratoconus epithelium: a novel finding highlighting a new potential focus for keratoconus research and treatment. Clin Exp Ophthalmol. 2010;38(1):43–8.PubMedCrossRef
45.
go back to reference Suzuki M, Amano S, Honda N, et al. Longitudinal changes in corneal irregular astigmatism and visual acuity in eyes with KCN. Jpn J Ophthalmol. 2007;51(4):265–9.PubMedCrossRef Suzuki M, Amano S, Honda N, et al. Longitudinal changes in corneal irregular astigmatism and visual acuity in eyes with KCN. Jpn J Ophthalmol. 2007;51(4):265–9.PubMedCrossRef
46.
47.
go back to reference Lass JH, Lembach RG, Park SB, et al. Clinical management of keratoconus. A multicenter analysis. Ophthalmology. 1990;97:433–45.PubMedCrossRef Lass JH, Lembach RG, Park SB, et al. Clinical management of keratoconus. A multicenter analysis. Ophthalmology. 1990;97:433–45.PubMedCrossRef
48.
go back to reference Crews MJ, Driebe WT, Stern GA. The clinical management of keratoconus: a 6 year retrospective study. CLAO J. 1994;20(3):194–7.PubMed Crews MJ, Driebe WT, Stern GA. The clinical management of keratoconus: a 6 year retrospective study. CLAO J. 1994;20(3):194–7.PubMed
50.
go back to reference Bikbov MM, Bikbova GM, Khabibullin AF. Corneal collagen cross-linking in keratoconus management. Vestnik Oftalmologii. 2011;127:21–5.PubMed Bikbov MM, Bikbova GM, Khabibullin AF. Corneal collagen cross-linking in keratoconus management. Vestnik Oftalmologii. 2011;127:21–5.PubMed
51.
go back to reference Nielsen K, Hjortdal J, Nohr EA, Ehlers N. Incidence and prevalence of keratoconus in Denmark. Acta Ophthalmol Scand. 2007;85(8):890–2.PubMedCrossRef Nielsen K, Hjortdal J, Nohr EA, Ehlers N. Incidence and prevalence of keratoconus in Denmark. Acta Ophthalmol Scand. 2007;85(8):890–2.PubMedCrossRef
53.
go back to reference Jonas JB, Nangia V, Matin A, Kulkarni M, Bhojwani K. Prevalence and associations of keratoconus in rural maharashtra in central India: the Central India Eye and Medical Study. Am J Ophthalmol. 2009;148(5):760–5.PubMedCrossRef Jonas JB, Nangia V, Matin A, Kulkarni M, Bhojwani K. Prevalence and associations of keratoconus in rural maharashtra in central India: the Central India Eye and Medical Study. Am J Ophthalmol. 2009;148(5):760–5.PubMedCrossRef
54.
56.
go back to reference Andreassen TT, Simonsen AH, Oxlund H. Biomechanical properties of keratoconus and normal corneas. Exp Eye Res. 1980;31(4):435–41.PubMedCrossRef Andreassen TT, Simonsen AH, Oxlund H. Biomechanical properties of keratoconus and normal corneas. Exp Eye Res. 1980;31(4):435–41.PubMedCrossRef
57.
go back to reference Chaerkady R, Shao H, Scott S-G, Pandey A, Jun AS, Chakravarti S. The keratoconus corneal proteome: loss of epithelial integrity and stromal degeneration. J Proteom. 2013;87:122–31.CrossRef Chaerkady R, Shao H, Scott S-G, Pandey A, Jun AS, Chakravarti S. The keratoconus corneal proteome: loss of epithelial integrity and stromal degeneration. J Proteom. 2013;87:122–31.CrossRef
58.
go back to reference Meek KM, Tuft SJ, Huang Y, et al. Changes in collagen orientation and distribution in keratoconus corneas. Investig Ophthalmol Vis Sci. 2005;46:1948–56.CrossRef Meek KM, Tuft SJ, Huang Y, et al. Changes in collagen orientation and distribution in keratoconus corneas. Investig Ophthalmol Vis Sci. 2005;46:1948–56.CrossRef
59.
go back to reference Zadnik K, Barr JT, Edrington TB, Everett DF, Jameson M, McMahon TT, et al. Baseline findings in the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) study. Investig Ophthalmol Vis Sci. 1998;39(13):2537–46. Zadnik K, Barr JT, Edrington TB, Everett DF, Jameson M, McMahon TT, et al. Baseline findings in the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) study. Investig Ophthalmol Vis Sci. 1998;39(13):2537–46.
60.
go back to reference Sherwin T, Brookes NH. Morphological changes in keratoconus: pathology or pathogenesis. Clin Exp Ophthalmol. 2004;32(2):211–7.PubMedCrossRef Sherwin T, Brookes NH. Morphological changes in keratoconus: pathology or pathogenesis. Clin Exp Ophthalmol. 2004;32(2):211–7.PubMedCrossRef
61.
go back to reference Cohen EJ. Keratoconus and normal-tension glaucoma: a study of the possible association with abnormal biomechanical properties as measured by corneal hysteresis. Trans Am Ophthalmol Soc. 2009;107:282–99.PubMedPubMedCentral Cohen EJ. Keratoconus and normal-tension glaucoma: a study of the possible association with abnormal biomechanical properties as measured by corneal hysteresis. Trans Am Ophthalmol Soc. 2009;107:282–99.PubMedPubMedCentral
62.
go back to reference Abu-Amero KK, Helwa I, Al-Muammar A, Strickland S, Hauser MA, Allingham RR, et al. Case-control association between CCT-associated variants and keratoconus in a Saudi Arabian population. J Negat Results BioMed. 2015;14(1):10.PubMedPubMedCentralCrossRef Abu-Amero KK, Helwa I, Al-Muammar A, Strickland S, Hauser MA, Allingham RR, et al. Case-control association between CCT-associated variants and keratoconus in a Saudi Arabian population. J Negat Results BioMed. 2015;14(1):10.PubMedPubMedCentralCrossRef
63.
64.
go back to reference Dirani M, Islam A, Shekar SN, Baird PN. Dominant genetic effects on corneal astigmatism: the Genes in Myopia (GEM) twin study. Investig Opthalmol Vis Sci. 2008;49(4):1339–44.CrossRef Dirani M, Islam A, Shekar SN, Baird PN. Dominant genetic effects on corneal astigmatism: the Genes in Myopia (GEM) twin study. Investig Opthalmol Vis Sci. 2008;49(4):1339–44.CrossRef
66.
go back to reference Zadnik K, Barr JT, Edrington TB, Nichols JJ, Wilson BS, Siegmund K, Gordon MO. Corneal scarring and vision in keratoconus: a baseline report from the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study. Cornea. 2000;19(6):804–12.PubMedCrossRef Zadnik K, Barr JT, Edrington TB, Nichols JJ, Wilson BS, Siegmund K, Gordon MO. Corneal scarring and vision in keratoconus: a baseline report from the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study. Cornea. 2000;19(6):804–12.PubMedCrossRef
67.
go back to reference Davidson AE, Hayes S, Hardcastle AJ, Tuft SJ. The pathogenesis of keratoconus. Eye (Lond). 2014;28:189–95.CrossRef Davidson AE, Hayes S, Hardcastle AJ, Tuft SJ. The pathogenesis of keratoconus. Eye (Lond). 2014;28:189–95.CrossRef
68.
go back to reference Panikkar K, Manayath G, Rajaraman R, Saravanan V. Progressive keratoconus, retinal detachment, and intracorneal silicone oil with obsessive-compulsive eye rubbing. Oman J Ophthalmol. 2016;9(3):170.PubMedPubMedCentralCrossRef Panikkar K, Manayath G, Rajaraman R, Saravanan V. Progressive keratoconus, retinal detachment, and intracorneal silicone oil with obsessive-compulsive eye rubbing. Oman J Ophthalmol. 2016;9(3):170.PubMedPubMedCentralCrossRef
69.
go back to reference Zhou L, Sawaguchi S, Twining SS, Sugar J, Feder RS, Yue BY. Expression of degradative enzymes and protease inhibitors in corneas with keratoconus. Investig Ophthalmol Vis Sci. 1998;7:1117–24. Zhou L, Sawaguchi S, Twining SS, Sugar J, Feder RS, Yue BY. Expression of degradative enzymes and protease inhibitors in corneas with keratoconus. Investig Ophthalmol Vis Sci. 1998;7:1117–24.
70.
go back to reference Rong SS, Ma STU, Yu XT, Ma L, Chu WK, Chan TCY, et al. Genetic associations for keratoconus: a systematic review and meta-analysis. Sci Rep. 2017;7(1):4620.PubMedPubMedCentralCrossRef Rong SS, Ma STU, Yu XT, Ma L, Chu WK, Chan TCY, et al. Genetic associations for keratoconus: a systematic review and meta-analysis. Sci Rep. 2017;7(1):4620.PubMedPubMedCentralCrossRef
71.
go back to reference Gomes JA, Tan D, Rapuano CJ, et al. Global consensus on keratoconus and ectatic disease. Cornea. 2015;34:359–69.PubMedCrossRef Gomes JA, Tan D, Rapuano CJ, et al. Global consensus on keratoconus and ectatic disease. Cornea. 2015;34:359–69.PubMedCrossRef
72.
go back to reference Georgiou T, Funnell CL, Cassels-Brown A, O’Conor R. Influence of ethnic origin on the incidence of keratoconus and associated atopic disease in Asians and white patients. Eye Lond. 2004;18:379–83.PubMedCrossRef Georgiou T, Funnell CL, Cassels-Brown A, O’Conor R. Influence of ethnic origin on the incidence of keratoconus and associated atopic disease in Asians and white patients. Eye Lond. 2004;18:379–83.PubMedCrossRef
73.
go back to reference Burnside RD, Lose EJ, Domínguez MG, Sánchez-Corona J, Rivera H, Carroll AJ, et al. Molecular cytogenetic characterization of two cases with constitutional distal 11q duplication/triplication. Am J Med Genet A. 2009;149A(7):1516–22.PubMedCrossRef Burnside RD, Lose EJ, Domínguez MG, Sánchez-Corona J, Rivera H, Carroll AJ, et al. Molecular cytogenetic characterization of two cases with constitutional distal 11q duplication/triplication. Am J Med Genet A. 2009;149A(7):1516–22.PubMedCrossRef
75.
go back to reference Pearson AR, Soneji B, Sarvananthan N, Sandford-Smith JH. Does ethnic origin influence the incidence or severity of keratoconus? Eye. 2000;14(4):625–8.PubMedCrossRef Pearson AR, Soneji B, Sarvananthan N, Sandford-Smith JH. Does ethnic origin influence the incidence or severity of keratoconus? Eye. 2000;14(4):625–8.PubMedCrossRef
76.
go back to reference Cornes BK, Khor CC, Nongpiur ME, Xu L, Tay W-T, Zheng Y, et al. Identification of four novel variants that influence central corneal thickness in multi-ethnic Asian populations. Hum Mol Genet. 2012;21(19):437–45.PubMedCrossRef Cornes BK, Khor CC, Nongpiur ME, Xu L, Tay W-T, Zheng Y, et al. Identification of four novel variants that influence central corneal thickness in multi-ethnic Asian populations. Hum Mol Genet. 2012;21(19):437–45.PubMedCrossRef
77.
go back to reference Tay KH, Chan WK. Penetrating keratoplasty for keratoconus. Ann Acad Med Singap. 1997;26:132–7.PubMed Tay KH, Chan WK. Penetrating keratoplasty for keratoconus. Ann Acad Med Singap. 1997;26:132–7.PubMed
79.
go back to reference Ziaei H, Jafarinasab MR, Javadi MA, Karimian F, Poorsalman H, Mahdavi M, et al. Epidemiology of keratoconus in an Iranian population. Cornea. 2012;31(9):1044–7.PubMedCrossRef Ziaei H, Jafarinasab MR, Javadi MA, Karimian F, Poorsalman H, Mahdavi M, et al. Epidemiology of keratoconus in an Iranian population. Cornea. 2012;31(9):1044–7.PubMedCrossRef
80.
go back to reference Li SW, Li ZX, Shi WY, et al. Clinical features of 233 cases of keratoconus. Zhonghua Yan Ke Za Zhi. 2005;41(7):610–3.PubMed Li SW, Li ZX, Shi WY, et al. Clinical features of 233 cases of keratoconus. Zhonghua Yan Ke Za Zhi. 2005;41(7):610–3.PubMed
81.
go back to reference Hao X-D, Chen P, Chen Z-L, Li S-X, Wang Y. Evaluating the association between keratoconus and reported genetic loci in a Han Chinese population. Ophthalm Genet. 2015;36(2):132–6.PubMedCrossRef Hao X-D, Chen P, Chen Z-L, Li S-X, Wang Y. Evaluating the association between keratoconus and reported genetic loci in a Han Chinese population. Ophthalm Genet. 2015;36(2):132–6.PubMedCrossRef
82.
go back to reference Gorskova EN, Sevost’ianov EN. Epidemiology of keratoconus in the Urals. Vestn Oftalmol. 1998;114:38–40.PubMed Gorskova EN, Sevost’ianov EN. Epidemiology of keratoconus in the Urals. Vestn Oftalmol. 1998;114:38–40.PubMed
83.
go back to reference Millodot M, Shneor E, Albou S, Atlani E, Gordon-Shaag A. Prevalence and associated factors of keratoconus in Jerusalem: a cross-sectional study. Ophthalmic Epidemiol. 2011;18(2):91–7.PubMedCrossRef Millodot M, Shneor E, Albou S, Atlani E, Gordon-Shaag A. Prevalence and associated factors of keratoconus in Jerusalem: a cross-sectional study. Ophthalmic Epidemiol. 2011;18(2):91–7.PubMedCrossRef
84.
go back to reference Assiri AA. Incidence and severity of keratoconus in Asir Province, Saudi Arabia. Br J Ophthalmol. 2005;89(11):1403–6.CrossRef Assiri AA. Incidence and severity of keratoconus in Asir Province, Saudi Arabia. Br J Ophthalmol. 2005;89(11):1403–6.CrossRef
85.
go back to reference Ihalainen A. Clinical and epidemiological features of keratoconus genetic and external factors in the pathogenesis of the disease. Acta Ophthalmol Scand. 1986;178(Suppl):55–64. Ihalainen A. Clinical and epidemiological features of keratoconus genetic and external factors in the pathogenesis of the disease. Acta Ophthalmol Scand. 1986;178(Suppl):55–64.
86.
go back to reference Tanabe U, Fujiki K, Ogawa A, Ueda S, Kanai A. Prevalence of keratoconus patients in Japan. J Jpn Opthalmol Soc. 1985;89:407–11. Tanabe U, Fujiki K, Ogawa A, Ueda S, Kanai A. Prevalence of keratoconus patients in Japan. J Jpn Opthalmol Soc. 1985;89:407–11.
87.
go back to reference Lee JE, Oum BS, et al. Evaluation of differentially expressed genes identified in keratoconus. Mol Vis. 2009;15:2480–7.PubMedPubMedCentral Lee JE, Oum BS, et al. Evaluation of differentially expressed genes identified in keratoconus. Mol Vis. 2009;15:2480–7.PubMedPubMedCentral
88.
go back to reference Takahashi A, Nakayasu K, Okisaka S, et al. Quantitative analysis of collagen fiberin keratoconus. J Jpn Opthalmol Soc. 1990;94:1068–73. Takahashi A, Nakayasu K, Okisaka S, et al. Quantitative analysis of collagen fiberin keratoconus. J Jpn Opthalmol Soc. 1990;94:1068–73.
89.
go back to reference Lema I, Duran JA. Inflammatory molecules in the tears of patients with keratoconus. Ophthalmology. 2005;4:654–9.CrossRef Lema I, Duran JA. Inflammatory molecules in the tears of patients with keratoconus. Ophthalmology. 2005;4:654–9.CrossRef
90.
go back to reference Wojcik KA, Kaminska A, Blasiak J, Szaflik J, Szaflik JP. Oxidative stress in the pathogenesis of keratoconus and Fuchs endothelial corneal dystrophy. Int J Mol Sci. 2013;14:19294–308.PubMedPubMedCentralCrossRef Wojcik KA, Kaminska A, Blasiak J, Szaflik J, Szaflik JP. Oxidative stress in the pathogenesis of keratoconus and Fuchs endothelial corneal dystrophy. Int J Mol Sci. 2013;14:19294–308.PubMedPubMedCentralCrossRef
91.
go back to reference Wilson SE, He YG, Weng J, Li Q, McDowall AW, Vital M, Chwang EL. Epithelial injury induces keratocyte apoptosis: hypothesized role for the interleukin-1 system in the modulation of corneal tissue organization. Exp Eye Res. 1996;62:325–7.PubMedCrossRef Wilson SE, He YG, Weng J, Li Q, McDowall AW, Vital M, Chwang EL. Epithelial injury induces keratocyte apoptosis: hypothesized role for the interleukin-1 system in the modulation of corneal tissue organization. Exp Eye Res. 1996;62:325–7.PubMedCrossRef
92.
go back to reference Kim W-J, Rabinowitz YS, Meisler DM, Wilson SE. Keratocyte apoptosis associated with keratoconus. Exp Eye Res. 1999;69:475–81.PubMedCrossRef Kim W-J, Rabinowitz YS, Meisler DM, Wilson SE. Keratocyte apoptosis associated with keratoconus. Exp Eye Res. 1999;69:475–81.PubMedCrossRef
93.
go back to reference Brown DJ, Lin B, Chwa M, Atilano SR, Kim DW, Kenney MC. Elements of the nitric oxide pathway can degrade TIMP-1 and increase gelatinase activity. Mol Vis. 2004;10:281–8.PubMed Brown DJ, Lin B, Chwa M, Atilano SR, Kim DW, Kenney MC. Elements of the nitric oxide pathway can degrade TIMP-1 and increase gelatinase activity. Mol Vis. 2004;10:281–8.PubMed
94.
go back to reference Gaskin JCF, Patel DV, McGhee CNJ. Acute corneal hydrops in keratoconus—new perspectives. Am J Ophthalmol. 2014;157(5):921–8. Gaskin JCF, Patel DV, McGhee CNJ. Acute corneal hydrops in keratoconus—new perspectives. Am J Ophthalmol. 2014;157(5):921–8.
95.
go back to reference Abu-Amero KK, Al-Muammar AM, Kondkar AA. Genetics of keratoconus: where do we stand? J Ophthalmol. 2014;2014:1–11.CrossRef Abu-Amero KK, Al-Muammar AM, Kondkar AA. Genetics of keratoconus: where do we stand? J Ophthalmol. 2014;2014:1–11.CrossRef
96.
go back to reference El Dib RP, de Freitas D. A systematic review of Ferrara’s ring in the treatment of keratoconus. J Refract Surg. 2008;24(9):865–6.PubMedCrossRef El Dib RP, de Freitas D. A systematic review of Ferrara’s ring in the treatment of keratoconus. J Refract Surg. 2008;24(9):865–6.PubMedCrossRef
97.
go back to reference Ertan A, Colin J. Intracorneal rings for keratoconus and keratectasia. J Cataract Refract Surg. 2007;33(7):1303–14.PubMedCrossRef Ertan A, Colin J. Intracorneal rings for keratoconus and keratectasia. J Cataract Refract Surg. 2007;33(7):1303–14.PubMedCrossRef
98.
go back to reference Wilson SE, Verity SM, Conger DL. Accuracy and reproducibility of the corneal analysis system and topographic modeling system. Cornea. 1992;11:28–35.PubMedCrossRef Wilson SE, Verity SM, Conger DL. Accuracy and reproducibility of the corneal analysis system and topographic modeling system. Cornea. 1992;11:28–35.PubMedCrossRef
100.
go back to reference Williams KA, Hornsby NB, Bartlett CM, Holland HK, Esterman AJ, Coster DJ. The Australian Corneal Graft Registry: 2004 report. Adelaide: Snap Printing; 2004. Williams KA, Hornsby NB, Bartlett CM, Holland HK, Esterman AJ, Coster DJ. The Australian Corneal Graft Registry: 2004 report. Adelaide: Snap Printing; 2004.
101.
go back to reference Ashwin PT, Mcdonnell PJ. Collagen cross-linkage: a comprehensive review and directions for future research. Br J Ophthalmol. 2009;94(8):965–70.PubMedCrossRef Ashwin PT, Mcdonnell PJ. Collagen cross-linkage: a comprehensive review and directions for future research. Br J Ophthalmol. 2009;94(8):965–70.PubMedCrossRef
102.
103.
104.
go back to reference Rabinowitz Y. The genetics of keratoconus. Ophthalmol Clin N Am. 2003;16(4):607–20.CrossRef Rabinowitz Y. The genetics of keratoconus. Ophthalmol Clin N Am. 2003;16(4):607–20.CrossRef
105.
go back to reference Stabuc-Silih M, Strazisar M, Ravnik-Glavac M, Hawlina M, Glavac D. Genetics and clinical characteristics of keratoconus. Acta Dermatovenerol Alp Pannonica Adriat. 2010;19:3–10. Stabuc-Silih M, Strazisar M, Ravnik-Glavac M, Hawlina M, Glavac D. Genetics and clinical characteristics of keratoconus. Acta Dermatovenerol Alp Pannonica Adriat. 2010;19:3–10.
106.
go back to reference Fink BA, Sinnott LT, Wagner H, Friedman C, Zadnik K, CLEK Study Group. The influence of gender and hormone status on the severity and progression of keratoconus. Cornea. 2010;29:65–72.PubMedCrossRef Fink BA, Sinnott LT, Wagner H, Friedman C, Zadnik K, CLEK Study Group. The influence of gender and hormone status on the severity and progression of keratoconus. Cornea. 2010;29:65–72.PubMedCrossRef
107.
go back to reference Wong TY, Foster PJ, Johnson GJ, Klein BE, Seah SK. The relationship between ocular dimensions and refraction with adult stature: the Tanjong Pagar Survey. Invest Ophthalmol Vis Sci. 2001;42(6):1237–42. Wong TY, Foster PJ, Johnson GJ, Klein BE, Seah SK. The relationship between ocular dimensions and refraction with adult stature: the Tanjong Pagar Survey. Invest Ophthalmol Vis Sci. 2001;42(6):1237–42.
108.
go back to reference Fotedar R, Wang JJ, Burlutsky G, Morgan IG, Rose K, Wong TY, et al. Distribution of axial length and ocular biometry measured using partial coherence laser interferometry (IOL Master) in an older white population. Ophthalmology. 2010;117(3):417–23.PubMedCrossRef Fotedar R, Wang JJ, Burlutsky G, Morgan IG, Rose K, Wong TY, et al. Distribution of axial length and ocular biometry measured using partial coherence laser interferometry (IOL Master) in an older white population. Ophthalmology. 2010;117(3):417–23.PubMedCrossRef
109.
go back to reference Burdon KP, Vincent AL. Insights into keratoconus from a genetic perspective. Clin Exp Optom. 2013;96(2):146–54.PubMedCrossRef Burdon KP, Vincent AL. Insights into keratoconus from a genetic perspective. Clin Exp Optom. 2013;96(2):146–54.PubMedCrossRef
110.
go back to reference Chwa M, Atilano SR, Hertzog D, Zheng H, Langberg J, Kim DW, et al. Hypersensitive response to oxidative stress in keratoconus corneal fibroblasts. Investig Opthalmol Vis Sci. 2008;49(10):4361–9.CrossRef Chwa M, Atilano SR, Hertzog D, Zheng H, Langberg J, Kim DW, et al. Hypersensitive response to oxidative stress in keratoconus corneal fibroblasts. Investig Opthalmol Vis Sci. 2008;49(10):4361–9.CrossRef
111.
go back to reference Buddi R, Lin B, Atilano SR, Zorapapel NC, Kenney MC, Brown DJ. Evidence of oxidative stress in human corneal diseases. J Histochem Cytochem. 2002;50:341–51.CrossRef Buddi R, Lin B, Atilano SR, Zorapapel NC, Kenney MC, Brown DJ. Evidence of oxidative stress in human corneal diseases. J Histochem Cytochem. 2002;50:341–51.CrossRef
112.
go back to reference Kenney MC, Brown DJ. The cascade hypothesis of keratoconus. Cont Lens Anterior Eye. 2003;26(3):139–46.CrossRef Kenney MC, Brown DJ. The cascade hypothesis of keratoconus. Cont Lens Anterior Eye. 2003;26(3):139–46.CrossRef
113.
go back to reference Shoham A, Hadziahmetovic M, Dunaief JL, Mydlarski MB, Schipper HM. Oxidative stress in diseases of the human cornea. Free Radic Biol Med. 2008;45:1047–55.PubMedCrossRef Shoham A, Hadziahmetovic M, Dunaief JL, Mydlarski MB, Schipper HM. Oxidative stress in diseases of the human cornea. Free Radic Biol Med. 2008;45:1047–55.PubMedCrossRef
114.
go back to reference Hao XD, Chen P, et al. Evaluating the association between keratoconus and reported genetic loci in a Han Chinese population. Ophthalmic Genet. 2015;36(2):132–6.PubMedCrossRef Hao XD, Chen P, et al. Evaluating the association between keratoconus and reported genetic loci in a Han Chinese population. Ophthalmic Genet. 2015;36(2):132–6.PubMedCrossRef
115.
go back to reference Tuft SJ, Hassan H, George S, Frazer DG, Willoughby CE, Liskova P. Keratoconus in 18 pairs of twins. Acta Ophthalmol. 2012;90:482–6.CrossRef Tuft SJ, Hassan H, George S, Frazer DG, Willoughby CE, Liskova P. Keratoconus in 18 pairs of twins. Acta Ophthalmol. 2012;90:482–6.CrossRef
116.
go back to reference Davidson AE, Borasio E, Liskova P, Khan AO, Hassan H, Cheetham ME, et al. Brittle cornea syndrome ZNF469 mutation carrier phenotype and segregation analysis of rare ZNF469 variants in familial keratoconus. Invest Ophthalmol Vis Sci. 2015;56:578–86.PubMedCrossRef Davidson AE, Borasio E, Liskova P, Khan AO, Hassan H, Cheetham ME, et al. Brittle cornea syndrome ZNF469 mutation carrier phenotype and segregation analysis of rare ZNF469 variants in familial keratoconus. Invest Ophthalmol Vis Sci. 2015;56:578–86.PubMedCrossRef
117.
go back to reference Burdon KP, Coster DJ, Charlesworth JC, Mills RA, Laurie KJ, Giunta C, et al. Apparent autosomal dominant keratoconus in a large Australian pedigree accounted for by digenic inheritance of two novel loci. Hum Genet. 2008;124(4):379–86.PubMedCrossRef Burdon KP, Coster DJ, Charlesworth JC, Mills RA, Laurie KJ, Giunta C, et al. Apparent autosomal dominant keratoconus in a large Australian pedigree accounted for by digenic inheritance of two novel loci. Hum Genet. 2008;124(4):379–86.PubMedCrossRef
118.
go back to reference Tyynismaa H, Sistonen P, Tuupanen S, Tervo T, Dammert A, Latvala T, et al. A locus for autosomal dominant keratoconus: linkage to 16q22.3-q23.1 in Finnish families. Investig Ophthalmol Vis Sci. 2002;43(10):3160–4. Tyynismaa H, Sistonen P, Tuupanen S, Tervo T, Dammert A, Latvala T, et al. A locus for autosomal dominant keratoconus: linkage to 16q22.3-q23.1 in Finnish families. Investig Ophthalmol Vis Sci. 2002;43(10):3160–4.
119.
go back to reference Hughes AE, Dash DP, Jackson AJ, Frazer DG, Silvestri G. Familial keratoconus with cataract: linkage to the long arm of chromosome 15 and exclusion of candidate genes. Investig Opthalmol Vis Sci. 2003;44(12):5063–6.CrossRef Hughes AE, Dash DP, Jackson AJ, Frazer DG, Silvestri G. Familial keratoconus with cataract: linkage to the long arm of chromosome 15 and exclusion of candidate genes. Investig Opthalmol Vis Sci. 2003;44(12):5063–6.CrossRef
120.
go back to reference Synowiec E, Wójcik KA, et al. Lack of association between polymorphisms of the DNA base excision repair genes MUTYH and hOGG1 and keratoconus in a Polish subpopulation. Arch Med Sci. 2015;11(5):1101–10. Synowiec E, Wójcik KA, et al. Lack of association between polymorphisms of the DNA base excision repair genes MUTYH and hOGG1 and keratoconus in a Polish subpopulation. Arch Med Sci. 2015;11(5):1101–10.
121.
go back to reference Bisceglia L, Bonis PD, Pizzicoli C, Fischetti L, Laborante A, Perna MD, et al. Linkage analysis in keratoconus: replication of locus 5q21.2 and identification of other suggestive loci. Investig Opthalmol Vis Sci. 2009;50(3):1081–6.CrossRef Bisceglia L, Bonis PD, Pizzicoli C, Fischetti L, Laborante A, Perna MD, et al. Linkage analysis in keratoconus: replication of locus 5q21.2 and identification of other suggestive loci. Investig Opthalmol Vis Sci. 2009;50(3):1081–6.CrossRef
122.
123.
go back to reference Falls HF, Allen AW. Dominantly inherited keratoconus: report of a family. J Hum Genet. 1969;17:317–24. Falls HF, Allen AW. Dominantly inherited keratoconus: report of a family. J Hum Genet. 1969;17:317–24.
124.
go back to reference Edwards M, Mcghee CN, Dean S. The genetics of keratoconus. Clin Exp Ophthalmol. 2001;29(6):345–51.PubMedCrossRef Edwards M, Mcghee CN, Dean S. The genetics of keratoconus. Clin Exp Ophthalmol. 2001;29(6):345–51.PubMedCrossRef
125.
go back to reference Wang Y, Rabinowitz Y, Rotter JHY. Genetic epidemiological study of keratoconus: evidence for major gene determination. Am J Med Genet. 2000;93(5):403–9.PubMedCrossRef Wang Y, Rabinowitz Y, Rotter JHY. Genetic epidemiological study of keratoconus: evidence for major gene determination. Am J Med Genet. 2000;93(5):403–9.PubMedCrossRef
126.
go back to reference Forstot SL, Goldstein JH, Damiano RE, Dukes DK. Familial keratoconus. Am J Ophthalmol. 1988;105(1):92–3.PubMedCrossRef Forstot SL, Goldstein JH, Damiano RE, Dukes DK. Familial keratoconus. Am J Ophthalmol. 1988;105(1):92–3.PubMedCrossRef
127.
go back to reference Elder M. Leber congenital amaurosis and its association with keratoconus and keratoglobus. J Pediatr Ophthalmol Strabismus. 1994;31(1):38–40.PubMedCrossRef Elder M. Leber congenital amaurosis and its association with keratoconus and keratoglobus. J Pediatr Ophthalmol Strabismus. 1994;31(1):38–40.PubMedCrossRef
129.
go back to reference Arbab M, Tahir S, et al. TNF-α genetic predisposition and higher expression of inflammatory pathway components in keratoconus. Investig Ophthalmol Vis Sci. 2017;58(9):3481–7.CrossRef Arbab M, Tahir S, et al. TNF-α genetic predisposition and higher expression of inflammatory pathway components in keratoconus. Investig Ophthalmol Vis Sci. 2017;58(9):3481–7.CrossRef
130.
go back to reference Karimian F, Aramesh S, Rabei HM, Javadi MA, Rafati N. Topographic evaluation of relatives of patients with keratoconus. Cornea. 2008;27(8):874–8.PubMedCrossRef Karimian F, Aramesh S, Rabei HM, Javadi MA, Rafati N. Topographic evaluation of relatives of patients with keratoconus. Cornea. 2008;27(8):874–8.PubMedCrossRef
131.
go back to reference Buehren J, Kook D, Yoon G, Kohnen T. Detection of subclinical keratoconus by using corneal anterior and posterior surface aberrations and thickness spatial profiles. Investig Ophthalmol Vis Sci. 2010;51(7):3424–32.CrossRef Buehren J, Kook D, Yoon G, Kohnen T. Detection of subclinical keratoconus by using corneal anterior and posterior surface aberrations and thickness spatial profiles. Investig Ophthalmol Vis Sci. 2010;51(7):3424–32.CrossRef
132.
go back to reference Cullen JF, Butler HG. Mongolism (Downs syndrome) and keratoconus. Br J Ophthalmol. 1963;47(6):321–30.CrossRef Cullen JF, Butler HG. Mongolism (Downs syndrome) and keratoconus. Br J Ophthalmol. 1963;47(6):321–30.CrossRef
133.
go back to reference Bechara SJ, Waring GO, Insler MS. Keratoconus in two pairs of identical twins. Cornea. 1996;15(1):90–3.PubMedCrossRef Bechara SJ, Waring GO, Insler MS. Keratoconus in two pairs of identical twins. Cornea. 1996;15(1):90–3.PubMedCrossRef
134.
go back to reference Mcmahon TT, Shin JA, Newlin A, Edrington TB, Sugar J, Zadnik K. Discordance for keratoconus in two pairs of monozygotic twins. Cornea. 1999;18(4):444–51.PubMedCrossRef Mcmahon TT, Shin JA, Newlin A, Edrington TB, Sugar J, Zadnik K. Discordance for keratoconus in two pairs of monozygotic twins. Cornea. 1999;18(4):444–51.PubMedCrossRef
135.
go back to reference Parker J, Ko WW, Pavlopoulos G, Wolfe PJ, Rabinowitz YS, Feldman ST. Videokeratography of keratoconus in monozygotic twins. J Refract Surg. 1996;12(1):180–3.PubMedCrossRef Parker J, Ko WW, Pavlopoulos G, Wolfe PJ, Rabinowitz YS, Feldman ST. Videokeratography of keratoconus in monozygotic twins. J Refract Surg. 1996;12(1):180–3.PubMedCrossRef
136.
go back to reference Han S, Chen P, Fan Q, Khor C-C, Sim X, Tay W-T, et al. Association of variants in FRAP1 and PDGFRA with corneal curvature in Asian populations from Singapore. Hum Mol Genet. 2011;20(18):3693–8.PubMedCrossRef Han S, Chen P, Fan Q, Khor C-C, Sim X, Tay W-T, et al. Association of variants in FRAP1 and PDGFRA with corneal curvature in Asian populations from Singapore. Hum Mol Genet. 2011;20(18):3693–8.PubMedCrossRef
137.
go back to reference Klein AP. Heritability analysis of spherical equivalent, axial length, corneal curvature, and anterior chamber depth in the Beaver Dam Eye Study. Arch Ophthalmol. 2009;127(5):649–55.PubMedPubMedCentralCrossRef Klein AP. Heritability analysis of spherical equivalent, axial length, corneal curvature, and anterior chamber depth in the Beaver Dam Eye Study. Arch Ophthalmol. 2009;127(5):649–55.PubMedPubMedCentralCrossRef
138.
go back to reference Biino G, Palmas MA, Corona C, Prodi D, Fanciulli M, Sulis R, et al. Ocular refraction: heritability and genome-wide search for eye morphometry traits in an isolated Sardinian population. Hum Genet. 2004;116(3):152–9.PubMedCrossRef Biino G, Palmas MA, Corona C, Prodi D, Fanciulli M, Sulis R, et al. Ocular refraction: heritability and genome-wide search for eye morphometry traits in an isolated Sardinian population. Hum Genet. 2004;116(3):152–9.PubMedCrossRef
139.
go back to reference Hammond CJ, Duncan DD, Snieder H, de Lange M, West SK, Spector TD, et al. The heritability of age-related cortical cataract: the twin eye study. Investig Ophthalmol Vis Sci. 2001;42(3):601–5. Hammond CJ, Duncan DD, Snieder H, de Lange M, West SK, Spector TD, et al. The heritability of age-related cortical cataract: the twin eye study. Investig Ophthalmol Vis Sci. 2001;42(3):601–5.
140.
go back to reference Lyhne N. The importance of genes and environment for ocular refraction and its determiners: a population based study among 20–45 year old twins. Br J Ophthalmol. 2001;85(12):1470–6.PubMedPubMedCentralCrossRef Lyhne N. The importance of genes and environment for ocular refraction and its determiners: a population based study among 20–45 year old twins. Br J Ophthalmol. 2001;85(12):1470–6.PubMedPubMedCentralCrossRef
141.
go back to reference Lim LS, Saw S-M, Jeganathan VSE, Tay WT, Aung T, Tong L, et al. Distribution and determinants of ocular biometric parameters in an Asian population: the Singapore Malay eye study. Investig Opthalmol Vis Sci. 2010;51(1):103–9.CrossRef Lim LS, Saw S-M, Jeganathan VSE, Tay WT, Aung T, Tong L, et al. Distribution and determinants of ocular biometric parameters in an Asian population: the Singapore Malay eye study. Investig Opthalmol Vis Sci. 2010;51(1):103–9.CrossRef
142.
go back to reference Ip JM, Huynh SC, Robaei D, Kifley A, Rose KA, Morgan IG, et al. Ethnic differences in refraction and ocular biometry in a population-based sample of 11–15-year-old Australian children. Eye. 2007;22(5):649–56.PubMedCrossRef Ip JM, Huynh SC, Robaei D, Kifley A, Rose KA, Morgan IG, et al. Ethnic differences in refraction and ocular biometry in a population-based sample of 11–15-year-old Australian children. Eye. 2007;22(5):649–56.PubMedCrossRef
143.
144.
go back to reference Yuen LH, He M, Aung T, Htoon HM, Tan DT, Mehta JS. Biometry of the cornea and anterior chamber in Chinese eyes: an anterior segment optical coherence tomography study. Investig Opthalmol Vis Sci. 2010;51(7):3433–40.CrossRef Yuen LH, He M, Aung T, Htoon HM, Tan DT, Mehta JS. Biometry of the cornea and anterior chamber in Chinese eyes: an anterior segment optical coherence tomography study. Investig Opthalmol Vis Sci. 2010;51(7):3433–40.CrossRef
145.
go back to reference Saw S-M, Carkeet A, Chia K-S, Stone RA, Tan DT. Component dependent risk factors for ocular parameters in Singapore Chinese children. Ophthalmology. 2002;109(11):2065–71.PubMedCrossRef Saw S-M, Carkeet A, Chia K-S, Stone RA, Tan DT. Component dependent risk factors for ocular parameters in Singapore Chinese children. Ophthalmology. 2002;109(11):2065–71.PubMedCrossRef
146.
go back to reference Wong TY, Klein R, Klein BE, Tomany SC. Refractive errors and 10-year incidence of age-related maculopathy. Investig Ophthalmol Vis Sci. 2002;43(9):2869–73. Wong TY, Klein R, Klein BE, Tomany SC. Refractive errors and 10-year incidence of age-related maculopathy. Investig Ophthalmol Vis Sci. 2002;43(9):2869–73.
147.
go back to reference Udar N, Atilano SR, Small K, Nesburn AB, Kenney MC. SOD1 haplotypes in familial keratoconus. Cornea. 2009;28(8):902–7.PubMedCrossRef Udar N, Atilano SR, Small K, Nesburn AB, Kenney MC. SOD1 haplotypes in familial keratoconus. Cornea. 2009;28(8):902–7.PubMedCrossRef
148.
go back to reference Gajecka M, Radhakrishna U, Winters D, Nath SK, Rydzanicz M, Ratnamala U, et al. Localization of a gene for keratoconus to a 5.6-Mb interval on 13q32. Investig Opthalmol Vis Sci. 2009;50(4):1531–9.CrossRef Gajecka M, Radhakrishna U, Winters D, Nath SK, Rydzanicz M, Ratnamala U, et al. Localization of a gene for keratoconus to a 5.6-Mb interval on 13q32. Investig Opthalmol Vis Sci. 2009;50(4):1531–9.CrossRef
150.
go back to reference De Bonis P, Laborante A, Pizzicoli C, et al. Mutational screening of VSX1, SPARC, SOD1, LOX, and TIMP3 in keratoconus. Mol Vis. 2011;17:2482–94.PubMedPubMedCentral De Bonis P, Laborante A, Pizzicoli C, et al. Mutational screening of VSX1, SPARC, SOD1, LOX, and TIMP3 in keratoconus. Mol Vis. 2011;17:2482–94.PubMedPubMedCentral
151.
go back to reference Ambekar R, Toussaint KC Jr, Johnson AW. The effect of keratoconus on the structural, mechanical, and optical properties of the cornea. J Mech Behav Biomed Mater. 2011;4(3):223–36.PubMedCrossRef Ambekar R, Toussaint KC Jr, Johnson AW. The effect of keratoconus on the structural, mechanical, and optical properties of the cornea. J Mech Behav Biomed Mater. 2011;4(3):223–36.PubMedCrossRef
152.
go back to reference Saee-Rad S, Raoofian R, Mahbod M, et al. Analysis of superoxide dismutase 1, dual-specificity phosphatase 1, and transforming growth factor, beta 1 genes expression in keratoconic and non-keratoconic corneas. Mol Vis. 2013;19:2501–7.PubMedPubMedCentral Saee-Rad S, Raoofian R, Mahbod M, et al. Analysis of superoxide dismutase 1, dual-specificity phosphatase 1, and transforming growth factor, beta 1 genes expression in keratoconic and non-keratoconic corneas. Mol Vis. 2013;19:2501–7.PubMedPubMedCentral
153.
go back to reference Paliwal P, Singh A, Tandon R, Titiyal JS, Sharma A. A novel VSX1 mutation identified in an individual with keratoconus in India. Mol Vis. 2009;15:2475–9.PubMedPubMedCentral Paliwal P, Singh A, Tandon R, Titiyal JS, Sharma A. A novel VSX1 mutation identified in an individual with keratoconus in India. Mol Vis. 2009;15:2475–9.PubMedPubMedCentral
154.
go back to reference Arnal E, Peris-Martínez C, Menezo JL, Johnsen-Soriano S, Romero FJ. Oxidative stress in keratoconus? Investig Opthalmol Vis Sci. 2011;52(12):8592–7.CrossRef Arnal E, Peris-Martínez C, Menezo JL, Johnsen-Soriano S, Romero FJ. Oxidative stress in keratoconus? Investig Opthalmol Vis Sci. 2011;52(12):8592–7.CrossRef
155.
go back to reference Cremona FA, Ghosheh FR, Rapuano CJ, Eagle RC, Hammersmith KM, Laibson PR, et al. Keratoconus associated with other corneal dystrophies. Cornea. 2009;28(2):127–35.PubMedCrossRef Cremona FA, Ghosheh FR, Rapuano CJ, Eagle RC, Hammersmith KM, Laibson PR, et al. Keratoconus associated with other corneal dystrophies. Cornea. 2009;28(2):127–35.PubMedCrossRef
156.
go back to reference Mcmonnies CW. Mechanisms of rubbing-related corneal trauma in keratoconus. Cornea. 2009;28(6):607–15.PubMedCrossRef Mcmonnies CW. Mechanisms of rubbing-related corneal trauma in keratoconus. Cornea. 2009;28(6):607–15.PubMedCrossRef
157.
go back to reference Lindsay RG, Bruce AS, Gutteridge IF. Keratoconus associated with continual eye rubbing due to punctal agenesis. Cornea. 2000;19(4):567–9.PubMedCrossRef Lindsay RG, Bruce AS, Gutteridge IF. Keratoconus associated with continual eye rubbing due to punctal agenesis. Cornea. 2000;19(4):567–9.PubMedCrossRef
158.
go back to reference Goldich Y, Marcovich AL, Barkana Y, Mandel Y, Hirsh A, Morad Y, et al. Clinical and corneal biomechanical changes after collagen cross-linking with riboflavin and UV irradiation in patients with progressive keratoconus. Cornea. 2012;31(6):609–14.PubMedCrossRef Goldich Y, Marcovich AL, Barkana Y, Mandel Y, Hirsh A, Morad Y, et al. Clinical and corneal biomechanical changes after collagen cross-linking with riboflavin and UV irradiation in patients with progressive keratoconus. Cornea. 2012;31(6):609–14.PubMedCrossRef
159.
go back to reference Jafri B, Lichter H, Stulting RD. Asymmetric keratoconus attributed to eye rubbing. Cornea. 2004;23(6):560–4.PubMedCrossRef Jafri B, Lichter H, Stulting RD. Asymmetric keratoconus attributed to eye rubbing. Cornea. 2004;23(6):560–4.PubMedCrossRef
160.
go back to reference Barr JT, Wilson BS, Gordon MO, Rah MJ, Riley C, Kollbaum PS, et al. Estimation of the incidence and factors predictive of corneal scarring in the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) study. Cornea. 2006;25(1):16–25.PubMedCrossRef Barr JT, Wilson BS, Gordon MO, Rah MJ, Riley C, Kollbaum PS, et al. Estimation of the incidence and factors predictive of corneal scarring in the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) study. Cornea. 2006;25(1):16–25.PubMedCrossRef
161.
go back to reference Grünauer-Kloevekorn C, Duncker GI. Keratoconus: epidemiology, risk factors and diagnosis. Klin Monabl Augenheilkd. 2006;223(6):493–502.CrossRef Grünauer-Kloevekorn C, Duncker GI. Keratoconus: epidemiology, risk factors and diagnosis. Klin Monabl Augenheilkd. 2006;223(6):493–502.CrossRef
162.
go back to reference Francois M, Chassaing N, Calvas P. Chapter 2: Genetics of keratoconus. In: Barbara A, editor. Textbook on keratoconus: new insights. New Delhi: Jaypee Brothers Medical Publishers Pvt.; 2012. p. 12–17. Francois M, Chassaing N, Calvas P. Chapter 2: Genetics of keratoconus. In: Barbara A, editor. Textbook on keratoconus: new insights. New Delhi: Jaypee Brothers Medical Publishers Pvt.; 2012. p. 12–17.
163.
go back to reference Cosar CB, Sridhar MS, Cohen EJ, Held EL, Alvim Pde T, Rapuano CJ, et al. Indications for penetrating keratoplasty and associated procedures, 1996–2000. Cornea. 2002;21(2):148–51.PubMedCrossRef Cosar CB, Sridhar MS, Cohen EJ, Held EL, Alvim Pde T, Rapuano CJ, et al. Indications for penetrating keratoplasty and associated procedures, 1996–2000. Cornea. 2002;21(2):148–51.PubMedCrossRef
164.
go back to reference Bareja U, Vajpayee RB. Posterior keratoconus due to iron nail injury—a case report. Indian J Ophthalmol. 1991;39(1):30. Bareja U, Vajpayee RB. Posterior keratoconus due to iron nail injury—a case report. Indian J Ophthalmol. 1991;39(1):30.
165.
go back to reference Sharma R, Titiyal JS, Prakash G, Sharma N, Tandon R, Vajpayee RB. Clinical profile and risk factors for keratoplasty and development of hydrops in North Indian patients with keratoconus. Cornea. 2009;28(4):367–70.PubMedCrossRef Sharma R, Titiyal JS, Prakash G, Sharma N, Tandon R, Vajpayee RB. Clinical profile and risk factors for keratoplasty and development of hydrops in North Indian patients with keratoconus. Cornea. 2009;28(4):367–70.PubMedCrossRef
166.
go back to reference Heon E. VSX1: a gene for posterior polymorphous dystrophy and keratoconus. Hum Mol Genet. 2002;11(9):1029–36.PubMedCrossRef Heon E. VSX1: a gene for posterior polymorphous dystrophy and keratoconus. Hum Mol Genet. 2002;11(9):1029–36.PubMedCrossRef
167.
go back to reference McGhee CN. 2008 Sir Norman McAlister Gregg Lecture: 150 years of practical observations on the conical cornea—what have we learned? Clin Exp Ophthalmol. 2009;37(2):160–76. McGhee CN. 2008 Sir Norman McAlister Gregg Lecture: 150 years of practical observations on the conical cornea—what have we learned? Clin Exp Ophthalmol. 2009;37(2):160–76.
168.
go back to reference Shapiro MB, France TD. The ocular features of Down’s syndrome. Am J Ophthalmol. 1985;99:659–63.PubMedCrossRef Shapiro MB, France TD. The ocular features of Down’s syndrome. Am J Ophthalmol. 1985;99:659–63.PubMedCrossRef
169.
go back to reference Austin MG, Schaefer RF. Marfan’s syndrome, with unusual blood vessel manifestations. AMA Arch Pathol. 1957;64:205–9.PubMed Austin MG, Schaefer RF. Marfan’s syndrome, with unusual blood vessel manifestations. AMA Arch Pathol. 1957;64:205–9.PubMed
170.
go back to reference Beckh U, Schonherr U, Naumann GO. Autosomal dominant keratoconus as the chief ocular symptom in Lobstein osteogenesis imperfecta tarda (in German). Klin Monbl Augenheilkd. 1995;206(04):268–72.PubMedCrossRef Beckh U, Schonherr U, Naumann GO. Autosomal dominant keratoconus as the chief ocular symptom in Lobstein osteogenesis imperfecta tarda (in German). Klin Monbl Augenheilkd. 1995;206(04):268–72.PubMedCrossRef
171.
go back to reference Wajntal A, Koiffmann CP, Mendonça BB, Epps-Quaglia D, Sotto MN, Rati PBM, et al. GAPO syndrome (McKusick 23074)—a connective tissue disorder: report on two affected sibs and on the pathologic findings in the older. Am J Med Genet. 1990;37(2):213–23.PubMedCrossRef Wajntal A, Koiffmann CP, Mendonça BB, Epps-Quaglia D, Sotto MN, Rati PBM, et al. GAPO syndrome (McKusick 23074)—a connective tissue disorder: report on two affected sibs and on the pathologic findings in the older. Am J Med Genet. 1990;37(2):213–23.PubMedCrossRef
172.
go back to reference Kuming BS, Joffe L. Ehlers–Danlos syndrome associated with keratoconus: a case report. S Afr Med J. 1977;52(10):403–5.PubMed Kuming BS, Joffe L. Ehlers–Danlos syndrome associated with keratoconus: a case report. S Afr Med J. 1977;52(10):403–5.PubMed
173.
go back to reference Robertson I. Keratoconus and the Ehlers–Danlos syndrome: a new aspect of keratoconus. Med J Aust. 1975;1:571–3.PubMedCrossRef Robertson I. Keratoconus and the Ehlers–Danlos syndrome: a new aspect of keratoconus. Med J Aust. 1975;1:571–3.PubMedCrossRef
174.
go back to reference Freedman J, Gombos GM. Bilateral macular coloboma, keratoconus, and retinitis pigmentosa. Ann Ophthalmol. 1971;3:664–5.PubMed Freedman J, Gombos GM. Bilateral macular coloboma, keratoconus, and retinitis pigmentosa. Ann Ophthalmol. 1971;3:664–5.PubMed
175.
go back to reference McMahon TT, Kim LS, Fishman GA, Stone EM, Zhao XC, Yee RW, et al. CRB1 gene mutations are associated with keratoconus in patients with Leber congenital amaurosis. Investig Ophthalmol Vis Sci. 2009;50:3185–7.CrossRef McMahon TT, Kim LS, Fishman GA, Stone EM, Zhao XC, Yee RW, et al. CRB1 gene mutations are associated with keratoconus in patients with Leber congenital amaurosis. Investig Ophthalmol Vis Sci. 2009;50:3185–7.CrossRef
176.
go back to reference Totan Y, Hep B, Cekic O, Gündüz A, Aydin E. Incidence of keratoconus in subjects with vernal keratoconjunctivitis: a videokeratographic study. Ophthalmology. 2001;108:824–7.PubMedCrossRef Totan Y, Hep B, Cekic O, Gündüz A, Aydin E. Incidence of keratoconus in subjects with vernal keratoconjunctivitis: a videokeratographic study. Ophthalmology. 2001;108:824–7.PubMedCrossRef
177.
go back to reference Stoiber J, Muss WH, Ruckhofer J, Thaller-Antlanger H, Alzner E, Grabner G. Recurrent keratoconus in a patient with Leber congenital amaurosis. Cornea. 2000;19(3):395–8.PubMedCrossRef Stoiber J, Muss WH, Ruckhofer J, Thaller-Antlanger H, Alzner E, Grabner G. Recurrent keratoconus in a patient with Leber congenital amaurosis. Cornea. 2000;19(3):395–8.PubMedCrossRef
178.
go back to reference Dharmaraj S. The phenotype of Leber congenital amaurosis in patients with AIPL1 mutations. Arch Ophthalmol. 2004;122(7):1029–37.PubMedCrossRef Dharmaraj S. The phenotype of Leber congenital amaurosis in patients with AIPL1 mutations. Arch Ophthalmol. 2004;122(7):1029–37.PubMedCrossRef
179.
go back to reference Wollensak G, Green WR, Temprano J. Keratoconus associated with corneal granular dystrophy in a patient of Italian origin. Cornea. 2002;21(1):121–2.PubMedCrossRef Wollensak G, Green WR, Temprano J. Keratoconus associated with corneal granular dystrophy in a patient of Italian origin. Cornea. 2002;21(1):121–2.PubMedCrossRef
181.
go back to reference Nucci P, Brancato R. Keratoconus and congenital hip dysplasia. Am J Ophthalmol. 1991;111(6):775–6.PubMedCrossRef Nucci P, Brancato R. Keratoconus and congenital hip dysplasia. Am J Ophthalmol. 1991;111(6):775–6.PubMedCrossRef
182.
go back to reference Greenfield G, Stein R, Romano A, Goodman RM. Blue sclerae and keratoconus: key features of a distinct heritable disorder of connective tissue. Clin Genet. 1973;4:8–16.PubMedCrossRef Greenfield G, Stein R, Romano A, Goodman RM. Blue sclerae and keratoconus: key features of a distinct heritable disorder of connective tissue. Clin Genet. 1973;4:8–16.PubMedCrossRef
183.
go back to reference Zala L, Ettlin C, Krebs A. Focal dermal hypoplasia with keratoconus, papillomatosis of esophagus and hidrocystomas (author’s transl). Dermatologica. 1975;150(3):176–85.PubMedCrossRef Zala L, Ettlin C, Krebs A. Focal dermal hypoplasia with keratoconus, papillomatosis of esophagus and hidrocystomas (author’s transl). Dermatologica. 1975;150(3):176–85.PubMedCrossRef
184.
185.
go back to reference Lee WJ, Kim JC, Shyn KH. Clinical evaluation of corneal diseases associated with floppy eyelid syndrome. Korean J Ophthalmol. 1996;10(2):116–21.PubMedCrossRef Lee WJ, Kim JC, Shyn KH. Clinical evaluation of corneal diseases associated with floppy eyelid syndrome. Korean J Ophthalmol. 1996;10(2):116–21.PubMedCrossRef
186.
go back to reference Stabuc-Silih M, Strazisar M, Hawlina M, et al. Absence of pathogenic mutations in VSX1 and SOD1 genes in patients with keratoconus. Cornea. 2010;29(2):172–6.PubMedCrossRef Stabuc-Silih M, Strazisar M, Hawlina M, et al. Absence of pathogenic mutations in VSX1 and SOD1 genes in patients with keratoconus. Cornea. 2010;29(2):172–6.PubMedCrossRef
187.
go back to reference Abu-Amero KK, Hellani AM, Al Mansouri SM, Kalantan H, Al Muammar A-M. High-resolution analysis of DNA copy number alterations in patients with isolated sporadic keratoconus. Mol Vis. 2011;17:822–6.PubMedPubMedCentral Abu-Amero KK, Hellani AM, Al Mansouri SM, Kalantan H, Al Muammar A-M. High-resolution analysis of DNA copy number alterations in patients with isolated sporadic keratoconus. Mol Vis. 2011;17:822–6.PubMedPubMedCentral
188.
go back to reference Bisceglia L, Ciaschetti M, Bonis PD, Campo PAP, Pizzicoli C, Scala C, et al. VSX1 mutational analysis in a series of Italian patients affected by keratoconus: detection of a novel mutation. Investig Opthalmol Vis Sci. 2005;46(1):39–45.CrossRef Bisceglia L, Ciaschetti M, Bonis PD, Campo PAP, Pizzicoli C, Scala C, et al. VSX1 mutational analysis in a series of Italian patients affected by keratoconus: detection of a novel mutation. Investig Opthalmol Vis Sci. 2005;46(1):39–45.CrossRef
189.
go back to reference Burmeister M, Novak J, Liang M-Y, Basu S, Ploder L, Hawes NL, et al. Ocular retardation mouse caused by Chx10 homeobox null allele: impaired retinal progenitor proliferation and bipolar cell differentiation. Nat Genet. 1996;12(4):376–84.PubMedCrossRef Burmeister M, Novak J, Liang M-Y, Basu S, Ploder L, Hawes NL, et al. Ocular retardation mouse caused by Chx10 homeobox null allele: impaired retinal progenitor proliferation and bipolar cell differentiation. Nat Genet. 1996;12(4):376–84.PubMedCrossRef
190.
go back to reference Chow RL, Snow B, Novak J, Looser J, Freund C, Vidgen D, et al. Vsx1, a rapidly evolving paired-like homeobox gene expressed in cone bipolar cells. Mech Dev. 2001;109(2):315–22.PubMedCrossRef Chow RL, Snow B, Novak J, Looser J, Freund C, Vidgen D, et al. Vsx1, a rapidly evolving paired-like homeobox gene expressed in cone bipolar cells. Mech Dev. 2001;109(2):315–22.PubMedCrossRef
191.
go back to reference Sherwin JC, Hewitt AW, Ruddle JB, Mackey DA. Genetic isolates in ophthalmic diseases. Ophthalmic Genet. 2008;29(4):149–61.PubMedCrossRef Sherwin JC, Hewitt AW, Ruddle JB, Mackey DA. Genetic isolates in ophthalmic diseases. Ophthalmic Genet. 2008;29(4):149–61.PubMedCrossRef
194.
go back to reference Fullerton J, Paprocki P, Foote S, Mackey DA, Williamson R, Forrest S. Identity-by-descent approach to gene localisation in eight individuals affected by keratoconus from north-west Tasmania, Australia. Hum Genet. 2002;110(5):462–70.PubMedCrossRef Fullerton J, Paprocki P, Foote S, Mackey DA, Williamson R, Forrest S. Identity-by-descent approach to gene localisation in eight individuals affected by keratoconus from north-west Tasmania, Australia. Hum Genet. 2002;110(5):462–70.PubMedCrossRef
195.
go back to reference Tang YG, Rabinowitz YS, Taylor KD, Li X, Hu M, Picornell Y, et al. Genomewide linkage scan in a multigeneration Caucasian pedigree identifies a novel locus for keratoconus on chromosome 5q14.3-q21.1. Genet Med. 2005;7(6):397–405.PubMedCrossRef Tang YG, Rabinowitz YS, Taylor KD, Li X, Hu M, Picornell Y, et al. Genomewide linkage scan in a multigeneration Caucasian pedigree identifies a novel locus for keratoconus on chromosome 5q14.3-q21.1. Genet Med. 2005;7(6):397–405.PubMedCrossRef
196.
go back to reference Li X, Rabinowitz YS, Tang YG, Picornell Y, Taylor KD, Hu M, et al. Two-stage genome-wide linkage scan in keratoconus sib pair families. Investig Opthalmol Vis Sci. 2006;47(9):3791–5.CrossRef Li X, Rabinowitz YS, Tang YG, Picornell Y, Taylor KD, Hu M, et al. Two-stage genome-wide linkage scan in keratoconus sib pair families. Investig Opthalmol Vis Sci. 2006;47(9):3791–5.CrossRef
197.
go back to reference Nielsen K, Heegaard S, Vorum H, Birkenkamp-Demtröder K, Ehlers N, Orntoft TF. Altered expression of CLC, DSG3, EMP3, S100A2, and SLPI in corneal epithelium from keratoconus patients. Cornea. 2005;24(6):661–8.PubMedCrossRef Nielsen K, Heegaard S, Vorum H, Birkenkamp-Demtröder K, Ehlers N, Orntoft TF. Altered expression of CLC, DSG3, EMP3, S100A2, and SLPI in corneal epithelium from keratoconus patients. Cornea. 2005;24(6):661–8.PubMedCrossRef
198.
go back to reference Nielsen K, Vorum H, Fagerholm P, Birkenkamp-Demtröder K, Honoré B, Ehlers N, et al. Proteome profiling of corneal epithelium and identification of marker proteins for keratoconus, a pilot study. Exp Eye Res. 2006;82(2):201–9.PubMedCrossRef Nielsen K, Vorum H, Fagerholm P, Birkenkamp-Demtröder K, Honoré B, Ehlers N, et al. Proteome profiling of corneal epithelium and identification of marker proteins for keratoconus, a pilot study. Exp Eye Res. 2006;82(2):201–9.PubMedCrossRef
199.
go back to reference Nielsen K, Birkenkamp-Demtröder K, Ehlers N, Orntoft TF. Identification of differentially expressed genes in keratoconus epithelium analyzed on microarrays. Investig Opthalmol Vis Sci. 2003;44(6):2466–76.CrossRef Nielsen K, Birkenkamp-Demtröder K, Ehlers N, Orntoft TF. Identification of differentially expressed genes in keratoconus epithelium analyzed on microarrays. Investig Opthalmol Vis Sci. 2003;44(6):2466–76.CrossRef
200.
go back to reference Ha NT, Nakayasu K, Murakami A, Ishidoh K, Kanai A. Microarray analysis identified differentially expressed genes in keratocytes from keratoconus patients. Curr Eye Res. 2004;28(6):373–9.PubMedCrossRef Ha NT, Nakayasu K, Murakami A, Ishidoh K, Kanai A. Microarray analysis identified differentially expressed genes in keratocytes from keratoconus patients. Curr Eye Res. 2004;28(6):373–9.PubMedCrossRef
201.
go back to reference Lu Y, Vitart V, Burdon KP, Khor CC, Bykhovskaya Y, Mirshahi A, et al. Genome-wide association analyses identify multiple loci associated with central corneal thickness and keratoconus. Nat Genet. 2013;45(2):155–63.PubMedPubMedCentralCrossRef Lu Y, Vitart V, Burdon KP, Khor CC, Bykhovskaya Y, Mirshahi A, et al. Genome-wide association analyses identify multiple loci associated with central corneal thickness and keratoconus. Nat Genet. 2013;45(2):155–63.PubMedPubMedCentralCrossRef
202.
go back to reference Hamilton JB. The significance of heredity in ophthalmology. Preliminary survey of hereditary eye diseases in Tasmania. Br J Ophthalmol. 1938;2:83–108.CrossRef Hamilton JB. The significance of heredity in ophthalmology. Preliminary survey of hereditary eye diseases in Tasmania. Br J Ophthalmol. 1938;2:83–108.CrossRef
203.
go back to reference Vincent AL, Jordan CA, Cadzow MJ, Merriman TR, Mcghee CN. Mutations in the zinc finger protein gene, ZNF469, contribute to the pathogenesis of keratoconus. Investig Opthalmol Vis Sci. 2014;55(9):5629–35.CrossRef Vincent AL, Jordan CA, Cadzow MJ, Merriman TR, Mcghee CN. Mutations in the zinc finger protein gene, ZNF469, contribute to the pathogenesis of keratoconus. Investig Opthalmol Vis Sci. 2014;55(9):5629–35.CrossRef
204.
205.
go back to reference Vitart V, Benčić G, Hayward C, Herman JŠ, Huffman J, Campbell S, et al. New loci associated with central cornea thickness include COL5A1, AKAP13 and AVGR8. Hum Mol Genet. 2010;19(21):4304–11.PubMedCrossRef Vitart V, Benčić G, Hayward C, Herman JŠ, Huffman J, Campbell S, et al. New loci associated with central cornea thickness include COL5A1, AKAP13 and AVGR8. Hum Mol Genet. 2010;19(21):4304–11.PubMedCrossRef
206.
go back to reference Vithana EN, Aung T, Khor CC, Cornes BK, Tay WT, Sim X, et al. Collagen-related genes influence the glaucoma risk factor, central corneal thickness. Hum Mol Genet. 2011;20(4):649–58.PubMedCrossRef Vithana EN, Aung T, Khor CC, Cornes BK, Tay WT, Sim X, et al. Collagen-related genes influence the glaucoma risk factor, central corneal thickness. Hum Mol Genet. 2011;20(4):649–58.PubMedCrossRef
207.
go back to reference Lu Y, Dimasi DP, Hysi PG, Hewitt AW, Burdon KP, Toh T, et al. Common genetic variants near the brittle cornea syndrome locus ZNF469 influence the blinding disease risk factor central corneal thickness. PLoS Genet. 2010;6(5):e1000947.PubMedPubMedCentralCrossRef Lu Y, Dimasi DP, Hysi PG, Hewitt AW, Burdon KP, Toh T, et al. Common genetic variants near the brittle cornea syndrome locus ZNF469 influence the blinding disease risk factor central corneal thickness. PLoS Genet. 2010;6(5):e1000947.PubMedPubMedCentralCrossRef
208.
go back to reference Hoehn R, Zeller T, Verhoeven VJM, Grus F, Adler M, Wolfs RC, et al. Population-based meta-analysis in Caucasians confirms association with COL5A1 and ZNF469 but not COL8A2 with central corneal thickness. Hum Genet. 2012;131(11):1783–93.PubMedCrossRef Hoehn R, Zeller T, Verhoeven VJM, Grus F, Adler M, Wolfs RC, et al. Population-based meta-analysis in Caucasians confirms association with COL5A1 and ZNF469 but not COL8A2 with central corneal thickness. Hum Genet. 2012;131(11):1783–93.PubMedCrossRef
209.
go back to reference Gao X, Gauderman WJ, Liu Y, Marjoram P, Torres M, Haritunians T, et al. A genome-wide association study of central corneal thickness in latinos. Investig Opthalmol Vis Sci. 2013;54(4):2435–43.CrossRef Gao X, Gauderman WJ, Liu Y, Marjoram P, Torres M, Haritunians T, et al. A genome-wide association study of central corneal thickness in latinos. Investig Opthalmol Vis Sci. 2013;54(4):2435–43.CrossRef
210.
go back to reference Abu A, Frydman M, Marek D, Pras E, Nir U, Reznik-Wolf H, et al. Deleterious mutations in the zinc-finger 469 gene cause brittle cornea syndrome. Am J Hum Genet. 2008;82(5):1217–22.PubMedPubMedCentralCrossRef Abu A, Frydman M, Marek D, Pras E, Nir U, Reznik-Wolf H, et al. Deleterious mutations in the zinc-finger 469 gene cause brittle cornea syndrome. Am J Hum Genet. 2008;82(5):1217–22.PubMedPubMedCentralCrossRef
211.
go back to reference Karolak JA, Gambin T, Rydzanicz M, Szaflik JP, Polakowski P, Frajdenberg A, et al. Evidence against ZNF469 being causative for keratoconus in Polish patients. Acta Ophthalmol. 2016;94(3):289–94.PubMedCrossRef Karolak JA, Gambin T, Rydzanicz M, Szaflik JP, Polakowski P, Frajdenberg A, et al. Evidence against ZNF469 being causative for keratoconus in Polish patients. Acta Ophthalmol. 2016;94(3):289–94.PubMedCrossRef
212.
go back to reference Li X, Bykhovskaya Y, Haritunians T, Siscovick D, Aldave A, Szczotka-Flynn L, et al. 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. 2011;21(2):421–9.PubMedPubMedCentralCrossRef Li X, Bykhovskaya Y, Haritunians T, Siscovick D, Aldave A, Szczotka-Flynn L, et al. 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. 2011;21(2):421–9.PubMedPubMedCentralCrossRef
213.
go back to reference Burdon KP, Macgregor S, Bykhovskaya Y, Javadiyan S, Li X, Laurie KJ, et al. Association of polymorphisms in the hepatocyte growth factor gene promoter with keratoconus. Investig Ophthalmol Vis Sci. 2011;52(11):8514–9.CrossRef Burdon KP, Macgregor S, Bykhovskaya Y, Javadiyan S, Li X, Laurie KJ, et al. Association of polymorphisms in the hepatocyte growth factor gene promoter with keratoconus. Investig Ophthalmol Vis Sci. 2011;52(11):8514–9.CrossRef
214.
go back to reference Bykhovskaya Y, Li X, Epifantseva I, Haritunians T, Siscovick D, Aldave A, et al. Variation in the lysyl oxidase (LOX) gene is associated with keratoconus in family-based and case-control studies. Investig Opthalmol Vis Sci. 2012;53(7):4152–7.CrossRef Bykhovskaya Y, Li X, Epifantseva I, Haritunians T, Siscovick D, Aldave A, et al. Variation in the lysyl oxidase (LOX) gene is associated with keratoconus in family-based and case-control studies. Investig Opthalmol Vis Sci. 2012;53(7):4152–7.CrossRef
215.
go back to reference Sahebjada S, Schache M, Richardson AJ, Snibson G, Daniell M, Baird PN. Association of the hepatocyte growth factor gene with keratoconus in an Australian population. PLoS One. 2014;9(1):e84067.PubMedPubMedCentralCrossRef Sahebjada S, Schache M, Richardson AJ, Snibson G, Daniell M, Baird PN. Association of the hepatocyte growth factor gene with keratoconus in an Australian population. PLoS One. 2014;9(1):e84067.PubMedPubMedCentralCrossRef
216.
go back to reference Yang X, Liu X, Peng J, Zheng H, Lu F, Gong B, et al. Evaluation of MYOC, ACAN, HGF, and MET as candidate genes for high myopia in a Han Chinese population. Genet Test Mol Biomark. 2014;18(6):446–52.CrossRef Yang X, Liu X, Peng J, Zheng H, Lu F, Gong B, et al. Evaluation of MYOC, ACAN, HGF, and MET as candidate genes for high myopia in a Han Chinese population. Genet Test Mol Biomark. 2014;18(6):446–52.CrossRef
217.
go back to reference Dudakova L, Palos M, Jirsova K, Stranecky V, Krepelova A, Hysi PG, et al. Validation of rs2956540:G > C and rs3735520:G > A association with keratoconus in a population of European descent. Eur J Hum Genet. 2015;23(11):1581–3.PubMedPubMedCentralCrossRef Dudakova L, Palos M, Jirsova K, Stranecky V, Krepelova A, Hysi PG, et al. Validation of rs2956540:G > C and rs3735520:G > A association with keratoconus in a population of European descent. Eur J Hum Genet. 2015;23(11):1581–3.PubMedPubMedCentralCrossRef
218.
go back to reference Teri M. Genomewide association studies and assessment of the risk of disease. N Engl J Med. 2010;363(2):166–76.CrossRef Teri M. Genomewide association studies and assessment of the risk of disease. N Engl J Med. 2010;363(2):166–76.CrossRef
219.
go back to reference Liskova P, Dudakova L, Krepelova A, Klema J, Hysi PG. Replication of SNP associations with keratoconus in a Czech cohort. Plos One. 2017;12(2):e0172365.PubMedPubMedCentralCrossRef Liskova P, Dudakova L, Krepelova A, Klema J, Hysi PG. Replication of SNP associations with keratoconus in a Czech cohort. Plos One. 2017;12(2):e0172365.PubMedPubMedCentralCrossRef
220.
go back to reference Lechner J, Dash DP, Muszynska D, Hosseini M, Segev F, George S, et al. Mutational spectrum of the ZEB1 gene in corneal dystrophies supports a genotype–phenotype correlation. Investig Opthalmol Vis Sci. 2013;54(5):3215–23.CrossRef Lechner J, Dash DP, Muszynska D, Hosseini M, Segev F, George S, et al. Mutational spectrum of the ZEB1 gene in corneal dystrophies supports a genotype–phenotype correlation. Investig Opthalmol Vis Sci. 2013;54(5):3215–23.CrossRef
221.
go back to reference Bem D, Yoshimura S-I, Nunes-Bastos R, Bond FF, Kurian MA, Rahman F, et al. Loss-of-function mutations in RAB18 cause Warburg Micro syndrome. Am J Hum Genet. 2011;88(4):499–507.PubMedCrossRef Bem D, Yoshimura S-I, Nunes-Bastos R, Bond FF, Kurian MA, Rahman F, et al. Loss-of-function mutations in RAB18 cause Warburg Micro syndrome. Am J Hum Genet. 2011;88(4):499–507.PubMedCrossRef
222.
go back to reference Udar N, Atilano SR, Brown DJ, Holguin B, Small K, Nesburn AB, et al. SOD1: a candidate gene for keratoconus. Investig Opthalmol Vis Sci. 2006;47(8):3345–51.CrossRef Udar N, Atilano SR, Brown DJ, Holguin B, Small K, Nesburn AB, et al. SOD1: a candidate gene for keratoconus. Investig Opthalmol Vis Sci. 2006;47(8):3345–51.CrossRef
223.
go back to reference Czugala M, Karolak JA, Nowak DM, Polakowski P, Pitarque J, Molinari A, et al. Novel mutation and three other sequence variants segregating with phenotype at keratoconus 13q32 susceptibility locus. Eur J Hum Genet. 2011;20(4):389–97.PubMedPubMedCentralCrossRef Czugala M, Karolak JA, Nowak DM, Polakowski P, Pitarque J, Molinari A, et al. Novel mutation and three other sequence variants segregating with phenotype at keratoconus 13q32 susceptibility locus. Eur J Hum Genet. 2011;20(4):389–97.PubMedPubMedCentralCrossRef
224.
go back to reference Guan T, Liu C, Ma Z, Ding S. The point mutation and polymorphism in keratoconus candidate gene TGFBI in Chinese population. Gene. 2012;503(1):137–9.PubMedCrossRef Guan T, Liu C, Ma Z, Ding S. The point mutation and polymorphism in keratoconus candidate gene TGFBI in Chinese population. Gene. 2012;503(1):137–9.PubMedCrossRef
225.
go back to reference Stabuc-Silih M, Ravnik-Glavac M, Glavac D, Hawlina M, Strazisar M. Polymorphisms in COL4A3 and COL4A4 genes associated with keratoconus. Mol Vis. 2009;15:2848–60.PubMedPubMedCentral Stabuc-Silih M, Ravnik-Glavac M, Glavac D, Hawlina M, Strazisar M. Polymorphisms in COL4A3 and COL4A4 genes associated with keratoconus. Mol Vis. 2009;15:2848–60.PubMedPubMedCentral
226.
go back to reference Abu-Amero KK, Kondkar AA, Azad TA, Sultan T, Kalantan H, Al-Muammar AM. Keratoconus is associated with increased copy number of mitochondrial DNA. Mol Vis. 2014;20:1203–8.PubMedPubMedCentral Abu-Amero KK, Kondkar AA, Azad TA, Sultan T, Kalantan H, Al-Muammar AM. Keratoconus is associated with increased copy number of mitochondrial DNA. Mol Vis. 2014;20:1203–8.PubMedPubMedCentral
227.
go back to reference Mikami T, Meguro A, Teshigawara T, Takeuchi M, Uemoto R, Kawagoe T, et al. Interleukin 1 beta promoter polymorphism is associated with keratoconus in a Japanese population. Mol Vis. 2013;19:845–51.PubMedPubMedCentral Mikami T, Meguro A, Teshigawara T, Takeuchi M, Uemoto R, Kawagoe T, et al. Interleukin 1 beta promoter polymorphism is associated with keratoconus in a Japanese population. Mol Vis. 2013;19:845–51.PubMedPubMedCentral
228.
go back to reference Saee-Rad S, Hashemi H, Miraftab M, Noori-Daloii MR, Chaleshtori MH, Raoofian R, et al. Mutation analysis of VSX1 and SOD1 in Iranian patients with keratoconus. Mol Vis. 2011;17(336–37):3128–36.PubMedPubMedCentral Saee-Rad S, Hashemi H, Miraftab M, Noori-Daloii MR, Chaleshtori MH, Raoofian R, et al. Mutation analysis of VSX1 and SOD1 in Iranian patients with keratoconus. Mol Vis. 2011;17(336–37):3128–36.PubMedPubMedCentral
229.
go back to reference Hughes AE, Bradley DT, Campbell M, Lechner J, Dash DP, Simpson DA, et al. Mutation altering the miR-184 seed region causes familial keratoconus with cataract. Am J Hum Genet. 2011;89(5):628–33.PubMedPubMedCentralCrossRef Hughes AE, Bradley DT, Campbell M, Lechner J, Dash DP, Simpson DA, et al. Mutation altering the miR-184 seed region causes familial keratoconus with cataract. Am J Hum Genet. 2011;89(5):628–33.PubMedPubMedCentralCrossRef
230.
go back to reference Lechner J, Porter LF, Rice A, Vitart V, Armstrong DJ, Schorderet DF, et al. Enrichment of pathogenic alleles in the brittle cornea gene, ZNF469, in keratoconus. Hum Mol Genet. 2014;23(20):5527–35.PubMedPubMedCentralCrossRef Lechner J, Porter LF, Rice A, Vitart V, Armstrong DJ, Schorderet DF, et al. Enrichment of pathogenic alleles in the brittle cornea gene, ZNF469, in keratoconus. Hum Mol Genet. 2014;23(20):5527–35.PubMedPubMedCentralCrossRef
231.
go back to reference Fukui K, Sasaki T, Imazumi K, Matsuura Y, Nakanishi H, Takai Y. Isolation and characterization of a GTPase activating protein specific for the Rab3 subfamily of small G proteins. J Biol Chem. 1997;272(8):4655–8.PubMedCrossRef Fukui K, Sasaki T, Imazumi K, Matsuura Y, Nakanishi H, Takai Y. Isolation and characterization of a GTPase activating protein specific for the Rab3 subfamily of small G proteins. J Biol Chem. 1997;272(8):4655–8.PubMedCrossRef
232.
go back to reference Borck G, Wunram H, Steiert A, Volk AE, Körber F, Roters S, et al. A homozygous RAB3GAP2 mutation causes Warburg Micro syndrome. Hum Genet. 2010;129(1):45–50.PubMedCrossRef Borck G, Wunram H, Steiert A, Volk AE, Körber F, Roters S, et al. A homozygous RAB3GAP2 mutation causes Warburg Micro syndrome. Hum Genet. 2010;129(1):45–50.PubMedCrossRef
233.
go back to reference Sahebjada S, Schache M, Richardson AJ, Snibson G, Macgregor S, Daniell M, et al. Evaluating the association between keratoconus and the corneal thickness genes in an independent Australian population. Investig Opthalmol Vis Sci. 2013;54(13):8224–8.CrossRef Sahebjada S, Schache M, Richardson AJ, Snibson G, Macgregor S, Daniell M, et al. Evaluating the association between keratoconus and the corneal thickness genes in an independent Australian population. Investig Opthalmol Vis Sci. 2013;54(13):8224–8.CrossRef
234.
go back to reference Rabinowitz YS, Maumenee IH, Lundergan MK, Puffenberger E, Zhu D, Antonarakis S, et al. Molecular genetic analysis in autosomal dominant keratoconus. Cornea. 1992;11(4):302–8.PubMedCrossRef Rabinowitz YS, Maumenee IH, Lundergan MK, Puffenberger E, Zhu D, Antonarakis S, et al. Molecular genetic analysis in autosomal dominant keratoconus. Cornea. 1992;11(4):302–8.PubMedCrossRef
235.
go back to reference Rosenfeld JA, Drautz JM, Clericuzio CL, Cushing T, Raskin S, Martin J, et al. Deletions and duplications of developmental pathway genes in 5q31 contribute to abnormal phenotypes. Am J Med Genet. 2011;155A(8):1906–16.PubMedCrossRef Rosenfeld JA, Drautz JM, Clericuzio CL, Cushing T, Raskin S, Martin J, et al. Deletions and duplications of developmental pathway genes in 5q31 contribute to abnormal phenotypes. Am J Med Genet. 2011;155A(8):1906–16.PubMedCrossRef
236.
go back to reference Aldave AJ, Bourla N, Yellore VS, Rayner SA, Khan MA, Salem AK, et al. Keratoconus is not associated with mutations in COL8A1 and COL8A2. Cornea. 2007;26(8):963–5.PubMedCrossRef Aldave AJ, Bourla N, Yellore VS, Rayner SA, Khan MA, Salem AK, et al. Keratoconus is not associated with mutations in COL8A1 and COL8A2. Cornea. 2007;26(8):963–5.PubMedCrossRef
237.
go back to reference Bradshaw AD, Puolakkainen P, Wight TN, Sage EH, Dasgupta J, Davidson JM. SPARC-null mice display abnormalities in the dermis characterized by decreased collagen fibril diameter and reduced tensile strength. J Investig Dermatol. 2003;120(6):949–55.PubMedCrossRef Bradshaw AD, Puolakkainen P, Wight TN, Sage EH, Dasgupta J, Davidson JM. SPARC-null mice display abnormalities in the dermis characterized by decreased collagen fibril diameter and reduced tensile strength. J Investig Dermatol. 2003;120(6):949–55.PubMedCrossRef
238.
go back to reference Wang Y, Jin T, Zhang X, Wei W, Cui Y, Geng T, et al. Common single nucleotide polymorphisms and keratoconus in the Han Chinese population. Ophthalmic Genet. 2013;34(3):160–6.PubMedCrossRef Wang Y, Jin T, Zhang X, Wei W, Cui Y, Geng T, et al. Common single nucleotide polymorphisms and keratoconus in the Han Chinese population. Ophthalmic Genet. 2013;34(3):160–6.PubMedCrossRef
239.
go back to reference Mok J-W, Baek S-J, Joo C-K. VSX1 gene variants are associated with keratoconus in unrelated Korean patients. J Hum Genet. 2008;53(9):842–9.PubMedCrossRef Mok J-W, Baek S-J, Joo C-K. VSX1 gene variants are associated with keratoconus in unrelated Korean patients. J Hum Genet. 2008;53(9):842–9.PubMedCrossRef
240.
go back to reference Tang YG, Picornell Y, Su X, Li X, Yang H, Rabinowitz YS. Three VSX1 gene mutations, L159M, R166W, and H244R, are not associated with keratoconus. Cornea. 2008;27(2):189–92.PubMedCrossRef Tang YG, Picornell Y, Su X, Li X, Yang H, Rabinowitz YS. Three VSX1 gene mutations, L159M, R166W, and H244R, are not associated with keratoconus. Cornea. 2008;27(2):189–92.PubMedCrossRef
241.
go back to reference Dash DP, George S, Oprey D, Burns D, Nabili S, Donnelly U, et al. Mutational screening of VSX1 in keratoconus patients from the European population. Eye. 2009;24(6):1085–92.PubMedCrossRef Dash DP, George S, Oprey D, Burns D, Nabili S, Donnelly U, et al. Mutational screening of VSX1 in keratoconus patients from the European population. Eye. 2009;24(6):1085–92.PubMedCrossRef
242.
go back to reference Macé M, Galiacy SD, Erraud A, Mejía JE, Etchevers H, Allouche M, et al. Comparative transcriptome and network biology analyses demonstrate antiproliferative and hyperapoptotic phenotypes in human keratoconus corneas. Investig Opthalmol Vis Sci. 2011;52(9):6181–91.CrossRef Macé M, Galiacy SD, Erraud A, Mejía JE, Etchevers H, Allouche M, et al. Comparative transcriptome and network biology analyses demonstrate antiproliferative and hyperapoptotic phenotypes in human keratoconus corneas. Investig Opthalmol Vis Sci. 2011;52(9):6181–91.CrossRef
243.
go back to reference Maruyama Y, Li Y, Zhang Y, Wang X, Sugar J, Yue BY. Mapping of Sp1 regulation sites in the promoter of the human alpha1-proteinase inhibitor gene. J Cell Biochem. 2002;85(3):482–9.PubMedCrossRef Maruyama Y, Li Y, Zhang Y, Wang X, Sugar J, Yue BY. Mapping of Sp1 regulation sites in the promoter of the human alpha1-proteinase inhibitor gene. J Cell Biochem. 2002;85(3):482–9.PubMedCrossRef
244.
go back to reference Paliwal P, Tandon R, Dube D, Kaur P, Sharma A. Familial segregation of a VSX1 mutation adds a new dimension to its role in the causation of keratoconus. Mol Vis. 2011;17:481–5.PubMedPubMedCentral Paliwal P, Tandon R, Dube D, Kaur P, Sharma A. Familial segregation of a VSX1 mutation adds a new dimension to its role in the causation of keratoconus. Mol Vis. 2011;17:481–5.PubMedPubMedCentral
245.
go back to reference Abu-Amero KK, Kalantan H, Al-Muammar AM. Analysis of the VSX1 gene in keratoconus patients from Saudi Arabia. Mol Vis. 2011;17:667–72.PubMedPubMedCentral Abu-Amero KK, Kalantan H, Al-Muammar AM. Analysis of the VSX1 gene in keratoconus patients from Saudi Arabia. Mol Vis. 2011;17:667–72.PubMedPubMedCentral
246.
go back to reference Aldave AJ, Yellore VS, Principe AH. Candidate gene screening for posterior polymorphous dystrophy. Cornea. 2005;24:151–5.PubMedCrossRef Aldave AJ, Yellore VS, Principe AH. Candidate gene screening for posterior polymorphous dystrophy. Cornea. 2005;24:151–5.PubMedCrossRef
247.
go back to reference Vincent AL, Jordan C, Sheck L, Niederer R, Patel DV, McGhee CN. Screening the visual system homeobox 1 gene in keratoconus and posterior polymorphous dystrophy cohorts identifies a novel variant. Mol Vis. 2013;19:852–60.PubMedPubMedCentral Vincent AL, Jordan C, Sheck L, Niederer R, Patel DV, McGhee CN. Screening the visual system homeobox 1 gene in keratoconus and posterior polymorphous dystrophy cohorts identifies a novel variant. Mol Vis. 2013;19:852–60.PubMedPubMedCentral
248.
go back to reference Eran P, Almogit A, David Z, Wolf HR, Hana G, Yaniv B, et al. The D144E substitution in the VSX1 gene: a non-pathogenic variant or a disease causing mutation? Ophthalmic Genet. 2008;29:53–9.PubMedCrossRef Eran P, Almogit A, David Z, Wolf HR, Hana G, Yaniv B, et al. The D144E substitution in the VSX1 gene: a non-pathogenic variant or a disease causing mutation? Ophthalmic Genet. 2008;29:53–9.PubMedCrossRef
249.
go back to reference Semina EV, Mintz-Hittner HA, Murray JC. Isolation and characterization of a novel human paired-like homeodomain-containing transcription factor gene, VSX1, expressed in ocular tissues. Genomics. 2000;63:289–93.PubMedCrossRef Semina EV, Mintz-Hittner HA, Murray JC. Isolation and characterization of a novel human paired-like homeodomain-containing transcription factor gene, VSX1, expressed in ocular tissues. Genomics. 2000;63:289–93.PubMedCrossRef
250.
go back to reference Shi Z, Jervis D, Nickerson PE, Chow RL. Requirement for the paired-like homeodomain transcription factor VSX1 in type 3a mouse retinal bipolar cell terminal differentiation. J Comp Neurol. 2011;520(1):117–29.CrossRef Shi Z, Jervis D, Nickerson PE, Chow RL. Requirement for the paired-like homeodomain transcription factor VSX1 in type 3a mouse retinal bipolar cell terminal differentiation. J Comp Neurol. 2011;520(1):117–29.CrossRef
251.
go back to reference Aldave AJ, Yellore VS, Salem AK, Yoo GL, Rayner SA, Yang H, et al. No VSX1 gene mutations associated with keratoconus. Investig Ophthalmol Vis Sci. 2006;47:2820–2.CrossRef Aldave AJ, Yellore VS, Salem AK, Yoo GL, Rayner SA, Yang H, et al. No VSX1 gene mutations associated with keratoconus. Investig Ophthalmol Vis Sci. 2006;47:2820–2.CrossRef
252.
go back to reference Liskova P, Ebenezer ND, Hysi PG, Gwilliam R, El-Ashry MF, Moodaley LC, et al. Molecular analysis of the VSX1 gene in familial keratoconus. Mol Vis. 2007;13:1887–91.PubMed Liskova P, Ebenezer ND, Hysi PG, Gwilliam R, El-Ashry MF, Moodaley LC, et al. Molecular analysis of the VSX1 gene in familial keratoconus. Mol Vis. 2007;13:1887–91.PubMed
253.
go back to reference Mintz-Hittner HA, Semina EV, Frishman LJ, Prager TC, Murray JC. VSX1 (RINX) mutation with craniofacial anomalies, empty sella, corneal endothelial changes, and abnormal retinal and auditory bipolar cells. Ophthalmology. 2004;111:828–36.PubMedCrossRef Mintz-Hittner HA, Semina EV, Frishman LJ, Prager TC, Murray JC. VSX1 (RINX) mutation with craniofacial anomalies, empty sella, corneal endothelial changes, and abnormal retinal and auditory bipolar cells. Ophthalmology. 2004;111:828–36.PubMedCrossRef
254.
255.
go back to reference Al-Muammar AM, Kalantan H, Azad TA, Sultan T, Abu-Amero KK. Analysis of the SOD1 gene in keratoconus patients from Saudi Arabia. Ophthalmic Genet. 2014;36(4):373–5.PubMedCrossRef Al-Muammar AM, Kalantan H, Azad TA, Sultan T, Abu-Amero KK. Analysis of the SOD1 gene in keratoconus patients from Saudi Arabia. Ophthalmic Genet. 2014;36(4):373–5.PubMedCrossRef
256.
go back to reference Jeoung JW, Kim MK, Park SS, Kim SY, Ko HS, Wee WR, et al. VSX1 gene and keratoconus. Cornea. 2012;31(7):746–50.PubMedCrossRef Jeoung JW, Kim MK, Park SS, Kim SY, Ko HS, Wee WR, et al. VSX1 gene and keratoconus. Cornea. 2012;31(7):746–50.PubMedCrossRef
257.
go back to reference Barbaro V, Iorio ED, Ferrari S, Bisceglia L, Ruzza A, Luca MD, et al. Expression of VSX1 in human corneal keratocytes during differentiation into myofibroblasts in response to wound healing. Investig Opthalmol Vis Sci. 2006;47(12):5243–50.CrossRef Barbaro V, Iorio ED, Ferrari S, Bisceglia L, Ruzza A, Luca MD, et al. Expression of VSX1 in human corneal keratocytes during differentiation into myofibroblasts in response to wound healing. Investig Opthalmol Vis Sci. 2006;47(12):5243–50.CrossRef
258.
go back to reference Hayashi T, Huang J, Deeb SS. RINX(VSX1), a novel homeobox gene expressed in the inner nuclear layer of the adult retina. Genomics. 2000;67(2):128–39.PubMedCrossRef Hayashi T, Huang J, Deeb SS. RINX(VSX1), a novel homeobox gene expressed in the inner nuclear layer of the adult retina. Genomics. 2000;67(2):128–39.PubMedCrossRef
259.
go back to reference Chow RL, Volgyi B, Szilard RK, Ng D, Mckerlie C, Bloomfield SA, et al. Control of late off-center cone bipolar cell differentiation and visual signaling by the homeobox gene Vsx1. Proc Natl Acad Sci. 2004;101(6):1754–9.PubMedCrossRefPubMedCentral Chow RL, Volgyi B, Szilard RK, Ng D, Mckerlie C, Bloomfield SA, et al. Control of late off-center cone bipolar cell differentiation and visual signaling by the homeobox gene Vsx1. Proc Natl Acad Sci. 2004;101(6):1754–9.PubMedCrossRefPubMedCentral
260.
go back to reference Ohtoshi A, Wang SW, Maeda H, Saszik SM, Frishman LJ, Klein WH, et al. Regulation of retinal cone bipolar cell differentiation and photopic vision by the CVC homeobox gene Vsx1. Curr Biol. 2004;14(6):530–6.PubMedCrossRef Ohtoshi A, Wang SW, Maeda H, Saszik SM, Frishman LJ, Klein WH, et al. Regulation of retinal cone bipolar cell differentiation and photopic vision by the CVC homeobox gene Vsx1. Curr Biol. 2004;14(6):530–6.PubMedCrossRef
261.
go back to reference Hosseini SM, Herd S, Vincent AL, Heon E. Genetic analysis of chromosome 20-related posterior polymorphous corneal dystrophy: genetic heterogeneity and exclusion of three candidate genes. Mol Vis. 2008;14:71–80.PubMedPubMedCentral Hosseini SM, Herd S, Vincent AL, Heon E. Genetic analysis of chromosome 20-related posterior polymorphous corneal dystrophy: genetic heterogeneity and exclusion of three candidate genes. Mol Vis. 2008;14:71–80.PubMedPubMedCentral
262.
263.
go back to reference Heon E, Mathers WD, Alward WL, Weisenthal RW, Sunden SL, Fishbaugh JA, et al. Linkage of posterior polymorphous corneal dystrophy to 20q11. Hum Mol Genet. 1995;4(3):485–8.PubMedCrossRef Heon E, Mathers WD, Alward WL, Weisenthal RW, Sunden SL, Fishbaugh JA, et al. Linkage of posterior polymorphous corneal dystrophy to 20q11. Hum Mol Genet. 1995;4(3):485–8.PubMedCrossRef
264.
go back to reference Valleix S, Nedelec B, Rigaudiere F, Dighiero P, Pouliquen Y, Renard G, et al. H244R VSX1 is associated with selective cone on bipolar cell dysfunction and macular degeneration in a PPCD family. Investig Opthalmol Vis Sci. 2006;47(1):48–54.CrossRef Valleix S, Nedelec B, Rigaudiere F, Dighiero P, Pouliquen Y, Renard G, et al. H244R VSX1 is associated with selective cone on bipolar cell dysfunction and macular degeneration in a PPCD family. Investig Opthalmol Vis Sci. 2006;47(1):48–54.CrossRef
265.
go back to reference Gwilliam R, Liskova P, Filipec M, Kmoch S, Jirsova K, Huckle EJ, et al. Posterior polymorphous corneal dystrophy in Czech families maps to chromosome 20 and excludes the VSX1 gene. Investig Opthalmol Vis Sci. 2005;46(12):4480–4.CrossRef Gwilliam R, Liskova P, Filipec M, Kmoch S, Jirsova K, Huckle EJ, et al. Posterior polymorphous corneal dystrophy in Czech families maps to chromosome 20 and excludes the VSX1 gene. Investig Opthalmol Vis Sci. 2005;46(12):4480–4.CrossRef
266.
go back to reference Baratz KH, Tosakulwong N, Ryu E, Brown WL, Branham K, Chen W, et al. E2-2 protein and Fuchs’s corneal dystrophy. N Engl J Med. 2010;11:1016–24.CrossRef Baratz KH, Tosakulwong N, Ryu E, Brown WL, Branham K, Chen W, et al. E2-2 protein and Fuchs’s corneal dystrophy. N Engl J Med. 2010;11:1016–24.CrossRef
267.
go back to reference Waring GO, Rodrigues MM, Laibson PR. Corneal dystrophies. II. Endothelial dystrophies. Surv Ophthalmol. 1978;23(3):147–68.PubMedCrossRef Waring GO, Rodrigues MM, Laibson PR. Corneal dystrophies. II. Endothelial dystrophies. Surv Ophthalmol. 1978;23(3):147–68.PubMedCrossRef
268.
go back to reference Bechara SJ, Grossniklaus HE, Waring GO, Wells JA. Keratoconus associated with posterior polymorphous dystrophy. Am J Ophthalmol. 1991;112(6):729–31.PubMedCrossRef Bechara SJ, Grossniklaus HE, Waring GO, Wells JA. Keratoconus associated with posterior polymorphous dystrophy. Am J Ophthalmol. 1991;112(6):729–31.PubMedCrossRef
269.
go back to reference Lam HY, Wiggs JL, Jurkunas UV. Unusual presentation of presumed posterior polymorphous dystrophy associated with iris heterochromia, band keratopathy, and keratoconus. Cornea. 2010;29(10):1180–5.PubMedPubMedCentralCrossRef Lam HY, Wiggs JL, Jurkunas UV. Unusual presentation of presumed posterior polymorphous dystrophy associated with iris heterochromia, band keratopathy, and keratoconus. Cornea. 2010;29(10):1180–5.PubMedPubMedCentralCrossRef
270.
go back to reference Krafchak CM, Pawar H, Moroi SE, Sugar A, Lichter PR, Mackey DA, et al. Mutations in TCF8 cause posterior polymorphous corneal dystrophy and ectopic expression of COL4A3 by corneal endothelial cells. Am J Hum Genet. 2005;77(5):694–708.PubMedPubMedCentralCrossRef Krafchak CM, Pawar H, Moroi SE, Sugar A, Lichter PR, Mackey DA, et al. Mutations in TCF8 cause posterior polymorphous corneal dystrophy and ectopic expression of COL4A3 by corneal endothelial cells. Am J Hum Genet. 2005;77(5):694–708.PubMedPubMedCentralCrossRef
271.
go back to reference Biswas S. Missense mutations in COL8A2, the gene encoding the alpha2 chain of type VIII collagen, cause two forms of corneal endothelial dystrophy. Hum Mol Genet. 2001;10(21):2415–23.PubMedCrossRef Biswas S. Missense mutations in COL8A2, the gene encoding the alpha2 chain of type VIII collagen, cause two forms of corneal endothelial dystrophy. Hum Mol Genet. 2001;10(21):2415–23.PubMedCrossRef
272.
go back to reference Kawata A, Kato S, Shimizu T, Hayashi H, Hirai S, Misawa H, et al. Aberrant splicing of human Cu/Zn superoxide dismutase (SODI) RNA transcripts. NeuroReport. 2000;11(12):2649–53.PubMedCrossRef Kawata A, Kato S, Shimizu T, Hayashi H, Hirai S, Misawa H, et al. Aberrant splicing of human Cu/Zn superoxide dismutase (SODI) RNA transcripts. NeuroReport. 2000;11(12):2649–53.PubMedCrossRef
273.
go back to reference Hirano M, Hung W-Y, Cole N, Azim A, Deng H-X, Siddique T. Multiple transcripts of the human Cu, Zn superoxide dismutase gene. Biochem Biophys Res Commun. 2000;276(1):52–6.PubMedCrossRef Hirano M, Hung W-Y, Cole N, Azim A, Deng H-X, Siddique T. Multiple transcripts of the human Cu, Zn superoxide dismutase gene. Biochem Biophys Res Commun. 2000;276(1):52–6.PubMedCrossRef
274.
go back to reference Noor R, Mittal S, Iqbal J. Superoxide dismutase—applications and relevance to human diseases. Med Sci Monit. 2002;8(9):RA210–5. Noor R, Mittal S, Iqbal J. Superoxide dismutase—applications and relevance to human diseases. Med Sci Monit. 2002;8(9):RA210–5.
275.
go back to reference Rosen DR, Siddique T, Patterson D, Figlewicz DA, Sapp P, Hentati A, et al. Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature. 1993;362(64 15):59–62.PubMedCrossRef Rosen DR, Siddique T, Patterson D, Figlewicz DA, Sapp P, Hentati A, et al. Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature. 1993;362(64 15):59–62.PubMedCrossRef
276.
go back to reference Behndig A, Svensson B, Marklund SL, Karlsson K. Superoxide dismutase isoenzymes in the human eye. Investig Ophthalmol Vis Sci. 1998;39:471–5. Behndig A, Svensson B, Marklund SL, Karlsson K. Superoxide dismutase isoenzymes in the human eye. Investig Ophthalmol Vis Sci. 1998;39:471–5.
277.
go back to reference Zelko IN, Mariani TJ, Folz RJ. Superoxide dismutase multigene family: a comparison of the CuZn-SOD (SOD1), Mn-SOD (SOD2), and EC-SOD (SOD3) gene structures, evolution, and expression. Free Radic Biol Med. 2002;33(3):337–49.PubMedCrossRef Zelko IN, Mariani TJ, Folz RJ. Superoxide dismutase multigene family: a comparison of the CuZn-SOD (SOD1), Mn-SOD (SOD2), and EC-SOD (SOD3) gene structures, evolution, and expression. Free Radic Biol Med. 2002;33(3):337–49.PubMedCrossRef
278.
go back to reference Behding A, Karlsson K, Johansson BO, Brannstrom T, Marklund SL. Superoxide dismutase isoenzymes in the normal and diseased human cornea. Investig Ophthalmol Vis Sci. 2001;42:2293–6. Behding A, Karlsson K, Johansson BO, Brannstrom T, Marklund SL. Superoxide dismutase isoenzymes in the normal and diseased human cornea. Investig Ophthalmol Vis Sci. 2001;42:2293–6.
279.
go back to reference Gondhowiardjo TD, van Haeringen NJ, Volker-Dieben HJ, Beekhuis HW, Kok JH, Van Rij G, et al. Analysis of corneal aldehyde dehydrogenase patterns in pathologic corneas. Cornea. 1993;12:146–54.PubMedCrossRef Gondhowiardjo TD, van Haeringen NJ, Volker-Dieben HJ, Beekhuis HW, Kok JH, Van Rij G, et al. Analysis of corneal aldehyde dehydrogenase patterns in pathologic corneas. Cornea. 1993;12:146–54.PubMedCrossRef
280.
go back to reference Kenny MC, Brown DJ, Rajeev B. Abstract: The elusive causes of keratoconus: a working hypothesis (CLAO J. 2000;26:10–13). Am J Ophthalmol. 2000;130(2):263. Kenny MC, Brown DJ, Rajeev B. Abstract: The elusive causes of keratoconus: a working hypothesis (CLAO J. 2000;26:10–13). Am J Ophthalmol. 2000;130(2):263.
281.
go back to reference Chwa M, Atilano SR, Reddy V, Jordan N, Kim DW, Kenney MC. Increased stress-induced generation of reactive oxygen species and apoptosis in human keratoconus fibroblasts. Investig Opthalmol Vis Sci. 2006;47(5):1902–10.CrossRef Chwa M, Atilano SR, Reddy V, Jordan N, Kim DW, Kenney MC. Increased stress-induced generation of reactive oxygen species and apoptosis in human keratoconus fibroblasts. Investig Opthalmol Vis Sci. 2006;47(5):1902–10.CrossRef
282.
go back to reference Ballinger SW, Houten BV, Conklin CA, Jin G-F, Godley BF. Hydrogen peroxide causes significant mitochondrial DNA damage in human RPE cells. Exp Eye Res. 1999;68(6):765–72.PubMedCrossRef Ballinger SW, Houten BV, Conklin CA, Jin G-F, Godley BF. Hydrogen peroxide causes significant mitochondrial DNA damage in human RPE cells. Exp Eye Res. 1999;68(6):765–72.PubMedCrossRef
283.
go back to reference Ballinger SW, Patterson C, Yan C-N, Doan R, Burow DL, Young CG, et al. Hydrogen peroxide- and peroxynitrite-induced mitochondrial DNA damage and dysfunction in vascular endothelial and smooth muscle cells. Circ Res. 2000;86(9):960–6.PubMedCrossRef Ballinger SW, Patterson C, Yan C-N, Doan R, Burow DL, Young CG, et al. Hydrogen peroxide- and peroxynitrite-induced mitochondrial DNA damage and dysfunction in vascular endothelial and smooth muscle cells. Circ Res. 2000;86(9):960–6.PubMedCrossRef
284.
go back to reference Wang X, Simpkins JW, Dykens JA, Cammarata PR. Oxidative damage to human lens epithelial cells in culture: estrogen protection of mitochondrial potential, ATP, and cell viability. Investig Opthalmol Vis Sci. 2003;44(5):2067–75.CrossRef Wang X, Simpkins JW, Dykens JA, Cammarata PR. Oxidative damage to human lens epithelial cells in culture: estrogen protection of mitochondrial potential, ATP, and cell viability. Investig Opthalmol Vis Sci. 2003;44(5):2067–75.CrossRef
285.
go back to reference Rohrbach M, Spencer HL, Porter LF, Burkitt-Wright EM, Bürer C, Janecke A, et al. ZNF469 frequently mutated in the brittle cornea syndrome (BCS) is a single exon gene possibly regulating the expression of several extracellular matrix components. Mol Genet Metab. 2013;109(3):289–95.PubMedPubMedCentralCrossRef Rohrbach M, Spencer HL, Porter LF, Burkitt-Wright EM, Bürer C, Janecke A, et al. ZNF469 frequently mutated in the brittle cornea syndrome (BCS) is a single exon gene possibly regulating the expression of several extracellular matrix components. Mol Genet Metab. 2013;109(3):289–95.PubMedPubMedCentralCrossRef
286.
go back to reference Burkitt Wright EM, Spencer HL, Daly SB, Manson FD, Zeef LA, Urquhart J, et al. Mutations in PRDM5 in brittle cornea syndrome identify a pathway regulating extracellular matrix development and maintenance. Am J Hum Genet. 2011;88:767–77.PubMedPubMedCentralCrossRef Burkitt Wright EM, Spencer HL, Daly SB, Manson FD, Zeef LA, Urquhart J, et al. Mutations in PRDM5 in brittle cornea syndrome identify a pathway regulating extracellular matrix development and maintenance. Am J Hum Genet. 2011;88:767–77.PubMedPubMedCentralCrossRef
287.
go back to reference Al-Hussain H, Zeisberger SM, Huber PR, Giunta C, Steinmann B. Brittle cornea syndrome and its delineation from the kyphoscoliotic type of Ehlers–Danlos syndrome (EDS VI): report on 23 patients and review of the literature. Am J Med Genet A. 2004;124A(1):28–34.PubMedCrossRef Al-Hussain H, Zeisberger SM, Huber PR, Giunta C, Steinmann B. Brittle cornea syndrome and its delineation from the kyphoscoliotic type of Ehlers–Danlos syndrome (EDS VI): report on 23 patients and review of the literature. Am J Med Genet A. 2004;124A(1):28–34.PubMedCrossRef
288.
go back to reference Christensen AE, Knappskog PM, Midtbø M, Gjesdal CG, Mengel-From J, Morling N, et al. Brittle cornea syndrome associated with a missense mutation in the zinc-finger 469 gene. Investig Opthalmol Vis Sci. 2010;51(1):47–52.CrossRef Christensen AE, Knappskog PM, Midtbø M, Gjesdal CG, Mengel-From J, Morling N, et al. Brittle cornea syndrome associated with a missense mutation in the zinc-finger 469 gene. Investig Opthalmol Vis Sci. 2010;51(1):47–52.CrossRef
289.
go back to reference Maier P, Broszinski A, Heizmann U, Bohringer D, Reinhardau T. Active transforming growth factor-beta2 is increased in the aqueous humor of keratoconus patients. Mol Vis. 2007;13:1198–202.PubMed Maier P, Broszinski A, Heizmann U, Bohringer D, Reinhardau T. Active transforming growth factor-beta2 is increased in the aqueous humor of keratoconus patients. Mol Vis. 2007;13:1198–202.PubMed
290.
go back to reference Saghizadeh M, Chwa M, Aoki A, Lin B, Pirouzmanesh A, Brown D, et al. Altered expression of growth factors and cytokines in keratoconus, bullous keratopathy and diabetic human corneas. Exp Eye Res. 2001;73(2):179–89.PubMedCrossRef Saghizadeh M, Chwa M, Aoki A, Lin B, Pirouzmanesh A, Brown D, et al. Altered expression of growth factors and cytokines in keratoconus, bullous keratopathy and diabetic human corneas. Exp Eye Res. 2001;73(2):179–89.PubMedCrossRef
291.
go back to reference Bykhovskaya Y, Canedo ALC, Wright KW, Rabinowitz YS. 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. 2013;36(3):244–7.CrossRef Bykhovskaya Y, Canedo ALC, Wright KW, Rabinowitz YS. 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. 2013;36(3):244–7.CrossRef
292.
go back to reference Chen J, Chen Y, Han SN. Comparison of TGF-β1 in tears and corneal haze following Epi-LASIK with and without mitomycin C. Int J Ophthalmol. 2013;6:312–5.PubMedPubMedCentral Chen J, Chen Y, Han SN. Comparison of TGF-β1 in tears and corneal haze following Epi-LASIK with and without mitomycin C. Int J Ophthalmol. 2013;6:312–5.PubMedPubMedCentral
293.
go back to reference Takács L, Csutak A, Balázs E, Módis L, Berta A. Expression of ßig-h3 is lower than normal in keratoconus corneas but increases with scarring. Cornea. 1999;18(5):599–605.PubMedCrossRef Takács L, Csutak A, Balázs E, Módis L, Berta A. Expression of ßig-h3 is lower than normal in keratoconus corneas but increases with scarring. Cornea. 1999;18(5):599–605.PubMedCrossRef
294.
go back to reference Pahuja N, Kumar NR, Shroff R, Shetty R, Nuijts RMMA, Ghosh A, et al. Differential molecular expression of extracellular matrix and inflammatory genes at the corneal cone apex drives focal weakening in keratoconus. Investig Opthalmol Vis Sci. 2016;57(13):5372–82.CrossRef Pahuja N, Kumar NR, Shroff R, Shetty R, Nuijts RMMA, Ghosh A, et al. Differential molecular expression of extracellular matrix and inflammatory genes at the corneal cone apex drives focal weakening in keratoconus. Investig Opthalmol Vis Sci. 2016;57(13):5372–82.CrossRef
295.
go back to reference Bhola NE, Balko JM, Dugger TC, Kuba MG, Sánchez V, Sanders M, et al. TGF-β inhibition enhances chemotherapy action against triple-negative breast cancer. J Clin Investig. 2013;123(3):1348–58.PubMedCrossRefPubMedCentral Bhola NE, Balko JM, Dugger TC, Kuba MG, Sánchez V, Sanders M, et al. TGF-β inhibition enhances chemotherapy action against triple-negative breast cancer. J Clin Investig. 2013;123(3):1348–58.PubMedCrossRefPubMedCentral
296.
go back to reference Gonzalo-Gil E, Galindo-Izquierdo M. Role of transforming growth factor-beta (TGF) beta in the physiopathology of rheumatoid arthritis. Reumatol Clín (Engl Ed). 2014;10(3):174–9.CrossRef Gonzalo-Gil E, Galindo-Izquierdo M. Role of transforming growth factor-beta (TGF) beta in the physiopathology of rheumatoid arthritis. Reumatol Clín (Engl Ed). 2014;10(3):174–9.CrossRef
297.
go back to reference Engler C, Chakravarti S, Doyle J, Eberhart CG, Meng H, Stark WJ, et al. Transforming growth factor-β signaling pathway activation in keratoconus. Am J Ophthalmol. 2011;151(5):752–9.PubMedPubMedCentralCrossRef Engler C, Chakravarti S, Doyle J, Eberhart CG, Meng H, Stark WJ, et al. Transforming growth factor-β signaling pathway activation in keratoconus. Am J Ophthalmol. 2011;151(5):752–9.PubMedPubMedCentralCrossRef
298.
go back to reference Yan X, Liu Z, Chen Y. Regulation of TGF-beta signaling by Smad7. Acta Biochim Biophys Sin (Shanghai). 2009;41(4):263–72.CrossRef Yan X, Liu Z, Chen Y. Regulation of TGF-beta signaling by Smad7. Acta Biochim Biophys Sin (Shanghai). 2009;41(4):263–72.CrossRef
299.
go back to reference Bai S, Cao X. A nuclear antagonistic mechanism of inhibitory Smads in transforming growth factor-β signaling. J Biol Chem. 2002;277:4176–82.CrossRef Bai S, Cao X. A nuclear antagonistic mechanism of inhibitory Smads in transforming growth factor-β signaling. J Biol Chem. 2002;277:4176–82.CrossRef
300.
go back to reference Schiller M, Javelaud D, Mauviel A. TGF-β-induced SMAD signaling and gene regulation: consequences for extracellular matrix remodeling and wound healing. J Dermatol Sci. 2004;35:83–92.PubMedCrossRef Schiller M, Javelaud D, Mauviel A. TGF-β-induced SMAD signaling and gene regulation: consequences for extracellular matrix remodeling and wound healing. J Dermatol Sci. 2004;35:83–92.PubMedCrossRef
301.
go back to reference Gomes LR, Terra LF, Wailemann RA, Labriola L, Sogayar MC. TGF-β1 modulates the homeostasis between MMPs and MMP inhibitors through p38 MAPK and ERK1/2 in highly invasive breast cancer cells. BMC Cancer. 2012;12(1):26.PubMedPubMedCentralCrossRef Gomes LR, Terra LF, Wailemann RA, Labriola L, Sogayar MC. TGF-β1 modulates the homeostasis between MMPs and MMP inhibitors through p38 MAPK and ERK1/2 in highly invasive breast cancer cells. BMC Cancer. 2012;12(1):26.PubMedPubMedCentralCrossRef
302.
go back to reference Evans RA, Tian YC, Steadman R, Phillips AO. TGF-β1-mediated fibroblast–myofibroblast terminal differentiation—the role of smad proteins. Exp Cell Res. 2003;282(2):90–100.PubMedCrossRef Evans RA, Tian YC, Steadman R, Phillips AO. TGF-β1-mediated fibroblast–myofibroblast terminal differentiation—the role of smad proteins. Exp Cell Res. 2003;282(2):90–100.PubMedCrossRef
303.
go back to reference Samarakoon R, Overstreet JM, Higgins PJ. TGF-β signaling in tissue fibrosis: redox controls, target genes and therapeutic opportunities. Cell Signal. 2013;25(1):264–8.PubMedCrossRef Samarakoon R, Overstreet JM, Higgins PJ. TGF-β signaling in tissue fibrosis: redox controls, target genes and therapeutic opportunities. Cell Signal. 2013;25(1):264–8.PubMedCrossRef
304.
go back to reference Karamichos D, Hutcheon AEK, Zieske JD. Transforming growth factor-β3 regulates assembly of a non-fibrotic matrix in a 3D corneal model. J Tissue Eng Regen Med. 2011;5(8):228–38.CrossRef Karamichos D, Hutcheon AEK, Zieske JD. Transforming growth factor-β3 regulates assembly of a non-fibrotic matrix in a 3D corneal model. J Tissue Eng Regen Med. 2011;5(8):228–38.CrossRef
305.
go back to reference Waddington SN, Crossley R, Sheard V, Howe SJ, Buckley SMK, Coughlan L, et al. Gene delivery of a mutant TGF beta 3 reduces markers of scar tissue formation after cutaneous wounding. Mol Ther. 2010;18:2104–11.PubMedPubMedCentralCrossRef Waddington SN, Crossley R, Sheard V, Howe SJ, Buckley SMK, Coughlan L, et al. Gene delivery of a mutant TGF beta 3 reduces markers of scar tissue formation after cutaneous wounding. Mol Ther. 2010;18:2104–11.PubMedPubMedCentralCrossRef
306.
go back to reference Szcześniak MW, Kabza M, Karolak JA, Rydzanicz M, Nowak DM, Ginter-Matuszewska B, et al. KTCNlncDB—a first platform to investigate lncRNAs expressed in human keratoconus and non-keratoconus corneas. Database. 2017. Szcześniak MW, Kabza M, Karolak JA, Rydzanicz M, Nowak DM, Ginter-Matuszewska B, et al. KTCNlncDB—a first platform to investigate lncRNAs expressed in human keratoconus and non-keratoconus corneas. Database. 2017.
307.
go back to reference Khaled ML, Bykhovskaya Y, Yablonski SE, Li H, Drewry MD, Aboobakar IF, et al. Differential expression of coding and long noncoding RNAs in keratoconus-affected corneas. Invest Ophthalmol Vis Sci. 2018;59(7):2717–28.CrossRef Khaled ML, Bykhovskaya Y, Yablonski SE, Li H, Drewry MD, Aboobakar IF, et al. Differential expression of coding and long noncoding RNAs in keratoconus-affected corneas. Invest Ophthalmol Vis Sci. 2018;59(7):2717–28.CrossRef
308.
go back to reference Xu J, Bai J, Zhang X, Lv Y, Gong Y, Liu L, et al. A comprehensive overview of lncRNA annotation resources. Brief Bioinform. 2017;18(2):236–49.PubMed Xu J, Bai J, Zhang X, Lv Y, Gong Y, Liu L, et al. A comprehensive overview of lncRNA annotation resources. Brief Bioinform. 2017;18(2):236–49.PubMed
312.
go back to reference Mencía A, Modamio-Høybjør S, Redshaw N, Morin M, Mayo-Merino F, Olavarrieta L, et al. Mutations in the seed region of human miR-96 are responsible for nonsyndromic progressive hearing loss. Nat Genet. 2009;41(5):609–13.PubMedCrossRef Mencía A, Modamio-Høybjør S, Redshaw N, Morin M, Mayo-Merino F, Olavarrieta L, et al. Mutations in the seed region of human miR-96 are responsible for nonsyndromic progressive hearing loss. Nat Genet. 2009;41(5):609–13.PubMedCrossRef
313.
go back to reference Sun D, Lee YS, Malhotra A, Kim HK, Matecic M, Evans C, et al. miR-99 family of microRNAs suppresses the expression of prostate-specific antigen and prostate cancer cell proliferation. Cancer Res. 2011;71(4):1313–24.PubMedPubMedCentralCrossRef Sun D, Lee YS, Malhotra A, Kim HK, Matecic M, Evans C, et al. miR-99 family of microRNAs suppresses the expression of prostate-specific antigen and prostate cancer cell proliferation. Cancer Res. 2011;71(4):1313–24.PubMedPubMedCentralCrossRef
314.
go back to reference Karali M, Peluso I, Gennarino VA, Bilio M, Verde R, Lago G, et al. miRNeye: a microRNA expression atlas of the mouse eye. BMC Genom. 2010;11(1):715.CrossRef Karali M, Peluso I, Gennarino VA, Bilio M, Verde R, Lago G, et al. miRNeye: a microRNA expression atlas of the mouse eye. BMC Genom. 2010;11(1):715.CrossRef
315.
go back to reference Landgraf P, Rusu M, Sheridan R, Sewer A, Iovino N, Aravin A, et al. A mammalian microRNA expression atlas based on small RNA library sequencing. Cell. 2007;129(7):1401–14.PubMedPubMedCentralCrossRef Landgraf P, Rusu M, Sheridan R, Sewer A, Iovino N, Aravin A, et al. A mammalian microRNA expression atlas based on small RNA library sequencing. Cell. 2007;129(7):1401–14.PubMedPubMedCentralCrossRef
316.
go back to reference Ryan DG, Oliveira-Fernandes M, Lavker RM. MicroRNAs of the mammalian eye display distinct and overlapping tissue specificity. Mol Vis. 2006;12(134–135):1175–84.PubMed Ryan DG, Oliveira-Fernandes M, Lavker RM. MicroRNAs of the mammalian eye display distinct and overlapping tissue specificity. Mol Vis. 2006;12(134–135):1175–84.PubMed
317.
318.
go back to reference Lechner J, Bae HA, Guduric-Fuchs J, Rice A, Govindarajan G, Siddiqui S, et al. Mutational analysis of MIR184 in sporadic keratoconus and myopia. Investig Opthalmol Vis Sci. 2013;54(8):5266–72.CrossRef Lechner J, Bae HA, Guduric-Fuchs J, Rice A, Govindarajan G, Siddiqui S, et al. Mutational analysis of MIR184 in sporadic keratoconus and myopia. Investig Opthalmol Vis Sci. 2013;54(8):5266–72.CrossRef
319.
go back to reference Dash DP, Silvestri G, Hughes AE. Fine mapping of the keratoconus with cataract locus on chromosome 15q and candidate gene analysis. Mol Vis. 2006;12:499–505.PubMed Dash DP, Silvestri G, Hughes AE. Fine mapping of the keratoconus with cataract locus on chromosome 15q and candidate gene analysis. Mol Vis. 2006;12:499–505.PubMed
320.
go back to reference McBride HM, Neuspiel M, Wasiak S. Mitochondria: more than just a powerhouse. Curr Biol. 2006;16(14):R551–60.PubMedCrossRef McBride HM, Neuspiel M, Wasiak S. Mitochondria: more than just a powerhouse. Curr Biol. 2006;16(14):R551–60.PubMedCrossRef
321.
go back to reference Nohl H. Generation of superoxide radicals as byproduct of cellular respiration. Ann Biol Clin. 1994;52(3):199–204. Nohl H. Generation of superoxide radicals as byproduct of cellular respiration. Ann Biol Clin. 1994;52(3):199–204.
322.
go back to reference Torroni A, Achilli A, Macaulay V, Richards M, Bandelt H. Harvesting the fruit of the human mtDNA tree. Trends Genet. 2006;22(6):339–45.PubMedCrossRef Torroni A, Achilli A, Macaulay V, Richards M, Bandelt H. Harvesting the fruit of the human mtDNA tree. Trends Genet. 2006;22(6):339–45.PubMedCrossRef
323.
go back to reference Carelli V, Achilli A, Valentino ML, Rengo C, Semino O, Pala M, et al. Haplogroup effects and recombination of mitochondrial DNA: novel clues from the analysis of Leber hereditary optic neuropathy pedigrees. Am J Hum Genet. 2006;78(4):564–74.PubMedCrossRef Carelli V, Achilli A, Valentino ML, Rengo C, Semino O, Pala M, et al. Haplogroup effects and recombination of mitochondrial DNA: novel clues from the analysis of Leber hereditary optic neuropathy pedigrees. Am J Hum Genet. 2006;78(4):564–74.PubMedCrossRef
324.
go back to reference Fuku N, Park KS, Yamada Y, Nishigaki Y, Cho YM, Matsuo H, et al. Mitochondrial haplogroup N9a confers resistance against type 2 diabetes in Asians. Am J Hum Genet. 2007;80(3):407–15.PubMedCrossRef Fuku N, Park KS, Yamada Y, Nishigaki Y, Cho YM, Matsuo H, et al. Mitochondrial haplogroup N9a confers resistance against type 2 diabetes in Asians. Am J Hum Genet. 2007;80(3):407–15.PubMedCrossRef
325.
go back to reference Hofmann S, Bezold R, Jaksch M, Oebrmaier-Kusser B, Mertens S, Kaufhold P, et al. Wolfram (DIDMOAD) syndrome and Leber hereditary optic neuropathy (LHON) are associated with distinct mitochondrial DNA haplotypes. Genomics. 1997;39(1):8–18.PubMedCrossRef Hofmann S, Bezold R, Jaksch M, Oebrmaier-Kusser B, Mertens S, Kaufhold P, et al. Wolfram (DIDMOAD) syndrome and Leber hereditary optic neuropathy (LHON) are associated with distinct mitochondrial DNA haplotypes. Genomics. 1997;39(1):8–18.PubMedCrossRef
326.
328.
go back to reference Abu-Amero KK, Azad TA, Sultan T, Kalantan H, Kondkar AA, Al-Muammar AM. Association of mitochondrial haplogroups H and R with keratoconus in Saudi Arabian patients. Investig Opthalmol Vis Sci. 2014;55(5):2827–31.CrossRef Abu-Amero KK, Azad TA, Sultan T, Kalantan H, Kondkar AA, Al-Muammar AM. Association of mitochondrial haplogroups H and R with keratoconus in Saudi Arabian patients. Investig Opthalmol Vis Sci. 2014;55(5):2827–31.CrossRef
329.
go back to reference Aktekin M, Sargon MF, Cakar P, Celik HH, Firat E. Ultrastructure of the cornea epithelium in keratoconus. Okajimas Folia Anat Jpn. 1998;75(1):45–53.PubMedCrossRef Aktekin M, Sargon MF, Cakar P, Celik HH, Firat E. Ultrastructure of the cornea epithelium in keratoconus. Okajimas Folia Anat Jpn. 1998;75(1):45–53.PubMedCrossRef
330.
go back to reference Atilano SR, Coskun P, Chwa M, Jordan N, Reddy V, Le K, et al. Accumulation of mitochondrial DNA damage in keratoconus corneas. Investig Opthalmol Vis Sci. 2005;46(4):1256–63.CrossRef Atilano SR, Coskun P, Chwa M, Jordan N, Reddy V, Le K, et al. Accumulation of mitochondrial DNA damage in keratoconus corneas. Investig Opthalmol Vis Sci. 2005;46(4):1256–63.CrossRef
331.
go back to reference Hao X-D, Chen P, Wang Y, Li S-X, Xie L-X. Mitochondrial DNA copy number, but not haplogroup is associated with keratoconus in Han Chinese population. Exp Eye Res. 2015;132:59–63.PubMedCrossRef Hao X-D, Chen P, Wang Y, Li S-X, Xie L-X. Mitochondrial DNA copy number, but not haplogroup is associated with keratoconus in Han Chinese population. Exp Eye Res. 2015;132:59–63.PubMedCrossRef
Metadata
Title
Genetic Aspects of Keratoconus: A Literature Review Exploring Potential Genetic Contributions and Possible Genetic Relationships with Comorbidities
Authors
Eleftherios Loukovitis
Konstantinos Sfakianakis
Panagiota Syrmakesi
Eleni Tsotridou
Myrsini Orfanidou
Dimitra Rafailia Bakaloudi
Maria Stoila
Athina Kozei
Spyridon Koronis
Zachos Zachariadis
Paris Tranos
Nikos Kozeis
Miltos Balidis
Zisis Gatzioufas
Aliki Fiska
George Anogeianakis
Publication date
01-12-2018
Publisher
Springer Healthcare
Published in
Ophthalmology and Therapy / Issue 2/2018
Print ISSN: 2193-8245
Electronic ISSN: 2193-6528
DOI
https://doi.org/10.1007/s40123-018-0144-8

Other articles of this Issue 2/2018

Ophthalmology and Therapy 2/2018 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.