The focus of this grant is to develop reliable topographic criteria for detecting subclinical forms of keratoconus to enable us to conduct critical pedigree analyses and delineate modes of inheritance of familial keratoconus. These data combined with cell lines established on the multiple keratoconus families ascertained will create a unique resource for future molecular genetic studies. 1,000 subjects(200 normals, 300 keratoconus probands and 500 keratoconus family members) will undergo ocular evaluation and videokeratography over a 5 year period to observe longitudinal clinical and topographic trends. The goal is to examine the relationship of videokeratography variables to biomicroscopic indicators - of disease status and develop criteria for 'mildly affected' (subclinical) keratoconus family members. Upon completion of the longitudinal analyses of study subjects and once criteria have been devised for identifying 'mildly affected' individuals, family data will be analyzed by complex segregation analysis techniques to determine the mode(s) of inheritance of the various definitions of the keratoconus phenotype. Establishing reliable criteria for 'mild' topographic phenotypes, critical for constructing accurate family pedigrees, will enable us to pursue a variety of molecular genetic linkage studies using permanent lymphoblastoid lines established on the many useful keratoconus family pedigrees ascertained thus far in this study. Identifying a gene or genes contributing to the pathogenesis of keratoconus may provide insights into devising medical therapy to arrest its progression and prevent the need for multiple contact lens changes and/or cornea transplantation in select individuals.

National Institute of Health (NIH)
National Eye Institute (NEI)
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Visual Sciences A Study Section (VISA)
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Cedars-Sinai Medical Center
Los Angeles
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Khaled, Mariam Lofty; Bykhovskaya, Yelena; Yablonski, Sarah E R et al. (2018) Differential Expression of Coding and Long Noncoding RNAs in Keratoconus-Affected Corneas. Invest Ophthalmol Vis Sci 59:2717-2728
Perez-Straziota, Claudia; Gaster, Ronald N; Rabinowitz, Yaron S (2018) Corneal Cross-Linking for Pediatric Keratcoconus Review. Cornea 37:802-809
Bykhovskaya, Yelena; Fardaei, Majid; Khaled, Mariam Lotfy et al. (2017) TSC1 Mutations in Keratoconus Patients With or Without Tuberous Sclerosis. Invest Ophthalmol Vis Sci 58:6462-6469
Bykhovskaya, Yelena; Li, Xiaohui; Taylor, Kent D et al. (2016) Linkage Analysis of High-density SNPs Confirms Keratoconus Locus at 5q Chromosomal Region. Ophthalmic Genet 37:109-10
Bykhovskaya, Yelena; Gromova, Anastasia; Makarenkova, Helen P et al. (2016) Abnormal regulation of extracellular matrix and adhesion molecules in corneas of patients with keratoconus. Int J Keratoconus Ectatic Corneal Dis 5:63-70
Bykhovskaya, Yelena; Margines, Benjamin; Rabinowitz, Yaron S (2016) Genetics in Keratoconus: where are we? Eye Vis (Lond) 3:16
Bykhovskaya, Yelena; Caiado Canedo, Ana L; Wright, Kenneth W et al. (2015) C.57 C > T Mutation in MIR 184 is Responsible for Congenital Cataracts and Corneal Abnormalities in a Five-generation Family from Galicia, Spain. Ophthalmic Genet 36:244-7
Kramerov, Andrei A; Saghizadeh, Mehrnoosh; Maguen, Ezra et al. (2015) Persistence of reduced expression of putative stem cell markers and slow wound healing in cultured diabetic limbal epithelial cells. Mol Vis 21:1357-67
Bykhovskaya, Yelena; Seldin, Michael F; Liu, Yutao et al. (2015) Independent origin of c.57 C?>?T mutation in MIR184 associated with inherited corneal and lens abnormalities. Ophthalmic Genet 36:95-7
Rabinowitz, Yaron S; Li, Xiaohui; Canedo, Ana Laura Caiado et al. (2014) Optical coherence tomography combined with videokeratography to differentiate mild keratoconus subtypes. J Refract Surg 30:80-7

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