Evaluation of Tomographic and Genetic Aspects of Keratoconus Patients Compared to Sounds Corneas

Study Overview
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Brief Summary
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Evaluation of tomographic (Pentacam) parameters and genetic parameters of Visual System Homeobox 1 (VSX1), Superoxide Dismutase (SOD1), Tissue Inhibitors of Metalloproteinases (TIMP3) genes of keratoconus patients diagnosed by clinical exam and topographic pattern. Basically we are screening patients that don't have keratoconus that those have keratoconus. The pentacam index of corneal curvature, thinnest point, corneal high order aberrations, posterior and anterior elevation, corneal densitometry, corneal volume were investigated. To analyze the genes, we took corneal epithelium samples of patients submitted to cross linking compared to (PRK) Photo Refractive Keratectomy ones. Also will be evaluated the genes of peripheral blood.

Detailed Description
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Keratoconus is a common disease that affects the cornea in both genders in all ethnic groups and that can manifest unilaterally or bilaterally in patients. Keratoconus due to a degenerative disease, its progression can be fast in various situations, affecting 1 in every 2,000 people, what results in severe structural changes of the cornea, which reduces its thickness and modify its normal curvature to a more conical shape. Keratoconus arises in adolescence and lasts for thirty to forty years of age, where it stabilizes and it is considered a major cause of corneal transplantation. Factors such as atopy, overuse of contact lenses and the act of rubbing the eyes are also related to the disease. The clinical picture consists of a lot of varied symptoms and it depends on the stage of disease progression. Currently it is known that genetic and environmental factors are involved in the desease emergence. Recently several genetic studies have aimed to identify mutations in genes which are directly linked to Keratoconus, such as VSX1, SOD1 and TIMP3 genes. However, despite the efforts directed towards the understanding of the genetic aspects of this disease, involving many genes, there are still many questions about the role of these genes in Keratoconus etiology. Thus, the present study aims to identify the presence of mutations in VSX1, SOD1 and TIMP3 genes, which are considered important candidates for the origin and development of this eye anomaly, through the analysis of their nucleotide sequences in corneal tissue and peripheral blood in Keratoconus patients, in their unilateral and bilateral forms. The results will allow to compare the presented mutations in different analysed tissues for unilateral and bilateral forms of Keratoconus and also compare them with the same tissues in healthy patients, in an attempt to establish what the likely inherited and/or acquired genetic mutations are causing this condition. Thus providing genetic data, still unpublished in Brazilian populations, which may offer subsidies for the characterization of the mutation dynamics and their patterns, on the origin and development of Keratoconus. Also will be evaluated the tomographic index as corneal curvature, thinnest point, corneal high order aberrations, posterior and anterior elevation, corneal densitometry, corneal volume. The idea is focused on that suspicious cornea that has the fellow eye with unequivocal keratoconus.

Official Title
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Evaluation of Tomographic and Genetic Aspects of Keratoconus Patients Compared to Sounds Corneas

Conditions
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Keratoconus, Keratoconus, Unspecified, Bilateral

Intervention / Treatment
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* Other: EVALUATION OF VSX1, SOD1, and TIMP3 genes


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients diagnosed with keratoconus in clinical examination, topography and tomography Patients with clinical examination, topography, and tomography aspect of sound cornea in one eye, and the fellow eye diagnosed with keratoconus by clinical examination, topography, and tomography. Patients diagnosed with keratoconus by clinical examination, topography, and tomography in both eyes (OU). Patients with some degree of ametropia that underwent to PRK and LASIK Exclusion Criteria: History of eye trauma, glaucoma, dysfunctional tear syndrome, rosacea, neurotrophic keratopathy, systemic or topical use of immunosuppressive drugs, previous ocular surgeries.

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Screening
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: keratoconus<br>Evaluation of Visual System Homeobox 1 (VSX1), Superoxide Dismutase (SOD1), Tissue Inhibitors of Metalloproteinases (TIMP3) genes. Keratoconus with fellow eye without topographic and tomographic keratoconous pattern.Evaluation of tomographic datas. Sometimes we picked up the sample of corneal epithelium, and peripheral blood sample from corneal cross linking surgeries, in that case of keratoconus progression. Group A Keratoconus/ like sound cornea. Group C Keratoconus / Keratoconus Group C Keratoconus / Keratoconus | Other: EVALUATION OF VSX1, SOD1, and TIMP3 genes<br>* Evaluation of VISX1, SOD1, TIMP3 genes in corneal epithelium, and in peripheral blood. Evaluation of pentacam parameters<br>* Other names: pentacam and gene evaluation;|
| Placebo Comparator: sound cornea<br>Evaluation of VSX1, SOD1, and TIMP3 genes. To analyze tomographic aspects, we evaluated the patients that underwent to LASIK (Lasei in situ Keratomileusis) with 2 year with follow up without any sign of ectasia To analyze the genes we picked up the sample of corneal epithelium, and peripheral blood sample from PRK (PhotoRefractive Keratectomy) surgeries. These patients showed topographic and tomographic normal pattern. Group B Sound Cornea / Sound Cornea | Other: EVALUATION OF VSX1, SOD1, and TIMP3 genes<br>* Evaluation of VISX1, SOD1, TIMP3 genes in corneal epithelium, and in peripheral blood. Evaluation of pentacam parameters<br>* Other names: pentacam and gene evaluation;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the tomographic parameters of keratoconus, subclinical keratoconus in relation to sound corneas and identify the mutations present in the genes VSX1, SOD1 and TIMP3 in individuals affected by keratoconus. | The aim of this study was to evaluate Evaluate the tomographic parameters of keratoconus, subclinical keratoconus in relation to sound corneas and identify the mutations present in the genes VSX1, SOD1 and TIMP3 in individuals affected by keratoconus in several forms of manifestation. | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tomographic parameters | Evaluating whether cross-referencing of known indexes may improve sensitivity and specificity in the detection of subclinical keratoconus; - Evaluate if there is a correlation between the different tomographic indices; To evaluate the cornea densitometry in patients with keratoconus and its absence. | 18 months | 
| Genetic evaluation, VISX1, SOD1, TIMP3 | Avalue if after removal of the epithelium there is a very large change in the curvature, elevations and topometry of the cornea; Identify the presence of mutations in the VSX1, SOD1 and TIMP3 genes, from nucleotide sequence analysis in tissues of the affected cornea, normal cornea and peripheral blood, in patients with this pathology in their several forms. Compare the mutations present in the different tissues analyzed, for the unilateral and bilateral forms of keratoconus and also to compare them with the same tissues in healthy patients; Establish which are the probable inherited and / or acquired genetic mutations that cause this pathology, from the analysis of the same in the peripheral blood of the affected individuals. | 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Keratoconus,Corneal Dystrophies, corneal Tomography, topography