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

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ClinicalTrials.gov Identifier: NCT03071302
Recruitment Status : Completed
First Posted : March 6, 2017
Last Update Posted : March 6, 2017
Sponsor:
Collaborator:
Fundação de Amparo à Pesquisa do Estado de São Paulo
Information provided by (Responsible Party):
Gildasio Castello de Almeida Junior, Sao Jose do Rio Preto Medical School

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Keratoconus Keratoconus, Unspecified, Bilateral Other: EVALUATION OF VSX1, SOD1, and TIMP3 genes Not Applicable

Detailed Description:
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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 210 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Screening
Official Title: Evaluation of Tomographic and Genetic Aspects of Keratoconus Patients Compared to Sounds Corneas
Actual Study Start Date : August 1, 2015
Actual Primary Completion Date : December 31, 2016
Actual Study Completion Date : December 31, 2016

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: keratoconus

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
Evaluation of VISX1, SOD1, TIMP3 genes in corneal epithelium, and in peripheral blood. Evaluation of pentacam parameters
Other Name: pentacam and gene evaluation

Placebo Comparator: sound cornea

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
Evaluation of VISX1, SOD1, TIMP3 genes in corneal epithelium, and in peripheral blood. Evaluation of pentacam parameters
Other Name: pentacam and gene evaluation




Primary Outcome Measures :
  1. 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. [ Time Frame: 18 months ]
    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.


Secondary Outcome Measures :
  1. Tomographic parameters [ Time Frame: 18 months ]

    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.


  2. Genetic evaluation, VISX1, SOD1, TIMP3 [ Time Frame: 18 months ]

    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.



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Ages Eligible for Study:   10 Years to 60 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03071302


Locations
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Brazil
Visum Eye Center / Immunogenetic laboratory of FAMERP
Sao Jose do Rio Preto, Sao Paulo, Brazil, 15015-020
Sponsors and Collaborators
Sao Jose do Rio Preto Medical School
Fundação de Amparo à Pesquisa do Estado de São Paulo
Investigators
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Principal Investigator: Gildasio C Almeida Jr, MD, PhD FAMERP, Visum Eye Center
Publications of Results:

Other Publications:
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Responsible Party: Gildasio Castello de Almeida Junior, PROF. DR., Sao Jose do Rio Preto Medical School
ClinicalTrials.gov Identifier: NCT03071302    
Other Study ID Numbers: CAAE 44071315.7.0000.5415
2015/17226-7 ( Other Grant/Funding Number: FAPESP )
First Posted: March 6, 2017    Key Record Dates
Last Update Posted: March 6, 2017
Last Verified: February 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Gildasio Castello de Almeida Junior, Sao Jose do Rio Preto Medical School:
Keratoconus,Corneal Dystrophies, corneal Tomography, topography
Additional relevant MeSH terms:
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Keratoconus
Corneal Diseases
Eye Diseases
Tissue Inhibitor of Metalloproteinase-3
Matrix Metalloproteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action