Identification and Validation of Functional Biomarkers for Keratoconus

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2012 by Narayana Nethralaya
Sponsor:
Collaborator:
Singapore Eye Research Institute
Information provided by (Responsible Party):
Dr Rohit Shetty, Narayana Nethralaya
ClinicalTrials.gov Identifier:
NCT01746823
First received: December 7, 2012
Last updated: March 5, 2014
Last verified: December 2012
  Purpose

There is currently no medication for containing KC, nor any adequate biomarkers to predict the disease. Furthermore, there is considerable confusion in the field regarding the pathophysiology of the disease and involvement of inflammation. To that end, this study is designed to address some of these questions by determining the proteomic profiles of KC patients with different clinical grades. This relatively large cohort study is expected to yield significant information regarding the molecules that are deregulated during progression of KC and may provide a framework to assign diagnostic biomarkers and therapeutic intervention points.


Condition Intervention
Keratoconus
Drug: Cyclosporins

Study Type: Observational [Patient Registry]
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Target Follow-Up Duration: 6 Months
Official Title: Identification of Disease Progression Specific Biomarkers and Their Pharmacologic Modulation for Keratoconus.

Resource links provided by NLM:


Further study details as provided by Narayana Nethralaya:

Primary Outcome Measures:
  • Keratoconus grade specific biomarker identification [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Onlabel use of anti-allergic topical treatment for inhibition of specific biomarkers to modify keratoconus disease progression [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples Without DNA

Tear samples and discarded epithelium from Keratoplasty surgeries.


Estimated Enrollment: 200
Study Start Date: April 2013
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Controls, Keratoconus
Sub group of Keratoconus to be treated with anti-inflammatory agents ie Cyclosporine-A
Drug: Cyclosporins
Other Name: Restasis

Detailed Description:

The screening of keratoconus involves keratoconus related clinical signs like retinoscopy scissors reflex, Munson sign, stromal thinning, Vogt's striae, and Fleischer's ring, but corneal topography is the most useful method in the diagnosis of keratoconus, especially in the absence of clinical signs.

Several devices are currently available for detecting early keratoconus by measuring anterior and posterior corneal topography and elevation(Mihaltz et al. 2009; Ishii et al. 2012). Corneal topographic and tomographic techniques which generate color-coded maps and topographic indices, are the most sensitive devices for confirming the diagnosis of keratoconus(Rabinowitz 1998; Rao et al. 2002) were used for diagnosis in this study. In addition, videokeratography has been shown to identify Forme fruste keratoconus (FFKC) in the absence of clinical signs of keratoconus. Videokeratographic indices such as the Klyce/Maeda criteria, the Rabinowitz criteria, and others have been developed to quantitatively analyze videokeratography and screen for keratoconus(Rao et al. 2002). These indices have been shown to identify keratoconus with a high degree of sensitivity and specificity. The Orbscan II is a three-dimensional slit-scan topography system for analysis of the corneal surfaces and anterior chamber and has been used on all patients in the study. It uses calibrated video and a scanning slit beam to measure x, y, and z locations of several thousand points. These points are used to construct topographic maps(Rao et al. 2002). The Pentacam (Oculus Inc) is a corneal tomographer technology which generates data on topograophy and elevation of anterior and posterior using a rotating Scheimpflug camera which has also been used on all subjects enrolled in this study. Various diagnostic parameters are available for keratoconus diagnosis depending on what mode of topography is being used. Maeda and Klyce designed a system to detect keratoconus. The system, which is based on linear discriminant analysis and a binary decision tree, identifies the map as representing keratoconus or nonkeratoconus and, based on a value from the discriminant analysis (the KPI), assigns the map an index expressed as a percentage that suggests the severity of keratoconus. At this time, however, Keratoconus Severity Index (KSI) and the Amsler-Krumeich classification are the most popular methods for grading keratoconus severity(Mihaltz et al. 2009; Ishii et al. 2012). KSI is based on indices estimated by a curvature map using Placido disk-based corneal topography, and Amsler-Krumeich classification defines the stage of keratoconus using biomicroscopy, mean central keratometry reading, spherical and cylindrical refraction change, and corneal thickness(Mihaltz et al. 2009; Ishii et al. 2012). This is the index that has been used for the final gradation of keratoconus stages of all subjects in this study.

  Eligibility

Ages Eligible for Study:   10 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Patients detected with corneal thinning by keratometry at a tertiary level hospital

Criteria

Inclusion Criteria:

  • Evidence of corneal thinning by any type of keratometry

Exclusion Criteria:

  • Corneal inflammation without evidence of ectasia
  • Retinal disorder subjects excluded
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01746823

Locations
India
Narayana Nethralaya Recruiting
Bangalore, Karnataka, India, 560010
Contact: Rohit Shetty, DNB, FRCS    91-9611102568    drrohitshetty@yahoo.com   
Principal Investigator: Rohit Shetty, MBBS, DNB, FRCS         
Sponsors and Collaborators
Narayana Nethralaya
Singapore Eye Research Institute
Investigators
Principal Investigator: Rohit Shetty, MBBS,DNB, FRCS Narayana Nethralaya
  More Information

Publications:
Responsible Party: Dr Rohit Shetty, Consultant, Cornea and Refractive Services, Narayana Nethralaya
ClinicalTrials.gov Identifier: NCT01746823     History of Changes
Other Study ID Numbers: NNKC-2011
Study First Received: December 7, 2012
Last Updated: March 5, 2014
Health Authority: India: Institutional Review Board

Keywords provided by Narayana Nethralaya:
Keratoconus
Proteomics

Additional relevant MeSH terms:
Keratoconus
Corneal Diseases
Eye Diseases
Cyclosporins
Cyclosporine
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Dermatologic Agents
Antirheumatic Agents

ClinicalTrials.gov processed this record on September 30, 2014