Identification and Validation of Functional Biomarkers for Keratoconus

Study Description

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Brief Summary:

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 or disease	Intervention/treatment
Keratoconus	Drug: Cyclosporins

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.

Study Design

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Study Type :	Observational [Patient Registry]
Estimated Enrollment :	200 participants
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.
Study Start Date :	April 2013
Estimated Primary Completion Date :	December 2015
Estimated Study Completion Date :	December 2015

Groups and Cohorts

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Group/Cohort	Intervention/treatment
Controls, Keratoconus; Sub group of Keratoconus to be treated with anti-inflammatory agents ie Cyclosporine-A	Drug: Cyclosporins; Other Name: Restasis

Outcome Measures

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :

1. Keratoconus grade specific biomarker identification [ Time Frame: 1 year ]

Secondary Outcome Measures :

1. Onlabel use of anti-allergic topical treatment for inhibition of specific biomarkers to modify keratoconus disease progression [ Time Frame: 2 years ]

Biospecimen Retention:   Samples Without DNA

Tear samples and discarded epithelium from Keratoplasty surgeries.

Eligibility Criteria

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Ages Eligible for Study:	10 Years to 80 Years (Child, Adult, Senior)
Sexes Eligible for Study:	All
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

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

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

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications:

Gontier J, Fisch U. Schirmer's test: its normal values and clinical significance. ORL J Otorhinolaryngol Relat Spec. 1976;38(1):1-10.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Shetty R, Ghosh A, Lim RR, Subramani M, Mihir K, Reshma AR, Ranganath A, Nagaraj S, Nuijts RM, Beuerman R, Shetty R, Das D, Chaurasia SS, Sinha-Roy A, Ghosh A. Elevated expression of matrix metalloproteinase-9 and inflammatory cytokines in keratoconus patients is inhibited by cyclosporine A. Invest Ophthalmol Vis Sci. 2015 Feb 3;56(2):738-50. doi: 10.1167/iovs.14-14831.

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
First Posted:	December 11, 2012
Last Update Posted:	March 6, 2014
Last Verified:	December 2012

Keywords provided by Dr Rohit Shetty, Narayana Nethralaya:

Keratoconus; Proteomics

Additional relevant MeSH terms:

Keratoconus; Corneal Diseases; Eye Diseases; Cyclosporins; Cyclosporine; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Immunosuppressive Agents	Immunologic Factors; Physiological Effects of Drugs; Antifungal Agents; Anti-Infective Agents; Dermatologic Agents; Antirheumatic Agents; Calcineurin Inhibitors