Identification and Validation of Functional Biomarkers for Keratoconus

NCT ID: NCT01746823

Last Updated: 2014-03-06

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 200 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2013-04-30
• Study Completion Date: 2015-12-31

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.

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.

Conditions

Keratoconus

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

Controls, Keratoconus

Sub group of Keratoconus to be treated with anti-inflammatory agents ie Cyclosporine-A

Cyclosporins

Intervention Type: DRUG

Interventions

Cyclosporins

Intervention Type: DRUG

Other Intervention Names

Restasis

Eligibility Criteria

Inclusion Criteria

• Evidence of corneal thinning by any type of keratometry

Exclusion Criteria

• Corneal inflammation without evidence of ectasia
• Retinal disorder subjects excluded

• Minimum Eligible Age: 10 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Singapore Eye Research Institute

OTHER

Sponsor Role: collaborator

Narayana Nethralaya

OTHER

Sponsor Role: lead

Responsible Party

Dr Rohit Shetty

Consultant, Cornea and Refractive Services

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Rohit Shetty, MBBS,DNB, FRCS

Role: PRINCIPAL_INVESTIGATOR

Narayana Nethralaya

Locations

Narayana Nethralaya

Bangalore, Karnataka, India

Site Status: RECRUITING

Countries

India

Facility Contacts

Rohit Shetty, DNB, FRCS

Role: primary

drrohitshetty@yahoo.com

91-9611102568

References

Gontier J, Fisch U. Schirmer's test: its normal values and clinical significance. ORL J Otorhinolaryngol Relat Spec. 1976;38(1):1-10. doi: 10.1159/000275252.

Reference Type: BACKGROUND

PMID: 943747 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 25648341 (View on PubMed)

Other Identifiers

NNKC-2011

Identifier Type: -

Identifier Source: org_study_id