Clinical trial NCT01746823: Identification and Validation of Functional Biomarkers for Keratoconus
Official title: Identification of Disease Progression Specific Biomarkers and Their Pharmacologic Modulation for Keratoconus.
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Keratoconus
Keywords: Keratoconus
Proteomics
Lead sponsor: Narayana Nethralaya
Sponsor class: OTHER
Collaborators: name: Singapore Eye Research Institute
First posted: 2012-12-11
Enrollment: 200
Sex: ALL
Minimum age (years): 10
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients detected with corneal thinning by keratometry at a tertiary level hospital

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.

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

Primary outcomes:
measure: Keratoconus grade specific biomarker identification
timeFrame: 1 year
Secondary outcomes:
measure: Onlabel use of anti-allergic topical treatment for inhibition of specific biomarkers to modify keratoconus disease progression
timeFrame: 2 years
Other outcomes:
Locations:
city: Bangalore
country: India
facility: Narayana Nethralaya
state: Karnataka
Study officials:
affiliation: Narayana Nethralaya
name: Rohit Shetty, MBBS,DNB, FRCS
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.