Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study

Purpose:

To describe the clinical course of keratoconus and to describe the relationships among its visual and physiological manifestations, including high- and low-contrast visual acuity, corneal curvature, slit lamp biomicroscopic findings, corneal scarring, and quality of life.
To identify risk factors and protective factors that influence the severity and progression of keratoconus.

Background:

Keratoconus is a bilateral, asymmetric, chronic, progressive ectasia of the cornea characterized by steepening and distortion of the cornea, thinning of the apical cornea, corneal scarring, and treatment-related sequelae, such as abrasions from contact lenses and surgical complications. Patients experience distorted vision that worsens with disease progression. Their vision is typically corrected with spectacles early in the disease and, later, with rigid contact lenses. Some patients eventually undergo corneal transplantation in one or both eyes. Keratoconus affects people in their prime earning years and profoundly affects their lives.

Previous large-scale studies of keratoconus have focused on incidence and prevalence, etiologies, or the clinical management of keratoconus. Few have characterized the course of the disease and risk factors for its progression in large samples of keratoconus patients. The incidence of vision-threatening corneal scarring in keratoconus is unknown. Patients’ most frequent questions--how rapidly their keratoconus will progress, how bad their vision will become, whether they will need corneal surgery, how successful their contact lenses will be--cannot be answered on the basis of the current body of knowledge.

The need for a prospective, observational study of keratoconus patients is great. Results from this study will address keratoconus patients’ unanswered questions and will enable eye care practitioners to manage this complex ocular disease better.

Description:

The Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study is a multicenter, observational study of 1,209 keratoconus patients followed for 3 years.

Patients are examined annually. Study measures include visual acuity, patient-reported quality of life, manifest refraction, keratometry, photodocumentation of the cornea to identify central corneal scarring, photodocumentation of the flattest contact lens that just clears the cornea, slit lamp biomicroscopy, and corneal topography. In rigid contact lens wearers, the fluorescein pattern of the patient’s habitual contact lenses is photodocumented.

Patients are examined at 15 clinical centers. The clinical centers enrolled 1,209 patients in 12 months.

Patient Eligibility:

Patients with keratoconus were eligible if they were at least 12 years old; had an irregular cornea as determined by keratometry, retinoscopy, or direct ophthalmoscopy in at least one eye; had Vogt’s striae, Fleischer’s ring, or corneal scarring characteristic of keratoconus in at least one eye; and planned to stay in the area for at least 3 years. They were ineligible if they had bilateral corneal transplants or bilateral nonkeratoconic eye disease (cataract, intraocular lenses, macular disease, or optic nerve disease other than glaucoma).

Patient Recruitment Status:

No longer recruiting. Comments: Completed. As of June 15, 1996, 1,209 patients were enrolled. Enrollment began June 1, 1995.

Current Status of Study:

Ongoing. Comments: The last CLEK patient follow-up visit was completed in August, 2004, and no additional data collection is planned. Data analysis and interpretation continue, however, and a number of manuscripts are in preparation or planned.

A comprehensive study archive is available on the web at: https://vrcc.wustl.edu/clekarchive/. This website, part of the official CLEK Study archive compiled after study close, contains extensive documentation of the study's protocol and procedures, detailed documentation of study forms, an introduction to the database, copies of internal newsletters and a bibliography of publications.

Results:

The Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study has found that:

Keratoconus patients are generally rigid gas permeable contact lens wearers with moderately steep corneas.
Corneal scarring is associated with decreased vision in keratoconus.
Contact lens wear increased the risk of incident scarring in keratoconus more than two-fold. These findings suggest the causal contribution of contact lens wear to corneal scarring in keratoconus and imply that corneal scarring might be reduced by modifying the contact lens fit.
Over seven years of follow-up, CLEK subjects exhibited a slow but clear increase in corneal curvature. Younger age and poorer high-contrast manifest refraction visual acuity at baseline predicted the rate of change in corneal curvature.
Over seven years of follow-up, keratoconus patients enrolled in the CLEK Study exhibited a slow but clear decrease in their best-corrected visual acuity with their vision under low-contrast conditions decreasing more rapidly than the vision under high-contrast viewing conditions. Better best-corrected visual acuity, steeper corneal curvature, and fundus abnormalities were predictive of greater acuity loss with time.
After controlling for disease severity in the form of corneal curvature, a keratoconic eye fitted with a rigid contact lens resulting in an apical touch fluorescein pattern did not have an increased risk of being scarred centrally at baseline. This “natural history” sample cannot determine causal proof that one method of fitting lenses is safer than another. To achieve this, a randomized clinical trial is needed.