OM t of c.iii - Vision Research Coordinating Center - Washington ...

2/1/99 Chapter 2 Study Design page 2-4
observational study addresses these deficiencies in our understanding of keratoconus
and its course.
Following the second study section review of the clinical trial and based on the
reviewers’ recommendations, the CLEK Executive Committee conducted a survey in
fall 1993 of all CLEK Study investigators involved in the pilot screening study. The 32
respondents (29 optometrists, 10 of whom are practicing or have practiced in
ophthalmologic settings, and 3 ophthalmologists/cornea specialists) classified 10 areas
of potential study in keratoconus as to their importance. Disease progression, etiology,
and corneal scarring were considered very important to study by 81%, 72%, and 63% of
the respondents respectively. Other high-ranking areas were corneal topography, the
best method for fitting contact lenses, and visual acuity. The survey results and a
subsequent series of conference calls to discuss these issues with the original clinical
trial clinic investigators led the CLEK Executive Committee to the conclusion that there
are important unanswered questions in keratoconus that should be studied before
attempting to conduct a clinical trial of optical management methods, namely to fully
describe keratoconus in the areas of its effect on vision, its progression, and its
accompanying corneal changes.
The need for such an observational study is underscored by recommendations
from the VRRC’s two summary statements and by the recommendation of the National
Advisory Eye Council in September 1993 on a previous proposal for a randomized
clinical trial in keratoconus patients. The initial summary statement, from the
October/November 1992 review, emphasized disease progression, stating, “Most of all,
[the reviewers] felt that disease progression should be the primary focus.” Further, they
identified specific parameters that should be evaluated to describe progression in
keratoconus, namely, “in lens-wearing keratoconus patients, changes in visual acuity ...
and lens fit are good clinical indicators of progression of keratoconus.... Given the
expense of this study [the previously proposed randomized clinical trial], it seems a
shame that the more important question of disease progression will not be evaluated.”
These same reviewers identified a strength of the study, a randomized clinical trial, as
“the development of a patient base for longitudinal studies in this population.”
The second summary statement, from June 1993, called for “pilot data
supporting the validity of the principal hypothesis [of the clinical trial] ... and by
estimates of the sensitivity of the proposed primary variables [visual acuity loss and
contact lens wearing time decrease] in the target population.” They observe that “the
natural history and progression of [keratoconus] is very poorly documented. This is
particularly true in patients who are not wearing contact lenses, since rather few
patients go through a complete evolution of the disease process in the absence of
contact lens intervention.” A more detailed request for pilot data noted, “No data was
provided from trial studies of the likelihood of participants losing two lines of vision or
failing to wear their contact lenses for at least ten hours a day.”
Further, in September 1993 the Council Action sheet from the National Advisory