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2/1/99 Chapter 1 Background page 1-16
corroborated this finding (Critchfield et al., 1988). Increased collagenase activity in
excised keratoconus corneas has been observed (Rehany et al., 1982). Corneas from
keratoconus patients contain less protein per mg of dry weight than normals. Reduced
protein content may indicate increased nonproteinaceous materials. A high amount of
polyanions including glycosaminoglycans are observed (Yue et al., 1988a). Plasma
membranes of keratoconus patient stromal cells may contained elevated amounts of
glycoconjugates. Glycoconjugates may be influential on cell differentiation and
migration by mediating differences between wounded (or migrating) and nonwounded
corneal epithelial cells. Keratoconus corneas contain reduced levels of a2-
macroglobulin, a proteinase inhibitor (Sawaguchi et al., 1994). Although there is no
certainty that these variations are associated with the pathogenesis of keratoconus,
these variations are of great interest (Yue et al., 1988b).
Central anterior corneal epithelial staining formations (trauma) are typical in
keratoconus (Dangel et al., 1984). Central corneal sensitivity is reduced in keratoconus,
especially in those keratoconus patients wearing contact lenses and is correlated with
disease severity in the contact lens-wearing subgroup (Zabala and Archila, 1988;
Millodot and Owens, 1983). It is possible that some keratoconus patients are destined to
scar rapidly. For example, two groups of keratoconus patients have been identified
based on stromal collagen content. Group I has collagen similar to normal controls, and
Group II has reduced collagen content (Yue et al., 1984). Unfortunately, to date, this
analysis cannot be performed in vivo.
1.8 History of the CLEK Study
• June 1988: CLEK Study concept initiated at the first Clinical Trials Workshop,
sponsored by the AOA Council on Research and the American Academy of
Optometry Research Committee.
• December 1988: Initial meeting, involving all members of the Executive Committee.
Pilot studies initiated.
• February 1989: Meeting with Richard Mowery, PhD, National Eye Institute staff.
• April 1989: Screening study initiated.
• May 1989: Major meeting in conjunction with the ARVO conference in Sarasota,
Florida. Representatives of potential clinical centers invited. Consensus that the
Study Group had indeed developed a high level of collaboration around a common
purpose, decision to proceed with additional pilot studies even as the Planning
Grant proposal was being prepared.
• August 1989: Planning grant submitted to National Eye Institute.
• March 1990: NEI Planning grant funded (R21 EY08652-01). Weekly conference calls
initiated between Drs. Barr (Ohio State University), Edrington (Southern California
College of Optometry), Gordon (Washington University), and Zadnik (UC
Berkeley).
• March-April 1990: Pilot randomization begun at SCCO by Timothy Edrington, to