B.W. Ziegelaar

Development and clinical assessment of an artificial cornea

Keratoprosthesis research has been a gradual, rather fragmentary process with advances being made by isolated groups of researchers. This has arisen partly because of poor funding in the area; research groups which have achieved commercial support have often had constraints upon the full disclosure of their findings. Despite these difficulties there has been real progress over the last decade by several independent groups. This article concentrates upon our own development of a hydrogel core-and-skirt keratoprosthesis, the Chirila KPro, in order to illustrate the scientific and clinical problems common to keratoprosthesis research. Pilot data from a clinical trial is presented and the priorities for future research are discussed.

Assessment of anticollagenase treatments after insertion of a keratoprosthetic material in the rabbit cornea

Purpose This study was performed to evaluate the enzyme production in response to implantation of the hydrogel material used in the experimental Chirila keratoprosthesis (KPro) and to assess the effects of five topical drugs on enzyme production and activity. KPros may be extruded from the cornea as a result of tissue melting, a process that involves excessive enzyme activity. To reduce the possibility of implant loss for the hydrogel Chirila KPro, a number of antiinflammatory drugs that have been used to treat other corneal melting conditions were investigated for their effect on initial collagenase activity after the implantation of KPro material into the rabbit cornea. Methods Poly(2-hydroxyethyl methacrylate) sponge pieces were implanted into rabbit corneas. Prednisolone, tetracycline, medroxyprogesterone, acetylcysteine, and sodium citrate were assessed for effects on gelatinolytic activity and stromal collagenase [matrix metalloprotease-1 (MMP-1)] production in vivo and in vitro by using zymography and Western blotting techniques. Results Whereas all five anticollagenase drugs were effective in reducing gelatinolytic activity in vitro, many were ineffective in vivo. However, medroxyprogesterone caused a reduction of gelatinolytic activity in vivo. The amount of MMP-1, as measured by immunoblotting, also was reduced by medroxyprogesterone treatment when compared with untreated controls. An increase in the apparent molecular weight of MMP-1 in operated corneas appears to be the result of the association of MMP-1 with collagen fragments resulting from the surgical trauma. Conclusion This study indicates that topical medroxyprogesterone may be a useful adjunctive therapy after prosthokeratoplasty.

Hydrophilic Sponges Based on 2-Hydroxyethyl Methacrylate. VI. Effect of Phase Sequence Inversion on the Characteristics of IPN between Sponges and Homogeneous Gels

Poly (2-hydroxyethyl methacrylate) (PHEMA) is currently used as a prosthetic polymer in an artificial cornea consisting of a skirt made of a PHEMA sponge attached to a transparent circular core of homogeneous PHEMA hydrogel. Along the interface between components, a gradient IPN was achieved by using PHEMA sponge as polymer I into which the precursor liquid monomer mixture for the central hydrogel diffused significantly prior to polymerization. In this study, the phase sequence was reversed in order to find whether the inversion affects the manufacture of prosthesis. By using the homogeneous hydrogel as polymer I, the diffusion of liquid monomer mixture for the sponge is negligible. As a result, the IPN region along the interface is very narrow and leads to a weak union between prosthetic polymers. The direct phase sequence (in which PHEMA sponge is polymer I) should be exclusively used for the manufacture of such prostheses.