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Aims-This study was designed to assess the relative efficacy of topical ganciclovir 0.15% gel and acyclovir 3/o ointment in the treatment of herpes simplex dendritic keratitis. Methods-Both treatment modalities were administered on a five times daily basis to patients suffering from herpes simplex keratitis. Patients were assigned randomly to one of the two treatment groups for the purpose of the trial. They were then examined on days 2, 7, 10, and 14 to assess the rate of healing of the dendritic ulceration. Results-There was no statistically significant difference detected in the rate of healing between the two treatment groups over the course of the trial. Conclusions-Review of the relative efficacy of topical ganciclovir and acyclovir in the treatment of herpes simplex dendritic keratitis showed that both treatment modalities were equally effective in their ability to heal the viral induced corneal ulceration. There were no significant side effects or adverse effects reported for either treatment modality.

Aim-Peripheralulcerative keratitis (PUK) is an ocular manifestation of rheumatoid arthritis and other similar systemic diseases. The purpose of this inquiry was to investigate the involvement of matrix metalloproteinases (MMPs) in the induction and/or maintenance of PUK. Methods-Substrate gel electrophoresis was used to characterise the MMP activities secreted by primary cultures of keratocytes derived from normal and perforated pathological corneal specimens, and those present in tears of normal subjects and patients with PUK. Substrate specificity and the in vivo activity status of the secreted MMPs was assessed by SDS-polyacrylamide gel electrophoresis of standard collagens incubated in the presence or absence of the various enzyme preparations. Results-In addition to MMP-2 of M r 66 000, cultured keratocytes derived from perforated corneas of patients with PUK abnormally produce the MMP-2 of apparent M r 62 000. Other MMPs and in particular MMP-9 of M r 92 000, also occur in the tears of these patients. Their visualisation on substrate polyacrylamide gels correlated with clinical manifestations of disease activity; during periods of disease quiescence they were barely detectable. The steroid prednisolone, frequently used in systemic therapy, had no eVect on the in vitro activity of MMP-2, or on its production by cultured corneal keratocytes. Although the in vitro activity of MMP-2 was inhibited by both Cu 2+ and Zn 2+, Cu 2+ apparently induced the keratocytes to produce activated enzyme and Zn 2+ irreversibly inhibited their production of MMP-2. Conclusion-Overexpression of corneal MMP-2 and tear film MMP-9 are characteristic features of patients with PUK and their activation may be a crucial facet of disease initiation or progression. Although eVective in systemic therapy for PUK, prednisolone had no direct control over corneal MMP-2 production or activity. Zn 2+ on the other hand inhibited both MMP-2 production and MMP-2 activity and may, therefore, be of therapeutic value if suitably formulated and used in conjunction with systemic steroid treatment. (Br J Ophthalmol 1999;83:1376-1383

Keratoconus is an ocular disorder in which the central cornea becomes thin, conical and frequently scarred. We are exploring the possibility that this condition is induced and maintained by proteases that exist in the corneal matrix in an activated form. In this study, the activities of the proteases secreted in vitro and in vivo by keratocytes of normal, clear keratoconic, scarred keratoconic and traumatically scarred corneas have been compared and partially characterised. Data obtained by assaying acyl transferase activity showed that the matrix metalloproteinases account for a minimum of 95% of the total protease secreted by cultured keratocytes. Their summated specific activity was consistently and significantly higher in the culture medium of keratoconic keratocytes than in the medium of other keratocyte cultures. Analysis of the individual protease activities secreted by these corneal keratocytes in vitro and in vivo by SDS-gelatin polyacrylamide gel electrophoresis showed that a gelatinase of molecular weight 65,000 is the major protease secreted by normal keratocytes. Whereas clear keratoconic and traumatically scarred corneal keratocytes secrete an additional activity of molecular weight 61,000, scarred keratoconic corneal keratocytes generally produced little or none of this gelatinase activity. Both activities may be ascribed to gelatinase A, and although the 61,000 molecular weight form may be a significant feature of keratoconus, neither appears to be active as secreted.