The antiherpetic effects of 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG) in vitro and in vivo were investigated in comparison with those of acyclovir (ACV) and 5-iodo-2'-deoxyuridine (IDU). ACV was found to be consistently superior to the other two agents in antiviral activity against all ocular isolates in vitro. In vivo tests in mice, in contrast, showed DHPG in ointment form to be more effective than ACV in treating herpetic keratitis. It was noted that even 0.03% DHPG ointment was as efficacious as 0.3% ACV ointment. Other studies using the same keratitis model also demonstrated that DHPG eyedrop solution is far more effective than IDU eyedrop solution. These results indicate that DHPG can be a useful antiviral agent in the treatment of herpetic keratitis.
Fluoroquinolones provide an important single antibiotic therapy for bacterial keratitis caused by Staphylococcus aureus and numerous gram-negative bacteria, including Pseudomonas aeruginosa. The pharmacokinetics of three ocular fluoroquinolones, norfloxacin (CHIBOXIN, Merck, Sharp & Dohme), ciprofloxacin (CILOXAN, Alcon Laboratories), and ofloxacin (OCUFLOX, Allergan Pharmaceuticals), have been studied in the human eye and in both the normal rabbit eye and rabbit models of keratitis. However, the pharmacokinetics of ciprofloxacin have not been previously studied in the tear film of rabbits. This study was done to determine the pharmacokinetics of topical ciprofloxacin in the rabbit tear film. Two drops of CILOXAN were applied to the eyes of normal rabbits. Tear samples were collected at 5, 10 and 30 minutes, and 1, 2, 4 and 6 hours after topical drug application. Tear samples were analyzed for ciprofloxacin concentrations by HPLC. Ciprofloxacin concentrations reached a peak at 5 minutes, then declined in a manner similar to that reported for norfloxacin and ofloxacin. The ciprofloxacin concentrations in tears were substantially higher throughout the length of the study than the MIC90 for most ocular pathogens including Staphylococcus aureus and Pseudomonas aeruginosa.
To determine definitively the epithelial origin of corneal resurfacing and to elucidate the immunologic mechanisms of epithelial rejection in a murine keratoepithelioplasty (KEP) model.After corneal epithelial removal and peritomy, donor corneal lenticules were grafted around the limbus (KEP procedure). The process of corneal reepithelialization was observed with 0.25% methylene blue staining. The origin of the renewed epithelium was determined by immunofluorescence. Syngeneic corneal lenticules were grafted to BALB/c mice. C3H/He, C57BL/6, BALB.K, DBA/2, and B10.D2 allogeneic corneal lenticules were grafted to BALB/c mice, and A.SW and A.TL allogeneic corneal lenticules were grafted to A.TH mice. Alloepithelial rejection was evaluated on the basis of clinical findings and histologic changes in grafted corneas.All KEP grafts were reepithelialized entirely at 3 days after surgery. The renewed epithelium proved to be derived from the lenticules in BALB/c eyes receiving C3H/He lenticules. In syngeneic grafts 5 days after KEP, the cornea recovered clarity and smoothness, which persisted to the end of the study. After complete reepithelialization, all allogeneic grafts also experienced a short duration of clear cornea. Then followed four characteristic phases of inflammatory epithelial response: initial phase, acute phase, chronic phase, and rejected phase. Histologic examination confirmed the progress and severity of inflammatory response. The mean onset times of initial phase in assorted grafts with mismatched histocompatibility antigens were: 7.9 +/- 1.8 days for both major and minor disparity grafts, 9.5 +/- 3.8 days for major disparity grafts, 18.2 +/- 5.5 days for major histocompatibility class I disparity grafts, 25.6 +/- 7.2 days for major histocompatibility class II disparity grafts, and 9.2 +/- 2.2 days for multiple minor disparity grafts.In donor corneal lenticule grafting to host eyes with corneal epithelium removed and conjunctival peritomy, the ocular surface was reepithelialized by lenticule-derived epithelium. Alloepithelial rejection in this model displayed characteristic manifestations and well-defined processes, enabling easy and precise evaluation of onset and intensity of graft rejection. Both major and minor histocompatibility antigens are related to corneal epithelial rejection.
