The development of corneal edema in herpes simplex virus type 1-infected rabbits following termination of therapy for corneal stromal disease.

One complication of combined antiviral/corticosteroid therapy for herpetic stromal disease in patients is rebound of disease upon termination of therapy. To develop a model of steroid rebound, rabbits were injected intrastromally with 10(3) pfu of HSV-1 (RE strain). Therapy with 1% trifluorothymidine (F3TdR) alone or in combination with immunosuppressive agents was initiated 7 days post-infection, at a time when epithelial disease had reached its peak and corneal thickness had begun to increase. Therapy was continued 5 times daily through day 18 post-infection. Following cessation of therapy 13 of 16 eyes receiving both 1% F3TdR and 0.125% prednisolone acetate experienced rebound of disease characterized by an increase in corneal thickness from 514 +/- 106 microns to 743 +/- 189 microns, reaching a maximum at 27 +/- 3 days post-infection. Rabbits receiving therapy with either phosphate buffered saline or F3TdR alone displayed rebound in 2 and 3 of 12 eyes, respectively. Rabbits receiving F3TdR combined with either cyclosporine or deoxycoformycin experienced rebound of disease in 9 of 20 and 6 of 16 eyes, respectively. Cultures of eye washings taken from eyes at the time of rebound were negative in all cases. The data indicate that only steroids significantly increased the proportion of eyes with rebounding stromal disease and corneal edema. These studies document steroid rebound of stromal disease in an animal model.