[Comparison of the effectiveness of acyclovir and vidarabine in superficial herpes keratitis]. Acyclovir and vidarabine in the treatment of ulcerative herpes simplex keratitis. A double-blind, multicenter clinical trial of acyclovir vs idoxuridine for treatment of epithelial herpes simplex keratitis. A randomised double-blind clinical trial of acyclovir (Zovirax) and adenine arabinoside in herpes simplex corneal ulceration. Combination therapy for dendritic keratitis with acyclovir and vidarabine. [Acyclovir and trifluorothymidine in herpetic kerato-uveitis. A comparative clinical study. Indications for corticoid therapy]. Randomised double-blind trial of acyclovir and idoxuridine in dendritic corneal ulceration. Ganciclovir ophthalmic gel (Virgan; 0.15%) in the treatment of herpes simplex keratitis. Ganciclovir ophthalmic gel, 0.15%: a valuable tool for treating ocular herpes.
In a double-blind clinical trial 28 patients with primary and recurrent herpetic corneal ulcerations were treated either with 3% Acyclovir eye ointment or 3% Adenosine Arabinoside eye ointment. In 11 out of 14 (78%) patients treated with Acyclovir and 8 out of 14 (57%) patients treated with Adenosine Arabinoside the ulcerations healed within a treatment period of 6.5 days and 8 days respectively (no statistical significance). However, the results revealed that Acyclovir was more effective. Both drugs were well tolerated. In a masked controlled study, we treated 41 patients who had active herpes simplex corneal ulcers with either 3% acyclovir of 3% vidarabine ointment five times daily for 14 days. There was no statistically significant difference between the two drugs with reference to mean healing time, efficacy of healing, development of stromal keratitis or iritis, post-treatment visual acuity, or adverse reaction. Thirty patients randomized to the Acyclovir (ACV) group (26 with dendritic lesions, 4 geographic lesions) and 34 patients randomized to the idoxuridine (IDU) treatment group (26 dendritic lesions, 8 geographic lesions) with epithelial herpetic keratitis were evaluated for efficacy and adverse reactions in a multi-center, double-masked, randomized, stratified trial. Patients were treated with either 3% acyclovir ophthalmic ointment or 0.5% idoxuridine ophthalmic ointment five times a day for 14 days. The results of the trial indicated no significant difference between ACV and IDU as antiviral agents in the treatment of epithelial herpetic keratitis. The overall healing patterns of ACV and IDU adjusted for lesion type and prognostic factors, including presenting condition (initial or recurrent disease), duration of symptoms, prior ophthalmic steroid use, and positive pretreatment herpesvirus culture, as well as, the healing patterns within each lesion type adjusted for these factors, were not significantly different between the two treatment groups. There was no significant difference between the two groups in the frequency of development of deeper involvement. The only significant difference (P less than 0.01) in the frequency of development of adverse reactions was found in the incidence of development of superficial punctate epitheliopathy (IDU-42%, ACV-11%). A double-blind clinical trial of 3% acyclovir (Zovirax) and 3% adenosine arabinoside (ara-A, Vidarabine) in 93 patients with herpetic corneal ulceration is presented. Ulcers in 45 (94%) of acyclovir-treated patients and 37 (82%) ara-A-treated patients healed within 14 days. Patients treated with acyclovir healed more rapidly than those treated with ara-A (p less than 0.01). No serious adverse effects were observed. We treated 32 patients with dendritic keratitis with a combination of acyclovir 3% ointment and vidarabine 3% ointment or acyclovir and placebo. Patients with acyclovir alone healed in an average time of 7.7 days, while patients on the combination healed in an average of 6 days. Only one patient in the acyclovir and vidarabine group had a healing time longer than 7 days, whereas six patients in the acyclovir and placebo group had healing times longer than 7 days. By the median test, this difference in healing times was statistically significant (p = 0.035), and the combination prevented cases of prolonged ulceration. The relative efficacy of aciclovir (ACV) and trifluorothymidine (TFT) was evaluated in a randomized, open clinical trial of 37 patients with herpetic kerato-uveitis. Twenty-one patients were treated with ACV and 16 with TFT. Topical steroids were withheld as long as the degree of inflammation permitted. Although both drugs were effective in healing the herpetic corneal ulcers, TFT had a significantly shorter healing time than ACV. However, ACV was more effective in treating the iridocyclitis than TFT. In 5 cases the keratouveitis responded to ACV alone, while only one case was successfully managed with TFT alone. Both drugs seemed to prevent steroid-induced epithelial complications and no significant side-effects were observed with either drug. The treatment of herpetic keratouveitis with single agents such as ACV and TFT is dependent upon rapidly instituting therapy and minimizing the use of topical steroids. The apparently good intraocular penetration of ACV and TFT may decrease the need for adjunctive steroid therapy and thereby minimize the risks of facilitated viral replication and steroid-dependence. The results of a randomised double-blind clinical trial of 3% acyclovir and 0.5% idoxuridine (IDU) ophthalmic ointments in 60 patients with corneal dendritic ulceration are presented. Ulcers in all 30 patients treated with acyclovir healed compared with 22 (76%) of 29 patients treated with IDU (P < 0.01). Patients treated with acyclovir healed more rapidly (average 4.4 days) than those who received IDU (average 9.2 days) (P < 0.01). No serious side effects were observed, though transient stinging was recorded in 8 patients receiving acyclovir and in 2 patients receiving IDU. Other side effects in the IDU treated group were watering in 2 patients and superficial punctate erosions in 6 patients. Ganciclovir is a broad-spectrum virustatic agent. Its efficacy and safety after ocular application have been demonstrated in studies of herpetic keratitis in rabbits. Two strengths of ganciclovir gel (0.05 and 0.15%) were compared with 3% acyclovir ointment in the treatment of superficial herpes simplex keratitis in humans.
                Two multicenter randomized clinical trials were carried out in Africa (Trial 1) and Europe (Trial 2). Sixty-seven patients (Trial 1) and 37 patients (Trial 2) from herpetic ulceration were recruited.
                The results showed no statistically significant difference between the treatment groups, although the healing rates tended to be better in the group receiving 0.15% ganciclovir gel, with healing rates of 85% (Trial 1) and 83% (Trial 2) as compared with 72% (Trial 1) and 71% (Trial 2) in the group receiving acyclovir ointment. Local tolerance was found to be superior with the gel formulation of ganciclovir with fewer complaints of discomfort (stinging, burning) or blurred vision after application of the drug. Systemic absorption of the drug was low. No hematologic changes were detected.
                These findings support the efficacy of ganciclovir gel in the treatment of ulcerative herpes simplex keratitis and demonstrate its superior local tolerance when compared with acyclovir ointment. Ocular herpes simplex virus (HSV) infection remains a major cause of corneal blindness. Several topical and oral antiviral medications have been used to treat herpetic keratitis. Advances in topical ophthalmic antivirals have been made over the past several decades. The first antivirals that were discovered were cytotoxic, while the antivirals developed more recently, such as acyclovir and ganciclovir, have exceeded these drugs in both efficacy and tolerability. Commercially available outside of the US since 1996, ganciclovir ophthalmic gel, 0.15% (GCV 0.15%, European tradename: Virgan((R))) is sold in more than 30 countries and has become the standard of care in treating acute herpetic keratitis. GCV 0.15% has been studied in animal models of ocular herpes, in healthy volunteers, and in several clinical studies. It has been found to be safe and effective at treating acute superficial herpetic keratitis. Previous preclinical studies of ganciclovir have shown activity against several common adenovirus strains and one recent clinical study demonstrated clinical effect against adenoviral conjunctivitis. This review is intended to provide a comprehensive overview of the GCV 0.15%, including a brief summary of the etiology and available treatments for ocular HSV, an explanation of GCV 0.15% mechanism of action, a compendium of preclinical and clinical GCV 0.15% studies, and an introduction into new areas of interest involving this drug.
Trifluridine and acyclovir are more effective than idoxuridine or vidarabine and similar in therapeutic effectiveness. Brivudine and ganciclovir are at least as effective as acyclovir. While not improving outcome, the combination of interferon and an antiviral agent may speed healing. The effectiveness of corneal epithelial débridement is improved by an antiviral agent.