Vidarabine therapy of simple and IDU-complicated herpetic keratitis. Treatment of herpes simplex keratitis: comparison of acyclovir and vidarabine. [On the treatment of dendritic keratitis with para-fluorophenylalanine]. [Studies on the effectiveness of non-specific and virostatic treatment of dendritic keratitis with special reference to the combination of 5-iodo-2-deoxyuridine and para-fluorphenylalanine]. Combination therapy of recombinant human alpha 2 interferon and acyclovir in the treatment of herpes simplex keratitis. Assessment of possible potentiating action of ultraviolet light on 5 iodo-2' deoxyuridine in superficial herpetic keratitis. Oral acyclovir in the management of dendritic herpetic corneal ulceration. [On the treatment of dendritic keratitis with p-fluorophenylalanine. (Preliminary report)]. Ganciclovir ophthalmic gel, 0.15%: a valuable tool for treating ocular herpes. Proflavine photodynamic viral inactivation in herpes simplex keratitis. Human leukocyte and fibroblast interferon in a combination therapy of dendritic keratitis. Role of debridement and interferon in the treatment of dendritic keratitis. Interferon-beta treatment of herpes simplex keratitis. Combination therapy for dendritic keratitis with acyclovir and alpha-interferon. Combination therapy for dendritic keratitis with human leucocyte interferon and trifluorothymidine. Acyclovir in the treatment of herpetic keratitis. [Comparative studies on the effect of cryotherapy and iodization in combination with unspecific and virostatic after-treatment in dendritic keratitis]. Combination therapy for dendritic keratitis. High-titer alpha-interferon and trifluridine. Efficacy of four antiviral agents in the treatment of uncomplicated herpetic keratitis. A comparison between acyclovir and trifluorothymidine ophthalmic ointment in the treatment of epithelial dendritic keratitis. A double blind, randomized parallel group trial. [Double-blind clinical trial of isoprinosine and placebo in herpetic keratitis]. Idoxuridine and iodization in the treatment of simple dendritic ulceration. Interferon in treatment of dendritic keratitis in humans: a preliminary report. Successful treatment of dendritic keratitis with human leukocyte interferon. A controlled clinical study. A COMPARISON OF IDU SOLUTION, IDU OINTMENT, AND CARBOLIZATION IN THE TREATMENT OF DENDRITIC CORNEAL ULCER. [Acyclovir and trifluorothymidine in herpetic kerato-uveitis. A comparative clinical study. Indications for corticoid therapy]. Ganciclovir ophthalmic gel (Virgan; 0.15%) in the treatment of herpes simplex keratitis. CONTROLLED STUDIES OF IDU IN THE TREATMENT OF HERPETIC KERATITIS. Role of débridement and trifluridine (trifluorothymidine) in herpes simplex dendritic keratitis. Acyclovir and vidarabine in the treatment of ulcerative herpes simplex keratitis. Double controlled comparison of IDU and trifluorothymidine in thirty-three patients with superficial herpetic keratitis. A comparison of acyclovir and idoxuridine as treatment for ulcerative herpetic keratitis. [Superficial herpes simplex keratitis. Double-blind comparative trial of acyclovir and idoxuridine (author's transl)]. TREATMENT OF HERPES SIMPLEX OF THE CORNEA WITH IDU. A DOUBLE-BLIND STUDY. [Superficial herpetic keratitis: comparative double-blind treatment with iododeoxycytidine and acyclovir]. Combination therapy for dendritic keratitis with acyclovir and vidarabine. The potency of interferon-alpha 2 and interferon-gamma in a combination therapy of dendritic keratitis. A controlled clinical study. Clincial experience of human leucocyte interferon in the management of herpetic keratitis. [Comparison of the effectiveness of acyclovir and vidarabine in superficial herpes keratitis]. AN EVALUATION OF DOUBLE-BLIND IDU THERAPY IN 100 CASES OF HERPETIC KERATITIS. [Double-blind treatment of ocular herpes simplex: Vira-A and acyclovir]. Double--blind clinical trial of adenine arabinoside and idoxuridine in herpetic corneal ulcers. Clinical evaluation of adenine arabinoside and trifluorothymidine in the treatment of corneal ulcers caused by herpes simplex virus. Cryotherapy of epithelial herpes simplex keratitis. A double-controlled evaluation of acyclovir and vidarabine for the treatment of herpes simplex epithelial keratitis. Comparative study of acyclovir and 5 I.D.U. in the management of viral corneal ulcer. Acyclovir and debridement in the treatment of ulcerative herpetic keratitis. A controlled trial of oral acyclovir for the prevention of stromal keratitis or iritis in patients with herpes simplex virus epithelial keratitis. The Epithelial Keratitis Trial. The Herpetic Eye Disease Study Group. Treatment of herpetic keratitis. TREATMENT OF HERPES SIMPLEX KERATITIS WITH 5-IODO-2'-DEOXYURIDINE. A double-blind, multicenter clinical trial of acyclovir vs idoxuridine for treatment of epithelial herpes simplex keratitis. Acyclovir and trifluorothymidine in herpetic keratitis: a multicentre trial. "Dye/light" Dye-induced photosensitization of herpes virus. A clinical trial on humans. Treatment of amoeboid herpetic ulcers with adenine arabinoside or trifluorothymidine. Clinical evaluation of trifluorothymidine in the treatment of herpes simplex corneal ulcers. A DOUBLE-BLIND STUDY OF IDU IN HUMAN HERPES SIMPLEX KERATITIS. Randomised double-blind trial of acyclovir and idoxuridine in dendritic corneal ulceration. Randomised double-blind trial of bromovinyldeoxyuridine (BVDU) and trifluorothymidine (TFT) in dendritic corneal ulceration. Randomised double-blind trial of acyclovir (Zovirax) and adenine arabinoside in herpes simplex amoeboid corneal ulceration. Oral acyclovir (Zovirax) in herpes simplex dendritic corneal ulceration. Bromovinyldeoxyuridine and interferon treatment in ulcerative herpetic keratitis: a double masked study. A randomised double-blind clinical trial of acyclovir (Zovirax) and adenine arabinoside in herpes simplex corneal ulceration. Combination therapy for dendritic keratitis with human leukocyte interferon and acyclovir. Trifluorothymidine versus adenine arabinoside in the treatment of herpes simplex keratitis. A controlled trial of adenine arabinoside and trifluorothymidine in herpetic keratitis. Acyclovir and idoxiuridine treatment of herpes simplex keratitis--a double blind clinical study. Epidermal growth factor in the topical treatment of herpetic corneal ulcers. The management of ocular herpes.
Large scale, multiclinic evaluations of vidarabine (Ara-A, Vira A, adenine arabinoside) for treating herpetic keratitis have been conducted as double-blind studies (169 patients) in comparison with IDU and open studies (146 patients). In the open studies, the disease in the majority of patients had been refractory to IDU. The effects of vidarabine and IDU were approximately the same in improvement of symptoms (lacrimination, photophobia, sensitivity) and percent of and time for corneal reepithelialization. With vidarabine, significantly more patients had improved distant visual acuity than did with IDU. In the open studies, vidarabine also was effective. Of 116 patients whose ulcers had not responded to IDU, 91 (78%) had reepithelialization within four weeks of treatment with vidarabine. On the basis of results from these studies, vidarabine appears to be a safe and effective drug for treating herpes simplex keratitis. At three university centres 66 patients presenting with herpetic dendritic or geographic ulcers participated in a double-blind comparative study of 3% acyclovir and 3% vidarabine ointment. There was healing in 31 (97%) of the 32 patients treated with acyclovir, in a mean time of 6.3 days, and in 30 (88%) of the 34 treated with vidarabine, in a mean time of 7.1 days. The two medications were statistically equally effective, no difference being demonstrated in the healing rate, in the frequency of punctate epithelial keratitis or stromal keratitis, or in the final visual acuity. nan nan No statistical difference was found in both partial and complete healing time in acute epithelial herpetic keratitis between the ACV-recombinant human alpha 2 IFN (both "eyedrops" and "eyerods") and Buffy coat human leucocyte alpha IFN. A highly significant difference was found in both partial and complete healing time between the ACV-IFN combination versus the ACV-Placebo combination. The combination of ACV and recombinant human alpha 2 arg IFN is a potent anti-herpetic treatment. nan A controlled trial of oral acyclovir in herpetic dendritic corneal ulcers was carried out on 31 patients. All patients received minimal wiping debridement of the ulcer, following which they were randomly allocated to receive either oral acyclovir or placebo for 7 days. At the end of treatment 67% of dendritic ulcers in patients receiving acyclovir had healed compared with 43% in placebo recipients. The proportion of ulcers healed in the 2 groups at 7 days showed no significant difference (p = 0.18), but the rate of healing was significantly faster in acyclovir group (p = 0.03). nan 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. We used the photodynamic inactivation technique with proflavine as the photoactive dye to treat herpetic epithelial keratitis in a preliminary study of patients who had idoxuridine toxicity or resistance. A comparative study with idoxuridine in treating dendritic ulcerations of the cornea showed a good therapeutic effect. But the investigation was suspended when adverse reactions, consisting of a generalized epithelial keratitis and an anterior uveitis, possibly of phototoxic origin, developed in a few patients receiving treatment. The ulcers treated by photodynamic inactivation apparently healed by a process of "debridement" followed by subsequent re-epithelialization. Thirty-eight patients with virologically proven dendritic keratitis were treated using either debridement plus human leukocyte interferon (HLI) or debridement plus human fibroblast interferon (HFI) in a randomized, double-blind study. We administered one drop of HLI or HFI (1 X 10(6) reference units/ml) daily and found no significant difference in the action of either type of interferon. In a controlled clinical study, 42 patients with dendritic keratitis were treated either with thermocautery plus human leukocyte interferon (HLI) or with minimal wiping debridement plus HLI. The results show that the efficiency with which primary debridement was carried out, determined the success of further therapy using interferon. We conclude that interferon works basically as a prophylactic agent and needs the support of further antiviral measures to be effective against dendritic keratitis. We tested a new preparation of interferon-beta (IFN-beta) to determine its efficacy and tolerability in the treatment of herpetic keratitis. The 20 patients admitted to the trial were selected from patients who had not received any previous treatment with virustatic agent; they were treated in a comparative, randomised open trial with eye drop containing IFN-beta or iododesoxyuridine (10 vs. 10). Examination of the data show that 10 out of 10 patients treated with IFN-beta respond positively to the treatment, furthermore it showed that IFN-beta produce no local or general toxicity. Fifty-nine patients with superficial herpetic keratitis were treated with 3% acyclovir ointment five times a day in combination with alpha-interferon (30 million IU/mL) or albumin-placebo once a day in a stratified double-masked clinical trial. All patients had minimal wiping of the superficial lesion to isolate virus. The healing time of the corneal ulcers was substantially lower with the combination of acyclovir and interferon than with the combination of acyclovir and placebo. Only minor toxic effects were observed. The combination of acyclovir and interferon appears to be the best presently known treatment for dendritic keratitis. nan Fourty-three eyes with active dendritic keratitis, nearly one third of which had failed to respond to other antiviral agents, were treated with acyclovir with or without preceding debridement. The patients were randomly selected. No statistical difference could be demonstrated between the 2 groups in terms of rate of healing or in efficacy of cure. Acyclovir also seemed to be effective in stromal corneal lesions. There were only minor side effects. nan Previous studies showed that the combination of trifluridine with human leukocyte interferon in the treatment of dendritic keratitis is effective, and that the best results were obtained with the highest titer then available (30 X 10(6) IU/mL). The present study was undertaken to see if an even higher titer (100 X 10(6) IU/mL) would be more effective. A statistically significant greater effectiveness of the higher titer could not be verified. To evaluate the efficacy of four antiviral agents--1% idoxuridine ointment (group 1), 2% trifluorothymidine ointment (group 2), 3% acyclovir ointment (group 3) and 1% bromovinyldeoxyuridine (BVDU) ointment (group 4)--in herpes simplex keratitis.
                Randomized double-blinded clinical trial.
                Tertiary care institution in New Delhi.
                Eighty patients with uncomplicated herpes simplex keratitis of recent onset who had not previously received antiviral treatment.
                Cure rate, frequency and severity of side effects.
                Cure rates of 60%, 90%, 90% and 95% were obtained in groups 1, 2, 3 and 4 respectively. The average healing time was 13.4, 8.9, 8.5 and 7.5 days respectively. Side effects (follicular conjunctivitis, epithelial keratopathy and stinging) were more frequent in group 1 than in the other groups.
                BVDU has a more pronounced therapeutic effect than idoxuridine, trifluorothymidine and acyclovir in uncomplicated epithelial herpetic disease of recent onset that has not previously been treated. This report presents the results of a double blind randomized study comprising 50 patients with epithelial herpes simplex keratitis. Twenty-five patients received 3% acyclovir ophthalmic ointment, the other 25 patients 2% trifluorothymidine (TFT) ophthalmic ointment. The mean duration of treatment in the 2 study groups before healing of the epithelial ulceration was obtained was 6.7 days and 5.9 days, respectively (no statistically significant difference). Two patient (8%) in the acyclovir group and 1 patient (4%) in the TFT group failed to heal within 14 days of treatment. No clinically significant adverse effects were recorded. nan nan Seventy-three patients with herpetic epithelial keratitis were randomly divided into three groups and were treated by local applications of human leukocyte interferon, thermocautery plus human leukocyte interferon, or thermocautery plus mock human leukocyte interferon to obtain information on whether therapy with human leukocyte interferon can serve as a substitute for mechanical debridement of the involved epithelium or can improve the results when given as additional therapy. Fifty-five patients (75%) yielded herpes simplex virus before treatment, and only the results in these patients with keratitis of proved viral etiology were included in the analysis. These results indicated that mechanical debridement cannot be replaced with local application of human leukocyte interferon (3-4 X 10(4) units per day). When given in addition to thermocautery, human leukocyte interferon may have been of some value in a number of patients. However, the results were not statistically significant. A more potent dosage of human leukocyte interferon might provide better results. There were 40 virologically confirmed cases of dendritic keratitis treated in a randomized double-blind placebo-controlled study. After thermomechanical debridement of the corneal epithelium, the patients received two drops of human leukocyte interferon (HLI) twice daily. The activity was 3 X 10(-6) units/ml. HLI significantly accelerated healing and inhibited virus shedding. It remains to be studied whether HLI will be equally effective in the prophylaxis of late herpes recurrences. nan 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. 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. nan Thirty-four patients with herpes simplex dendritic keratitis were randomized into three treatment categories: Group A had débridement alone; group B, trifluridine (trifluorothymidine) alone; and group C, débridement and trifluridine. Patients treated with débridement alone had a statistically higher failure rate than did the other two groups. No statistically significant difference was observed between trifluridine treatment alone and débridement combined with trifluridine treatment, with regard to healing time. Our results suggest that débridement alone is suboptimal therapy for herpes simplex dendritic keratitis and that débridement combined with trifluridine appears to offer no advantage over trifluridine alone. 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-three patients were followed in a double controlled study to test the efficacy of IDU and TFT on superficial epithelial herpes simplex virus infection. Sixteen received TFT and 17, IDU. There were four failures in patients on IDU therapy and no failures in the 16 patients using TFT. These results indicate a trend for greater efficacy of TFT than IDU. In those patients who healed with IDU and with TFT, there was no difference in the number of days to heal in each group. Sixty patients were treated with either acyclovir 2% ointment or idoxuridine 1% ointment 5 times a day in a stratified randomised double-blind clinical trial. The 2 antiviral agents were equally effective. In a double-blind, randomized trial 52 patients with superficial herpes simplex keratitis were treated with a new antiviral compound, acylclovir (ACV) 3% ointment, or with idoxuridine (IDU) 0.5% ointment. No statistically significant difference was found in the number of patients cured with either drug, but healing was achieved more rapidly with ACV than with IDU. nan nan 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. Forty-five patients with virologically confirmed dendritic keratitis were treated in a randomized, double-blind controlled study with a basic therapy of trifluorothymidine (TFT) eye drops. In addition they received different human recombinant interferon (rHu IFN) eye drops. The following results were obtained for average healing times: TFT plus one drop daily of rHu IFN-alpha 2 arg (30 million iu/ml): 3.3 days, TFT plus rHu IFN-gamma (30 million iu/ml): 3.9 days, TFT plus a mixture of alpha plus gamma (0.3 million iu/ml each): 6.1 days, TFT plus a mixture of alpha plus gamma (1.5 million iu/ml each): 3.3 days. High-titer gamma interferon did not significantly differ from high-titer alpha interferon in the combination therapy of dendritic keratitis. A mixture of alpha plus gamma at a moderate titer (1.5 million iu/ml each) was as effective as a high-titer mono-preparation. Adding a low-titer interferon mixture gave no better therapeutic results than antiviral monotherapy. Thus it seems possible to save about 90% of interferon commonly used in the combination therapy of dendritic keratitis by applying a mixture of different suitable interferons instead of interferon monospecies. nan 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. nan nan The results are reported of a fully controlled randomized double-blind clincial trial of adenine arabinoside and idoxuridine ointment in sixty patients with herpetic ulceration of the cornea. Although both antivirals showed a trend towards superiority over placebo, the therapeutic effect did not reach statistical significance in spite of the known efficacy in laboratory animals. Further studies in rabbits are reported; these indicate that systemic immunity may play a role in combating virus proliferation in recurrent disease, and it is considered this disguises the efficacy of topical antiviral therapy in clinical trials, thus necessitating an estimated requirement for approximately fifty patients per treatment group to obtain significant effects. It is concluded that an antiviral is valuable in the treatment of ulcerative herpetic keratitis, particularly in primary disease and in the presence of systemic and local immunosuppression after the use of topical adrenocorticosteroid. In recurrent disease, where a trigger factor is known, experience has shown that therapy can be profitably administered before the onset of clinical disease. One hundred two unselected patients with ulceration of the cornea due to herpes simples virus were treated with either adenine arabinoside or trifluorothymide; the trial was double-blind, stratified, and radomized. The two drugs were given topically five times per day, and the rate of healing was observed and recorded. The series included 87 patients with dendritic ulcers and 15 with amoeboid ulcers. Dendritic ulcers of the cornea can be accurately measured, and the healing process can be easily followed. In this situation no statistically significant difference between the efficacy of adenine arabinoside and that of trifluorothymidine was demonstrated. Amoeboid ulcers are more difficult to evaluate than dendritic ulcers, and their responses to treatment vary considerably; however, data from this small group of patients suggest that trifluorothymodine may be more effective than adenine arabinoside for the treatment of amoeboid ulcers. nan nan Thus, we found that the role of Acyclovir in the treatment of viral corneal ulcer is definitely better and quicker. It takes less time for healing of corneal ulcer and as a result less hospitalisation is needed. We treated 25 patients with dendritic keratitis with debridement and 3% acyclovir ointment and another 25 with acyclovir alone. The patients were randomly assigned to the two treatment groups. There were only minimal adverse effects in both groups. The combination of debridement and acyclovir produced a significantly more rapid healing rate than did acyclovir alone. Factors associated with prolonged healing time were duration of symptoms (longer than one week), length of the epithelial defect (greater than 4 mm), proximity of the defect to the corneoscleral limbus (less than 2 mm), and the presence of stromal inflammation. To evaluate the efficacy of oral acyclovir in preventing stromal keratitis or iritis in patients with epithelial keratitis caused by herpes simplex virus (HSV).
                Patients with HSV epithelial keratitis of 1-week or less duration were treated with topical trifluridine and were randomly assigned to receive a 3-week course of oral acyclovir, 400 mg 5 times a day (hereafter referred to as the acyclovir group), or placebo (hereafter referred to as the placebo group). The development of HSV stromal keratitis or iritis was assessed during 12 months of follow-up.
                Stromal keratitis or iritis developed in 17 (11%) of the 153 patients in the acyclovir group and in 14 (10%) of the 134 patients in the placebo group. Compared with the placebo group, the adjusted rate ratio for the development of stromal keratitis or iritis in the acyclovir group was 1.16 (95% confidence interval, 0.56-2.43). The development of stromal keratitis or iritis was more frequent in patients with a history of HSV stromal keratitis or iritis than in those without such a history (23% vs 9%; P = .01).
                For patients with HSV epithelial keratitis treated with topical trifluridine, no apparent benefit of a 3-week course of oral acyclovir in preventing HSV stromal keratitis or iritis was seen during the subsequent year. The 1-year rate of development of stromal keratitis or iritis was lower than previously reported in the literature, except in patients with a history of HSV stromal keratitis or iritis. Idoxuridine which was first used in 1960 (Kaufman et al., 1962), has been for many years the only antiviral agent available in the treatment of herpetic keratitis. It is however no more successful than is mechanical removal of diseased epithelium (Patterson & Jones, 1967), and furthermore it may give rise to serious toxic side effects. The search for an alternative medication is therefore a pressing one. Trifluorothymidine (F3T) has, in recent years, been shown to be more effective than IDU and to be free from significant toxicity. Both of these drugs are pyrimidine nucleosides. Adenine Arabinoside or Arabinoside-A (Ara-A) is, by contrast, a purine nucleoside. It is thought to exert its antiviral effect by blocking DNA polymerase and ribonucleotide reductase. nan 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%). nan A series of 21 patients with herpetic corneal ulcers was treated by photodynamic inactivation (using a single application of neutral red 1 per cent solution followed by a 15-min exposure to a 40 watt light of 440--550 nm), carbolization, or idoxuridine (IDU) ointment. No significant difference was found in the number that healed, the mean healing time, or the number of recurrences after any of the three treatments. In previous studies adenine arabinoside and trifluorothymidine were found to be equally effective treatments for dendritic ulcers of the cornea, but a trend emerged which suggested that in amoeboid ulcers trifluorothymidine was more effective. The collection of additional cases confirms the superiority of trifluorothymidine in such cases. nan nan 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. The results of a randomised double-blind clinical trial of 0.1% bromovinyldeoxyuridine (BVDU) and 1% trifluorothymidine (TFT) in 60 patients with corneal dendritic ulceration are presented. There was no significant difference between BVDU and TFT in terms of numbers of ulcers healed (p = 0.61), mean healing time (p = 0.065), and cumulative healing rate (p = 0.058). No serious side effects were observed, though transient stinging was recorded in five patients receiving TFT and in three patients receiving BVDU. One patient in the group treated with TFT developed a punctate epitheliopathy. Fifty-one patients were treated in a dual-centre, double-blind comparison of acyclovir and adenine arabinoside in herpetic amoeboid (geographic) corneal ulceration. Twenty-four of the 25 patients receiving acyclovir healed in a mean time of 12.2 days, while 24 of the 26 patients treated with adenine arabinoside healed in a mean time of 11.0 days. There was no statistically significant difference between the two groups in terms of healing. A second analysis, excluding any patients who had received antiviral treatment immediately prior to entry into the study, showed that 18 of the 19 who received acyclovir healed in an average of 11.7 days and 18 of the 19 recipients of adenine arabinoside healed in a mean time of 11.2 days. Again the difference was not statistically significant. Sixty patients with simple dendritic corneal ulceration were randomly assigned to double blind treatment with either acyclovir tablets (400 mg) or acyclovir ophthalmic ointment administered five times daily. There was no significant difference in the proportions of patients healed in either treatment group (88.9% on oral acyclovir and 96.6% on acyclovir ointment). The median healing time was five days in both groups. No systemic or significant local side effects were noted in either treatment group. Trough levels of acyclovir in the tear fluid of those who received the oral preparation were within or above the range of mean in-vitro ID50 levels for herpes simplex virus type 1. We conclude that oral administration of acyclovir (400 mg, five times daily) may be an effective alternative to topical therapy in selected patients. Bromovinyldeoxyuridine is a potent and safe antiherpes compound that in combination with a placebo treatment promoted the partial and complete healing of herpetic epithelial disease in 22 patients in average times of 4-6 days and 8.5 days respectively. However, when BVDU was combined with 1.5 X 10(6) IU of recombinant a 2C interferon, partial and complete healing times for keratitis in 19 patients were reduced to 2-6 days and 4-6 days respectively. No toxic effects of the medications were observed in any patient. 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 45 patients with virologically verified dendritic keratitis with a combination of interferon and acyclovir 3% or with placebo and acyclovir 3% in a double-masked study. One drop of human leukocyte interferon (30 X 10(6) IU/ml) or albumin-placebo was administered daily. Acyclovir ointment was applied five times daily. The mean healing time of the corneal ulcers in 24 patients treated with interferon and acyclovir was 3.9 days and the mean healing time in 21 patients treated with placebo and acyclovir was seven days. The difference was significant (P less than .001). Trifluorothymidine (TFT) and adenine arabinoside (ara-A) are effective antiviral drugs with a very low toxicity for the cornea. In our study no difference between these 2 drugs in antiviral activity was noted. The average healing time for TFT was 11-14 days and for ara-A 10-54 days. These data differ markedly from those of other studies. This was the result of the use of additional criteria for healing of the lesion. Not only absence of fluorescein staining of the cornea but also the absence of oedema and cystic changes in the epithelium over the previous ulcer were considered criteria for healing. In addition to clearly defined healing criteria and the healing time we found the interval between the first symptoms and the commencement of the therapy of greatest importance in the clinical evaluation of antiviral drug efficacy. An effort was made to approximate this relationship for TFT and ara-A mathematically. The effectiveness of two anti-viral agents, adenine arabinoside and trifluorothymidine, were studied in cases of human superficial herpetic keratitis (dendritic ulceration). A highly satisfactory response to each drug was demonstrated in most cases. 38 patients with herpes simplex keratitis were treated in double blind clinical trial. 18 patients (10 with pure epithelial and 8 with accompanying stromal affection) were treated with 3% acyclovir (ACV) eye ointment, and 20 patients (10 with pure epithelial and 10 with accompanying stromal affection) were treated with 0.5% idoxiuridine (IDU). The cure rate was 94% in the ACV group compared to 70% in the IDU group. This was significantly higher in the ACV group. Only minor adverse reactions were recorded. The tolerability and efficacy of epidermal growth factor (EGF) in the topical treatment of herpetic corneal ulcers in addition to topical acyclovir have been evaluated in a double-blind, placebo-controlled, randomized study in two groups of patients. The time required for complete reepithelialization of the cornea was recorded, and the data obtained were analyzed statistically. In the EGF group, the reepithelialization was significantly faster than in the control group. Tolerability of EGF was always excellent. These results indicate that EGF is safe and effective in reducing the healing time of herpetic corneal ulcers. nan
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.