Biomedical subjects
Publications and source records attributed to M G Falcon.
Thirty patients with bilateral herpetic keratitis were evaluated, 40% of whom were atopic. Stromal keratitis occurred in 40% of the eyes and recurrent ulceration in 68%. Four patients (5 eyes) developed secondary microbial keratitis. Visual acuity decreased to 6/60 or less because of corneal opacification in 17% of the eyes.
Acycloguanosine (9-[-hydroxyethoxymethyl]guanine) (Wellcome 248U) has a highly specific and potent antiviral action against herpes-simplex virus (H.S.V.) types I and II in cell-culture systems and in animal models of H.S.V. infection in the brain, skin, and eye. Its efficacy in man was tested in twenty-four patients with dendritic corneal epithelial ulcers treated by minimal wiping debridement. Patients were randomly allocated to treatment with 3% acycloguanosine eye ointment or placebo. There were seven recurrences or recrudescences of typical corneal epithelial herpetic lesions within 1 week of debridement in the twelve patients who received placebo, and no recurrences in the twelve who received acycloguanosine. Four further patients with dendritic ulcers have been electively treated with topical acycloguanosine alone. Their ulcers all healed briskly. No adverse effects were seen with the acycloguanosine therapy. These results establish that acycloguanosine is a clinically effective antiviral drug against H.S.V. infection in man.
We describe experiments, using the multiple microinoculation technique, to produce superficial herpes simplex keratitis in the rabbit cornea, which showed a potent antiviral effect of acycloguanosine.
We present a retrospective study of fifty patients who developed raised intraocular pressure in association with herpes simplex kerato-uveitis. We consider the incidence, clinical features, management and prognosis, and discuss the mechanisms which may be responsible.
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The multiple microtrephination technique was used in the rabbit cornea to compare the activity against herpes simplex virus (hsv) of adenine arabinoside (ara-A), ara-A 5'monophosphate (ara-AMP) and hypoxanthine arabinoside (ara-Hx), and to determine the effect of addition of adenosine deaminase inhibitor (ADAI) to each. The greatest antiviral activity was shown by ara-AMP, and the least by ara-Hx. ADAI increased the activity of ara-A but had no effect on ara-AMP or ara-Hx.
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The discriminate use of topically applied corticosteroids to modify or abolish the inflammatory response in herpetic stromal keratitis, has, as its objectives, the prevention of visual loss from corneal scarring and disorganization and a lessening of the morbidity associated with this disese. Steroids may be expected to have a profound anti-inflammatory effect in antibody-complement mediated inflammation and are effective in delayed hypersensitivity as in homograft rejection. The equally profound effect of pharmacological vasoconstriction may enable steroids to impede both afferent and efferent pathways in an immunological reflex arc, and they may be expected to reduce inflammation of nonimmunogenic origin. The adverse effects of the misapplication of these potent drugs in herpetic keratitis, in terms of an increase in the rate of complications and in the severity and morbidity of the disease, should be emphasized again.
Various theories of recurrence of herpetic disease are outlined to indicate the potential role that interferon, interferon-inducers, or a hypothetical perfect synthetic antiviral may have in preventing recurrences, and the possibilities of minimizing trigger effects are considered. Attention is drawn to certain aspects of the management of herpetic eye disease that have a direct bearing on the incidence of subsequent recurrence. There is a need to initiate a movement to mobibize ophthalmologists everywhere to educate general practitioners in order to restrain them from harmfully using steroids in undiagnosed red eyes.
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We define in this paper a rational approach to the management of the various stages of herpetic eye disease. We consider in more detail comparisons between idoxuridine (IDU), trifluorothymidine (F3T), and adenine arabinoside (Ara-a) (derived largely from clinical trials in herpetic ulcers). We discuss metaherpetic ulcers and certain aspects of keratoplasty.
55 patients with dendritic ulcer have been treated in a double-blind randomised manner by minimal wiping debridement of their ulcers followed by daily application of either partially purified human interferon (P.I.N.F.) or placebo. There were 6 recurrences of epithelial herpetic disease in 30 patients who received P.I.N.F. and 13 in 25 who received placebo. This provides the long-awaited data proving the antiviral effect of exogenous interferon in treatment of naturally occurring viral disease in man, and furnishes a sighting shot on the lower edge of the target of effective therapy.
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An open trial suggested that monkey interferon had a therapeutic effect on ulcerative vaccinial keratitis in humans. A randomized, double-blind, placebo-controlled trial of either monkey interferon or drops of idoxuridine (given hourly by day and at 2-hr intervals by night for three days) suggested a therapeutic effect from idoxuridine but not from monkey interferon. Results of experiments with rabbits suggested that a daily application of human interferon (1.1 X 10(7) international units/ml) would be effective in the prevention of herpetic ulcers but might not affect established lesions. Preliminary results are encouraging in a placebo-controlled, randomized trial of human interferon given once daily for seven days for prevention of recrudescence of epithelial herpetic lesions after minimal wiping debridement with a cotton-tipped swab. The design of the trial is closely analogous to that of the experiments with rabbits and permits ethically acceptable, placebo-controlled trials of antiviral agents.