Idu and the Treatment of Herpes Simplex Keratitis.

5-IoDo-2'-DEOXYURIDINE (IDU) is an antimetabolite that acts by displacing thymidine from deoxyribonucleic acid (DNA). This results in inhibition of DNA synthesis, which particularly affects virus particles in the active replication of herpes simplex keratitis in rabbits (Kaufman, Nesburn, and Maloney, 1962; Perkins, Wood, Sears, Prusoff, and Welch, 1962). Following the report of effective treatment with IDU of human herpes simplex keratitis in an uncontrolled trial (Kaufman, Martola, and Dohlman, 1962), many publications have reiterated the efficacy of the drug (for example, Corrigan, Gilkes, and Roberts, 1962; Bennett, 1962; Havener and Wachtel, 1963; Maxwell, 1963; Gordon and Karnofsky, 1963). Despite the fact that the majority of favourable reports on the efficacy of IDU have rested on uncontrolled trials of the drug, there have surprisingly been few attempts to produce objective results by means of double-blind controlled clinical trials. Notable exceptions are the papers of Burns (1963), Patterson and others (1963) and Jepson (1964), but these are open to some criticism. The clinical diagnosis ofherpes simplex infection was not confirmed by virus culture in any of these trials and there was no indication whether any other therapy had been administered before admission to the trial. Moreover, in these studies the patients received cycloplegics, and Patterson and others in addition used hot bathings, and steroids may have been used in the group of patients studied by Burns. Burns and Patterson and others treated their cases as outpatients attending daily whenever possible, and there were multiple observers in both of these trials. Jepson's patients were seen at weekly intervals. The clinical experience of some observers has been less uniformly successful (Davidson, 1962; Luntz and MacCallum, 1963; Thygeson, Sexton, and Corwin, 1963). In view of the disparity in these observations we determined on a doubleblind trial of the drug IDU, for no report on a strictly controlled trial was then available. In constructing the trial we fully realized the advantage in using "control" drops as a placebo. However, herpes simplex keratitis is a serious and blinding disease and we felt it would be unjustifiable to give no treatment at all. (See Bradford Hill, 1963, and British Medical Journal, 1963). We resolved the difficulty by using as "control" drops a 1 per cent. solution of gamma globulin, which has not been conclusively shown to be ineffective in the treatment of human herpes simplex keratitis and might be expected to raise the level of antibodies locally.