Some strains of herpesvirus have loicler dissemination than others and may penetrate into the eye and multiply in the endothelium without virus persisting in the stroma. In evaluating chemotherapeutic response, both the strain of the virus and the frequency of drug administration are important; less frequent drug administration gives a poorer therapeutic response. The drug in ointment is more effective than the drug in saline or in dimethyl sulfoxide.

Maloney, Emily D. (University of Florida College of Medicine, Gainesville), and Herbert E. Kaufman . Multiplication and therapy of Toxoplasma gondii in tissue culture. J. Bacteriol. 88: 319–321. 1964.—The effect of temperature on the rate of multiplication of the RH strain of Toxoplasma gondii and the results of treatment with pyrimethamine, an antifolic, at various temperatures were studied in tissue culture. At 37 C incubation, the organism was found to have a lag time of 10.5 hr and a mean generation time thereafter of 4.85 hr for binary multiplication during the exponential phase of growth. At 34 C, the lag time was 12 hr and generation time was 5.26 hr. When the organisms were incubated at 31 C, the lag time was 12.5 hr and generation time was 11.1 hr. Treatment of infected monkey kidney tissue cultures with 0.05 mg per 100 ml of pyrimethamine at 37 C for 4 days killed all organisms and permitted survival of the mice which were injected with the cultures. When cultures were incubated at 34 C, a dose of 0.6 mg per 100 ml was required to spare any mice, and with a 31 C incubation even this dose was only slightly effective when therapy was continued for 4 days. If the treatment was prolonged for 7 days before injection of the cultures into mice, however, no difference in therapy with different rates of multiplication was found. Since the rates of multiplication at 34 and 31 C are similar to the rates of multiplication of some naturally occurring strains, these data confirm the fact that prolonged therapy, as used by many, is rational.

Recently 5-iodo-2′-deoxyuridine (IDU) has been shown to be effective in experimental herpetic keratitis of rabbits as well as in herpes simplex keratitis in man.1,2Since the discovery of the therapeutic antiviral activity of this compound, a search for additional compounds has been made. The first success came with the finding that a series of substituted 5-haloginated cytidines also possessed therapeutic antiviral activity in experimental keratitis.3These compounds, although possessing superior solubility, and perhaps stability, were as active as the original compound IDU, being metabolized to this compound by the cells and depending for antiviral activity on the ability of the cell to convert and de-aminate the compound. The mechanism of the action of these agents, therefore, was identical to that of IDU and the other 5-haloginated uridines. Recently, Underwood reported that cytosine arabinoside is also active in the treatment of experimental herpes simplex keratitis.4This compound differs

Herpes simplex virus can be eliminated from rabbit kidney tissue culture and human amnion tissue culture and vaccinia virus can be eliminated from rabbit kidney tissue culture by treatment with 5-iodo-2′-deoxyuridine in concentrations from 10 μg/ml to 1 mg/ml if the drug containing media was changed daily. This “cure” of virus infection is possible even when cytopathogenic changes are easily recognizable before treatment is begun, and such treatment results in prevention of progression of such virus induced changes. This property appears to be unique for therapeutically active anti-viral compounds and may facilitate the screening of agents active against other viruses and the more detailed study of the therapeutically active anti-viral agents now known.

IDU which stands at room temperature, although decomposing extremely slowly, loses antiviral activity fairly rapidly as measured by tissue culture assay. Similarly, miniscule amounts of Us major degradation product, iodouracil, inhibit the antiviral activity of IDU, and, iodouracil appears toxic to the human cornea. This loss of effectiveness of IDU with age, although documented in tissue culture, tvas not observed in vivo in experimental keratitis in the rabbit. Although the tissue culture results and the finding of minimal toxicitij in man support our clinical impression of biologic instability of IDU, the clinical significance of these findings is not yet certain.

The recently modified fluorescence inhibition test for antibodies to toxoplasmosis is safe and relatively simple to perform. It appears to detect antibodies early in the course of acute systemic infection but is less sensitive than either the dye test or hemagglutination test in detecting chronic infection. Although hemagglutinating antibodies develop later than dye test antibodies in the course of acute systemic toxoplasmosis, the hemagglutination test correlates very well in titer ivith serum from patients toith subacute or chronic infection, such as that seen in ocular disease. Since most of the proved cases of ocular toxoplasmosis have low dye titers that might well be undetected in the less sensitive FI test, this test appears to be inadequate for the study of ocular toxoplasmosis.

The indiscriminate clinical use of corticosteroids "when the eye is red" has contributed greatly to the severity and variety of herpes simplex keratitis.1,2Similarly, the deleterious effects of corticosteroids on experimental herpes simplex keratitis have been well documented.3,4Since, when used indiscriminately, corticosteroids are dangerous, and since the antiviral agents described to date are not effective in treating iritis or disease accompanied by folds in Descemet's membrane,5it would be desirable if topical corticosteroids could be used with safety. The preparation, 5-iodo-2'-deoxyuridine (IDU), is a specific antiviral agent that stops viral replication.6,7The experiments described below document the effects of the combination of IDU with corticosteroids. Methods and Materials Albino rabbits were infected with strains of herpes simplex virus as previously described.6Drops of IDU were administered as a 0.1% solution and hydrocortisone as a 0.5% solution. In some experiments, when the two were given

5-Iodo-2′-deoxyuridine (IDU) has previously been shown to cure or ameliorate herpes simplex infection of the cornea, even when the infection is severe and far advanced. Studies on vaccinia infection of the cornea treated with IDU indicate that this keratitis is similarly improved or clinically cured. In about half of the treated eyes no virus could be detected after treatment; whereas, virus was present in all control eyes.

The adverse effect of corticosteroids on the clinical course of herpes simplex keratitis of man and animals is well documented.1Previous diagnostic virus cultures and fluorescent antibody studies of patients suggested that in many untreated patients with herpes simplex keratitis, the lesions healed fairly promptly and that virus could only occasionally be cultured from corneas later than 2 or 3 weeks from the onset of symptoms.2,3In corticosteroid-treated patients, however, it appeared that lesions persisted and that virus could be cultured from the epithelium much longer after the onset of symptoms. If, in fact, virus persisted in the epithelium following corticosteroid administration, this persistence might in itself be responsible for disastrous stromal changes and iritis either through an antigen-antibody reaction or by toxin production. Since sufficiently precise information was not available on patients, the studies reported below concern the persistence of virus following corticosteroid therapy and the effect