The effect of K-582, a new antifungal agent, on experimental Candida keratitis.

K-582, a new basic peptide antibiotic, was tested in rabbits with experimental Candida keratitis. It was shown that the K-582-treated group showed statistically highly significant therapeutic effects on days 2 and 3, as compared with the control group (day 2: P less than 0.001; day 3: P less than 0.001). The culture study showed that the average number of colonies was 1,573.1 in the controls and 463.3 in the treated group, and the difference was highly significant statistically (P less than 0.001). No ocular or systemic toxic effects were observed with this drug. K-582 is a promising new drug for the treatment of Candida keratitis.

Recombinant human interferon alpha D in HSV-1 recurrence in the rabbit.

Recombinant human interferon alpha subtype D (RIFN alpha D) was effective in reducing the shedding of herpes simplex virus type-1 (HSV-1) induced by 6-hydroxydopamine iontophoresis followed by topical epinephrine application in previously infected rabbit corneas. A treatment schedule of RIFN alpha D, two drops QID was superior to one drop BID. RIFN alpha A also appeared to be effective in reducing viral shedding. Rabbits treated with RIFN alpha D during two episodes of adrenergically induced HSV-1 shedding, but not during anticipated episodes of spontaneous shedding, did not show a significant reduction in shedding of virus. Interferon was present in significantly higher concentration in tear samples following treatment with RIFN alpha D as compared with RIFN alpha A.

Corneal epithelial cell--derived thymocyte-activating factor (CETAF).

Supernatants of a primary rabbit corneal epithelial cell culture and an established corneal cell line (SIRC) were assayed for their ability to enhance mitogen-induced C3H/HeJ mouse thymocyte proliferation. Significant levels of thymocyte-enhancing activity were detected in supernatants from both primary cultures and SIRC. Maximal levels of activity were found after 48 to 72 hr of culture in serum-free medium with 1 X 10(5) cells/ml. When monolayers of SIRC were disrupted. supernatants of these cultures consistently contained levels of activity higher than those of undisrupted control cultures. When supernatants from SIRC cultures (both serum-free and containing greater than 10% fetal calf serum) were subjected to gel filtration on AcA 54 and Sephacryl S-200, corneal epithelial cell-derived thymocyte-activating factor was eluted as two major peaks, between mol. wt 95,000 and 55,000 and mol. wt. 30,000 and 15,000. These results indicate that corneal epithelial cells, similar to keratinocytes, produce an Interleukin 1-like activity lacking species specificity, which enhances the proliferative capacity of thymocytes. Therefore corneal epithelial cells may interact with the immune system through the production of this cytokine.

Herpetic keratitis in zinc-deficient rabbits.

In a study of 57 rabbits, we found that zinc played a vital role in the growth of the rabbit and in its immunocompetence. Both humoral and cellular immunity were depressed in the zinc-deficient rabbit. Not only did zinc-deficient animals fail to gain weight, differing in that respect from rabbits on a regular diet, but they also had a high death rate, in contrast with no deaths among normal rabbits. Herpes simplex virus keratitis, both epithelial and stromal, was more severe in the zinc-deficient rabbit but was not improved by local zinc replacement (zinc sulphate ointment, 0.05%); Zinc sulphate ointment (1%), which is four times stronger than commercially available zinc ophthalmic preparations, was severely toxic for the rabbit cornea.

Biologic properties of the thymocyte-activating factor (CETAF) produced by a rabbit corneal cell line (SIRC).

Rabbit corneal epithelial cell cultures produce a cytokine (CETAF) that greatly enhances the proliferation of C3H/HeJ mouse thymocytes. The rabbit corneal cell line SIRC was used to generate CETAF activity in the culture supernatant. CETAF was then partially purified by Sephacryl S-200 gel filtration, where peaks of activity eluted in a molecular weight range of 95,000-55,000 (CETAF I) and 30,000-15,000 (CETAF II). Similar to the epidermal cell-derived thymocyte-activating factor (ETAF), CETAF (I and II) stimulated the growth of a human dermal fibroblast line (CRL 1445) in a dose-dependent manner, but failed to enhance the proliferation of an Interleukin 2 (IL 2)-dependent T-cell line (CT 6). Although CETAF did not exhibit any IL 2 activity, it clearly enhanced the IL 2 production by C3H/HeJ mouse splenocytes stimulated with suboptimal doses of lectins. Crude SIRC supernatants as well as the partially purified CETAF preparations showed a marked inhibition of polymorphonuclear neutrophil migration at high concentrations, but were significantly chemotactic when diluted samples were tested. CETAF release by SIRC cells was increased by stimulation with mitomycin C, phorbolmyristate acetate, hydroxyurea, silica, lipopolysaccaride B, and when the cells were cultured under serum-free conditions. These observations suggest that corneal epithelial cells may not only interact with the immune system in a way similar to keratinocytes, but may also stimulate corneal stromal cell through the production of CETAF.

Staphylococcal blepharitis.

A detailed discussion of various aspects of staphylococcal blepharitis is presented. These include epidemiology, pathogenesis and immunity, microbiologic characteristics, clinical signs, associated systemic diseases, differential diagnosis, and treatment.

Tretinoin and corneal epithelial wound healing.

The entire corneal epithelium of each of 16 rabbits was removed bilaterally. Tretinoin (vitamin A acid) ointment was applied topically twice daily to the eyes of one half of the experimental animals, and the ointment base alone was applied to the eyes of the other half (the controls). On days 1, 2, and 3 after the removal of the epithelium, the healing of the denuded corneas of the animals receiving tretinoin was significantly (P = .01, .01, and .05, respectively) more advanced than the healing of the corneas of the control animals.

Treatment of herpes simplex keratitis with levamisole.

A model of chronic herpetic keratitis was developed by injecting rabbits subconjunctivally with a corticosteroid. A levamisole hydrochloride-treated group of these rabbits developed milder, more rapidly healing epithelial lesions than an untreated group. Although most of the untreated rabbits developed stromal disease, almost all of the lesions in the levamisole-treated animals were limited to the epithelium.

Combined amphotericin B and rifampin treatment of experimental Candida albicans keratitis.

In a model of experimental Candida albicans keratitis in rabbits, treatment with a combination of amphotericin B and rifampin was compared with treatment with amphotericin B alone. Both modes of therapy substantially reduced the number of organisms in the cornea below the number in untreated control corneas. In the group treated with combined therapy, there were significantly fewer organisms in the cornea after three days of therapy than in the group treated with amphotericin B alone. The results of this study indicate that the treatment of C albicans keratitis in rabbits with combined amphotericin B and rifampin is more effective than treatment with amphotericin B alone.

Quantitative antibiotic sensitivity determinations of Staphylococcus aureus isolated from eye cultures.

The sensitivities of 108 strains of Staphylococcus aureus, isolated from patients with a variety of ocular conditions, were tested quantitatively against nine antibiotics by means of a microtiter broth-dilution method. Of the nine antibiotics, cephalothin sodium had the lowest (and therefore the best) minimum bactericidal concentration (MBC) and minimum inhibitory concentration (MIC). The MBC and MIC of gentamicin sulfate were very close to those of cephalothin. The MBCs and MICs of erythromycin, ampicillin sodium, penicillin, tetracycline, methicillin sodium, and carbenicillin disodium were moderately good. Chloramphenicol had the poorest response.

Combined gentamicin-tobramycin-corticosteroid treatment. II. Effect on gentamicin-resistant Pseudomonas keratitis.

In an experimental model of Pseudomonas keratitis produced by a gentamicin sulfate-resistant, tobramycin sulfate-sensitive strain of P aeruginosa, the results of two treatment regimens-(1) with gentamicin and tobramycin alone and (2) with gentamicin, tobramycin, and a steroid-were evaluated. All of the animals exhibited ultimately the same amount of corneal inflammation and corneal scarring. In the group receiving the antibiotic-steroid combination, the corneal lesions healed more slowly.

Herpes simplex keratitis treatment with vitamin A.

We produced chronic experimental herpetic keratitis by dropping PH-strain herpes simplex virus on scarified rabbit corneas and then injecting the rabbits subconjunctivally with low doses of corticosteroid (namely, triamcinolone acetonide suspension). Vitamin-A-treated rabbits developed milder, more rapidly healing epithelial lesions than untreated rabbits. Whereas most of the untreated rabbits developed moderate or severe stromal disease, most of the vitamin-A-treated rabbits developed only mild stromal disease or none at all.

High doses of subconjunctival corticosteroid and antibody-forming cells in the eye and draining lymph nodes.

After the intracorneal injection of rabbit eyes with bovine gamma-globulin, the subconjunctival administration of a corticosteroid in either the ipsilateral or contralateral eye resulted in essentially the same changes: a reduction in the number of antibody-forming cells in the draining lymph nodes and a reduction in the ocular inflammatory response.

Natural and cloned human leukocyte interferon in herpesvirus infections of rabbit eyes.

Human buffy-coat interferon and a leukocyte subtype (LeIF-A) obtained by gene cloning in Escherichia coli were equally effective in ameliorating the course of herpetic keratitis in rabbits when applied topically at a daily dose of 0.5 X 10(6) units per eye for six days commencing one day before infection. When given intramuscularly at the same dose, there was no alteration in the course of the disease. Topical treatments with LeIF-A were equally effective in suppressing epithelial damage seven days after infection, regardless of whether treatment commenced one day before infection or two days after infection. However, treatment from the day before infection also caused a significant decrease in epithelial defect two days after infection.

Treatment of vaccinial keratitis with vidarabine.

Vaccinial epithelial keratitis was produced in rabbits. When the therapeutic effect of vidarabine on the experimentally-induced disease was evaluated and compared to the effect of idoxuridine, vidarabine was found to be highly effective, substantially more effective than idoxuridine, and nontoxic to the eye.

Ocular microbial flora in immunodeficient patients.

The eyes of 20 patients with primary immunodeficiency syndromes were examined, and microbial cultures of their lids and conjunctivae were made. Nine patients had a history of recurrent external ocular infections, and six of these had active blepharitis or blepharoconjunctivitis at the time of examination. A single pathogenic bacterium was isolated from the lids and conjunctivae of six patients with a history of infection; a mixture of two possible pathogens was cultured from eyes of three other patients. Three of the nine patients with infections had impaired B-cell and intact T-cell immunity, whereas three patients had impaired B cell and T-cell immunity. Two patients had chronic granulomatous disease in which a defect in phagocytosis was the predominant immunologic abnormality, and one patient (with mucocutaneous candidiasis) had intact B- and T-cell function at the time of testing. Although the immunodeficient patients had a higher incidence of lid or conjunctival infection than 20 age-matched controls, the microbial flora of the lids and conjunctivae did not differ between the two groups.

Experimental herpetic keratitis in the guinea pig.

A model of herpetic keratitis with type 1 Herpesvirus hominis was established in the guinea pig. The administration of 10 mg triamcinolone acetonide subconjunctivally in both eyes resulted in an amelioration of the clinical course of the disease process, whereas 40 mg injected peritoneally did not. The possible pathophysiology of these responses is discussed.

Oculogenital transmission of type 2 herpes simplex virus in adults.

Type 2 (genital) herpes simplex virus (HSV-2) was isolated from three patients (two adults and an 11-year-old girl) with acute ocular infections. Two of these patients had acute blepharoconjunctivitis and one had acute keratoconjunctivitis. Genital herpes infections had preceded the eye infections in the two adults. This was not the case in the 11-year-old, but she had been in close contact with her sister who had apparently had the genital disease. The study strongly suggests transmission of HSV-2 from the genital site to the eye.

The microbial flora in extended-wear soft contact-lens wearers.

Of 857 cultures of material collected from the eyelids, conjunctivae, and contact lenses of 51 extended-wear soft-contact-lens wearers, 44 (5%) grew potential pathogens. The aphakic patients wearing contact lenses had fewer recoverable pathogens (24 of 295 or 8%) than a group of preoperative cataract patients (63 of 295 or 21%). On five occasions, positive cultures accompanied clinical symptoms, and on three occasions, repeated cultures grew the same potential pathogen.

The treatment of herpetic reinfection with levamisole.

The effect of levamisole on both clinical disease and virus recovery was studied in rabbits that were first infected with herpes simplex virus in one eye and then reinfected 14 days later by inoculation of the second eye. Reinfected rabbits treated with levamisole before reinfection developed significantly milder and smaller lesions than untreated controls. Virus recovery from the corneas was also less in the levamisole-treated animals than in the untreated controls.