Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022568 (keratitis)
 5,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present paper reviews the adverse side effects caused by topically applied antiviral agents in herpetic keratitis. The effective treatment of herpetic keratitis with IDU, a chemotherapeutic agent, was first reported in 1962. After its introduction into ophthalmic therapy for herpetic keratitis, drops of IDU were administered every hour by day combined with ointment every two hours by night. The therapy often continued for months or in some cases, even more than one year. Numerous reports on its side effects have appeared. The side effects can be classified into two categories. The first category is allergic contact blepharodermatitis, a type IV delayed hypersensitivity reaction. Its occurrence is difficult to foresee. This category I side effect rarely results in the destruction of the ocular tissues. The second category of side effects is a drug-induced toxic side effect resulting in punctate epithelial keratitis, papillary conjunctivitis or follicular hypertrophy and lacrimal punctal obstruction. After withdrawal of IDU, these ill effects usually subside soon. When IDU is further continued, the destructive change of the tissues will ensue. Conjunctival cicatrization, symblepharon, corneal neovascularization, cicatrization and irreversible punctal occlusion have been reported in cases with prolonged IDU treatment. In addition to IDU for therapy of herpetic keratitis, we are fortunate to have F3T, Ara-A and acyclovir. They show no cross sensitivity reaction nor any cross toxic reaction to each other. However, if administered more than several times daily and continued for a prolonged period of time, these antiviral agents, like IDU, can also result in reversible side effects and, further, irreversible tissue destruction. Conjunctival cicatrization and permanent punctal occlusion caused by prolonged administration of F3T have been reported. Prompt recognition of the untoward reactions and withdrawal of the antiviral agent will result in the subsidence of the toxic reaction changes and prevent the eye from irreversible destruction. The recognition, prevention and management of the untoward side effects also are discussed.
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PMID:[Adverse side effects caused by topically applied antiviral agents in herpetic keratitis]. 248 Apr 57

(E)-5-(2-Bromovinyl)-2'-deoxyuridine (1; BrVUdR) inhibits the replication of herpes simplex virus type 1 (HSV-1) and of varicella-zoster virus (VZV) in vitro at concentrations of 0.01 to 0.23 mumol/l, whereas herpes simplex virus type 2 (HSV-2) is influenced only at 5.5 to 27 mumol/l. In comparison to some classical and newly developed antiherpetics, i. e. 5-iodo-2'-desoxyuridine (2; idoxuridine, IDU), 9-beta-D-arabinofuranosyladenine (4; vidarabine Ara-A), 9-(2-hydroxyethoxymethyl) guanine (5; acyclovir, ACV) and 2'-fluoro-5-iodo-1-beta-D-aracytosine (6;FIAC) the following order of decreasing activity was found:1 greater than 6 greater than 5 greater than 2 greater than 4 (against HSV-1) and 6 greater than 2 greater than 5 greater than 1 greater than 4 (against HSV-2). The high selectivity of the antiviral effect of BrVUdR towards HSV-1 and TZV is based on the fact, that proliferation of different mammalian cell lines is inhibited by 50% only at concentrations as high as 90 to 170 mumol/l, resulting in a therapeutical index of 1000 to 10,000. Successful treatment of an HSV-1 encephalitis in mice as well as an HSV-1 keratitis of rabbits confirmed the efficiency of 1 in experimental animal infections. No toxic side effects in both local and systemic applications were observed. Promising data from cell culture and animal experiments recommend 1 as a potential candidate for the local and systemic treatment of HSV-1 and VZV infections in man.
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PMID:[(E)-5-(2-bromovinyl)-2'-desoxyuridine--a new nucleoside analog with selective inhibitory action against herpesviruses. Studies in cell culture and animal experiments]. 282 99

Amantadine is well established as the preferred antiviral agent for the prophylaxis of influenza A and may also be beneficial therapeutically when used early in the course of the disease. Idoxuridine is applicable only in the treatment of herpetic keratitis. Currently, acyclovir is the most effective agent for the treatment of herpes simplex and varicella-zoster virus infections. Ribavirin has recently been released for use in aerosol form for severe respiratory syncytial virus infections that occur in infants and young children. Vidarabine, which previously was the drug of choice in the treatment of severe herpetic infections, has now been replaced by the more effective acyclovir. Ganciclovir, an experimental agent, has shown promise against cytomegalovirus infections in patients who have undergone kidney or liver transplantation, but its effects are only temporary in patients who have undergone bone marrow transplantation and patients with acquired immunodeficiency syndrome (AIDS) who have cytomegalovirus infections.
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PMID:Antiviral agents. 350 Mar 76

Thymidine kinase (TK) activity was examined in extracts of TK-deficient cells infected with low passage isolates of herpes simplex virus type 1 (HSV-1) obtained from patients with herpetic keratitis. TK activity induced by the virus, relative phosphorylation rates of thymidine and iododeoxyuridine (IUDR), and Km values for thymidine and for IUDR were compared for TK induced by the different viral isolates. Four of the five isolates showing IUDR resistance in vitro and in vivo also exhibited alterations in properties of the viral TK. Two induced very low levels of viral TK. Three (including one with reduced TK) had increased Km values for IUDR. A fifth IUDR-resistant isolate induced TK similar to the IUDR-sensitive isolates. The results indicate that modification of viral gene for TK may be responsible for development of clinical resistance to IUDR in many occurrences of herpetic keratitis.
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PMID:Thymidine kinase activity of ocular herpes simplex isolates resistant to IUDR therapy. 375 71

Since the herpes simplex virus locates latently in the ganglia and is reactivated by certain triggers, the important problem in treatment is to prevent or reduce recurrence. The present study investigates the role of mechanical debridement in lessening the recurrence of dendritic keratitis in patients with herpetic epithelial keratitis. Group A was treated with mechanical debridement plus IDU, Group B with IDU alone. Also studied was the effect of steroid subconjunctival injection on herpetic recurrence in patients with herpetic stromal keratitis: Group C was treated with intravenous infusion of pepsin-treated gamma-globulin (PTGG) and steroid subconjunctival injection, Group D with steroid subconjunctival injection alone and Group E with intravenous infusion of PTGG alone. The recurrence rates of dendritic keratitis were 19% in Group A and 40% in Group B (average follow-up periods: 24 and 25 months). The recurrence rates of stromal keratitis were 61% in Group C, 64% in Group D, and 36% in Group E (average follow-up periods: 20, 19 and 15 months). The difference between Groups D and E was statistically significant (chi 2 test, P less than 0.05). The recurrence rates of dendritic keratitis were 18% in Group C, 21% in Group D and 7% in Group E. In conclusion, mechanical debridement tended to reduce the recurrence of herpetic epithelial keratitis and steroid subconjunctival injection to increase the recurrence of epithelial or stromal keratitis.
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PMID:Herpetic keratitis therapy to reduce recurrence. 382 98

The inhibition of herpetic keratitis by a combination of Poly I:C with DEAE-Dextran and IUDR was studied in rabbit eyes. This treatment was administered 72 h after HSV inoculation (daily) for 3 days and continued once daily for another 2-3 days. A significant improvement was detected in rabbit eyes beginning on the first day of treatment, and there was minimal scarring. This improvement in herpetic keratitis coincided with a decrease in the virus titer isolated from rabbit eyes and an increase in interferon titer detected in rabbit tears. The cornea and trigeminal ganglia of treated and control rabbits were tested in order to prove whether this combined treatment could inhibit the migration of HSV from the cornea to the trigeminal ganglia. During the active stage of the disease, HSV was isolated in a lower titer from the cornea of the treated rabbits and from the ganglia of only half of this rabbit group. During the latent stage of the disease, no HSV was isolated from the cornea of either rabbit group, but HSV was isolated from the ganglia explants of the treated rabbits in a somewhat lower titer than from the controls. This treatment administered 3 days after the virus inoculation could not prevent the migration of HSV from the infected cornea towards the trigeminal ganglia.
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PMID:The effect of poly I:C and IUDR on the inhibition of HSV in rabbit eyes. 618 66

Clinical resistance of herpetic keratitis to antiviral agents constitutes one of the reasons for failure of treatment after their administration. A retrospective study of 42 cases of superficial herpetic keratitis resistant to IDU, IDU and IDC, and Ara-A demonstrated that in 2 out of 3 cases this resistance appeared in patients previously treated locally with antiviral compounds for anterior ocular lesions. Patients resistant to IDU were then treated with Ara-A, and those not responding to Ara-A, with TFT. Resistance may be observed following this new treatment during the subsequent relapses.
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PMID:[Clinical resistance of herpetic keratitis to antiviral agents (author's transl)]. 626 Aug 50

We applied the direct immunoperoxidase method to estimate the susceptibility to IDU of 17 strains of the virus which were isolated from the patients with active epithelial lesions of herpetic keratitis. All the strains were found to be sensitive below the IDU concentration of 5 micrograms/ml. The findings obtained by this method were in good agreement with those by the fluorescent antibody technique. The present method is specific and simple. It offers clear-cut interpretation and a permanent record of the results.
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PMID:Use of the immunoperoxidase technique for estimation of susceptibility of herpes simplex virus to IDU. 631 9

Only a few agents with antiviral activity are available for routine clinical use. Amantadine hydrochloride is effective in the prophylaxis of influenza A. In addition, accumulated evidence shows that amantadine has some therapeutic effect when used early in the course of an influenza A infection. Idoxuridine and adenine arabinoside have found application as topical agents in the treatment of herpes simplex keratitis. Adenine arabinoside has also been approved for the treatment of disseminated infections due to herpes zoster and herpes simplex. Acyclovir sodium has been approved as a topical agent in the treatment of limited mucocutaneous herpes simplex viral infections in immunosuppressed patients and of initial episodes of genital herpes simplex infections in patients with normal immunity. Ribavirin, an experimental agent with a wide spectrum of activity in vitro, has not fulfilled expectations in clinical trials. Because of the eradication of smallpox, methisazone has become obsolete as a prophylactic agent in smallpox.
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PMID:Antiviral agents. 633 31

Masked controlled rabbit studies were done to determine the toxic effects on corneal wound healing of the antiviral ointments 0.5% idoxuridine, 3% Ara A, and 3% acyclovir, and the antiviral drops 0.1% idoxuridine, 3% Ara AMP, and 1% trifluridine. Ara A, acyclovir, trifluridine and idoxuridine drops had no significant effects on the rate of closure of epithelial wounds. Idoxuridine ointment given 5 times a day significantly retarded the rate of epithelial wound closure, but not when given 4 times a day. Only Ara AMP caused a retardation of epithelial healing and an actual increase in the defect after 4 days of treatment. Histopathologically all drugs, except acyclovir, showed a toxic effect on the regenerating epithelium. All drugs, except acyclovir, showed retarded stromal wound healing with reduced bursting strength and collagen content. Ara AMP had increased bursting strength and collagen content possibly because of greater inflammation. Acyclovir, in comparison to all the other medications studied, appeared to have minimal to no toxic effects on experimental epithelial and stromal wound healing, and on this basis is the agent of choice for use in herpes simplex stromal keratitis with ulceration and as a prophylactic agent for long-term use after penetrating keratoplasty.
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PMID:Antiviral medications and corneal wound healing. 647 19


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