["Herpetic keratitis". Various expressions require different therapeutic approaches]. / "Herpeskeratitis". Unterschiedliche Ausprägungsformen erfordern unterschiedliche Therapieansätze.

Herpes simplex virus (HSV) is a common cause of keratitis. "Herpetic keratitis" is a chameleon, which is well treatable today if the various types of clinical expression of this disease are known to the ophthalmologist and treatment is adjusted accordingly. Types of expression include 1. epithelial keratitis (dendritica/geographica), 2. stromal keratitis (necrotizing vs. non-necrotizing = "interstitial keratitis"), 3. endotheliitis (=disciform keratitis), 4. neurotrophic keratopathy (=so-called metaherpetic keratitis) and 5. (vascularized) corneal scars. A concomitant ocular hypertension should be treated predominantly non-surgically (no prostaglandin analogues). Topical artificial tears (if necessary with acyclovir ointment at night) in the quiet interval are recommended to limit the tendency towards recurrences. After keratoplasty and in cases of severe recurrences of herpetic keratitis, systemic acyclovir application (2×400 mg/day) for at least 1 year is indispensable! Overall, HSV has lost its "terror" today, even after keratoplasty, given adequate management.

Pseudodentritic keratitis associated with meibomitis in young healthy males.

PURPOSE: To report unusual corneal manifestations of pseudodendritic keratitis in cases of coexisting meibomian gland dysfunction (MGD). METHODS: Retrospective chart review of five cases of MGD with associated atypical corneal lesions was carried out. Information including patient's age, symptoms and their duration, clinical features, methods of diagnosis, treatment, and outcome were abstracted from the medical records. Pseudodendritic keratitis and MGD was defined before the data collection. RESULTS: All five patients were males within the age range of 6-24 years. Common symptoms were irritation and watering. MGD, which was defined as stenosis of meibomian gland orifices and/or turbid meibomian secretions, was seen in all the patients. Corneal lesions were epithelial, raised and dendritic in morphology. Blood investigations carried out to rule out tyrosinemia in three of the patients were negative. Bandage contact lens facilitated disappearance of these lesions in five eyes. CONCLUSIONS: Corneal involvement in the form of pseudodendritic keratitis may be associated with MGD. Application of bandage contact lens facilitated prompt resolution, suggesting mechanical factor with or without other etiological factors may be at interplay in producing these innocuous corneal lesions.

The treatment of herpes simplex virus epithelial keratitis.

PURPOSE: Epithelial keratitis is the most common presentation of ocular infection by herpes simplex virus (HSV). Quantitative assessment of available therapy is needed to guide evidence-based ophthalmology. This study aimed to compare the efficacy of various treatments for dendritic or geographic HSV epithelial keratitis and to evaluate the role of various clinical characteristics on epithelial healing. METHODS: Following a systematic review of the literature, information from clinical trials of HSV dendritic or geographic epithelial keratitis was extracted, and the methodological quality of each study was scored. Methods of epithelial cauterization and curettage were grouped as relatively equivalent physicochemical therapy, and solution and ointment formulations of a given topical antiviral agent were combined. The proportion healed with 1 week of therapy, a scheduled follow-up day that approximated the average time of resolution with antiviral therapy, was selected as the primary outcome based on a masked evaluation of maximum treatment differences in published healing curves. The proportion healed at 14 days was recorded as supplemental information. Fixed-effects and random-effects meta-analysis models were used to obtain summary estimates by pooling results from comparative treatment trials. Hypotheses about which prognostic factors might affect epithelial healing during antiviral therapy were developed by multivariate analysis of the Herpetic Eye Disease Study dataset. RESULTS: After excluding 48 duplicate reports, 14 nonrandomized studies, 15 studies with outdated or similar treatments, and 29 trials lacking sufficient data on healing or accessibility, 76 primary reports were identified. These reports involved 4,251 patients allocated to 93 treatment comparisons of dendritic epithelial keratitis in 28 categories and 9 comparisons of geographic epithelial keratitis in 6 categories. For dendritic keratitis, idoxuridine was better than placebo at 7 days (combined odds ratio [OR], 3.59; 95% confidence interval [CI], 1.92-6.70), and at 14 days (OR, 4.17; 95% CI, 1.33-13.04), but pooling was limited by lack of homogeneity and low study quality. Direct comparisons at 1 week of treatment showed that trifluridine or acyclovir was significantly better than idoxuridine (OR, 3.12 and 4.56; 95% CI, 1.55-6.29 and 2.76-7.52, respectively), and indirect comparisons were also consistent with a clinically significant benefit. Vidarabine was not significantly better than idoxuridine in pooled treatment comparisons at 1 week (OR, 1.20; 95% CI, 0.72-2.00) but was better in 2 indirect comparisons (OR, 4.22 and 4.78; 95% CI, 1.69-10.54 and 2.15-10.65, respectively). At 14 days, trifluridine (OR, 6.05; 95% CI, 2.50-14.66), acyclovir (OR, 2.88; 95% CI, 1.39-4.78), and vidarabine (OR, 1.24; 95% CI, 0.65-2.37) were each better than idoxuridine. Trials of geographic epithelial keratitis also suggested that trifluridine, acyclovir, and vidarabine were more effective that idoxuridine. Other topical antiviral agents, such as bromovinyldeoxuridine, ganciclovir, and foscarnet, appeared equivalent to trifluridine or acyclovir. Oral acyclovir was equivalent to topical antiviral therapy and did not hasten healing when used in combination with topical treatment. Antiviral agents did not increase the speed of healing when compared to debridement but reduced the risk of recrudescent epithelial keratitis. The combination of physicochemical treatment with an antiviral agent seemed to be better than either physicochemical or antiviral treatment alone, but the heterogeneous cauterization and curettage techniques and the various treatment combinations limited valid quantitative summary effect measures. The combination of topical interferon with an antiviral agent was significantly better than antiviral therapy at 7 days (OR, 13.49; 95% CI, 7.39-24.61) but not at 14 days (OR, 2.36; 95% CI, 0.82-6.79). Finding apparent heterogeneity for some pooled estimates suggested that dissimilarities in patients, interventions, outcomes, or other logistical aspects of clinical trials occur across studies. CONCLUSIONS: The available evidence on the acute treatment of presumed HSV epithelial keratitis demonstrates the effectiveness of antiviral treatment and shows the log-logistic healing curve of treated dendritic epithelial keratitis. Topical trifluridine, acyclovir, and vidarabine were significantly more effective than idoxuridine but similar in relative effectiveness for dendritic epithelial keratitis. Physicochemical methods of removing infected corneal epithelium are effective, but adjunctive virucidal agents are needed to avert recrudescent epithelial keratitis. Whether debridement in combination with antiviral therapy is more beneficial than antiviral chemotherapy alone appears likely but remains inconclusive. The combination of topical interferon with an antiviral agent significantly speeds epithelial healing. Future trials of the acute treatment of HSV epithelial keratitis must aim to achieve adequate statistical power for assessing the primary outcome and should consider the effect of lesion size and other characteristics on treatment response.

Treatment of cats with ocular disease attributable to herpesvirus infection: 17 cases (1983-1993).

Medical records of 17 cats with ocular disease attributable to herpesvirus injection were reviewed. Herpesvirus infection was confirmed by a positive result on an immunofluorescent antibody test or by detection of dendritic corneal ulcers. Cats were 3 months to 23 years old (mean, 4.8 years). Sex or breed predilections were not evident. Vaccination history was available for 13 cats, 9 of which had been adequately vaccinated against feline viral rhinotracheitis, calici, and panleukopenia viruses. Six cats had a history of respiratory tract disease. Twelve cats were tested for FeLV, and 3 had positive results; 7 cats were tested for feline immunodeficiency virus, with 1 positive result. The most common ocular abnormality seen was conjunctivitis (13/17 cats), followed by dendritic corneal ulcers (10/17 cats). Keratitis was detected in 6 of 17 cats, and nondendritic corneal ulcers in 3 of 17 cats. Corneal sequestra were evident on initial examination or developed during the follow-up period in 4 of 17 cats. Keratoconjunctivitis sicca was diagnosed in 2 of 17 cats, and anterior uveitis was evident in 1 of 17 cats. All cats had 2 or more clinical ocular abnormalities associated with herpesvirus infection. Treatment with topically applied antiviral medications was instituted in 14 cats, including idoxuridine in 7, vidarabine in 4, and trifluridine in 3. Antibiotics were used topically in 10 cats, and atropine was used in 3 cats. Topical administration of corticosteroids was used in 2 cats. Recombinant human alpha-interferon was given orally to 3 cats in conjunction with topical administration of antiviral agents. In addition to medical treatment, 4 cats were treated surgically.(ABSTRACT TRUNCATED AT 250 WORDS)

Experimental keratitis in rabbits by human HSV-1 variants: prevention and treatment.

The efficacy of different therapies and vaccine preparations was assessed for treating or preventing herpetic ocular keratitis induced by experimental inoculation in rabbits with two HSV-1 variants that display different pathogenetic potential. Early administration of acyclovir (ACV) promoted fast healing and prevented neurologic involvements: alpha-interferon (alpha-IFN) was less efficient than ACV; combined therapy with both drugs increased the antiviral effects. In an attempt to prevent the disease, rabbits were vaccinated with a slightly pathogenic HSV-1 variant or with a secreted form of an engineered HSV-1 glycoprotein gB (gB-1s) and were subsequently challenged with a highly pathogenic HSV-1 variant. Immunization of rabbits with gB-1s was much more efficient than immunization with live virus in reducing the severity of herpetic keratitis and in preventing CNS disease.

[Effects of T cell subsets on mouse herpetic keratitis].

Immune splenocytes were obtained from C3H/He mice, which had been inoculated with herpes simplex virus (HSV) type 1 by the corneal route 6 or 12 days previously, and restimulated by lipopolysaccharide-induced lymphoblasts infected with HSV. These cells were either not treated or treated with anti-L3T4 antibody plus complement/anti-Lyt-2 antibody plus complement, and were transferred to subconjunctiva of mice with HSV corneal infection. Adoptive transfer of non-treated cells diminished corneal ulcers, when the splenocytes were transferred from mice inoculated 12 days previously. This effect was reduced by depletion of Lyt-2 bearing cells, but not reduced by depletion of L3T4 bearing cells. Adoptive transfer of splenocytes from mice inoculated 6 days previously did not diminish corneal++ ulcers. These findings demonstrate that HSV specific cytotoxic T lymphocytes (CTL) play an important role in the late phase of recovery from HSV corneal infection.

Ocular shedding of herpes simplex virus.

The presence, frequency, and relationship of ocular and oral shedding of herpes simplex virus to previous herpes keratitis was investigated. This was to determine if a history of herpes keratitis predisposes to shedding of the herpes simplex virus into the tear film and/or mouth. Swabs were collected from the eyes and mouth of two groups of patients thrice weekly over a two- to four-month period. Group A comprised nine patients with a history of herpes labialis, group B 15 patients with a history of herpes keratitis. Herpes simplex virus type 1 was isolated from 1.33% of mouth specimens but was not identified in any of the ocular specimens. There was no significant difference between groups A and B in terms of ocular or oral shedding. Oral shedding appears to be independent of a previous herpes keratitis. The tear film is an unlikely source of virus in persons either with no history of herpes keratitis or between attacks in those patients with a history of previous herpes keratitis.

[Treatment of experimental HSV keratitis with recombinant human interferon (rHuIFN): a clinical and scanning electron microscopic study].

Treatment of experimental HSV keratitis in rabbits with rHuIFN alpha-1 instillations was studied Clinical and scanning electron microscopic observations revealed that local application of rHuIFN alpha-1 protected the target cells against virus invasion and restrained development of HSV keratitis. The initial punctate lesions did not expand uniformly but linearly to form dendritic patterns due to varying sensitivity of cells to virus.

[The use of an immunoglobulin in the comprehensive treatment of ophthalmic herpes]. / Primenenie immunoglobulina v kompleksnom lechenii oftal'mogerpesa.

The paper analyses results after treatment of 30 patients with herpetic keratitis by means of a specific antiherpetic immunoglobulin manufactured at the Sverdlovsk Research Institute of Virus Infections. As compared with traditional treatment, the terms of clinical recovery and the number of bed-days reduced. The preparation can be used in a complex treatment of patients with a herpetic disease.

Effective antibody therapy in herpes simplex virus ocular infection. Characterization of recipient immune response.

The immunotherapeutic potential of a monoclonal antibody specific for glycoprotein D of herpes simplex virus was evaluated in a murine ocular infection model. Passive transfer of antibody at microgram concentrations was able to promote resolution of corneal opacity and hasten healing of blepharitis. Antibody treatment did not prevent development of either a cellular or humoral antiviral immune response. In fact, kinetic studies revealed that the early delayed-type hypersensitivity response was significantly more vigorous in the treated group than in the controls. Potential explanations as to how a single microgram inoculation of antibody could exert a therapeutic effect are discussed.

[Clinical analysis of recurrences of herpes simplex keratitis].

The rates of recurrence in 180 cases of herpes simplex keratitis in 1, 2 and 3 years after the primary attack were found to be 20%, 31.5% and 34.5% respectively, irrespective of sex and types of the lesions. The recurrence rate was significantly higher in cases complicated with corneal neovascularization or iritis and slightly higher in children and older patients. The factors involved and possible measures for reducing the recurrence rate were discussed.

Bromovinyldeoxyuridine and interferon treatment in ulcerative herpetic keratitis: a double masked study.

Bromovinyldeoxyuridine is a potent and safe antiherpes compound that in combination with a placebo treatment promoted the partial and complete healing of herpetic epithelial disease in 22 patients in average times of 4-6 days and 8.5 days respectively. However, when BVDU was combined with 1.5 X 10(6) IU of recombinant a 2C interferon, partial and complete healing times for keratitis in 19 patients were reduced to 2-6 days and 4-6 days respectively. No toxic effects of the medications were observed in any patient.

[Cryoimmunotherapy of herpetic and metaherpetic keratitis]. / Kryoimunoterapie herpetické a metaherpetické keratitidy.

In 11 patients with relapsing herpetic keratitis and metaherpetic ulcers cryoimmunotherapy, as recommended by Amoils, was applied. Under instillation anaesthesia three cryocycles were made using a temperature of -80 degrees on the entire area of the lesion with subsequent instillation of 60 drops (1 drop per minute) of serum obtained from 15 ml of the patient's blood mixed with 5 ml gamma globulin. In all 11 patients progression of the disease was arrested, though it could not be checked by previous conservative therapy. The cornea cleared and vision improved. The method is effective, simple and expands therapeutic procedures which can be used in these tiresome conditions.

[New developments in the treatment of keratitis of Pseudomonas aeruginosa etiology]. / Novoe v lechenii keratitov sinegnoinoi étiologii.

Effectiveness of treatment of 23 patients (23 eyes) with keratitis of Pseudomonas aeruginosa etiology was analysed. The complex treatment including activated carbon fiber material (AUVM "Dneper") allowed to arrest the purulent process in 91.3% of cases, increased the effectiveness of the treatment, shortened the patient's stay in the hospital by 4.2 bed-days, increased visual acuity in 78.2% of patients.

Herpes simplex ocular / Herpes simplex ocular

Em muitos países a ceratite hepética é a segunda causa de perda visual unilateral, precedida apenas pelos traumatismos. Apesar dos avanços no conhecimento da patogênese do herpes sismples ocular alguns aspectos da enfermidade näo estäo completamente esclarecidos. O propósito deste trabalho é resumir conhecimentos atuais sobre epidemiologia, patogênese, manifestaçöes clínicas, achados laboratoriais, e tratamento do herpse simples ocular

[Dynamics of cellular immunity indices in patients with ophthalmic herpes treated with a herpetic polyvaccine]. / Dinamika nekotorykh pokazatelei kletochnogo immuniteta u bol'nykh oftal'mogerpesom pri lechenii gerpeticheskoi polivaktsinoi.

Specific vaccine therapy resulted in clinical improvement or stabilization of the pathological process in some patients with herpetic conjunctivitis. The vaccine exerted an immunopotentiating effect on the immune status of the subjects under study the direction of which depended upon the initial status of the parameters examined. In some cases the positive clinical effect of the vaccine therapy was accompanied by a decrease in lymphocyte sensitization to herpes simplex virus and normalization of the lymphocyte count.