Therapeutic interventions for herpes simplex virus epithelial keratitis.

BACKGROUND: Many clinical trials have been performed on the acute treatment of dendritic epithelial keratitis. Surveys of ocular antiviral pharmacology and of herpes simplex virus (HSV) eye disease have evaluated different interventions, but a systematic review of all comparative clinical studies has not previously been undertaken. OBJECTIVES: The objective of this review was to compare the effects of various therapeutic interventions for dendritic or geographic HSV epithelial keratitis. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials - CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) in The Cochrane Library (Issue 3, 2007), MEDLINE (1966 to September 2007), EMBASE (1980 to September 2007), LILACS (up to September 2007), SIGLE (1980 to September 2007), ZETOC (21 September 2007), BIOSIS (up to 2005), JICT-EPlus (up to 2005), Index Medicus (1960 to 1965), Excerpta Medica Ophthalmology (1960 to 1973), reference lists of primary reports and review articles, and conference proceedings pertaining to ocular virology. SELECTION CRITERIA: This review included comparative clinical trials that assessed one-week or two-week healing rates of topical ophthalmic or oral antiviral agents and or physical or chemical debridement in people with active epithelial keratitis. DATA COLLECTION AND ANALYSIS: The review author extracted data and assessed trial quality. Interventions were compared by the proportions of participants healed at seven days and at fourteen days after trial enrolment. MAIN RESULTS: This review included data from 99 trials that randomised a total of 5363 participants. The topical application of vidarabine, trifluridine, acyclovir or ganciclovir resulted in a high proportion of participants healing within one week of treatment. Among these antiviral agents, no treatment emerged as significantly better for the therapy of dendritic epithelial keratitis. Insufficient placebo-controlled studies were available to assess debridement and other physical or physicochemical methods of treatment. Interferon monotherapy had a slight beneficial effect on dendritic epithelial keratitis but was not better than other antiviral agents. Interferon was very effective when combined with another antiviral agent such as trifluridine. AUTHORS' CONCLUSIONS: Currently available antiviral agents are effective and nearly equivalent. The combination of a nucleoside antiviral with either debridement or with interferon seems to speed healing. Future trials of the acute treatment of HSV epithelial keratitis must aim to achieve adequate statistical power for assessing the primary outcome of epithelial healing and should consider the effect of lesion size and other characteristics on treatment response.

Therapeutic interventions for herpes simplex virus epithelial keratitis.

BACKGROUND: Many clinical trials have been performed on the acute treatment of dendritic epithelial keratitis. Surveys of ocular antiviral pharmacology and of herpes simplex virus (HSV) eye disease have evaluated different interventions, but a systematic review of all comparative clinical studies has not previously been undertaken. OBJECTIVES: The objective of this review was to compare the effects of various therapeutic interventions for dendritic or geographic HSV epithelial keratitis. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials - CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) in The Cochrane Library (Issue 3, 2006), MEDLINE (1966 to July 2006, week 3), EMBASE (1980 to 2006, week 30), LILACS (up to August 2006), SIGLE (1980 to March 2005), ZETOC (1 August 2006), BIOSIS (up to 2005), JICT-EPlus (up to 2005), Index Medicus (1960 to 1965), Excerpta Medica Ophthalmology (1960 to 1973), reference lists of primary reports and review articles, and conference proceedings pertaining to ocular virology. SELECTION CRITERIA: This review included comparative clinical trials that assessed one-week or two-week healing rates of topical ophthalmic or oral antiviral agents and or physical or chemical debridement in people with active epithelial keratitis. DATA COLLECTION AND ANALYSIS: The review author extracted data and assessed trial quality. Interventions were compared by the proportions of participants healed at seven days and at fourteen days after trial enrolment. MAIN RESULTS: This review included data from 98 trials that randomised a total of 5211 participants. Compared to idoxuridine, the topical application of vidarabine, trifluridine, or acyclovir resulted in a significantly greater proportion of participants healing within one week of treatment. Among these latter three antiviral agents, no treatment emerged as significantly better for the therapy of dendritic epithelial keratitis. Insufficient placebo-controlled studies were available to assess debridement and other physical or physicochemical methods of treatment. Interferon monotherapy had a slight beneficial effect on dendritic epithelial keratitis but was not better than other antiviral agents. Interferon was very effective when combined with another antiviral agent such as trifluridine. AUTHORS' CONCLUSIONS: Currently available antiviral agents are effective and nearly equivalent. The combination of a nucleoside antiviral with either debridement or with interferon seems to speed healing. Future trials of the acute treatment of HSV epithelial keratitis must aim to achieve adequate statistical power for assessing the primary outcome of epithelial healing and should consider the effect of lesion size and other characteristics on treatment response.

Prevalence and spectrum of bacterial co-infection during fungal keratitis.

AIMS: To estimate the propensity of keratomycosis for parallel or secondary bacterial infection and to explore affinities among fungal and bacterial co-isolates. METHODS: A retrospective review of laboratory records over 24 years yielded 152 episodes of culture positive fungal keratitis. After collating 65 corneal specimens having bacterial co-isolates, polymicrobial co-infection was defined as detection of concordant bacteria on smear and culture or on two or more different media. RESULTS: 30 (20%) keratomycoses met laboratory criteria for polymicrobial infection. The risk of bacterial co-infection was 3.2 (95% confidence interval, 1.7 to 5.8) times greater with yeast keratitis than with filamentous fungal keratitis. CONCLUSIONS: Bacterial co-infection occasionally complicates fungal keratitis, particularly candidiasis.

Interventions for herpes simplex virus epithelial keratitis.

BACKGROUND: Many clinical trials have been performed on the acute treatment of dendritic epithelial keratitis. Surveys of ocular antiviral pharmacology and of herpes simplex virus eye disease have evaluated different interventions, but a systematic review of all comparative clinical studies has not previously been undertaken. OBJECTIVES: The objective of this review is to compare the effects of various treatments for dendritic or geographic herpes simplex virus epithelial keratitis. SEARCH STRATEGY: Sources searched for relevant studies were the Cochrane Central Register of Controlled Trials - CENTRAL (which contains the Cochrane Eyes and Vision Group trials register), (Issue 3 2002), MEDLINE (1966 to August 2002), EMBASE (1980 to August 2002), LILACS (up to 2002), Index Medicus (1960 to 1965), Excerpta Medica Ophthalmology (1960 to 1973), reference lists of primary reports and review articles, and conference proceedings pertaining to ocular virology. SELECTION CRITERIA: This review includes comparative clinical trials that assessed one-week and/or two-week healing rates of topical ophthalmic or oral antiviral agents and/or physical or chemical debridement in people with active epithelial keratitis. DATA COLLECTION AND ANALYSIS: The reviewer extracted data and assessed trial quality. Interventions were compared by the proportions of participants healed at seven days and at fourteen days after trial enrollment. MAIN RESULTS: This review includes data from 97 trials that randomised a total of 5102 participants. Compared to idoxuridine, the topical application of vidarabine, trifluridine, or acyclovir generally resulted in a significantly greater proportion of participants healing within one week of treatment. Among these three antiviral agents, no treatment emerged as significantly better for the therapy of dendritic epithelial keratitis. Insufficient placebo-controlled studies were available to assess debridement and other physical or physicochemical methods of treatment. Interferon monotherapy had a slight beneficial effect on dendritic epithelial keratitis, but not better than other antiviral agents, although interferon was very useful combined with debridement or with another antiviral agent such as trifluridine. REVIEWER'S CONCLUSIONS: Currently available antiviral agents are effective and nearly equivalent. The combination of a nucleoside antiviral with either debridement or with interferon seems to speed healing. Future trials of the acute treatment of herpes simplex virus epithelial keratitis must aim to achieve adequate statistical power for assessing the primary outcome of epithelial healing and should consider the effect of lesion size and other characteristics on treatment response.

Age of the emergence of negative attitudes toward strabismus.

INTRODUCTION: Strabismus impacts a variety of psychosocial variables in both children and adults. Poor self-esteem, lack of confidence, altered interpersonal relationships, and difficulty with employment procurement have been reported. The purpose of this study was to determine the age at which children perceive strabismus in dolls and to evaluate their reactions. METHODS: Three identical dolls were altered so that one was orthotropic, one esotropic, and one exotropic. Thirty-four naïve children between 3 and 7 years of age were individually placed in a waiting room with the 3 dolls as the only toys with which to play. A one-way mirror allowed a hidden observer to tabulate the number of positive and negative behaviors exhibited toward each doll. After a 10-minute observation period, the children were asked a short series of questions about their preferences and attitudes toward the dolls. Odds ratios were then determined for both the observed behaviors and the expressed responses to the strabismic dolls compared with the orthotropic dolls. RESULTS: Children aged 5(3/4) years and older were 73 times more likely than younger children to express a negative feeling about the strabismic dolls when asked (P =.003). Additionally, when comparing the strabismic dolls with the orthotropic doll, children aged 3 to 4(1/4) years did not notice a difference, children aged 4(1/2) to 5(1/4) years tended to describe the eyes as "different," and children aged 5(3/4) years or older almost uniformly gave a negative description of the strabismic dolls. CONCLUSIONS: A negative attitude toward strabismus appears to emerge at approximately 6 years of age. The biopsychosocial determinants of dislike and hostility toward ocular deviations are apparently acquired, learned responses.

Molecular screening of donor corneas for fungi before excision.

PURPOSE: To develop panfungal and Candida albicans species-specific polymerase chain reaction (PCR) assays to screen donor eyes for fungal contamination before corneal excision. METHODS: PCR primers were designed for either the broad-spectrum detection of fungal DNA or the specific detection of C. albicans DNA. Their sequences were based on rDNA regions highly conserved among and specific to fungi and C. albicans, respectively. PCR conditions with the two primer sets were optimized and tested for sensitivity using purified C. albicans genomic DNA and a plasmid containing the relevant region of C. albicans DNA. The specificity of the primer sets was established using higher eukaryotic, fungal, prokaryotic, and viral DNAs as PCR templates. Donor eye swab specimens were collected before corneal excision. DNA was extracted from the specimens and tested by both PCR assays. RESULTS: The lower limit of detection for both primer sets was consistently 10(3) genome equivalents, when using genomic DNA as a template and 10(2) copies of plasmid. The fungal PCR assay amplified DNA from all fungal species tested but did not amplify any of the selected mammalian, bacterial, or viral DNA. The C. albicans PCR detected the C. albicans DNA but was negative for all other DNA substrates, including the other fungal templates. Thirty-five percent of the donor eye samples tested were positive for fungus, and 19% were positive for C. albicans DNA. CONCLUSIONS: The PCR assays allowed the rapid screening of DNA extracted from specimens collected from corneal donors for potential fungal contamination. The assay was highly sensitive and specific for screening corneal surfaces. The results suggest that approximately one-third of donor eyes tested harbor fungi on the ocular surface.

The Draize eye test.

Hundreds of substances are used daily that can damage eyesight. People's eyes are open to accidental or intentional exposure during the production, transportation, use, and disposal of chemical preparations. Ensuring the safety of consumer products was born during the mid twentieth century in the aftermath of chemical warfare research, and was motivated by the hazards of unsafe cosmetics. Justified by an exigency for public protection, the Draize eye test became a governmentally endorsed method to evaluate the safety of materials meant for use in or around the eyes. The test involves a standardized protocol for instilling agents onto the cornea and conjunctiva of laboratory animals. A sum of ordinal-scale items of the outer eye gives an index of ocular morbidity. Advances in ocular toxicology are challenging the validity, precision, relevance, and need of the Draize eye test. Preclinical product-safety tests with rabbits and other mammals also raise ethical concerns of animal wellbeing. Some use the Draize test as a rallying point for how animals are treated in science and industry. A battery of cellular systems and computer models aim to reduce and ultimately to replace whole-animal testing. Molecular measures of ocular toxicity may eventually allow comprehensive screening in humans. The Draize eye test was created and refined for humanitarian reasons and has assuredly prevented harm. Its destiny is to be progressively supplanted as in vitro and clinical alternatives emerge for assessing irritancy of the ocular surface.

Recall bias in a prospective cohort study of acute time-varying exposures: example from the herpetic eye disease study.

Recall bias is possible in a prospective cohort study when exposure status is transient and must be periodically recalled, and ascertainment occurs after symptom onset. We know of no published demonstration of such bias at play in a prospective cohort study. In a substudy of a randomized clinical trial, 308 participants were prospectively followed to investigate potential acute triggers of ocular herpes simplex virus (HSV) recurrences. Participants reported on the presence of systemic infection or high psychological stress (exposures) on a home log that was completed weekly for up to 15 months and mailed to the study's coordinating centers. By protocol, exposure reporting was to occur on the last day of the week (Sunday) so that a prospective 1-week lag period between exposure and outcome in the following week could be assessed. The study outcome was development of a recurrence of ocular HSV disease documented by clinical examination. Using 35 weekly reports of exposure properly completed before the week of an outcome, there was no evidence of higher risk of HSV recurrence associated with systemic infection (rate ratio = 0.62, 95% confidence interval [CI]: 0.19-2.02) or high psychological stress rate (ratio = 0.0, 95% CI: 0.0-undefined). In contrast, when the analysis was based on 26 weekly reports of exposure improperly completed on or after the date of outcome, the risk of recurrence associated with systemic infection was estimated to be 4-fold (rate ratio = 4.07, 95% CI: 1.84-8.98), and there was a suggestion of a 2-fold risk associated with high psychological stress (rate ratio = 2.02, 95% CI: 0.69-5.91). Without real-time monitoring of exposure reporting, preservation of the temporal exposure-disease relationship-an implicit assumption of the prospective cohort study design-may be particularly tenuous when transient exposures are investigated longitudinally.

Interventions for herpes simplex virus epithelial keratitis.

BACKGROUND: Many clinical trials have been performed on the acute treatment of dendritic epithelial keratitis. Surveys of antiviral pharmacology and of herpes simplex virus eye disease have evaluated different commercially available agents, but a systematic review of all comparative clinical studies has not previously been undertaken. OBJECTIVES: The objective of this review is to compare the effects of various treatments for dendritic or geographic herpes simplex virus epithelial keratitis. SEARCH STRATEGY: Sources searched for relevant studies were the Cochrane Eyes and Vision Group specialized register, The Cochrane Controlled Trials Register - CENTRAL, MEDLINE, EMBASE, Index Medicus, Excerpta Medica Ophthalmology, reference lists of primary reports, review articles, and corneal textbooks and conference proceedings pertaining to ocular virology. SELECTION CRITERIA: This review includes comparative clinical trials that assessed oral or topical ophthalmic antiviral agents, or physical or chemical debridement in people with active epithelial keratitis. DATA COLLECTION AND ANALYSIS: The reviewer extracted data and assessed trial quality. Interventions were compared by the proportions of participants healed at seven days and at fourteen days after trial enrollment. MAIN RESULTS: This review includes data from 96 trials which randomised a total of 4991 participants. Compared to idoxuridine, the topical application of vidarabine, trifluridine, or acyclovir generally resulted in a significantly greater proportion of participants healing within one week of treatment. Among these three antiviral agents, no treatment emerged as significantly better for the therapy of dendritic epithelial keratitis. Insufficient placebo-controlled studies were available to assess debridement and other physical and physicochemical methods of treatment. Interferon monotherapy had a slight beneficial effect on dendritic epithelial keratitis, but not better than other antiviral agents, and was useful with debridement. REVIEWER'S CONCLUSIONS: Currently available and investigational antiviral agents are effective and nearly equivalent, but the combination of an antiviral nucleoside and interferon seems to speed healing. Future trials of the acute treatment of herpes simplex virus 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.

Candidal endophthalmitis after keratoplasty.

PURPOSE: To report a case of explosive fungal endophthalmitis after penetrating keratoplasty and to review additional published and unpublished cases to consider possible strategies for prevention. METHODS: Records of this patient with postkeratoplasty candidal endophthalmitis and previously reported cases of postkeratoplasty candidal endophthalmitis were reviewed. Additional information of 26 unpublished cases was obtained from the Eye Bank Association of America. RESULTS: After standard keratoplasty, the patient developed precipitous endophthalmitis on the second postoperative day. Abundant contamination with Candida was found in the residual donor corneoscleral rim, and Candida albicans was isolated from the aqueous humor of the recipient. Despite therapy with local antimicrobial agents, intraocular amphotericin B, and systemic fluconazole, the patient had a poor outcome with hand-motion visual acuity. Of the 44 collected cases of postkeratoplasty candidal endophthalmitis, 40 (91%) had the same organism cultured from the donor rim or medium. Forty-three donor corneas had been preserved in cold storage medium at 4 degrees C. Of 15 cases in which the outcome was available, 9 (60%) resulted in visual acuity of 20/200 or worse. CONCLUSION: Case reports confirm the occurrence of donor-to-host transmission of postkeratoplasty candidal endophthalmitis. Despite the low reported incidence, the poor prognosis of the affected eye in the ajority of these cases suggests the need for antifungal supplementation of cold preservation media and other preventative strategies.

Curvularia keratitis.

PURPOSE: To determine the risk factors and clinical signs of Curvularia keratitis and to evaluate the management and outcome of this corneal phaeohyphomycosis. METHODS: We reviewed clinical and laboratory records from 1970 to 1999 to identify patients treated at our institution for culture-proven Curvularia keratitis. Descriptive statistics and regression models were used to identify variables associated with the length of antifungal therapy and with visual outcome. In vitro susceptibilities were compared to the clinical results obtained with topical natamycin. RESULTS: During the 30-year period, our laboratory isolated and identified Curvularia from 43 patients with keratitis, of whom 32 individuals were treated and followed up at our institute and whose data were analyzed. Trauma, usually with plants or dirt, was the risk factor in one half; and 69% occurred during the hot, humid summer months along the US Gulf Coast. Presenting signs varied from superficial, feathery infiltrates of the central cornea to suppurative ulceration of the peripheral cornea. A hypopyon was unusual, occurring in only 4 (12%) of the eyes but indicated a significantly (P = .01) increased risk of subsequent complications. The sensitivity of stained smears of corneal scrapings was 78%. Curvularia could be detected by a panfungal polymerase chain reaction. Fungi were detected on blood or chocolate agar at or before the time that growth occurred on Sabouraud agar or in brain-heart infusion in 83% of cases, although colonies appeared only on the fungal media from the remaining 4 sets of specimens. Curvularia was the third most prevalent filamentous fungus among our corneal isolates and the most common dematiaceous mold. Corneal isolates included C senegalensis, C lunata, C pallescens, and C prasadii. All tested isolates were inhibited by 4 micrograms/mL or less of natamycin. Topical natamycin was used for a median duration of 1 month, but a delay in diagnosis beyond 1 week doubled the average length of topical antifungal treatment (P = .005). Visual acuity improved to 20/40 or better in 25 (78%) of the eyes. CONCLUSIONS: Curvularia keratitis typically presented as superficial feathery infiltration, rarely with visible pigmentation, that gradually became focally suppurative. Smears of corneal scrapings often disclosed hyphae, and culture media showed dematiaceous fungal growth within 1 week. Natamycin had excellent in vitro activity and led to clinical resolution with good vision in most patients with corneal curvulariosis. Complications requiring surgery were not common but included exophytic inflammatory fungal sequestration, treated by superficial lamellar keratectomy, and corneal perforation, managed by penetrating keratoplasty.

Colorimetric indicators of microbial contamination in corneal preservation medium.

PURPOSE: To compare acid-base and oxidation-reduction indicators and to investigate the effect of buffer and temperature on the colorimetric detection of microbial growth in corneal preservation media. METHODS: Corneal preservation media containing gentamicin, without or with HEPES buffer, were prepared with either phenol red or AlamarBlue indicators (AccuMed International, Westlake, OH, U.S.A.). Both media were inoculated with Staphylococcus aureus, Streptococcus sanguis, Pseudomonas aeruginosa, Serratia marcescens, or Candida albicans and then incubated at 4 degrees C, 22 degrees C, or 35 degrees C. The pH or percent reduction were determined hourly for eight hours, then daily for one week. RESULTS: The length of time before a confirmed change in pH or reduction occurred varied by microorganism, storage temperature, and buffering capacity. At 4 degrees C, none of the microorganisms caused a detectable pH change in buffered medium within one day after inoculation, although two bacterial species reduced AlamarBlue within four hours. At 22 degrees C and 35 degrees C, all bacteria except P. aeruginosa produced a pH shift within a few hours, and all tested bacterial species reduced AlamarBlue. For bacteria producing detectable pH changes, HEPES-buffered medium took longer to change than medium without HEPES. C. albicans was not detectable in HEPES-buffered medium at any temperature by phenol red and was only detectable by AlamarBlue after 2-3 days at 22 degrees C and 35 degrees C. CONCLUSION: Acidic shifts in refrigerated corneal preservation medium do not occur during contamination by several microorganisms. AlamarBlue, a redox indicator, is more sensitive than phenol red in detecting some bacteria. C. albicans is not reliably detected by pH or redox indicators.

The collagen-binding adhesin is a virulence factor in Staphylococcus aureus keratitis.

A collagen-binding strain of Staphylococcus aureus produced suppurative inflammation in a rabbit model of soft contact lens-associated bacterial keratitis more often than its collagen-binding-negative isogenic mutant. Reintroduction of the cna gene on a multicopy plasmid into the mutant helped it regain its corneal adherence and infectivity. The topical application of a collagen-binding peptide before bacterial challenge decreased S. aureus adherence to deepithelialized corneas. These data suggest that the collagen-binding adhesin is involved in the pathogenesis of S. aureus infection of the cornea.

Epstein-Barr virus dacryoadenitis.

PURPOSE: To describe the clinical features of lacrimal gland inflammation associated with Epstein-Barr virus infection. METHODS: The clinical records, laboratory data, and radiographs of patients who had inflammation of one or both lacrimal glands that had begun less than 4 weeks previously were reviewed. RESULTS: Sixteen patients with dacryoadenitis were encountered between 1980 and 1996, a cumulative frequency of approximately one case per 10,000 new ophthalmic outpatients. Six individuals had serologic or other evidence of recent Epstein-Barr virus infection and were distinguished by the presence of regional lymphadenopathy, no purulent discharge, and a duration of symptoms of 6 weeks. CONCLUSION: Epstein-Barr virus is a probable cause of unilateral and bilateral dacryoadenitis in young adults.

Vibrio ocular infections on the U.S. Gulf Coast.

PURPOSE: To describe the epidemiology of Vibrio eye infections. METHOD: We reviewed the records of a patient from our institution with V. vulnificus keratitis and conducted a literature search for other cases of ocular infections with Vibrio species. RESULTS: A 39-year-old fisherman was struck in his left eye with an oyster shell fragment, developed suppurative V. vulnificus keratitis, and was successfully treated with combined cefazolin and gentamicin. Including our patient, 17 cases of eye infections with Vibrio spp. have been reported, and 11 (65%) involved exposure to seawater or shellfish. Of the seven cases due to V. vulnificus (six keratitis and one endophthalmitis), six had known exposure to shellfish or seawater along the U.S. coast of the Gulf of Mexico. Of five cases of V. alginolyticus conjunctivitis, three had been exposed to fish or shellfish. Three infections with V. parahaemolyticus (one keratitis and two endophthalmitis) were reported; two of these occurred in people exposed to brackish water on or near the Gulf Coast. Two cases of postsurgical endophthalmitis, one with V. albensis and one with V. fluvialis, also were reported. CONCLUSIONS: In addition to septicemia, gastroenteritis, and wound infections, halophilic noncholera Vibrio species can cause sight-threatening ocular infections. Ocular trauma by shellfish from contaminated water is the most common risk factor for Vibrio conjunctivitis and keratitis. Nearly one half of reported Vibrio infections of the eye occurred along the U.S. coast of the Gulf of Mexico.

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.

Microbiologic analysis of bottled water: is it safe for use with contact lenses?

OBJECTIVE: To analyze commercially available bottled water as a possible source of microbial contamination of contact lenses. METHODS: Two different lots of 23 brands of noncarbonated bottled water were tested for coliforms, total bacteria, fungi, and free-living amebae. A sample consisted of three separate 100-ml aliquots from one lot of each brand (46 samples). Aliquots were vacuum-filtered using a 0.45-microm Nalgene analytical filter unit, and the membrane filter was placed on a filter pad in a Petri dish containing test medium. Plates were examined under a stereomicroscope, and the number of colony-forming units (CFUs) was calculated for each sample. To test for the presence of free-living amebae, three aliquots totaling approximately 3800 ml were concentrated using 8-microm filters, and the filters were placed on non-nutrient agar with live Enterobacter aerogenes. To assess the possibility of contaminating contact lenses, etafilcon lenses were rinsed in 2-ml aliquots of four brands of bottled water and then cultured. RESULTS: Seventeen (37%) of 46 samples, representing 11 (48%) of 23 brands, contained viable micro-organisms. Bacteria, including coliforms, were recovered from 12 samples of 8 brands. Yeasts or molds were recovered from seven samples of five brands. Free-living amebae were isolated from two samples, and fresh-water algae were found in both samples of one brand. Nine (20%) of 46 samples, representing 7 (30%) of the 23 brands, had more than 500 CFUs per ml or contained coliforms. Sterile contact lenses became contaminated when exposed for 1 minute to two of four brands of water from which micro-organisms were recovered. CONCLUSION: Some bottled waters contain high numbers of potential ocular pathogens. Bottled water is not safe for routine use with contact lenses.

Laboratory diagnosis of Acanthamoeba keratitis using buffered charcoal-yeast extract agar.

PURPOSE: To evaluate the use of buffered charcoal-yeast extract agar for the isolation of Acanthamoeba from clinical specimens. METHODS: We retrospectively reviewed laboratory records of patients with ocular acanthamebic infection from October 1993 to September 1997 to compare the recovery of Acanthamoeba from clinical specimens inoculated onto various media. We then compared the experimental recovery of 10 corneal isolates of Acanthamoeba on buffered charcoal-yeast extract and blood agars. RESULTS: Paired data for buffered charcoal-yeast extract and blood agars were available from 24 cultures performed in 13 cases of ocular acanthamebic infection. Acanthamebic trails were detected on both buffered charcoal-yeast extract and blood agars in nine cultures, only on buffered charcoal-yeast extract agar in nine cultures, and only on blood agar in one culture (P = .027). In the experimental study, all 10 clinical isolates produced trails on buffered charcoal-yeast extract agar, and the mean recovery after 10 days of incubation ranged from 38% to 95% of the original inoculum number. For seven of the 10 isolates, more than 70% of the original inoculum was recovered on buffered charcoal-yeast extract agar. Only two of the 10 strains produced persistent trails on the blood agar, and the mean recoveries after 10 days of incubation were 0.67% and 1.17%. Recovery was significantly better on buffered charcoal-yeast extract agar than blood agar (P < or = .0003). CONCLUSION: Buffered charcoal-yeast extract agar is an excellent commercially available culture medium for the recovery of Acanthamoeba.