Megan E. Shoff

The relative value of confocal microscopy and superficial corneal scrapings in the diagnosis of Acanthamoeba keratitis.

Purpose: To compare the relative diagnostic value of confocal microscopy and superficial corneal cultures in the diagnosis of Acanthamoeba keratitis by using clinical and microbiologic definitions of disease. Methods: Results of confocal microscopy, superficial corneal smear, and superficial corneal culture were analyzed for validity against 2 different microbiologic and a clinical composite standard for Acanthamoeba keratitis. Results: In patients with both clinical characteristics and objective evidence of Acanthamoeba keratitis, confocal microscopy exhibited a sensitivity of 90.6% (95% confidence interval [CI]: 79.3%-96.9%) and a specificity of 100% (95% CI: 95.0%-100%). In patients with either positive culture or smear evidence of Acanthamoeba keratitis, confocal microscopy showed a sensitivity of 90.9% (95% CI: 78.3%-97.5%) and specificity of 90.1% (95% CI: 81.5%-95.6%). In strictly culture-positive patients, confocal microscopy showed a sensitivity of 92.9% (95% CI: 76.5%-99.1%) and a specificity of 77.3% (95% CI: 67.7%-85.2%). Of the 53 patients with Acanthamoeba keratitis, confocal microscopy was positive in 48 patients, whereas corneal smears and cultures were positive in 30 of 41 and 23 of 42 patients, respectively. Sensitivity of Acanthamoeba culture was 52.8% (95% CI: 38.6%-66.7%) in patients with a clinical diagnosis of Acanthamoeba keratitis. Simultaneous testing of smear and superficial corneal scraping resulted in a sensitivity of 83.0% (95% CI: 70.2%-91.9%), independent of the results of confocal microscopy. Conclusions: As confocal microscopy comes into wider clinical use, it remains in need of clinical and pathologic correlation. When performed and interpreted by an experienced operator, confocal microscopy is both sensitive and specific in the diagnosis of Acanthamoeba keratitis. Contemporaneous corneal scrapings are independently sensitive in the detection of Acanthamoeba keratitis, and a combination of both diagnostic modalities offers the highest likelihood of rapidly and accurately diagnosing Acanthamoeba keratitis in patients with atypical keratitis.

Prognostic Factors Affecting Visual Outcome in Acanthamoeba Keratitis

OBJECTIVE To identify clinical and demographic factors associated with a worse visual outcome in Acanthamoeba keratitis (AK). DESIGN Retrospective, case control study. PARTICIPANTS A total of 72 eyes of 65 patients with AK who were diagnosed at the University of Illinois Eye and Ear Infirmary between May of 2003 and May of 2007 with treatment complete by October of 2007. The first affected eye was analyzed in bilateral disease. METHODS Patient demographic, clinical characteristics, treatment methods, and final visual outcome data were collected through medical record reviews for all patients diagnosed with AK. Cases were defined as patients with AK with a visual outcome worse than 20/25 or those requiring penetrating keratoplasty (PKP). Controls were defined as patients with AK with a visual outcome of 20/25 or better. Logistic regression was used to estimate the odds ratio (OR) identifying prognostic factors associated with a worse visual outcome. MAIN OUTCOME MEASURES Final visual outcome worse than 20/25. RESULTS AK was confirmed through microbiologic evidence in 48 of 65 eyes (73.8%) or with confocal microscopy in 62 of 65 eyes (95.4%). Final visual acuity data were available in 61 of 65 eyes (93.8%); of these 61 eyes, 40 (65.6%) achieved a final visual acuity of 20/25 or better. In multivariable analysis, deep stromal involvement or the presence of a ring infiltrate at presentation was independently associated with worse visual outcomes (OR, 10.27; 95% confidence interval [CI], 2.91-36.17). Symptom duration before diagnosis was statistically predictive of disease stage at presentation (OR, 4.43; 95% CI, 0.99-19.83; multivariable analysis) but not final visual outcome (OR, 2.55; 95% CI, 0.83-7.88; univariate analysis). PKP was performed in 11 of 12 eyes with active disease. CONCLUSIONS Corneal disease staging at presentation with slit-lamp examination was highly predictive of worse outcomes, allowing the identification of patients who might benefit from more aggressive medical or surgical intervention. Unlike in previous reports, patient-reported duration of symptoms before treatment was not reliable in predicting the final visual result in our series.

Survival of Acanthamoeba Cysts after Desiccation for More than 20 Years

ABSTRACT Acanthamoeba is a free-living ameba that is found throughout the world and that causes encephalitis, keratitis, and cutaneous infections in humans. It has two stages in its life cycle: a trophic stage and a resistant cyst stage. We describe here the ability of Acanthamoeba cysts to survive desiccation for more than 20 years.

Successful Treatment of Chronic Stromal Acanthamoeba Keratitis with Oral Voriconazole Monotherapy

Purpose: To describe the treatment of chronic stromal Acanthamoeba keratitis (AK) with oral voriconazole monotherapy. Methods: All cases of chronic stromal AK recalcitrant to traditional therapy subsequently treated with systemic voriconazole seen at the University of Illinois Eye and Ear Infirmary between June 2003 and July 2009 were reviewed for clinical presentation, clinical course, and outcome. Results: Three eyes of 2 patients were identified with culture-confirmed chronic stromal AK unresponsive to traditional antiacanthamoebal therapies, requiring topical corticosteroids to maintain corneal clarity. Oral voriconazole 200 mg twice daily achieved a rapid but transient reduction of inflammation and elimination of corticosteroid dependency but, in both patients, recrudesced approximately 6 weeks after its discontinuation. Subsequent repeated and/or extended use of oral voriconazole alone resulted in complete resolution ranging from 7 to 11 months off all medications with final best-corrected visual acuity ranging from 20/20 to 20/25. Conclusions: Recalcitrant chronic Acanthamoeba stromal keratitis was successfully treated with extended systemic voriconazole administration with good preservation of vision. The clinical resolution of chronic stromal keratitis in our 2 cases suggests that voriconazole may have a larger role in the treatment of AK.

Polymicrobial Keratitis: Acanthamoeba and Infectious Crystalline Keratopathy

PURPOSE To report the early presentation, cause, and successful medical management of combined Acanthamoeba keratitis (AK) and infectious crystalline keratopathy (ICK). DESIGN Interventional case series. METHODS Retrospective review of 111 AK patients diagnosed and managed at the University of Illinois Eye and Ear Infirmary between June 1, 2003 and November 30, 2008 for an additional diagnosis of infectious keratitis. RESULTS Of 5 AK patients with microbiologic evidence of an additional bacterial keratitis during their active AK treatment, concomitant ICK developed in 3 patients. All patients were examined within 3 weeks of their AK diagnosis and were found to have characteristic signs and symptoms consistent with ICK. Bacterial culture results at the time of AK diagnosis were negative in 2 patients, but subsequent culture results were positive for Streptococcus oralis. Initial culture results demonstrated light growth of methicillin-sensitive Staphylococcus aureus in the remaining patient, who had received partial antibiotic treatment. Topical corticosteroids were used before diagnosis in 2 patients and were in use in only 1 patient after AK diagnosis. All infections resolved with medical therapy alone. One patient later required penetrating keratoplasty for visual rehabilitation. CONCLUSIONS In patients with AK, ICK can develop early and without either the use of corticosteroids or a preexisting epithelial defect, inconsistent with previously suggested mechanisms and major risk factors for secondary infection. Combined AK and ICK may exhibit increased pathogenicity with the onset of severe, often new, pain and acceleration of localized tissue loss and resultant scarring. Although early recognition and aggressive medical treatment were successful in resolving the combined infections in our cases, Acanthamoeba coinfection, and perhaps endosymbiosis, should be considered in the evaluation and clinical management of AK, especially in those cases progressing atypically. Further research is needed to understand the precise mechanism of the introduction of coinfectious pathogens and their role in the pathogenicity of AK.

Genotypic identification of Acanthamoeba sp. isolates associated with an outbreak of acanthamoeba keratitis.

Purpose: To determine whether increased rates of Acanthamoeba keratitis (AK) are due to changes in municipal water treatment or to emergence of a more pathogenic strain of Acanthamoeba. Methods: Previous sequence analysis of the 18S ribosomal DNA of Acanthamoeba isolates resulted in the identification of 15 different genotypic classes. These analyses indicate that AK cases are associated predominantly (∼97%) with a single genotype (designated T4) of Acanthamoeba and rarely with other genotypes (eg, T3 and T11). In this study, we test the hypothesis that a new or more pathogenic genotype of Acanthamoeba is the cause of the recent surge in AK. Results: We determined the genotype of 15 Acanthamoeba sp. isolates from AK cases associated with this outbreak using sequence analysis of a region of the 18S ribosomal DNA. Our results indicate that these isolates are predominantly genotype T4 (87%), with the remaining isolates being genotype T3 (13%). Both genotypes have previously been observed in AK cases. Conclusions: There is no support for the hypothesis that the current AK outbreak is associated with infection by a new more pathogenic Acanthamoeba genotype. In addition, these results offer support for the hypothesis that the increased AK incidence may be because of changes in water treatment protocols leading to increased bacterial colonization of the water supply and subsequent increases of already present Acanthamoeba sp, ultimately culminating in an increase of AK cases.

Multisystemic infection with an Acanthamoeba sp in a dog

UNLABELLED CASE DESCRIPTION-A 10-month-old Boxer was evaluated for fever and signs of cervical pain. CLINICAL FINDINGS-Physical examination revealed lethargy, fever, and mucopurulent ocular and preputial discharge. On neurologic examination, the gait was characterized by a short stride. The dog kept its head flexed and resisted movement of the neck, consistent with cervical pain. Clinicopathologic findings included neutrophilic leukocytosis, a left shift, and monocytosis. Cervical radiographs were unremarkable. Cerebrospinal fluid analysis revealed neutrophilic pleocytosis and high total protein content. On the basis of signalment, history, and clinicopathologic data, a diagnosis of steroid-responsive meningitis-arteritis was made. TREATMENT AND OUTCOME The dog was treated with prednisone (3.2 mg/kg [1.45 mg/lb], PO, q 24 h), for 3 weeks with limited response. Consequently, azathioprine (2 mg/kg [0.9 mg/lb], PO, q 24 h) was administered. Three weeks later, the dog was evaluated for tachypnea and lethargy. Complete blood count revealed leukopenia, neutropenia, and a left shift. Thoracic radiography revealed a diffuse bronchointerstitial pattern. The dog subsequently went into respiratory arrest and died. On histologic evaluation, amoebic organisms were observed in the lungs, kidneys, and meninges of the brain and spinal cord. A unique Acanthamoeba sp was identified by use of PCR assay. CLINICAL RELEVANCE This dog developed systemic amoebic infection presumed to be secondary to immunosuppression. The development of secondary infection should be considered in animals undergoing immunosuppression for immune-mediated disease that develop clinical signs unrelated to the primary disease. Although uncommon, amoebic infection may develop in immunosuppressed animals. Use of a PCR assay for identification of Acanthamoeba spp may provide an antemortem diagnosis.

Shifting Distribution of Chicago-Area Acanthamoeba Keratitis Cases

were estimated to cost

Isolation, morphologic, serologic and molecular identification of Acanthamoeba T4 genotype from the liver of a Temminck's tragopan (Tragopan temminckii)

1.94 and

Effect of Low Concentrations of Benzalkonium Chloride on Acanthamoebal Survival and Its Potential Impact on Empirical Therapy of Infectious Keratitis

72.12 per infant, respectively. There were 4 247 000 births in the United States in 2008. Assuming an average of 354 000 births per month, the average monthly cost of universal prophylaxis for ophthalmia neonatorum would be