Elmer Y. Tu

Corneal pathology in microphthalmia with linear skin defects syndrome.

PURPOSE To describe the histopathology of the cornea in microphthalmia with linear streaks (MLS) syndrome. METHODS Two patients with MLS syndrome underwent penetrating keratoplasty. This study describes the histopathology and investigates immunophenotype of the corneal extracellular matrix by using keratan sulfate and collagen type III antibodies. RESULTS Clinical examination revealed bilateral sclerocornea and characteristic skin changes. By light microscopy, central corneal stroma in both patients showed vascularization and irregular thick collagen lamellae typical of sclerocornea. In addition, corneal thinning, anterior synechiae, and the absence of the Descemet membrane were noted, which was suggestive of Peters anomaly. Diffuse and intense anti-keratan sulfate staining and minimal anti-collagen type III stromal staining were seen in both corneal buttons. CONCLUSIONS The cornea in MLS may clinically resemble sclerocornea. Histologic features resemble those previously described in sclerocornea and also seen in anterior segment dysgeneses. Keratan sulfate and collagen type III labeling suggests that the corneal extracellular matrix resembled cornea and not sclera.Objective:To examine characteristics of circumcised and uncircumcised Latino and black men who have sex with men (MSM) in the United States and assess the association between circumcision and HIV infection. Methods:Using respondent-driven sampling, 1154 black MSM and 1091 Latino MSM were recruited from New York City, Philadelphia, and Los Angeles. A 45-minute computer-assisted interview and a rapid oral fluid HIV antibody test (OraSure Technologies, Bethlehem, PA) were administered to participants. Results:Circumcision prevalence was higher among black MSM than among Latino MSM (74% vs. 33%; P < 0.0001). Circumcised MSM in both racial/ethnic groups were more likely than uncircumcised MSM to be born in the United States or to have a US-born parent. Circumcision status was not associated with prevalent HIV infection among Latino MSM, black MSM, black bisexual men, or black or Latino men who reported being HIV-negative based on their last HIV test. Further, circumcision was not associated with a reduced likelihood of HIV infection among men who had engaged in unprotected insertive and not unprotected receptive anal sex. Conclusions:In these cross-sectional data, there was no evidence that being circumcised was protective against HIV infection among black MSM or Latino MSM.

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.

Early results of Descemet-stripping and automated endothelial keratoplasty (DSAEK) in patients with glaucoma drainage devices.

Purpose: To evaluate the outcome of Descemet-stripping and automated endothelial keratoplasty (DSAEK) in patients with glaucoma tube shunts in the anterior chamber. Methods: Retrospective review of 4 patients with a history of tube shunt placement that experienced corneal decompensation and subsequently underwent DSAEK at 1 institution. Details of the surgical procedures as well as postoperative features including graft attachment, visual acuity, intraocular pressure (IOP), graft clarity, and central corneal thickness were recorded. Results: There were no graft detachments postoperatively. In all but 1 case, the corneal edema resolved with a corresponding decrease in corneal thickness. In 1 case, where there was excessive donor tissue manipulation intraoperatively, the edema failed to resolve. This patient underwent a repeat DSAEK with subsequent graft attachment and resolution of the corneal edema. In all 4 patients, the tube shunt was revised at the time of DSAEK. The tube was not tied or plugged in any of the patients. Except for 1 patient with fibrin reaction, there were no IOP spikes postoperatively. At the 6-month follow-up, the visual acuity had improved in all patients and the IOP had not changed significantly from preoperative levels. Conclusion: This small series suggests that DSAEK is a viable and effective option in patients with existing tube shunts. The presence of a tube did not affect the rate of graft dislocation; however, it appeared to increased the rate of complications postoperatively. These early outcomes support the use of DSAEK as an alternative to penetrating keratoplasty in this patient population.

Practice patterns and opinions in the treatment of acanthamoeba keratitis

Purpose: Management of acanthamoeba keratitis remains challenging for ophthalmologists. We conducted a survey of members of The Cornea Society to elicit expert opinions on the diagnosis and treatment of acanthamoeba keratitis. Methods: An online survey was sent to all subscribers of The Cornea Society via the kera-net listserv. Descriptive statistics were performed. Results: Eighty-two participants completed the online survey. Of the 82 respondents, 76.8% included the combination of clinical examination and culture in their diagnostic strategy and 43.9% used confocal microscopy. Most respondents (97.6%) had used combination therapy with multiple agents to treat acanthamoeba keratitis at some point in the past, whereas a smaller proportion (47.6%) had ever used monotherapy. Respondents most commonly chose polyhexamethylene biguanide as the ideal choice for monotherapy (51.4%), and dual therapy with a biguanide and diamidine as the ideal choice for combination therapy (37.5%). The majority of respondents (62.2%) reported using topical corticosteroids at least some of the time for acanthamoeba keratitis. Keratoplasty was an option considered by most respondents (75.6%), although most (85.5%) would only perform surgery after medical treatment failure. Conclusions: There was a wide range of current practice patterns for the diagnosis and treatment of acanthamoeba keratitis. The lack of sufficiently powered comparative effectiveness studies and clinical trials makes evidence-based decision-making for this disease difficult.

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.

Report of the eye bank association of America medical advisory board subcommittee on fungal infection after corneal transplantation

Purpose: To investigate the incidence of fungal infections after corneal transplantation to determine whether storage media supplementation with an antifungal should be considered. Methods: Adverse reactions reported to the Eye Bank Association of America through the online adverse reaction reporting system between January 1, 2007, and December 31, 2010, were reviewed to identify cases of recipient fungal infection. Data were collected regarding the donor, the donor cornea, recovery and processing, and mate culture and clinical course of the recipients. Results: Thirty-one cases of culture-proven fungal keratitis (n = 14) and endophthalmitis (n = 17) were reported out of 221,664 corneal transplants performed using corneal tissue distributed by domestic eye banks (1.4 cases per 10,000 transplants performed). Although the annual incidence of postkeratoplasty fungal infection has not increased significantly since 2005, a trend toward an increasing rate of fungal infection has been observed. Fungal infections were more commonly reported after endothelial keratoplasty procedures (0.022%) than penetrating keratoplasty procedures (0.012%), but the difference was not statistically significant (P = 0.076). Additionally, no association was found between fungal infection after endothelial keratoplasty and whether the lamellar tissue cut was performed by the surgeon or the eye bank technician. Seventy-three percent (16 of 22) of the fungal cultures performed on the mate corneas were positive, with infection developing in 67% (10 of 15) of recipient eyes (endophthalmitis in 6 eyes and keratitis in 4 eyes). Conclusions: Although a nonsignificant increasing trend in the rate of fungal infection has been observed over the past 6 years, it is not sufficiently compelling to pursue antifungal supplementation of donor storage media.

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.

Use of Infliximab in the Treatment of Peripheral Ulcerative Keratitis in Crohn Disease

PURPOSE To report the effectiveness of infliximab in the treatment of peripheral ulcerative keratitis (PUK) associated with Crohn disease. DESIGN Retrospective, interventional case series. METHODS SETTING Institutional, academic referral setting. patient or study population: Six eyes of 3 patients with PUK associated with Crohn disease that failed or were intolerant to traditional immunosuppression such as oral prednisone and cyclophosphamide. INTERVENTION OR OBSERVATION PROCEDURE(S): Infliximab intravenous infusion 5 mg/kg every 2 to 8 weeks. MAIN OUTCOME MEASURE(S) Subjective outcome such as pain improvement and objective outcomes such as visual acuity, signs of inflammation, and progression of corneal thinning. RESULTS Symptom of pain improved in all patients. Visual acuity remained stable in 4 of 6 eyes, improved in 1 of 6 eyes, and worsened in 1 of 6 eyes (secondary to stromal scar). Rapid resolution of inflammation and arrest of further thinning were observed in all 6 eyes. Similar effects were observed on recurrence treated with repeat dosing of infliximab in 5 of 6 eyes. CONCLUSIONS Infliximab produced a rapid, dramatic, repeatable suppression of corneal inflammation, pain, and keratolysis in PUK associated with Crohn disease. Although the effect of long-term therapy with these agents is unknown, infliximab should be considered in patients with Crohn-associated PUK not amenable to traditional therapy. Larger prospective studies are needed to determine the efficacy of infliximab in this aggressive disease entity.