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1.  Association between Cytotoxic and Invasive Pseudomonas aeruginosa and Clinical Outcomes in Bacterial Keratitis 
JAMA ophthalmology  2013;131(2):147-153.
Clinical isolates of Pseudomonas aeruginosa can be characterized as cytotoxic or invasive, based on their differing effects on host cells. Previous studies have shown that strain type influences pathology in animal models. The aim of this study was to determine if invasive and cytotoxic strains differentially impact clinical presentation, outcome, or therapeutic response in bacterial keratitis.
P.aeruginosa isolates from the NEI-funded Steroids for Corneal Ulcers Trial (SCUT) were subtyped as invasive or cytotoxic strains. The main outcome measure compared between the two subtypes was change in visual acuity at three months using Huber robust regression, adjusting for topical corticosteroid treatment.
Of the 101 confirmed P.aeruginosa isolates from the SCUT, 74 had a classically invasive or cytotoxic genotype. While corneal ulcers caused by genotypically invasive P.aeruginosa strains presented with significantly better visual acuity than those caused by genotypically cytotoxic P.aeruginosa strains when adjusting for the effect of ulcer location (p=0.008), invasive ulcers improved significantly less than cytotoxic ulcers at three months (0.35 logMAR (three and a half line difference), 95% CI 0.04 to 0.66 p=0.03). When compared with topical moxifloxacin alone, adjunctive treatment with topical corticosteroids was associated with significantly more improvement in visual acuity in the invasive subgroup (p=0.04), but was associated with less improvement in vision in the cytotoxic subgroup (p=0.07).
The results of this study suggest that rational profiling of differentially expressed virulence determinants, e.g. cytotoxicity and invasiveness for P.aeruginosa, could be used as a tool for decision making in management of infections to optimize outcome.
PMCID: PMC3796098  PMID: 23411878
Pseudomonas aeruginosa; bacterial keratitis; virulence; type III secretion
2.  Antibiotic Use as a Tragedy of the Commons: A Cross-Sectional Survey 
Background. Many believe antibiotic use results in a tragedy of the commons, since overuse may lead to antibiotic resistance and limiting use would benefit society. In contrast, mass antibiotic treatment programs are thought to result in community-wide benefits. A survey was conducted to learn the views of infectious disease experts on the individual- and societal-level consequences of antibiotic use. Methods. The survey instrument was designed to elicit opinions on antibiotic use and resistance. It was sent via SurveyMonkey to infectious disease professionals identified through literature searches. Descriptive statistics were used to analyze the data. Results. A total of 1,530 responses were received for a response rate of 9.9%. Nearly all participants believed antibiotic use could result in a tragedy of the commons, at least in certain circumstances (96.0%). Most participants did not believe mass antibiotic treatment programs could produce societal benefits in an antibiotic-free society (91.4%) or in the United States (94.2%), though more believed such programs would benefit antibiotic-free societies compared to the United States (P < 0.001). Conclusions. The experts surveyed believe that antibiotic use can result in a tragedy of the commons and do not believe that mass treatment programs benefit individuals or society.
PMCID: PMC3920666  PMID: 24587818
3.  The epidemiological dynamics of infectious trachoma may facilitate elimination 
Epidemics  2011;3(2):10.1016/j.epidem.2011.03.004.
Trachoma programs use mass distributions of oral azithromycin to treat the ocular strains of Chlamydia trachomatis that cause the disease. There is debate whether infection can be eradicated or only controlled. Mass antibiotic administrations clearly reduce the prevalence of chlamydia in endemic communities. However, perfect coverage is unattainable, and the World Health Organization's goal is to control infection to a level where resulting blindness is not a public health concern. Here, we use mathematical models to assess whether more ambitious goals such as local elimination or even global eradication are possible.
We fit a class of non-linear, stochastic, susceptible–infectious–susceptible (SIS) models which allow positive or negative feedback, to data from a recent community-randomized trial in Ethiopia, and make predictions using model averaging.
The models predict that reintroduced infection may not repopulate the community, or may do so sufficiently slowly that surveillance might be effective. The preferred model exhibits positive feedback, allowing a form of stochastic hysteresis in which infection returns slowly after mass treatment, if it returns at all. Results for regions of different endemicity suggest that elimination may be more feasible than earlier models had predicted.
If trachoma can be eradicated with repeated mass antibiotic distributions, it would encourage similar strategies against other bacterial diseases whose only host is humans and for which effective vaccines are not available.
PMCID: PMC3869790  PMID: 21624783
Mathematical model; Stochastic model; Eradication; Chlamydia; Azithromycin; Quasi-stationary distribution; Backward bifurcation
4.  Elimination and Eradication of Neglected Tropical Diseases with Mass Drug Administrations: A Survey of Experts 
Lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminths, and trachoma are the five most prevalent neglected tropical diseases in the world, and each is frequently treated with mass drug administrations. We performed a survey of neglected tropical diseases experts to elicit their opinions on the role of mass drug administrations for the elimination of these infections.
Methodology/Principal Findings
We sent an online survey to corresponding authors who had published an article about a neglected tropical disease from 2007 to 2011. Of 825 unique authors who were invited to complete the survey, 365 (44.2%) responded, including 234 (28.4%) who answered questions regarding one of the five most prevalent neglected tropical diseases. Respondents had varying opinions about the goals of programmatic activities for their chosen neglected tropical disease, with elimination or eradication identified as the most important goal by 87% of lymphatic filariasis respondents, 66% of onchocerciasis respondents, 55% of trachoma respondents, 24% of schistosomiasis respondents, and 21% of soil-transmitted helminth respondents. Mass drug administrations, other non-medication health measures, and education were generally thought to be more important for elimination than vector control, development of a new tool, or the presence of a secular trend. Drug resistance was thought to be a major limitation of mass drug administrations for all five neglected tropical diseases. Over half of respondents for lymphatic filariasis and trachoma thought that repeated mass drug administrations could eliminate infection within ten years of the initiation of mass treatments.
Respondents for lymphatic filariasis, onchocerciasis, and trachoma were more enthusiastic about the prospects of elimination and eradication than were respondents for schistosomiasis or soil-transmitted helminths. Mass drug administrations were generally believed to be among the most important factors for the success of elimination efforts for each of the five neglected tropical diseases, highlighting the opportunity for integrating drug distributions.
Author Summary
Mass drug administrations are used for each of the five most common neglected tropical diseases: lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminths, and trachoma. Three of these infections—lymphatic filariasis, onchocerciasis, and trachoma—are officially targeted for elimination, and mass drug administrations play a key role in the elimination plans for each. While progress has been demonstrated for each of these diseases, it is unclear whether researchers of these diseases think that elimination is feasible, or whether mass drug administrations should play an important role given the potential for drug resistance. We performed a survey of neglected tropical diseases experts to assess their opinions on the likelihood of elimination and the role of mass drug administrations for the five most common neglected tropical diseases. Most experts in lymphatic filariasis, onchocerciasis, and trachoma thought elimination was the appropriate goal of treatment programs, whereas most experts in schistosomiasis and soil-transmitted helminths thought that treatment programs were intended to control, but not eliminate, infection. Drug resistance was thought to be a major limitation for each of the infections. Although there were differences between the five infections, mass drug administrations, non-medication health measures, and education were generally thought to be the most important pieces of a control program.
PMCID: PMC3855072  PMID: 24340111
5.  The Steroid Controversy in Bacterial Keratitis 
Archives of ophthalmology  2009;127(9):10.1001/archophthalmol.2009.221.
PMCID: PMC3845457  PMID: 19752446
7.  Nocardia keratitis: Clinical course and effect of corticosteroids 
American journal of ophthalmology  2012;154(6):934-939.e1.
To compare the clinical course of Nocardia spp keratitis with keratitis due to other bacterial organisms, and to assess the effect of corticosteroids as adjunctive therapy using data collected from the Steroids for Corneal Ulcers Trial (SCUT).
Sub-group analysis of a randomized controlled trial
Multicenter randomized controlled trial
Study Population
500 patients with bacterial keratitis, randomized 1:1 to topical corticosteroid or placebo who had received at least 48 hours of topical moxifloxacin
Intervention/Observation Procedure
Topical prednisolone phosphate 1% or placebo; clinical course of Nocardia keratitis
Main outcome measures
Best spectacle-corrected visual acuity and infiltrate/scar size at 3 months from enrollment
Of 500 patients enrolled in the trial, 55 (11%) had a Nocardia corneal ulcer. Patients with Nocardia ulcers had better presentation visual acuity compared to non-Nocardia ulcers (median Snellen 20/45 compared to 20/145, P<0.001), and comparable 3-month visual acuity (median 20/25 versus 20/40, P=0.25). Nocardia ulcers had approximately 2 lines less improvement in visual acuity compared to non-Nocardia ulcers (0.21 logMAR, 95% CI 0.09 to 0.33 logMAR, P=0.001). This difference may reflect the better starting visual acuity in patients with Nocardia ulcers. In Nocardia ulcers, corticosteroids were associated with an average 0.4 mm increase in 3-month infiltrate/scar size (95% CI 0.03 to 0.77mm, P=0.03).
Nocardia ulcers responded well to treatment. They showed less overall improvement in visual acuity than non-Nocardia ulcers, but had better presentation acuity. Corticosteroids may be associated with worse outcomes.
PMCID: PMC3498612  PMID: 22959881
8.  Fluoroquinolone Treatment and Susceptibility of Isolates From Bacterial Keratitis 
JAMA ophthalmology  2013;131(3):10.1001/jamaophthalmol.2013.1718.
To analyze the relationship between fluoroquinolone use at presentation and minimum inhibitory concentration in bacterial keratitis.
The Steroids for Corneal Ulcers Trial was a randomized, double-masked, placebo-controlled trial assessing the effect of adjunctive topical corticosteroid treatment on outcomes in bacterial keratitis. After presentation, all patients were treated with moxifloxacin hydrochloride, 0.5%. We compare antibiotic use at presentation with minimum inhibitory concentration against moxifloxacin for all isolates. Separate analyses accounted for organism species and fluoroquinolone generation.
Topical fluoroquinolone use at presentation was reported in 92 of 480 cases (19.2%). Causative organisms in the 480 cases included Streptococcus pneumoniae (247 cases [51.5%]), Pseudomonas aeruginosa (109 cases [22.7%]), and Nocardia species (55 cases [11.5%]). Isolates from patients who reported fluoroquinolone use at presentation had a 2.01-fold–higher minimum inhibitory concentration (95% CI, 1.39-fold to 2.91-fold; P <.001). Fourth-generation fluoroquinolones were associated with a 3.48-fold–higher minimum inhibitory concentration than those isolates that were not exposed to pretreatment at enrollment (95% CI, 1.99-fold to 6.06-fold; P <.001).
This study provides evidence that prior use of fluoroquinolones is associated with antibiotic resistance.
PMCID: PMC3833086  PMID: 23307105
10.  Topical Fluoroquinolone Use as a Risk Factor for In Vitro Fluoroquinolone Resistance in Ocular Cultures 
Archives of ophthalmology  2011;129(4):10.1001/archophthalmol.2011.45.
To determine whether recent use of topical fluoroquinolones is a risk factor for in vitro fluoroquinolone resistance in Staphylococcus aureus ocular isolates.
Disk diffusion susceptibility testing for ciprofloxacin, moxifloxacin, and gatifloxacin was performed for all ocular isolates of S aureus at the Francis I. Proctor Foundation microbiology laboratory from January 1, 2005, to December 31, 2008. The medical records of patients with positive S aureus cultures were reviewed to determine topical or systemic fluoroquinolone use within the 3 months prior to culture. The Fisher exact test was used to compare the proportion of patients who used topical fluoroquinolones in the past 3 months among fluoroquinolone-sensitive and -resistant cases. Logistic regression was used to determine risk factors for fluoroquino-lone resistance.
Of 200 S aureus cultures, 41 were resistant to ciprofloxacin, moxifloxacin, and gatifloxacin (20.5%). Fluoroquinolone-resistant S aureus isolates were from older patients (mean [SD] age, 65.5 [25.0] years) compared with fluoroquinolone-susceptible isolates (mean [SD] patientage, 52.1 [22.1] years) (P=.003). Use of fluoroquinolones within the 3 months before testing was more frequent in resistant isolates (29%) than in susceptible isolates (11%) (P=.005), as was recent hospitalization (22% of resistant isolates, 0% of susceptible isolates) (P<.001). In the multivariate regression analysis, topical fluoroquinolone use within 3 months was a significant predictor of fluoroquinolone resistance (P=.046), along with age, systemic immunosuppression, and topical fluoroquinolone use between 3 and 6 months before testing.
Recent topical fluoroquinolone use is significantly associated with fluoroquinolone resistance in S aureus isolates from ocular cultures.
PMCID: PMC3830547  PMID: 21482865
11.  Prior Elicitation and Bayesian Analysis of the Steroids for Corneal Ulcers Trial 
Ophthalmic epidemiology  2012;19(6):10.3109/09286586.2012.735332.
To elicit expert opinion on the use of adjunctive corticosteroid therapy in bacterial corneal ulcers. To perform a Bayesian analysis of the Steroids for Corneal Ulcers Trial (SCUT), using expert opinion as a prior probability.
The SCUT was a placebo-controlled trial assessing visual outcomes in patients receiving topical corticosteroids or placebo as adjunctive therapy for bacterial keratitis. Questionnaires were conducted at scientific meetings in India and North America to gauge expert consensus on the perceived benefit of corticosteroids as adjunct treatment. Bayesian analysis, using the questionnaire data as a prior probability and the primary outcome of SCUT as a likelihood, was performed. For comparison, an additional Bayesian analysis was performed using the results of the SCUT pilot study as a prior distribution.
Indian respondents believed there to be a 1.21 Snellen line improvement, and North American respondents believed there to be a 1.24 line improvement with corticosteroid therapy. The SCUT primary outcome found a non-significant 0.09 Snellen line benefit with corticosteroid treatment. The results of the Bayesian analysis estimated a slightly greater benefit than did the SCUT primary analysis (0.19 lines verses 0.09 lines).
Indian and North American experts had similar expectations on the effectiveness of corticosteroids in bacterial corneal ulcers; that corticosteroids would markedly improve visual outcomes. Bayesian analysis produced results very similar to those produced by the SCUT primary analysis. The similarity in result is likely due to the large sample size of SCUT and helps validate the results of SCUT.
PMCID: PMC3830548  PMID: 23171211
Bacterial keratitis; Corneal ulcer; Clinical trial; Statistics; Prior distribution
12.  Corticosteroids for Bacterial Keratitis 
Archives of ophthalmology  2011;130(2):10.1001/archophthalmol.2011.315.
To determine whether there is a benefit in clinical outcomes with the use of topical corticosteroids as adjunctive therapy in the treatment of bacterial corneal ulcers.
Randomized, placebo-controlled, double-masked, multicenter clinical trial comparing prednisolone sodium phosphate, 1.0%, to placebo as adjunctive therapy for the treatment of bacterial corneal ulcers. Eligible patients had a culture-positive bacterial corneal ulcer and received topical moxifloxacin for at least 48 hours before randomization.
Main Outcome Measures
The primary outcome was best spectacle-corrected visual acuity (BSCVA) at 3 months from enrollment. Secondary outcomes included infiltrate/scar size, reepithelialization, and corneal perforation.
Between September 1, 2006, and February 22, 2010, 1769 patients were screened for the trial and 500 patients were enrolled. No significant difference was observed in the 3-month BSCVA (−0.009 logarithm of the minimum angle of resolution [logMAR]; 95% CI, −0.085 to 0.068; P = .82), infiltrate/scar size (P = .40), time to reepithelialization (P = .44), or corneal perforation (P > .99). A significant effect of corticosteroids was observed in subgroups of baseline BSCVA (P = .03) and ulcer location (P = .04). At 3 months, patients with vision of counting fingers or worse at baseline had 0.17 logMAR better visual acuity with corticosteroids (95% CI, −0.31 to −0.02; P = .03) compared with placebo, and patients with ulcers that were completely central at baseline had 0.20 logMAR better visual acuity with corticosteroids (−0.37 to −0.04; P = .02).
We found no overall difference in 3-month BSCVA and no safety concerns with adjunctive corticosteroid therapy for bacterial corneal ulcers.
Application to Clinical Practice
Adjunctive topical corticosteroid use does not improve 3-month vision in patients with bacterial corneal ulcers.
PMCID: PMC3830549  PMID: 21987582
16.  Voriconazole for Fungal Keratitis 
Ophthalmology  2013;120(9):10.1016/j.ophtha.2013.06.016.
PMCID: PMC3830553  PMID: 24001540
17.  Acanthamoeba Keratitis in South India: A Longitudinal Analysis of Epidemics 
Ophthalmic epidemiology  2012;19(2):10.3109/09286586.2011.645990.
In light of the increased incidence of contact lens associated Acanthamoeba keratitis in recent years, this study analyzed longitudinal trends of its incidence among predominantly non-contact lens wearers in a high-volume referral center in South India.
A retrospective analysis of microbiology laboratory records at the Aravind Eye Hospital from 1988–2009 was performed. The Maximum Excess Events Test (MEET) was used to identify epidemics of Acanthamoeba keratitis.
There were a total of 38,529 unique cases of infectious keratitis evaluated over this time period, of which 372 were culture-positive for Acanthamoeba. Only three cases (0.9%) of Acanthamoeba keratitis occurred among contact lens wearers. MEET identified unique Acanthamoeba keratitis epidemics in 1993 and 2002.
Discrete epidemics of Acanthamoeba keratitis occurred among a rural, non-contact lens wearing, population in South India in 1993 and 2002.
PMCID: PMC3830554  PMID: 22364672
Acanthamoeba; Cornea; Epidemic; India; Keratitis
18.  The Steroids for Corneal Ulcers Trial 
Archives of ophthalmology  2011;130(2):10.1001/archophthalmol.2011.303.
To provide comprehensive trial methods and baseline data for the Steroids for Corneal Ulcers Trial and to present epidemiological characteristics such as risk factors, causative organisms, and ulcer severity.
Baseline data from a 1:1 randomized, placebo-controlled, double-masked clinical trial comparing prednisolone phosphate, 1%, with placebo as adjunctive therapy for the treatment of bacterial corneal ulcers. Eligible patients had a culture-positive bacterial corneal ulcer and had been taking moxifloxacin for 48 hours. The primary outcome for the trial is best spectacle-corrected visual acuity at 3 months from enrollment. This report provides comprehensive baseline data, including best spectacle-corrected visual acuity, infiltrate size, microbio-logical results, and patient demographics, for patients enrolled in the trial.
Of 500 patients enrolled, 97% were in India. Two hundred twenty patients (44%) were agricultural workers. Median baseline visual acuity was 0.84 logMAR (Snellen, 20/125) (interquartile range, 0.36-1.7; Snellen, 20/50 to counting fingers). Baseline visual acuity was not significantly different between the United States and India. Ulcers in India had larger infiltrate/scar sizes (P=.04) and deeper infiltrates (P=.04) and were more likely to be localized centrally (P=.002) than ulcers enrolled in the United States. Gram-positive bacteria were the most common organisms isolated from the ulcers (n=366, 72%).
The Steroids for Corneal Ulcers Trial will compare the use of a topical corticosteroid with placebo as adjunctive therapy for bacterial corneal ulcers. Patients enrolled in this trial had diverse ulcer severity and on average significantly reduced visual acuity at presentation.
PMCID: PMC3830555  PMID: 21987581
19.  Comparison of Natamycin and Voriconazole for the Treatment of Fungal Keratitis 
Archives of ophthalmology  2010;128(6):672-678.
To conduct a therapeutic exploratory clinical trial comparing clinical outcomes of treatment with topical natamycin vs topical voriconazole for fungal keratitis.
The multicenter, double-masked, clinical trial included 120 patients with fungal keratitis at Aravind Eye Hospital in India who were randomized to receive either topical natamycin or topical voriconazole and either had repeated scraping of the epithelium or not.
Main Outcome Measures
The primary outcome was best spectacle-corrected visual acuity (BSCVA) at 3 months. Other outcomes included scar size, perforations, and a sub-analysis of BSCVA at 3 months in patients with an enrollment visual acuity of 20/40 to 20/400.
Compared with those who received natamycin, voriconazole-treated patients had an approximately 1-line improvement in BSCVA at 3 months after adjusting for scraping in a multivariate regression model but the difference was not statistically significant (P=.29). Scar size at 3 months was slightly greater with voriconazole after adjusting for scraping (P=.48). Corneal perforations in the voriconazole group (10 of 60 patients) were not significantly different than in the natamycin-treated group (9 of 60 patients) (P>.99). Scraping was associated with worse BSCVA at 3 months after adjusting for drug (P=.06). Patients with baseline BSCVA of 20/40 to 20/400 showed a trend toward a 2-line improvement in visual acuity with voriconazole (P=.07).
Overall, there were no significant differences in visual acuity, scar size, and perforations between voriconazole- and natamycin-treated patients. There was a trend toward scraping being associated with worse outcomes.
Application to Clinical Practice
The benefit seen with voriconazole in the subgroup of patients with baseline visual acuity of 20/40 to 20/400 needs to be validated in a confirmatory clinical trial.
Trial Registration Identifier: NCT00557362
PMCID: PMC3774126  PMID: 20547942
20.  The Mycotic Ulcer Treatment Trial 
JAMA ophthalmology  2013;131(4):422-429.
To compare topical natamycin vs voriconazole in the treatment of filamentous fungal keratitis.
This phase 3, double-masked, multicenter trial was designed to randomize 368 patients to voriconazole (1%) or natamycin (5%), applied topically every hour while awake until reepithelialization, then 4 times daily for at least 3 weeks. Eligibility included smear-positive filamentous fungal ulcer and visual acuity of 20/40 to 20/400.
Main Outcome Measures
The primary outcome was best spectacle-corrected visual acuity at 3 months; secondary outcomes included corneal perforation and/or therapeutic penetrating keratoplasty.
A total of 940 patients were screened and 323 were enrolled. Causative organisms included Fusarium (128 patients [40%]), Aspergillus (54 patients [17%]), and other filamentous fungi (141 patients [43%]). Natamycin-treated cases had significantly better 3-month best spectacle-corrected visual acuity than voriconazole-treated cases (regression coefficient=−0.18 logMAR; 95% CI, −0.30 to −0.05; P=.006). Natamycin-treated cases were less likely to have perforation or require therapeutic penetrating keratoplasty (odds ratio=0.42; 95% CI, 0.22 to 0.80; P=.009). Fusarium cases fared better with natamycin than with voriconazole (regression coefficient=−0.41 logMAR; 95% CI, −0.61 to −0.20; P<.001; odds ratio for perforation=0.06; 95% CI, 0.01 to 0.28; P<.001), while non-Fusarium cases fared similarly (regression coefficient=−0.02 logMAR; 95% CI, −0.17 to 0.13; P=.81; odds ratio for perforation=1.08; 95% CI, 0.48 to 2.43; P=.86).
Natamycin treatment was associated with significantly better clinical and microbiological outcomes than voriconazole treatment for smear-positive filamentous fungal keratitis, with much of the difference attributable to improved results in Fusarium cases.
Application to Clinical Practice
Voriconazole should not be used as monotherapy in filamentous keratitis.
Trial Registration Identifier: NCT00996736
PMCID: PMC3769211  PMID: 23710492
23.  Practice Patterns and Opinions in the Management of Recurrent or Chronic Herpes Zoster Ophthalmicus 
Cornea  2012;31(7):786-790.
The objective of this study was to determine current practices and opinions among cornea specialists for treating and preventing recurrences of Herpes Zoster Ophthalmicus (HZO).
In November 2010, a survey of 15 questions was distributed to the Cornea Society listserv. Questions identified respondents’ treatment practices for recurrent HZO and opinions regarding prolonged antiviral prophylaxis and zoster vaccine.
Of 100 respondents, the majority were cornea specialists (83/98, 85%). Eighty-seven percent (84/97) reported treating recurrent or chronic cases of HZO in the last year. The most common choice of treatment in the posed recurrent HZO clinical scenario was a combination of oral antiviral and topical corticosteroid (63/100, 63%), although significant variability existed in the duration of oral antiviral administration. Fifty-four respondents (56%) believed prolonged acyclovir prophylaxis could reduce recurrent signs of HZO; 28% (27/98) believed recurrences of HZO could be reduced after the period of acyclovir administration. For patients with a history of HZO, most respondents reported not recommending the adult zoster vaccine (63/98, 64%), but 46% (43/94) believed the vaccine could reduce recurrent signs or did not know.
Many cornea specialists are managing recurrent or chronic cases of HZO, but there is variability in the use of topical corticosteroids and antivirals. Additionally, no consensus exists on the efficacy of prolonged antiviral therapy or the adult zoster vaccine to reduce chronic or recurrent disease. These results demonstrate the need for further systematic study of treatment and prophylaxis for recurrent and chronic HZO.
PMCID: PMC3729033  PMID: 22269677
Herpes Zoster Ophthalmicus; Recurrence; Management; Practice Patterns
24.  Correction: Assessment of Transmission in Trachoma Programs over Time Suggests No Short-Term Loss of Immunity 
PLoS Neglected Tropical Diseases  2013;7(7):10.1371/annotation/c64f02de-c1f1-48ee-ac79-06b5a6c7b65a.
PMCID: PMC3729331
25.  Organism, MIC, and Outcome in a Fungal Corneal Ulcer Clinical Trial 
Cornea  2012;31(6):662-667.
To analyze the minimum inhibitory concentration (MIC) of isolates from fungal keratitis to natamycin and voriconazole, and to assess the relationship between organism, MIC, and clinical outcome.
Data were collected as part of a randomized, controlled, double-masked clinical trial. Main outcome measures included best spectacle-corrected visual acuity (BSCVA), infiltrate/scar size, time to re-epithelialization, and perforation. Speciation and analysis of MIC to natamycin and voriconazole was done according to NCCLS standards. The relationship between MIC and organism, organism and outcome measure, and each outcome measure and MIC was assessed.
Of 120 samples obtained in the trial, 84 isolates had an identifiable organism and were available for further analyses. Fusarium spp and Aspergillus spp were the most commonly-isolated organisms. MIC was significantly different across the groups of organisms (P=0.0001). A higher MIC was significantly associated with an increased likelihood of perforation (OR 2.03, 95%CI 1.02 to 4.04, P=0.04). There was no significant association between MIC and 3-week visual acuity (0.058, 95%CI -0.01 to 0.13, P=0.11), 3-month visual acuity (0.01, 95%CI -0.08 to 1.04, P=0.79), 3-week infiltrate/scar size (0.12, 95% CI -0.02 to 0.27, P=0.10), 3-month infiltrate/scar size (0.12, 95%CI -0.02 to 0.25, P=0.09), or time to re-epithelialization (HR 1.19, 95%CI 0.98 to 1.45, P=0.08).
A higher MIC was associated with an increased odds of perforation. The results of this study suggest that resistance to antifungal medication may be associated with worse outcomes in fungal keratitis.
PMCID: PMC3695737  PMID: 22333662
fungus; keratitis; susceptibility; voriconazole; natamycin

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