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Background: For bacterial infections, the susceptibility to antibiotics in vitro has been associated with clinical outcomes in vivo, although the importance of minimum inhibitory concentration (MIC) has been debated. In this study, we analyzed the association of MIC on clinical outcomes in bacterial corneal ulcers, while controlling for organism and severity of disease at presentation., Methods: Data were collected as part of a National Eye Institute-funded, randomized, controlled trial (the Steroids for Corneal Ulcers Trial [SCUT]). All cases enrolled in SCUT had a culture-positive bacterial corneal ulcer and received moxifloxacin. The MIC to moxifloxacin was measured by E test. Outcomes included best spectacle-corrected visual acuity, infiltrate/scar size, time to re-epithelialization, and corneal perforation., Results: Five hundred patients with corneal ulcers were enrolled in the trial, and 480 were included in this analysis. The most commonly isolated organisms were Streptococcus pneumoniae and Pseudomonas aeruginosa. A 2-fold increase in MIC was associated with an approximately 0.02 logMAR decrease in visual acuity at 3 weeks, approximately 1 letter of vision loss on a Snellen chart (0.019 logMAR; 95% confidence interval [CI], .0040-.033; P = .01). A 2-fold increase in MIC was associated with an approximately 0.04-mm larger infiltrate/scar size at 3 weeks (0.036 mm; 95% CI, .010-.061; P = .006). After controlling for organism, a higher MIC was associated with slower time to re-epithelialization (hazards ratio, 0.92; 95% CI, .86-.97; P = .005)., Conclusions: In bacterial keratitis, a higher MIC to the treating antibiotic is significantly associated with worse clinical outcomes, with approximately 1 line of vision loss per 32-fold increase in MIC., Clinical Trials Registration: NCT00324168.

Purpose: The purpose of this study was to determine whether clinical signs of infectious keratitis can be used to identify the causative organism., Methods: Eighty photographs of eyes with culture-proven bacterial keratitis or smear-proven fungal keratitis were randomly selected from 2 clinical trials. Fifteen cornea specialists from the F. I. Proctor Foundation and the Aravind Eye Care System assessed the photographs for prespecified clinical signs of keratitis, and they identified the most likely causative organism., Results: Clinicians were able to correctly distinguish bacterial from fungal etiology 66% of the time (P < 0.001). The Gram stain, genus, and species were accurately predicted 46%, 25%, and 10% of the time, respectively. The presence of an irregular/feathery border was associated with fungal keratitis, whereas a wreath infiltrate or an epithelial plaque was associated with bacterial keratitis., Conclusions: Cornea specialists correctly differentiated bacterial from fungal keratitis more often than chance, but in fewer than 70% of cases. More specific categorization led to less successful clinical distinction. Although certain clinical signs of infectious keratitis may be associated with a bacterial or fungal etiology, this study highlights the importance of obtaining appropriate microbiological testing during the initial clinical encounter.

Purpose: 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., Methods: 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., Results: 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., Conclusion: Discrete epidemics of Acanthamoeba keratitis occurred among a rural, non-contact lens wearing, population in South India in 1993 and 2002.

Purpose: This study aims to determine uveitis specialists' practice patterns, preferences, and perceptions of corticosteroid-sparing therapies for the initial treatment of chronic noninfectious uveitis., Methods: A survey was distributed to the American Uveitis Society and Proctor email listservs in order to restrict the respondents to specialists who likely have extensive experience in the use of immunomodulatory therapy. Topics included effectiveness, usage, and preferences related to seven immunomodulatory treatments., Results: Among the 45 responders, the majority (59%) had greater than 10 years of experience treating uveitis. Methotrexate was the most commonly used initial therapy for anterior, intermediate, and posterior/panuveitis (85%, 57%, and 37%), and the most preferred for anterior (55%). Mycophenolate mofetil was the most preferred for intermediate (35%) and posterior/panuveitis (42%). Primary reasons not to prescribe a treatment were effectiveness for azathioprine, safety/tolerability for cyclosporine and cyclophosphamide, and a mixture of cost, safety/tolerability, and difficulty of administration for the biologic drugs., Conclusions: Within the group of highly experienced uveitis specialists, methotrexate is still the most commonly used initial treatment. Although newer biologic drugs are seen as effective, they are not commonly used, or even preferred, as initial corticosteroid-sparing treatment.

Purpose: To characterize the level of depression in patients with ocular inflammatory disease and to determine predictors of depression in this population., Design: Prospective cross-sectional survey and medical record review., Methods: Participants were consecutive patients with noninfectious ocular inflammatory disease in a university-based tertiary referral center. Subjects were given the self-administered Beck Depression Inventory-II (BDI-II), National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25), and additional supplemental questions. Medical records were reviewed for clinical characteristics. Univariate analyses were conducted to compare clinical characteristics between patients with and without a positive screen for depression, and a multivariate regression model was performed to determine the most significant predictors of depression., Results: Of the 104 participants, 26.9% screened positive for depression with the BDI-II. Of these subjects, only 39.3% had been previously diagnosed with depression. NEI VFQ-25 scores were significantly lower in depressed patients in all subscales except driving and color vision. Predictors of depression were inadequate emotional support, lower visual functioning (VFQ composite score), history of changing immunomodulatory treatment, and current oral corticosteroid use., Conclusions: Depression may be a significant but underrecognized comorbid condition in patients with ocular inflammatory disease. Worse visual function was associated with depression. The authors recommend heightened awareness of potential depression in patients with ocular inflammatory disease., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: To compare the clinical course and effect of adjunctive corticosteroid therapy in Pseudomonas aeruginosa with those of all other strains of bacterial keratitis., Methods: Subanalyses were performed on data collected in the Steroids for Corneal Ulcers Trial (SCUT), a large randomized controlled trial in which patients were treated with moxifloxacin and were randomly assigned to 1 of 2 adjunctive treatment arms: corticosteroid or placebo (4 times a day with subsequent reduction). Multivariate analysis was used to determine the effect of predictors, organism, and treatment on outcomes, 3-month best-spectacle-corrected visual acuity (BSCVA), and infiltrate/scar size. The incidence of adverse events over a 3-month follow-up period was compared using Fisher's exact test., Results: SCUT enrolled 500 patients. One hundred ten patients had P. aeruginosa ulcers; 99 of 110 (90%) enrolled patients returned for follow-up at 3 months. Patients with P. aeruginosa ulcers had significantly worse visual acuities than patients with other bacterial ulcers (P = 0.001) but showed significantly more improvement in 3-month BSCVA than those with other bacterial ulcers, adjusting for baseline characteristics (-0.14 logMAR; 95% confidence interval, -0.23 to -0.04; P = 0.004). There was no significant difference in adverse events between P. aeruginosa and other bacterial ulcers. There were no significant differences in BSCVA (P = 0.69), infiltrate/scar size (P = 0.17), and incidence of adverse events between patients with P. aeruginosa ulcers treated with adjunctive corticosteroids and patients given placebo., Conclusions: Although P. aeruginosa corneal ulcers have a more severe presentation, they appear to respond better to treatment than other bacterial ulcers. The authors did not find a significant benefit with corticosteroid treatment, but they also did not find any increase in adverse events. (ClinicalTrials.gov number, NCT00324168.).

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.

Purpose: To describe an observed therapeutic effect of ranibizumab in untreated contralateral eyes of patients with bilateral uveitis-related cystoid macular edema., Methods: The authors conducted an open-label, prospective, nonrandomized, interventional study to evaluate the effect of intravitreal ranibizumab injections for the off-label treatment of persistent uveitic cystoid macular edema. Patients were given 3 monthly injections of 0.5 mg intravitreal ranibizumab in the eye with worse vision. Subsequent monthly ranibizumab injections were administered based on macular thickness measurements. Best-spectacle corrected visual acuity measurements and optical coherence tomography scans were performed on both eyes at baseline and at monthly follow-up visits., Results: Three of the seven patients in our nonrandomized consecutive case series presented with controlled uveitis and cystoid macular edema bilaterally. Two of the three patients demonstrated a significant improvement in visual acuity and a reduction in macular edema in both eyes after three monthly injections to the study eye. One patient experienced limited effect bilaterally possibly because of the presence of epiretinal membranes in both eyes., Conclusion: The authors observed a beneficial effect of ranibizumab in both eyes of patients who were treated unilaterally for uveitis-related cystoid macular edema. This warrants further investigation of the pharmacokinetics and systemic availability of ranibizumab, particularly in patients with uveitis.

Aims: The purpose of this study was to estimate the duration of treatment necessary for sequential acanthamoeba laboratory tests from corneal scrapings to become negative, and to assess predictors that affect this duration period., Methods: We included all patients with at least one positive acanthamoeba culture or Giemsa stain at the F.I. Proctor Foundation Microbiology Laboratory from 1996 to 2009. A parametric survival analysis was performed among patients with repeat cultures to assess significant predictors for extended clearance time. Simulations were performed to estimate clearance time in the entire patient population, assuming imperfect sensitivity., Results: Thirty-seven patients with laboratory evidence of acanthamoeba had testing at 69 time points. The median clearance time among eyes with repeat cultures was 42.5 days (interquartile range (IQR) 22.0-82.0 days; unadjusted parametric model). Initial visual acuity was the only predictor significantly associated with clearance time in univariate analyses (P<0.0001). Using initial visual acuity as a predictor for clearance time among the entire patient population, the estimated clearance time decreased to 38.7 days (95% confidence interval (CI) 27.9-53.5 days). When the imperfect sensitivity of the culture technique was also taken into account, the estimated clearance time was 44.1 days (95% CI 31.9-61.0 days)., Conclusion: The duration of infection with acanthamoeba keratitis undergoing treatment has not been well characterized. In this report we estimate a median clearance time of approximately 6 weeks, with an IQR of 22-82 days.

Objective: To determine whether recent use of topical fluoroquinolones is a risk factor for in vitro fluoroquinolone resistance in Staphylococcus aureus ocular isolates., Methods: 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 fluoroquinolone resistance., Results: 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] patient age, 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., Conclusion: Recent topical fluoroquinolone use is significantly associated with fluoroquinolone resistance in S aureus isolates from ocular cultures.

Purpose: To calculate the incidence rates of ocular complications and vision loss in HLA-B27-associated uveitis and to explore the effect of chronic inflammation on clinical outcomes., Design: Retrospective longitudinal cohort study., Methods: The clinical records of 99 patients (148 uveitis-affected eyes) with HLA-B27-associated uveitis seen at a tertiary care center were included. The main outcome measures were ocular complications (posterior iris synechiae, band keratopathy, posterior subcapsular [PSC] cataracts, ocular hypertension, hypotony, cystoid macular edema, and epiretinal membrane) and vision loss. Anterior chamber inflammation was defined as ≥1+ grade inflammation. Chronic uveitis was defined as persistent inflammation with relapse in <3 months after discontinuing treatment or requiring medications to suppress inflammation for >3 months after reviewing the patient's entire clinical course., Results: The clinical course was most commonly acute/recurrent (75%) or chronic (20%). The most common complications to develop during follow-up were ocular hypertension (0.10/eye-year) and PSC cataracts (0.09/eye-year). In multivariate analysis, the presence of posterior synechiae at presentation, inflammation, corticosteroid-sparing therapy, corticosteroid injections, chronic disease, and male gender were associated with a statistically significant increased risk of developing vision loss (20/50 or worse). Chronic disease course was associated with a 7-fold increased risk of visual impairment (hazard ratio [HR] = 6.8, P < .0001). The presence of inflammation during follow-up was associated with an increased risk of developing visual impairment (HR = 6.2, P < .0001). In multivariate analysis, chronic disease course and topical corticosteroids were associated with an increased risk of developing any incident ocular complication (HR = 2.2, P = .04 and HR = 3.3, P = .01, respectively)., Conclusions: Poorly controlled inflammation was associated with the development of ocular complications including vision loss. Patients with chronic inflammation were also at greater risk of complications., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Purpose: To report treatment results with infliximab in 2 pediatric Vogt-Koyanagi-Harada syndrome (VKH) patients., Design: Interventional case series., Methods: Medical records of 2 patients were reviewed., Results: In 1 case with bilateral complete serous detachments, there was improvement but persistent fluid after 2 months of high-dose prednisone, methotrexate, and infliximab therapy. Infliximab was discontinued, and cyclophosphamide monthly intravenous injections were initiated with resolution of all subretinal fluid within 3 weeks. The second patient had mild subretinal fluid around the right optic nerve head tracking into the macula. Treatment with prednisone, methotrexate, and infliximab was initiated, with resolution of the subretinal fluid. Prednisone was tapered off within 4 months, and the inflammation remains controlled., Conclusions: Infliximab as adjunctive therapy in pediatric VKH showed a benefit in reducing systemic corticosteroid exposure in 1 patient, but incomplete timely resolution of inflammation in another patient.

Objective: To conduct a therapeutic exploratory clinical trial comparing clinical outcomes of treatment with topical natamycin vs topical voriconazole for fungal keratitis., Methods: 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 subanalysis of BSCVA at 3 months in patients with an enrollment visual acuity of 20/40 to 20/400., Results: 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)., Conclusions: 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 clinicaltrials.gov Identifier: NCT00557362.

It is unclear how the prevalence of clinically active trachoma correlates with the prevalence of ocular chlamydial infection at the community level. In 24 villages from a cluster-randomized clinical trial of mass azithromycin distributions in Ethiopia, the correlation between the prevalence of clinical activity (on examination) and chlamydial infection (by polymerase chain reaction) was moderately strong before mass antibiotic treatments (Pearson's correlation coefficient r = 0.75, 95% confidence interval [CI] = 0.52-0.87), but decreased at each time point during four biannual treatments (at 24 months, r = 0.15, 95% CI = -0.14-0.41). One year after the final treatment, the correlation coefficient had increased, but not to the pre-treatment level (r = 0.55, 95% CI = 0.30-0.73). In a region with hyperendemic trachoma, conjunctival examination was a useful indicator of the prevalence of chlamydial infection before treatments, less useful during mass treatments, but regained utility by one year after treatments had stopped.

Purpose: To determine the association between tobacco smoking history and uveitis., Design: Retrospective, case-control study., Participants: A total of 564 patients with ocular inflammation seen in the Proctor Foundation uveitis clinic between 2002 and 2009, and 564 randomly selected patients seen in the comprehensive eye clinic within the same time period., Methods: A retrospective medical record review of all cases and controls., Main Outcome Measures: A logistic regression analysis was conducted with ocular inflammation as the main outcome variable and smoking as the main predictor variable, while adjusting for age, gender, race, and median income., Results: The odds of a smoker having ocular inflammation were 2.2-fold that of a patient who had never smoked (95% confidence interval [CI], 1.7-3.0; P<0.001). All anatomic subtypes of uveitis were associated with a positive smoking history, with odds ratios (ORs) of 1.7 (95% CI, 1.2-2.4; P = 0.002) for anterior uveitis, 2.7 (95% CI, 1.4-5.6; P = 0.005) for intermediate uveitis, 3.2 (95% CI, 1.3-7.9; P = 0.014) for posterior uveitis, and 3.9 (95% CI, 2.4-6.1; P<0.001) for panuveitis. In patients with panuveitis and cystoid macular edema (CME), the OR was 8.0 (95% CI, 3.3-19.5; P<0.001) compared with 3.1 (95% CI, 1.8-5.2; P<0.001) for patients without CME. Patients with intermediate uveitis and CME also had a higher OR (OR 8.4; 95% CI, 2.5-28.8; P = 0.001) compared with patients without CME (OR 1.5; 95% CI, 0.6-3.8; P = 0.342). Patients with a smoking history were at greater odds of having infectious uveitis (OR 4.5; 95% CI, 2.3-9.0; P<0.001) than noninfectious uveitis (OR 2.1; 95% CI, 1.6-2.8; P<0.001), although both were associated with smoking., Conclusions: A history of smoking is significantly associated with all anatomic subtypes of uveitis and infectious uveitis. The association was greater in patients with intermediate uveitis and panuveitis with CME compared with those without CME. In view of the known risks of smoking, these findings, if replicated, would give an additional reason to recommend smoking cessation in patients with uveitis., (Copyright 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

We report the isolation of Corynebacterium macginleyi from the corneal ulcer culture of a patient, later enrolled in the Steroids for Corneal Ulcer Trial (SCUT). To our knowledge this is the first published report from North America of the recovery of C. macginleyi from a serious ocular infection.

Purpose: To describe the use of fluocinolone acetonide implants (Retisert) in Vogt-Koyanagi-Harada disease (VKH)., Design: Interventional case series., Methods: Retrospective review of medical records., Results: Two patients with VKH requiring high-dose systemic corticosteroid therapy to control their inflammation and bilateral serous retinal detachments received bilateral fluocinolone acetonide implants. Upon tapering of systemic corticosteroids, one patient had recurrent serous retinal detachments and the other patient's anterior chamber and vitreous inflammation returned., Conclusions: The authors' experience with fluocinolone acetonide implants in VKH has been mixed with an inability to fully taper off of systemic corticosteroids.

Purpose: The purpose of this study was to determine the practice patterns of ophthalmologists in the management of fungal corneal ulcers., Methods: In December 2007, a survey of 13 questions addressing the actual and preferred treatment of fungal ulcers was sent to the kera-net e-mail listserv facilitated by the Cornea Society., Results: Ninety-two respondents from North America, South America, Asia, Europe, and Australia participated by completing the electronic questionnaire. Natamycin was the most commonly used topical treatment for ulcers caused by filamentous fungi (96%) followed by amphotericin (75%) and voriconazole (63%). However, voriconazole was most often listed as the preferred topical treatment in an ideal world (79%) compared with 55% for natamycin. Approximately half of the respondents use combination topical therapy (56%) and the remainder monotherapy. The majority of respondents rescrape the epithelium at some time during the course of treatment, but the frequency of rescraping varied among the different topical treatments. The most common reasons cited for not using their preferred treatment were cost and a desire for further evidence to support preferred treatment., Conclusion: There appears to be significant variation in the management of fungal corneal ulcers. Although natamycin was the most commonly used treatment for ulcers caused by filamentous fungi, voriconazole was the most preferred as the ideal treatment. These results highlight the need for more evidence regarding the efficacy of the newer topical antifungals.

Purpose: To evaluate the effect of intravitreal ranibizumab injections (Lucentis; Genentech Inc, South San Francisco, California, USA) on refractory cystoid macular edema (CME) in patients with controlled uveitis who have failed oral and regional corticosteroid treatment, the mainstays of current medical therapy., Design: Prospective, noncomparative, interventional case series., Methods: Seven consecutive patients with controlled uveitis and refractory CME who had failed corticosteroid treatment were studied. One eligible patient chose not to participate and another did not complete follow-up for nonmedical reasons. Intravitreal ranibizumab injections (0.5 mg) were given monthly for 3 months, followed by reinjection as needed. The primary outcome was the mean change in best spectacle-corrected visual acuity (VA) from baseline to 3 months, and the secondary objective was the mean change in central retinal thickness (CRT) on ocular coherence tomography. Six-month outcomes were also assessed., Results: At 3 months, the mean increase in acuity for the 6 patients who completed follow-up was 13 letters (2.5 lines), and the mean decrease in CRT was 357 mum. Both VA and CRT improved significantly between baseline and 3 months (P = .03 for each). Although most patients required reinjection, this benefit was maintained at 6 months. There were no significant ocular or systemic adverse effects., Conclusions: Intravitreal ranibizumab led to an increase in VA and regression of uveitis-associated CME in patients refractory to or intolerant of standard corticosteroid therapy. Further studies of this promising treatment are warranted.

Background: The causes of ethnic and caste-based disparities in mental health are poorly understood., Aim: The study aimed to identify mediators underlying caste-based disparities in mental health in Nepal., Subjects and Methods: A mixed methods ethnographic and epidemiological study of 307 adults (Dalit/Nepali, n=75; high caste Brahman and Chhetri, n=232) was assessed with Nepali versions of Beck Depression (BDI) and Anxiety (BAI) Inventories., Results: One-third (33.7%) of participants were classified as depressed: Dalit/Nepali 50.0%, high caste 28.4%. One quarter (27.7%) of participants were classified as anxious: Dalit/Nepali 50.7%, high caste 20.3%. Ethnographic research identified four potential mediators: Stressful life events, owning few livestock, no household income, and lack of social support. The direct effect of caste was 1.08 (95% CI -1.10-3.27) on depression score and 4.76 (95% CI 2.33-7.19) on anxiety score. All four variables had significant indirect (mediation) effects on anxiety, and all but social support had significant indirect effects on depression., Conclusion: Caste-based disparities in mental health in rural Nepal are statistically mediated by poverty, lack of social support, and stressful life events. Interventions should target these areas to alleviate the excess mental health burden born by Dalit/Nepali women and men.

Aims: The aim of the study was to conduct a preliminary clinical trial to assess whether adjunctive topical corticosteroids improve outcomes in bacterial keratitis and, if no difference was found, to determine the feasibility and sample size necessary for conducting a larger trial to answer this question., Methods: In this single centre, double-masked clinical trial, 42 patients with culture-confirmed bacterial keratitis at Aravind Eye Hospital in India were randomised to receive either topical prednisolone phosphate or placebo. All patients received topical moxifloxacin. The primary outcome was best spectacle-corrected visual acuity (BSCVA) at 3 months, adjusting for enrolment BSCVA and arm. Other pre-specified outcomes included re-epithelialisation time, infiltrate/scar size and adverse events., Results: Compared with placebo, patients in the steroid group re-epithelialised more slowly (hazard ratio 0.47, 95% CI 0.23 to 0.94). There was no significant difference in BSCVA or infiltrate/scar size at 3 weeks or 3 months. To have 80% power to detect a two-line difference in acuity, 360 cases would be required., Conclusions: Although corticosteroid treatment resulted in a statistically significant delay in re-epithelialisation, this did not translate to a significant difference in visual acuity, infiltrate/scar size or adverse events. To assess the effect of steroids on acuity, a larger trial is warranted and feasible.

Background/aims: To study the susceptibility of Fusarium and Aspergillus isolated from keratitis to amoxicillin, cefazolin, chloramphenicol, moxifloxacin, tobramycin and benzalkonium chloride (BAK)., Methods: 10 isolates of Fusarium and 10 isolates of Aspergillus from cases of fungal keratitis at Aravind Eye Hospital in South India were tested using microbroth dilution for susceptibility to amoxicillin, cefazolin, chloramphenicol, moxifloxacin, tobramycin and BAK. The minimum inhibitory concentration (MIC) median and 90th percentile were determined., Results: BAK had the lowest MIC for both Fusarium and Aspergillus. Chloramphenicol had activity against both Fusarium and Aspergillus, while moxifloxacin and tobramycin had activity against Fusarium but not Aspergillus., Conclusions: The susceptibility of Fusarium to tobramycin, moxifloxacin, chloramphenicol and BAK and of Aspergillus to chloramphenicol and BAK may explain anecdotal reports of fungal ulcers that improved with antibiotic treatment alone. While some of the MICs of antibiotics and BAK are lower than the typically prescribed concentrations, they are not in the range of antifungal agents such as voriconazole, natamycin and amphotericin B. Antibiotics may, however, have a modest effect on Fusarium and Aspergillus when used as initial treatment prior to identification of the pathological organism.

Purpose: Prior cataract surgery is a recognized risk factor for the development of Mooren''s ulcer, but the demographic and clinical features of a large cohort of such patients have not been described., Methods: The authors performed a retrospective review of demographic and clinical data from 14 eyes in 13 patients who developed Mooren's ulcer following extracapsular cataract extraction at Aravind Eye Hospital in Madurai, South India., Results: Eight (62%) of the 13 patients were men and 5 (39%) were women. The median age in our population was 65 years, with a range of 45 to 85 years. The median number of months from surgery to the onset of Mooren's ulcer was 19, with a range of 4 to 156 months. Of the 14 eyes with prior cataract surgery, the location of the ulcer was at or contiguous with the wound in 10 eyes (71%), which was 2.5 times more likely than other circumlimbal locations, and only one patient (8%) had bilateral disease., Conclusions: Mooren''s ulcer may occur following extracapsular cataract extraction and when it does it is most likely to be unilateral and contiguous with the wound. These findings support the notion that exposure of normally concealed corneal antigens may contribute to the pathogenesis of Mooren''s ulcer in some patients.

Purpose: To determine whether clinical outcomes in bacterial keratitis are associated with antibiotic susceptibility., Design: Retrospective, ancillary study using data and samples from a completed randomized clinical trial., Methods: Forty-two patients were enrolled with culture-confirmed bacterial keratitis at Aravind Eye Hospital in South India. All patients received topical moxifloxacin and were randomized to receive either topical prednisolone phosphate or placebo. Outcomes included time to epithelialization, best spectacle-corrected visual acuity (BSCVA), and infiltrate/scar size at three months. Bacterial isolates were cultured, and minimum inhibitory concentration (MIC) to moxifloxacin was measured using Etests. Multiple linear regression was used to assess the effect of MIC on outcome, adjusting for enrollment characteristics., Results: MIC was associated with three-month infiltrate/scar size: each two-fold increase in MIC was associated with a 0.33-mm average diameter increase in scar size (P=.01). MIC was not associated with three-month BSCVA (P=.71) or time to epithelialization (P=.35)., Conclusions: MIC was associated with infiltrate/scar size in bacterial keratitis. An ongoing larger, multicenter trial should provide further information on whether this association is maintained across subgroups of organisms.

Purpose: Subgroup data from a pivotal phase 3 study comparing ranibizumab (LUCENTIS) with verteporfin (VISUDYNE) photodynamic therapy (PDT) in patients with predominantly classic choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) were retrospectively analyzed to identify patient and disease characteristics that may predict visual acuity (VA) treatment outcomes., Design: Retrospective subgroup analysis of 12-month data from the ANCHOR study., Methods: Univariate analyses were performed to assess VA outcomes across subgroups based on patients' gender and baseline age, VA score, CNV lesion size, CNV lesion type, and duration of neovascular AMD, followed by multivariate analyses to identify predictors of the VA score change from baseline at 12 months. main outcome measures: Proportion of patients losing <15 letters and proportion gaining > or =15 letters from baseline VA; mean change from baseline VA., Results: On average, all subgroups of ranibizumab-treated patients did better than PDT patients for all three VA outcome measures. In the multivariate analysis, lower baseline VA score, smaller baseline CNV lesion size, and younger baseline age were associated with greater gain of letters with ranibizumab treatment and less loss of letters with PDT., Conclusions: Subgroup analysis of 12-month data from the ANCHOR study showed ranibizumab to be superior to PDT in all subgroups evaluated, and was consistent with the subgroup analysis of 24-month data from the other pivotal phase 3 study of ranibizumab (MARINA) in showing that the most important predictors of VA outcomes were, in decreasing order of impact, the patient's baseline VA score, CNV lesion size, and age.

Objective: To assess pharmacodynamic responses to ranibizumab, an inhibitor of vascular endothelial growth factor A (VEGF-A), in a study of the treatment of minimally classic or occult with no classic choroidal neovascularization secondary to age-related macular degeneration (AMD) (designated MARINA [Minimally Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab in the Treatment of Neovascular AMD]) and to compare these responses with those in a sham-injection control group., Design: Retrospective (prespecified and ad hoc) analyses of 24-month data., Participants: Seven hundred sixteen patients, randomized to 0.3-mg ranibizumab (n = 238), 0.5-mg ranibizumab (n = 240), or a sham injection (n = 238)., Methods: Stereoscopic fundus photography and fluorescein angiography (FA) were done at baseline and months 3, 6, 12, and 24. Optical coherence tomography (OCT) was performed at a subset of investigative sites (46 patients) at baseline, day 7, and months 1 and 12., Main Outcome Measures: Prespecified secondary end points were mean change from baseline in total area of choroidal neovascularization and total area of leakage from choroidal neovascularization at months 12 and 24. Prespecified exploratory FA end points included mean change from baseline in the areas of the choroidal neovascularization lesion and serous sensory retinal detachment (SSRD) at months 12 and 24. Post hoc exploratory FA outcome measures included the proportion of patients with no leakage from choroidal neovascularization and mean change from baseline over time in the area of subretinal fibrous tissue/disciform scar. The prespecified exploratory end point for OCT was mean change from baseline over time in center point thickness., Results: At 12 and 24 months, statistically significant benefits of ranibizumab over sham treatment were observed for mean change from baseline in the areas of choroidal neovascularization lesion, total choroidal neovascularization, leakage from choroidal neovascularization, SSRD, and disciform scar/subretinal fibrosis. At 12 months (final OCT), the mean change in foveal center point thickness on OCT was a significant decrease in the ranibizumab group compared with the sham group., Conclusions: Patients with minimally classic or occult with no classic neovascular AMD treated with ranibizumab demonstrated improvement that was consistent for visual acuity, FA, and OCT outcomes and superior to that in sham-treated patients.

Objective: To characterize the susceptibility of filamentous fungi isolated from keratitis to amphotericin B, natamycin, caspofungin acetate, itraconazole, voriconazole, and posaconazole., Methods: Ninety isolates from fungal keratitis cases at Aravind Eye Hospital in South India were tested using macrobroth dilution for susceptibility to amphotericin B, natamycin, caspofungin, itraconazole, voriconazole, and posaconazole. The minimum inhibitory concentration (MIC) median and 90th percentile were determined., Results: The 90 isolates included 41 Aspergillus species, 38 Fusarium species, and 11 others. The triazoles and caspofungin had the lowest MICs against Aspergillus species; voriconazole, amphotericin B, and posaconazole had the lowest MICs against Fusarium species, and none of the Fusarium species were inhibited by itraconazole or caspofungin. Amphotericin B had significantly lower MICs compared with natamycin, but after correcting for the typical prescription dose, natamycin was superior., Conclusion: No single agent was universally most effective, but voriconazole and other triazoles demonstrated the broadest spectrum. Itraconazole and caspofungin were not effective against Fusarium species., Clinical Relevance: Fungal ulcers are commonly treated empirically; drugs are typically selected without regard to susceptibility data. The nonocular infectious disease literature suggests modern fungal susceptibility methods are clinically relevant, but ocular studies are limited. Our results suggest antifungal therapy might be tailored to individual organisms.

Objective: An examination of clinically relevant subgroups of patients in the MARINA study of ranibizumab in treatment of minimally classic or occult with no classic choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) was done. Objectives were to determine the effectiveness of ranibizumab across subgroups, compare the effectiveness of ranibizumab with that of sham injection within subgroups, and evaluate the relationship between selected baseline characteristics and visual acuity (VA) outcomes., Design: Retrospective subgroup analyses of 24-month data from the MARINA study., Participants and Controls: Seven hundred sixteen patients were randomly assigned to 0.3 mg ranibizumab (n = 238), 0.5 mg ranibizumab (n = 240), or sham treatment (n = 238)., Methods: Efficacy outcomes were compared across subgroups based on patients' gender, age, baseline VA score, baseline CNV lesion size, CNV lesion type, and duration of neovascular AMD using univariate analyses. Multivariate analyses were performed on the change from baseline to 24 months in VA score to assess further the correlation between baseline characteristics and VA outcome., Main Outcome Measures: Proportion of patients losing <15 letters from baseline, proportion gaining > or =15 letters from baseline, and mean VA score change from baseline., Results: For each of the 3 VA end points, all subgroups of ranibizumab-treated patients did better on average than the sham-treated patients. Increasing age, larger CNV lesion size at baseline, and a higher baseline VA score were all associated with greater loss of letters in the sham group or less gain of letters in the ranibizumab groups. However, the net benefit of ranibizumab versus sham treatment was greater in patients who scored higher than in those who scored lower in baseline VA., Conclusions: This subgroup analysis of 24-month data from the MARINA study indicates that ranibizumab treatment was associated with an average increase from baseline VA in all subgroups evaluated, and that ranibizumab treatment was superior to sham treatment across all subgroups. The most important predictors of VA outcomes were, in decreasing order of importance, baseline VA score, CNV lesion size, and age.

The present study was carried out in 33 cases of cyanotic congenital heart disease (CCHD) to determine the prevalence of iron deficiency anemia (IDA) and its correlation to hyperviscosity symptoms in terms of hematocrit levels. Furthermore, the study was aimed at assessing the response to low dose iron therapy (60 mg of elemental iron once daily) in relieving symptoms of hyperviscosity. All these cases were evaluated for presence of symptoms of hyperviscosity and later subjected to various hematological & biochemical parameters of iron deficiency anemia including hemoglobin (Hb), pack cell volume (PCV), mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), serum iron, total iron binding capacity respectively. Results showed presence of IDA in 6/33 cases (18.2%) and hyperviscosity symptoms in 10/33 cases (30.3%). Amongst the group with symptoms of hyperviscosity, in the subset having IDA these symptoms were observed at PCV levels of 0.52 L/L to 0.58 L/L in contrast to the subset not deficient in iron where the symptoms occurred at a PCV 0.68 L/L. Relief of symptoms of hyperviscosity was evident with a minimal rise of mean hemoglobin by 2.1 gm/dl. It was concluded that IDA was not an uncommon finding in CCHD cases and that it leads to symptoms of hyperviscosity at a level of PCV much lower than those known to produce these symptoms. Finally low dose iron therapy was found effective in relieving the symptoms of hyperviscosity.

Serum alpha-1 acid glycoprotein levels were measured in 27 patients with idiopathic peripheral retinal vasculitis (Eales' disease) and 31 healthy subjects by single radial immunodiffusion technique. The levels were found to be significantly increased in both moderate and severe types of the disease. The serum levels of this protein paralleled the severity of the disease. The increased alpha-1 acid glycoprotein in serum showed a significant fall to near normal levels during the quiescent stage. Our observations support the hypothesis that idiopathic peripheral retinal vasculitis is an immune mediated disease. It is proposed that serum alpha-1 acid glycoprotein may be considered as a reliable parameter of the activity and the degree of severity of the disease, as well as an useful tool for monitoring the efficacy of treatment.

The isozyme profile of lactic dehydrogenase (LDH) is being studied in this laboratory, mainly for the diagnosis in the suspected cases of myocardial infarction (MI). The isozymes are separated by polyacrylamide gel electrophoresis and the quantitative assay of the isoenzymes is done by enzyme staining followed by scanning with the help of an automatic scanner. In normal cases, the ratio of the two isozymes H4 and H3M is approximately 0.5. In almost all cases of myocardial infarction the ratio becomes 1 or more and sometimes increases up to 2. In the suspected and potential cases of infarction the ratio tends to become more than 0.5 (usually 0.7) but remains lower than 1. Thus, the measurement of the ratio may be a very helpful diagnostic index in the suspected and potential cases and may also be used for prognostic purposes as well.