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Corneal ulcers are a common cause of blindness in low-income and middle-income countries, usually resulting from traumatic corneal abrasions during agricultural work. Antimicrobial prophylaxis of corneal abrasions can help prevent corneal ulcers, but delays in the initiation of therapy are frequent. We aimed to assess whether a community-based programme for corneal ulcer prevention would reduce the incidence of corneal ulceration.A cluster-randomised trial was performed in village development committees (VDCs) in Nepal. VDCs in the catchment area of Bharatpur Eye Hospital, Nepal with less than 15 000 people were eligible for inclusion. We randomly assigned (1:1) VDCs to either an intervention group or a control group. In the intervention VDCs, existing female community health volunteers (FCHVs) were trained to diagnose corneal abrasions and provide a 3-day course of ophthalmic antimicrobials to their patients. In the control VDCs, FCHVs did not provide this intervention. Participants were not masked given the nature of the intervention. Both groups were followed up for 3 years for photographic evidence of corneal ulceration. The primary outcome was the incidence of corneal ulceration, determined by masked assessment of corneal photographs. The analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, NCT01969786.We assessed 112 VDCs, of which 24 were enrolled. The study was performed between Feb 4, 2014, and Oct 20, 2017. 12 VDCs were randomly assigned to the intervention group and 12 to the control group. 252 539 individuals were included in the study (130 579 in the intervention group and 121 960 in the control group). FCHVs diagnosed and provided antimicrobials for 4777 corneal abrasions. The census identified 289 corneal ulcers among 246 893 person-years in the intervention group (incidence 1·21 cases [95% CI 0·85-1·74] per 1000 person-years) and 262 corneal ulcers among 239 170 person-years in the control group (incidence 1·18 cases [0·82-1·70] per 1000 person-years; incidence rate ratio 1·03 [95% CI 0·63-1·67]; p=0·93). Medication allergy was self-reported in 0·2% of participants.We did not detect a reduction in the incidence of corneal ulceration during the first 3 years of a community-based corneal ulcer prevention programme. Further study might be warranted in more rural areas where basic eye care facilities are not available.National Eye Institute.

PurposeTo determine whether exposure to unclean cooking fuels was associated with subsequent cataract progression as reported in previous cross-sectional studies.DesignProspective cohort study.MethodsThis is a secondary observational analysis of the community-based Antioxidants in Prevention of Cataracts trial (ClinicalTrials.gov ID NCT01664819). The exposure of interest was cooking fuel type, measured at baseline. Main outcome measures were baseline cataract severity and self-reported cataract surgery at a 15-year visit.ResultsBaseline and 15-year follow-up data were available for 798 and 579 participants, respectively. Wood or kerosene was used by 711 of 798 (89.1%) baseline participants, including 539 of 579 (93.1%) participants with complete follow-up. Cooking fuel type was not associated with cataract severity at baseline (P=.443). Of 8334 person-years of follow-up, 90 cataract surgeries were observed over 15 years (1.08 surgeries per 100 person-years; 95% CI=0.87-1.32). Use of wood or kerosene was not associated with 15-year incidence of cataract surgery relative to use of propane (adjusted P=.154). Cataract surgery was more common in older individuals (HR=1.1 per year, 95% CI=1.1-1.2, P < .001), those with baseline myopia (HR=2.1, 95% CI=1.2-3.5, P=.009), and women (HR=3.5, 95% CI=1.2-10.1, P=.019).ConclusionsThis study found no association between unclean cooking fuels and cataract progression over a 15-year period. No other modifiable risk factors were associated with incident self-reported cataract surgery.

PurposeTo determine whether a community health worker (CHW) program increases referrals to local eye care providers and ultimately reduces the incidence of corneal ulcers.DesignCluster-randomized trial performed from 2014 to 2017 in rural South India.MethodsThis was a community-based study that included all inhabitants of 42 rural South Indian communities. CHWs were trained to diagnose corneal abrasions and assist participants in seeking care at a local vision center. Given the nature of the intervention, the trial was not masked. The main outcome measure was incident corneal ulcer, defined as an active infiltrate or evidence of a new opacity, as assessed by means of penlight examination during an annual door-to-door census.ResultsTwenty-one study clusters were randomized to the CHW intervention and 21 to no intervention. Vision centers diagnosed 195 corneal abrasions from the intervention clusters during the 2-year study (rate, 223 per 100,000 person-years; 95% CI, 28-1743) and 62 from the control clusters (rate, 62 per 100,000 person-years; 95% CI, 8-496; incidence rate ratio, 3.57; 95% CI, 2.01-6.35; P < .001). The estimated incidence of corneal ulceration during the study period was 60 per 100,000 person-years (95% CI, 25-141) in the intervention group and 32 per 100,000 person-years (95% CI, 13-80) in the control group (incidence rate ratio, 1.86; 95% CI, 0.5-6.4; P=.32).ConclusionsA CHW program resulted in 3.5 times more referrals to local eye care providers for corneal abrasions, but no difference could be detected in the incidence of corneal ulceration. CHW programs provide a mechanism for increasing referrals to eye hospitals.Trial registrationClinicalTrials.gov ID: NCT02284698.

Background/aimsWe aimed to examine risk factors for corneal ulcer in a rural and peri-urban setting in Nepal.MethodsThis population-based matched case–control study was nested in a cluster randomised trial in 24 village development committees in Nepal. Incidence density sampling was used to match incident corneal opacity cases to controls, matching on time of opacity, age, sex and location. Cases and controls were invited to participate in a survey of risk factors for corneal ulcer. Risk factors were evaluated using conditional logistic regression to account for matching.ResultsOf the 540 participants with incident opacities identified in the trial, 433 were willing to participate in this substudy and matched to a control. Compared with controls, cases had lower odds of having any education vs no education (adjusted OR, aOR 0.60, 95% CI 0.39 to 0.94), working in non-manual labour occupations vs manual labour occupations (aOR 0.64, 95% CI 0.42 to 0.95) and preferring medical shops for ocular trauma versus eye care system centres (aOR 0.58, 95% CI 0.37 to 0.92). Cases had higher odds of protective goggle use versus no protection (aOR 3.8, 95% CI 1.3 to 11.0) and having an ocular injury vs none (aOR 7.7, 95% CI 4.3 to 13.6) compared with controls.ConclusionWe found ocular injury, manual labour and lower education to be strongly associated with the development of corneal ulcer. Given the persistent burden of corneal blindness in this area, prevention efforts could target efforts to increase access to care in areas where these factors are common.

Objective To compare oral voriconazole vs placebo in addition to topical antifungals in the treatment of filamentous fungal keratitis. Design Non-prespecified, secondary case-control analysis from a multicenter, double-masked, randomized placebo-controlled clinical trial. Methods Study Participants : Patients with smear-positive filamentous fungal ulcers and visual acuity of 20/400 or worse who eventuated to therapeutic penetrating keratoplasty (TPK). Intervention : Study participants were randomized to oral voriconazole vs oral placebo; all received topical antifungal drops. Main Outcome Measures : TPK button culture positivity. Results A total of 95 of 194 (49.5%) study participants enrolled at Madurai, Coimbatore, or Pondicherry, India eventuated to TPK in an average of 20.9 days (standard deviation 15.2 days, range 2-71 days). TPK button cultures were available for 67 of 95 (71%) of the TPKs performed and were positive for filamentous fungus in 45 of 67 (67%) cases. For each 1-day increase in the time to TPK there was 0.94-fold decreased odds of fungal culture positivity (95% confidence interval [CI] 0.90–0.98, P = .005). Those randomized to oral voriconazole had 1.26-fold increased odds of TPK button culture positivity after controlling for time to TPK and baseline organism, but this was not statistically significant (95% CI 0.32–4.87; P = .74). Those who underwent TPK for lack of response to medical therapy were 10.64-fold more likely to be culture positive than if the indication for surgery was perforation and this was statistically significant (95% CI 2.16–51.70; P = .003). Conclusions There appears to be no benefit to adding oral voriconazole to topical antifungal agents in the treatment of severe filamentous fungal ulcers. Infection rather than inflammation appears to be the reason for the worsening clinical picture in many of these patients.

IntroductionCorneal opacity is a leading cause of blindness worldwide. In resource-limited settings, untreated traumatic corneal abrasions may result in infection and ultimately, opacity. Although antimicrobial treatment of corneal ulcers may successfully cure infections, the scarring that accompanies the resolution of infection can still result in visual impairment. Prevention may be the optimal approach for reducing corneal blindness. Studies have employed community health workers to provide prompt administration of antimicrobials after corneal abrasions to prevent infections, but these studies were not designed to determine the effectiveness of such a programme.Methods and analysisThe Village-Integrated Eye Worker trial (VIEW) is a cluster-randomised trial designed to assess the effectiveness of a community health worker intervention to prevent corneal ulcers. Twenty-four Village Development Committees (VDCs) in Nepal were randomised to receive a corneal ulcer prevention programme or to no intervention. Female Community Health Volunteers (FCHVs) in intervention VDCs are trained to diagnose corneal abrasions, provide antimicrobials and to refer participants when needed. An annual census is conducted over 3 years in all study VDCs to assess the incidence of corneal ulceration via corneal photography (primary outcome). Masked outcome assessors grade corneal photographs to determine the presence or absence of incident corneal opacities. The primary analysis is negative binomial regression to compare the incidence of corneal ulceration by study arm.Ethics and disseminationThe University of California San Francisco Committee on Human Research, Nepal Netra Jyoti Sangh and the Nepal Health Research Council have given ethical approval for the trial. The results of this trial will be presented at local and international meetings and submitted to peer-reviewed journals for publication.Trial registration numberNCT01969786; Pre-results.

Objectives We propose new classification criteria for Sjogren’s Syndrome (SS), which are needed considering the emergence of biological agents as potential treatments and their associated co-morbidity. These criteria target individuals with signs/symptoms suggestive of SS.

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. C ONCLUSIONS. 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. (Eur J Ophthalmol 2008; 18: 351-5)

To investigate the association between Mooren's ulcer and intestinal hookworm infestation in South India.Prospective observational case-control study.Fifteen patients with Mooren's ulcer and 30 age- and gender-matched controls seen at Aravind Eye Hospital.Stool samples from the Mooren's ulcer patients and controls were collected and analyzed for presence of hookworm infestation.Prevalence of hookworm infestation in Mooren's ulcer patients and controls.There was a statistically significant correlation between intestinal hookworm infestation and the occurrence of Mooren's ulcer (P = 0.009). Retrospective exploratory subgroup analyses suggested that the correlation between intestinal hookworm infestation and the occurrence of Mooren's ulcer in men (P0.0001) was stronger than the correlation in women, with no statistically significant difference being observed in the prevalence of hookworm infestation between women with Mooren's ulcer and female control subjects (P0.99). Similarly, when both the Mooren's ulcer and the control subject groups were analyzed retrospectively by age50 years or age50, subjects with an age over 50 demonstrated a stronger correlation between hookworm infestation and Mooren's ulcer than controls (P = 0.017), whereas there was no statistically significant difference in the prevalence of hookworm infection between Mooren's ulcer subjects and control subjectsor = 50 (P = 0.31).Intestinal hookworm infestation appears to be associated with the development of Mooren's ulcer in South India. Although the power of our retrospective exploratory subgroup analyses was limited by multiple testing and small sample sizes, these data suggest further that the correlation between intestinal hookworm infestation and the development of Mooren's ulcer may be greatest in male patients with more advanced age.

Purpose To determine the intra-observer and inter-observer reliability of a novel ocular staining score among trained ophthalmologists. Design Reliability analysis within a prospective, observational, multicenter cohort study. Methods Those enrolled in the National Institutes of Health–funded Sjogren's International Collaborative Clinical Alliance (SICCA) who presented for follow-up at the University of California San Francisco, Aravind Eye Hospital, Johns Hopkins University, and the University of Pennsylvania were included. Study participants were graded using the ocular staining score by at least 2 masked SICCA-trained ophthalmologists. The primary outcome for this study was the intraclass correlation coefficient (ICC) for the total ocular staining score. ICCs were also calculated for tear break-up time (TBUT) and conjunctival and corneal staining. Results Total ocular staining score had an ICC of 0.91 for the right eye (95% confidence interval [CI] 0.85–0.96) and 0.90 for the left eye (95% CI 0.83–0.97). Corneal staining (right eye 0.86, 95% CI 0.76–0.93, left eye 0.90, 95% CI 0.81–0.95) and conjunctival staining (right eye 0.87, 95% CI 0.80–0.93, left eye 0.85, 95% CI 0.75–0.93) demonstrated excellent agreement. The ICC for TBUT was slightly lower (right eye 0.77, 95% CI 0.64–0.89; left eye 0.81, 95% CI 0.68–0.90). Conclusions Previous studies have shown that the ocular staining score is correlated with other diagnostic components of Sjogren syndrome. In this study, we demonstrate high reliability in grading among trained ophthalmologists, completing the validation of this test.

purpose To describe the relationship between the clinical exam for trachoma and the polymerase chain reaction (PCR) for ocular chlamydia. methods One hundred children in a trachoma-endemic area of Ethiopia were examined three times and swabbed twice for PCR analysis. The assays were compared, and an analysis of the variance between exam and PCR was performed. results Inter-examiner agreement was 0.57 (Cohen's κ), inter-PCR agreement 0.98, and agreement between examiner and PCR, 0.26–0.34. The positive predictive value of the exam in identifying infection was 66%. Inter-examiner variance accounted for 30% of the total variance between the exam and PCR, with the remainder presumably due to an underlying difference in what the exam and PCR measure. conclusions Despite modest inter-grader reliability and correlation with evidence of infection, the clinical exam is widely used due to its convenience and low cost. Efforts to make laboratory tests for ocular Chlamydia trachomatismore affordable would be useful.

We assessed how much of the observed decline in the prevalence of trachoma in a district of Western Nepal was due to an antibiotic treatment program and how much to an underlying secular trend outside of the program. Although antibiotic treatments clearly have an effect at 6 months, we were unable to show that this effect persisted at 12 months; in fact, long-term gains may be due to a secular trend in the area.

To investigate the rate of undiagnosed rheumatologic diseases and hepatitis C infection among patients with the clinical diagnosis of Mooren ulcer seen at Aravind Eye Hospital, Madurai, South India.Twenty-one patients with the clinical diagnosis of Mooren ulcer and 44 control patients underwent a complete ophthalmic history and examination, as well as serologic testing for antinuclear antibodies, rheumatoid factor, antineutrophil cytoplasmic antibodies, herpes simplex virus 1 antibodies, and hepatitis C virus antibodies.There were no statistically significant differences in the rates of seropositivity for antinuclear antibodies, rheumatoid factor, antineutrophil cytoplasmic antibodies, herpes simplex virus 1 antibodies, and hepatitis C virus antibodies between patients with Mooren ulcer and control patients. Two patients with Mooren ulcer and four control patients were found to have a rheumatoid factor titer of greater than 1:20. One of the control patients, but none of the patients with Mooren ulcer, was found to have serologic evidence of hepatitis C infection. A history of corneal trauma, surgery, or infection was reported by 68% of patients with Mooren ulcer, compared with 20% of control patients (P.001). Among patients with Mooren ulcer, bilateral disease occurred in 37% of patients, visual acuity was reduced to light perception in 15% of eyes, and perforation occurred in 19% of eyes.Nineteen (90%) of 21 patients with the clinical diagnosis of Mooren ulcer were found to have no evidence of an underlying rheumatologic disease by history, examination, or serologic testing, and none was seropositive for hepatitis C. However, patients with Mooren ulcer were more likely than control patients to report a history of corneal trauma, surgery, or infection.

The World Health Organization has distributed millions of doses of azithromycin to control the ocular chlamydial infection that causes trachoma. Theoretically, a loftier goal of elimination is feasible. Here, we demonstrate that, although local elimination of infection in the most severely affected communities is difficult, it is possible with biannual antibiotic distributions.

Purpose To compare the clinical features and antibiotic susceptibility of ocular methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive Staphylococcus aureus (MSSA). Design Cross-sectional study. Methods The Proctor clinical laboratory database was reviewed to identify all ocular isolates of S. aureus collected between July 1, 1998 and July 31, 2006. Results Of 915 S. aureus isolates, there were 88 MRSA isolates in 41 different patients. The proportion MRSA increased from 4.1% in 1998 to 1999 to 16.7% in 2005 to 2006. A total of 78.0% of patients with MRSA had blepharoconjunctivitis, 2.4% had cellulitis, 2.4% had dacryocystitis, 14.6% had keratitis, and 2.4% had endophthalmitis. The diagnoses associated with MSSA were not statistically different. A total of 63.6% of MRSA isolates were sensitive to bacitracin, 100% to vancomycin, 14.8% to ciprofloxacin, 14.8% to erythromycin, 97.7% to sulfisoxazole, and 93.2% to tetracycline. Conclusions MRSA has become a more common ocular pathogen but, as with MSSA, causes mild disease. MRSA should be treated with vancomycin.

September 15, 1997 marked the golden anniversary of the Francis I. Proctor Foundation, which was established in affiliation with the University of California in San Francisco. Over 50 years, 182 fellows from 27 countries have been trained in programs focusing on the study of infectious and inflammatory eye disease, and the prevention of blindness worldwide. Many of the people and events that have contributed to the success of the Proctor Foundation are presented in this brief essay. ( Surv Ophthalmol 42 :548–556, 1998.

The clinical manifestations of Sjogren's syndrome (SS) and sarcoidosis can be identical. Of the 1600 patients whom we have evaluated for dryness of the mouth and eyes, 300 proved to have SS and 5 had sarcoidosis. The patients with sarcoidosis had combinations of salivary gland enlargement, elevated antinuclear antibody titers, reduced salivary flow rates, and keratoconjunctivitis sicca, findings typically associated with SS. Finding non-caseating granulomas in a labial salivary gland biopsy specimen may be the only way to definitively differentiate these two disorders.

Eduardo C. Alfonso, MD; Jorge Cantu-Dibildox, MD; Wuqaas M. Munir, MD; Darlene Miller, DHSc, MPH; Terrence P. O’Brien, MD; Carol L. Karp, MD; Sonia H. Yoo, MD; Richard K. Forster, MD; William W. Culbertson, MD; Kendall Donaldson, MD; Jill Rodila, MD; Yunhee Lee, MDObjective: To describe the clinical presentation and course of patients who developed keratitis due to Fusarium while wearing nontherapeutic soft contact lenses.Methods: A retrospective review of microbiologic records from January 1, 2004, through April 15, 2006, was performed, identifying all patients with corneal ulceration and a culture positive for Fusarium species. Medical records of 34 patients were reviewed for clinical characteristics, treatment regimens, and microbiologic features.Results: The most common antimicrobial medications administered prior to Fusarium diagnosis were antibacterials in 31 of 34 patients. No distinct preponderance of any one brand of either contact lens or solution was identified. The microbiologic cultures found Fusarium oxysporum in 20 cases, Fusarium solani in 3 cases, Fusarium species not further identifiable in 10 cases, and no growth in 1 case. Patients with a delayed onset of treatment had a tendency for prolonged treatment until cure.Conclusions: Fusarium has previously been an unusual organism in the etiology of infectious keratitis in the setting of nontherapeutic soft contact lens wear. A delay in proper diagnosis and intervention may contribute to a prolonged treatment course. The microbial spectrum of contact lens–related keratitis may be evolving with higher participation of Fusarium species compared with prior reports.

Aims/background—To determine the epidemiological characteristics and risk factors predisposing to corneal ulceration in Madurai, south India, and to identify the specific pathogenic organisms responsible for infection. Methods—All patients with suspected infectious central corneal ulceration presenting to the ocular microbiology and cornea service at Aravind Eye Hospital, Madurai, from 1 January to 31 March 1994 were evaluated. Sociodemographic data and information pertaining to risk factors were recorded, all patients were examined, and corneal cultures and scrapings were performed. Results—In the 3 month period 434 patients with central corneal ulceration were evaluated. A history of previous corneal injury was present in 284 patients (65.4%). Cornea cultures were positive in 297 patients (68.4%).Of those individuals with positive cultures 140 (47.1%) had pure bacterial infections, 139 (46.8%) had pure fungal infections, 15 (5.1%) had mixed bacteria and fungi, and three (1.0%) grew pure cultures of Acanthamoeba. The most common bacterial pathogen isolated was Streptococcus pneumoniae, representing 44.3% of all positive bacterial cultures, followed by Pseudomonas spp (14.4%). The most common fungal pathogen isolated was Fusarium spp, representing 47.1% of all positive fungal cultures, followed by Aspergillus spp (16.1%). Conclusions—Central corneal ulceration is a common problem in south India and most often occurs after a superficial corneal injury with organic material. Bacterial and fungal infections occur in equal numbers with Streptococcus pneumoniae accounting for the majority of bacterial ulcers and Fusarium spp responsible for most of the fungal infections. These findings have important public health implications for the treatment and prevention of corneal ulceration in the developing world. (Br J Ophthalmol 1997;81:965‐971)

AIMS The study was undertaken to test the feasibility of using the LOCS III cataract grading scale in the field and to determine the rate of cataract progression over a 1 year period of time. METHODS For 150 subjects between the ages of 33 and 55 who attended the refraction clinic at Aravind Eye Hospital in Madurai, India, lens abnormalities were graded at the slit lamp using the LOCS III scale. One year later, 99 of the subjects were re-evaluated by the same methodology to assess the amount of lens change. RESULTS Interrater reliability was high. A change of 0.5 or more in lens colour, cortical, nuclear, or posterior subcapsular cataract was observed in at least one eye of 54% of the subjects. CONCLUSION The LOCS III grading scale is a feasible method for measuring lens changes in the field with the slit lamp. Cataract progression in India is rapid enough to permit intervention studies to be performed with relatively small numbers of subjects over a short period of time (that is, 600 subjects for 2 years).

Purpose To determine whether topical corticosteroids as adjunctive therapy for bacterial keratitis improves long-term clinical outcomes. Design Randomized, placebo-controlled, double-masked clinical trial. Methods This multicenter trial compared 1.0% prednisolone sodium phosphate to placebo in the treatment of bacterial keratitis among 500 patients with culture-positive ulcers receiving 48 hours of moxifloxacin before randomization. The primary endpoint was 3 months from enrollment, and 399 patients were evaluated at 12 months. The outcomes examined were best spectacle-corrected visual acuity (BSCVA) and scar size at 12 months. Based on previous results, regression models with adjustments for baseline status and/or causative organism were used for analysis. Results No significant differences in clinical outcomes by treatment group were seen with the prespecified regression models (BSCVA: −0.04 logMAR, 95% CI, −0.12 to 0.05, P = .39; scar size: 0.03 mm, 95% CI, −0.12 to 0.18, P = .69). A regression model including a Nocardia -treatment arm interaction found corticosteroid use associated with a mean 1-line improvement in BSCVA at 12 months among patients with non- Nocardia ulcers (−0.10 logMAR, 95% CI, −0.19 to −0.02, P = .02). No significant difference was observed in 12-month BSCVA for Nocardia ulcers (0.18 logMAR, 95% CI, −0.04 to 0.41, P = .16). Corticosteroids were associated with larger mean scar size at 12 months among Nocardia ulcers (0.47 mm, 95% CI, 0.06-0.88, P = .02) and no significant difference was identified by treatment for scar size for non- Nocardia ulcers (−0.06 mm, 95% CI, −0.21 to 0.10, P = .46). Conclusions Adjunctive topical corticosteroid therapy may be associated with improved long-term clinical outcomes in bacterial corneal ulcers not caused by Nocardia species.

Purpose: The addition of antibiotics to infusion solutions for cataract surgery is becoming increasingly popular. The authors developed an in vitro model to evaluate antibacterial effects of this use of antibiotics. Methods: Clinical isolates and/or reference strains of the following organisms were examined: coagulase-negative Staphylococcus spp, Staphylococcus aureus , Streptococcus pneumoniae , Streptococcus viridans , Streptococcus spp, Enterococcus spp, Proprionibacterium acnes , Moraxella nonliquifaciens , and Pseudomonas aeruginosa . Standardized suspensions of each organism were incubated with a control solution (Balanced Salt Solution) or Balanced Salt Solution containing the following antibiotics: vancomycin (20 μg/ml} or gentamicin (8 μg/ml) or gentamicin and vancomycin combined (8 and 20 μg/ml, respectively). Suspensions were incubated for 30, 60, and 120 minutes at room temperature. Samples were centrifuged, and the organisms were washed with Balanced Salt Solution before quantitative culturing. Each organism also was incubated for 48 hours in Mueller-Hinton broth with the same antibiotic concentrations. Results: Most of the organisms were not affected by exposure to the antibiotics for up to 140 minutes. P. aeruginosa and M. nonliquifaciens were exceptions, decreasing in colony numbers even with 30 minutes of exposure. Several Staphylococcus spp yielded variable results. All organisms demonstrated nearly complete inhibition of growth when exposed for an extended time to the appropriate antibiotic in broth. Conclusions: Exposure to antibiotics for a short period of time, such as during intraocular surgery, generally has no effect on organisms commonly responsible for endophthalmitis. The use of antibiotics in this manner should be critically reassessed until further study.

Purpose We studied supratarsal injection of corticosteroid as a new therapeutic modality for treating severe vernal keratoconjunctivitis to determine its efficacy in treating patients refractory to all conventional therapy. Methods Twelve patients with vernal keratoconjunctivitis resistant to all established therapy were prospectively studied by randomly assigning them to receive supratarsal injection of either short- or intermediate-acting corticosteroid. Relief of symptoms and resolution of clinical signs were evaluated. Patients were followed up to four years to identify side effects. Results All patients experienced dramatic symptomatic relief within one to five days, regardless of the type of corticosteroid injected. Marked decrease in cobblestone papillae was noted in 14.9 days (mean) after short-acting corticosteroid injection and 12.8 days after intermediate-acting corticosteroid injection (P = .65). Shield ulcers and limbal involvement resolved in one to three weeks, independent of the corticosteroid used (P = .90). No complications were observed with supratarsal injection of short-acting corticosteroid. One patient developed persistent increase of intraocular pressure after injection of intermediate-acting corticosteroid. Conclusions The dramatic symptomatic and clinical improvement suggests that supratarsal injection of corticosteroid may be a valuable therapeutic approach to treating refractory vernal keratoconjunctivitis. Short-acting and intermediate-acting corticosteroids were equally efficacious. Because of the lack of intraocular pressure increase observed with short-acting corticosteroid, we favor its use in supratarsal injection.

Objective: To determine the incidence of corneal ulceration in Madurai District, South India.Design: Retrospective incidence study.Setting: General community.Patients: All patients who reside in Madurai District and presented to an ophthalmologist in 1993 with corneal ulceration.Main Outcome Measure: Cases of corneal ulceration.Results: 1148 cases of corneal ulceration were recorded in the medical records of those ophthalmologists who maintained records. Based upon the recorded number of cases, the annual incidence per 10,000 population was 3.4. The ratio of male to female patients was 1.6: 1.0. When the estimated number of cases from those without records was added to the total number of recorded cases the annual incidence was 11.3 per 10,000 population.Conclusion: Corneal ulceration is a common occurrence in South India. While the true incidence of this problem is impossible to determine because of the lack of medical records, we believe our estimation of the incidence to be close to the true incidence ...

Dulku raises an important point and one that we fully agree with. A clinical trial has 1 primary outcome; all other analyses are either secondary prespecified or post hoc exploratory analyses and should be noted as such. In our study, the subgroup analysis assessing the effect of corticosteroids in severe bacterial ulcers was prespecified prior to any of the results being available, so the cut points chosen for the subgroups were decided a priori based on clinical interest. We made an attempt to limit the number of subgroup analyses in an effort to reduce the chances of making a type I error. It is still possible that our finding that steroids are of benefit in patients with ulcers of greater severity is not true. However, the fact that this finding was corroborated across various subgroups representing different ways of measuring severity such as worse visual acuity, central location of the ulcer, deeper ulcer, and larger infiltrate increases the credibility of our finding. We completely agree that this result, along with any others that we subsequently find, will need to be confirmed in future randomized trials.

PURPOSE. Conjunctival infection with non-chlamydial bacteria may play an important role in the progression of trachoma, especially with regard to the development of corneal opacity and blindness. To further characterize the microbiological profile of bacterial conjunctival infections in cicatricial trachoma, a conjunctival swabbing of adults in rural Ethiopia was performed. METHODS. In a cross-sectional study conducted in nine Ethiopian villages with hyperendemic trachoma, persons 40 years of age or older with signs or symptoms consistent with trichiasis were recruited and conjunctival swabbing for bacterial pathogens was performed. RESULTS. Conjunctival examination and swabbing on 112 females and 36 males were performed. Of the 148 study participants, 101 (68.2%) were confirmed to have trichiasis, and 118 (80%) had conjunctival swabs positive for bacteria. In multivariate analyses, growth of pathogenic conjunctival bacteria was independently associated with trichiasis (odds ratio [OR] 6.93; 95% confidence interval [CI] 2.71–17.7) and female sex (OR 5.90; 95% CI 2.09–16.7). Females were more likely to have swabs positive for Streptococcus pneumoniae or Haemophilus influenzae than were males (OR 9.09; 95% CI 1.17–70.8). CONCLUSIONS. In a region of Ethiopia with endemic trachoma, conjunctival bacterial growth was more common in females than that in males. S. pneumoniae and H. influenzae, both of which frequently colonize the nasopharynx of children, were more common in females, suggesting that the preponderance of infection in females may be attributable to close contact with children. This finding is consistent with the theory that childcare activities may preferentially expose females to ocular chlamydial infection. (ClinicalTrials.gov number, NCT00221364.) (Invest Ophthalmol Vis Sci. 2012;53:5208– 5212) DOI:10.1167/iovs.12-9984

OBJECTIVE To determine the association between patterns of inflammation in labial salivary glands (LSG) and the ocular component of Sjogren's syndrome (SS). METHODS We classified LSG biopsy specimens from 618 patients with suspected SS as showing focal lymphocytic sialadenitis (FLS), other chronic sialadenitis (CS), or other diagnoses. We then determined the association of the other component of primary SS, keratoconjunctivitis sicca (KCS), with FLS, CS, parotid flow rate, and xerostomia. RESULTS FLS, rather than CS, was associated with a diagnosis of KCS (chi 2 = 191, P < 0.0001). The severity of KCS correlated directly with the severity of FLS (r = 0.52, P < 0.0001), but not of CS, and correlated inversely with parotid flow rate in those patients who had FLS (r = -0.29), but not in those who had CS (r = -0.03). Xerostomia was marginally associated with KCS (chi 2 = 5, P = 0.02). CONCLUSION The stronger KCS association found in patients whose LSG biopsies show FLS makes FLS the best criterion presently available for diagnosing the salivary component of SS. CS is a common feature of labial salivary glands but is neither associated with SS nor an end stage of primary SS. Histopathologic examination of salivary tissue is currently essential for diagnosing primary SS as well as secondary SS in which KCS is lacking, especially cases to be included in studies of SS.

To determine the incidence and associated risk factors for ulcerative keratitis in northern California.In this large-population, retrospective, cohort study, all medical records with diagnosis coding for corneal ulcers during a consecutive 12-month period were reviewed. Incidence rates were calculated using a dynamic population model. Multivariate relative risk regression was conducted to evaluate potential risk factors for ulcerative keratitis.Within the target population of 1 093 210 patients, 302 developed ulcerative keratitis. The incidence of ulcerative keratitis was 27.6 per 100 000 person-years (95% confidence interval, 24.6-30.9). The incidence of corneal ulceration in contact lens wearers was 130.4 per 100 000 person-years (95% confidence interval, 111.3-151.7), with an adjusted relative risk of 9.31 (7.42-11.7; P.001) compared with non-contact lens wearers, who had an incidence of ulcerative keratitis of 14.0 per 100 000 person-years (11.7-16.6). Seven of 2944 people known to be infected with human immunodeficiency virus developed ulcerative keratitis, with 5 being contact lens wearers. The incidence of ulcerative keratitis in human immunodeficiency virus-positive patients was 238.1 per 100 000 person-years (95% confidence interval, 95.7-490.5), with an odds ratio of 9.31 (7.42-11.7; P.001) compared with human immunodeficiency virus-negative patients, who had an incidence of ulcerative keratitis of 27.1 per 100 000 person-years (24.1-30.3).The incidence of ulcerative keratitis in this population is higher than previously reported. This may be owing to the increasing prevalence of contact lens wear.

Trachoma is the leading infectious cause of blindness. The World Health Organization has set a goal of reducing the trachoma disease burden to a level where it is no longer a public health concern by the year 2020. Some investigators feel that local elimination of ocular chlamydia infection is possible, but little has been done to study the likelihood of reintroduction of infection from neighboring areas. Mass administration of azithromycin has been shown to dramatically reduce the prevalence of infection in many villages in central Ethiopia. However, after treatment is discontinued, infection returns. Reintroduction of infection could occur from the few remaining infected cases in a treated community or from outside the community. People traveling between villages might be responsible thus complicating the elimination of trachoma.We conducted a survey to assess the travel pattern of the Gurage zone residents in Ethiopia. Seven hundred and seventeen households with at least one child aged 1-5 years in 48 villages were surveyed to collect the details of travel in 1 month prior to the survey.Seventy-eight percent of the surveyed households had at least one traveler, with the majority being women. Pre-school children, the main reservoir of clinically active infection, rarely traveled. Most travel was to the market or to school, and most for less than 1 day.Travel routinely takes place in these villages. Trachoma control programs in this area might consider treating areas with the same markets and schools in the same period to increase the efficacy of mass treatment.

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.

Summary Background Trachoma-control programmes distribute oral azithromycin to treat the ocular strains of chlamydia that cause the disease and to control infection. Theoretically, elimination of infection is feasible if untreated individuals receive an indirect protective effect from living in repeatedly treated communities, which is similar to herd protection in vaccine programmes. We assessed indirect protection against trachoma with mass azithromycin distributions. Methods In a cluster randomised trial, 24 subkebeles (government-defined units) in Amhara, Ethiopia, were randomised, with use of a simple random sample, to distribution four times per year of single-dose oral azithromycin to children aged 1–10 years (12 subkebeles, 4764 children), or to delayed treatment until after the study (control; 12 subkebeles, 6014 children). We compared the prevalence of ocular chlamydial infection in untreated individuals 11 years and older between baseline and 12 months in the treated subkebeles, and at 12 months between the treated and control subkebeles. Health-care and laboratory personnel were blinded to study group. Analysis was intention to treat. The study is registered with clinicaltrials.gov, number NCT00322972. Findings At 12 months, 637 children aged 1–10 years and 561 adults and children aged 11 years and older were analysed in the children-treated group, and 618 and 550, respectively, in the control group. The mean prevalence of infection in children decreased from 48·4% (95% CI 42·9–53·9) to 3·6% (0·8–6·4) after four mass treatments. At 12 months, the mean prevalence of infection in the untreated age group (≥11 years) was 47% (95% CI 33–57) less than baseline (p=0·002), and 35% (95% CI 1–57) less than that in untreated communities (p=0·04). Interpretation Frequent treatment of children, who are a core group for transmission of trachoma, could eventually eliminate infection from the entire community. Herd protection is offered by repeated mass antibiotic treatments, providing a strategy for elimination of a bacterial disease when an effective vaccine is unavailable. Funding National Institutes of Health.

Background Antibiotics are a major tool in the WHO's trachoma control program. Even a single mass distribution reduces the prevalence of the ocular chlamydia that causes trachoma. Unfortunately, infection returns after a single treatment, at least in severely affected areas. Here, we test whether additional scheduled treatments further reduce infection, and whether infection returns after distributions are discontinued. Methods Sixteen communities in Ethiopia were randomly selected. Ocular chlamydial infection in 1- to 5-year-old children was monitored over four biannual azithromycin distributions and for 24 months after the last treatment. Findings The average prevalence of infection in 1- to 5-year-old children was reduced from 63.5% pre-treatment to 11.5% six months after the first distribution (P, Author Summary Trachoma is one of the leading causes of blindness in the developing world. The World Health Organization has a multi-pronged approach to controlling the ocular chlamydial infection that causes the disease, including distributing antibiotics to entire communities. Even a single community treatment dramatically reduces the prevalence of the infection. Unfortunately, infection returns back into communities after treatment, at least in severely affected areas such as rural Ethiopia. Here, we assess whether additional scheduled treatments in 16 communities in the Gurage area of Ethiopia further reduce infection, and whether the disease returns after distributions are stopped. In communities with the highest levels of trachoma ever studied, we find that repeated mass oral azithromycin distributions gradually reduce the prevalence of trachoma infection in a community, as long as these treatments are given frequently enough and to enough people in the community. Unfortunately, infection returns into the communities after the last treatment. Sustainable changes or complete local elimination of infection will be necessary to stop the return of ocular chlamydial in communities with very high prevalence of the disease.

Corneal ulceration is one of the most frequent causes of blindness in developing countries. Between September 1985 and August 1987, 405 patients with corneal ulceration were examined at Tribhuvan University Teaching Hospital in Kathmandu, Nepal. Males and females were equally affected. The most common predisposing cause of ulceration was corneal trauma, usually with organic agricultural materials. Microorganisms were grown from 324 (80%) of the ulcers. Pure bacterial cultures were obtained from 256 (63.2%) of the patients, whereas pure fungal cultures were obtained from 27 (6.7%) of the patients. In 41 patients (10.1%), corneal cultures yielded a mixed growth of bacteria and fungi. Of a total of 398 bacterial isolates, 124 (31.1%) were positive for Streptococcus pneumoniae, the most commonly isolated organism in the series. Other frequently isolated bacteria included Staphylococcus epidermidis, S. aureus, and Pseudomonas species. Of 68 positive fungal isolates obtained, 32 (47.0%) were identified as Aspergillus species. Candida species and Fusarium species were less commonly seen.

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.Trial registration number:NCT00324168

PURPOSE. Trachoma remains the leading infectious cause of blindness worldwide. The World Health Organization (WHO) recommends mass antibiotic distributions in its strategy to eliminate blinding trachoma. To determine the most effective antibiotic treatment strategy, it is essential to have a diagnostic test that can correctly measure the true status of ocular Chlamydia trachomatis infection in individuals, particularly after treatment. A newer ribosomal ribonucleic acid (rRNA)-based amplification test was compared with the current DNA-based polymerase chain reaction (PCR) for the detection of C. trachomatis. METHODS. An rRNA-based assay and PCR were performed on swab specimens taken from the right upper tarsal conjunctiva of 240 children aged 1 to 5 years living among 16 endemic villages in the Gurage Zone, Ethiopia. RESULTS. The rRNA-based test detected ocular C. trachomatis infection in 142 (59%) subjects compared with 67 (28%) detected by PCR (McNemar's test, P < 0.0001). The rRNA-based test gave positive results for all subjects who were positive by PCR and detected infection in 75 (31%) additional subjects. CONCLUSIONS. The rRNA-based test appears to have significantly greater sensitivity than PCR for the detection of ocular C. trachomatis infection in children in trachoma-endemic villages. The increased sensitivity of the rRNA-based test may be due to its ability to detect low levels of C. trachomatis infection in individuals, which can occur especially after antibiotic treatment. Data from past studies in which PCR was used to assess the prevalence of infectious trachoma after community-wide antibiotic treatments could have underestimated the true prevalence of infection.

Purpose To compare polymerase chain reaction (PCR) to microbial culture for the detection and identification of bacterial and fungal pathogens in microbial keratitis. Design Prospective cohort study. Methods A total of 108 consecutive corneal ulcers were cultured and analyzed by PCR using pan-bacterial and pan-fungal primers. PCR products were cloned, sequenced, and compared to culture results using standard bioinformatics tools. Results Of the 108 samples, 56 were culture-positive, 25 for bacteria and 31 for fungi; 52 were culture-negative. After eliminating false-positive PCR products, 94 of 108 were positive by PCR, 37 for bacteria and 57 for fungi. Nineteen of 25 bacterial culture-positive samples were positive by PCR, and 29 of 31 samples culture-positive for fungi were positive by PCR. The majority of sequenced PCR products matched the positive culture results. Of the 52 culture-negative samples, 46 (88%) yielded pathogen deoxyribonucleic acid (DNA) PCR products, 18 bacterial and 28 fungal. These represented a variety of species, including at least three novel previously uncultured microbes. Conclusions PCR detects microbial DNA in the majority of bacterial and fungal corneal ulcers, and identifies potentially pathogenic organisms in a high proportion of culture-negative cases. Yield and concordance with culture are higher for fungal than bacterial ulcers. Practical use of the technique is limited by artefactual amplification of nonpathogenic organisms. PCR may be used as an adjunct to culture to identify potential pathogens in microbial keratitis.

There are various approaches to control trachoma. These include the elimination of the ocular strains of Chlamydia trachomatis that cause the disease and to decrease the spread of infection by other measures such as fly control. Here, we examined how these two are related (i.e., how treating children with antibiotics affects carriage of Chlamydia by flies). Flies were collected in villages that had received mass oral azithromycin distribution and were compared with flies in untreated villages. Polymerase chain reaction (PCR) was performed to detect chlamydial DNA on the flies. Conjunctival swabs were also taken to assay for chlamydial prevalence in the children. Chlamydia was found on 23% of the flies in the untreated villages but only 0.3% in treated villages. Prevalence of trachoma in children proved to be an excellent predictor of the prevalence on flies (correlation coefficient, 0.89). Thus, treating children with antibiotics may drastically reduce the role of flies as a vector.

To describe the clinical characteristics at presentation of a large cohort of patients with Mooren's ulcer in South India.The medical records of patients with Mooren's ulcer examined in the cornea clinic at Aravind Eye Hospital Madurai, Tamil Nadu, India, over a 10-year period were reviewed in this retrospective observational case series.The cohort contained 242 eyes of 166 patients. All patients were from South India, and men outnumbered women by a ratio of 4.7:1. The median and mean ages at presentation were 65 and 61 years, respectively, with a range of 13-95 years. One eye was affected in 90 of 166 (54%) patients. Visual acuity in the affected eye at presentation ranged from 6/6 to light perception, and was 6/12 or better in 34 of 242 (14%) eyes, between 6/12 and 3/60 in 168 (69%) eyes, and worse than 3/60 in 40 (17%) eyes. Partial peripheral corneal ulceration was observed in 222 (92%) eyes, complete peripheral corneal ulceration was observed in 15 (6%) eyes and total corneal ulceration was observed in 5 (2%) eyes. For those 222 eyes with partial peripheral ulceration, 152 (68%) showed temporal involvement, 129 (58%) showed nasal involvement, 116 (52%) showed inferior involvement and 30 (14%) showed superior involvement. Perforation was observed in 26 (11%) eyes, and was more common in eyes with peripheral as compared with total ulceration (p0.001). Identified risk factors in the cohort included evidence of prior corneal surgery (22%), corneal trauma (17%) and corneal infection (2%).Mooren's ulcer is a rare and potentially blinding eye condition observed not infrequently in the cornea clinic at Aravind Eye Hospital. Men are affected more often than women and may present with either unilateral or bilateral disease. Perforation is observed in approximately 1 in 10 affected eyes at presentation and occurs most often in the setting of peripheral ulceration. The occurrence of prior corneal surgery, trauma or infection in nearly one third of patients supports theories of exposure to corneal antigen in the pathogenesis of this disorder.

Aim: To determine whether topical antifungal prophylaxis distributed by paid village health workers (VHWs) in south India is necessary after corneal abrasion to prevent fungal keratitis in a population where half of the ulcers are fungal. Methods: Two panchayaths (village administrative units in Madurai district with a combined population of 48 039 were followed prospectively for 18 months by 15 VHWs who were trained to identify post-traumatic corneal abrasions. Patients fulfilling the eligibility criteria were randomised into two groups and treated with either 1% chloramphenicol and 1% clotrimazole ointment or 1% chloramphenicol and a placebo ointment three times a day for 3 days. Patients, doctors and VHWs were blinded to treatment. Results: During the 18-month period, 1365 people reported to VHWs with ocular injuries, of whom 374 with corneal abrasions were eligible for treatment. Of these, 368 (98.5%) abrasions healed without complications. Two patients had mild localised allergic reactions to the ointment, two dropped out and two patients in the placebo group developed microscopic culture-negative corneal stromal infiltrates that healed in 1 week with natamycin drops. Conclusions: Both fungal and bacterial ulcers that occur after traumatic corneal abrasions seem to be effectively prevented in a village setting using only antibiotic prophylaxis.

Aim: To determine if antioxidant supplements (β carotene and vitamins C and E) can decrease the progression of cataract in rural South India. Methods: The Antioxidants in Prevention of Cataracts (APC) Study was a 5 year, randomised, triple masked, placebo controlled, field based clinical trial to assess the ability of interventional antioxidant supplements to slow cataract progression. The primary outcome variable was change in nuclear opalescence over time. Secondary outcome variables were cortical and posterior subcapsular opacities and nuclear colour changes; best corrected visual acuity change; myopic shift; and failure of treatment. Annual examinations were performed for each subject by three examiners, in a masked fashion. Multivariate modelling using a general estimating equation was used for analysis of results, correcting for multiple measurements over time. Results: Initial enrolment was 798 subjects. Treatment groups were comparable at baseline. There was high compliance with follow up and study medications. There was progression in cataracts. There was no significant difference between placebo and active treatment groups for either the primary or secondary outcome variables. Conclusion: Antioxidant supplementation with β carotene, vitamins C and E did not affect cataract progression in a population with a high prevalence of cataract whose diet is generally deficient in antioxidants.

Corneal ulceration and subsequent corneal scarring are at present a leading cause of ocular morbidity and unilateral blindness in developing countries.1 In response to the findings of the Bhaktapur Eye Study in Nepal,2 prevention studies were initiated in three countries in South East Asia (Bhutan, Burma and India) to validate the hypothesis that corneal ulcers which occur after traumatic abrasions can be prevented in the setting of diverse health care systems and in populations with different prevalences of bacterial and fungal pathogens causing ulceration. The recently completed 18 month study in Bhutan3 validated the findings of the Nepal study by demonstrating that bacterial ulcers that occur after traumatic corneal abrasion can be effectively eliminated by a grass roots public health approach, even under the conditions that prevail in isolated rural villages. Corneal ulcer prevention in Bhutan, where 98% of the ulcers are caused by bacterial pathogens,3 was accomplished by a simple public health strategy that local volunteer village health workers were taught to employ within the existing healthcare structure. In Burma, a country of 42 million ethnically diverse people in South East Asia, corneal ulceration is a significant cause of unilateral blindness superseded only by cataract and trachoma.4,5 Based on hospital data projected to a defined population, the World Health Organization estimates that there are 710 corneal ulcers per 100 000 population every year.6 This figure is comparable to the incidence in Nepal2 of 799 per 100 000. Prevalence studies based on data from the microbiology laboratory at the national hospital in Yangon indicate that one third of all corneal ulcers are caused by bacteria, a third are fungal, and a third are mixed bacterial and fungal infections.6 Fungal pathogens have been reported as a major cause of microbial keratitis in several countries in Africa7 and Asia8 as well, inevitably posing extremely difficult management problems. However, the situation in Burma is exceptional. Two thirds of all culture positive corneal ulcers grow fungal organisms, and coupled with the high incidence of corneal infection in the country, the blinding sequelae for the population are disastrous. It is widely believed that fungal ulcers occur after a traumatic event, usually a corneal abrasion caused by organic material.9 Therefore, it seems feasible that applying a topical antifungal ointment prophylactically to the injured eye might prevent fungal keratitis from occurring. This study proposes to test this hypothesis in a population where the ulcer incidence is high and the main risk factor for fungal keratitis is corneal trauma. Because the incidence of bacterial keratitis and mixed infections is also high, all corneal abrasions were also treated prophylactically with antibiotic ointment. In addition, we propose to test the effectiveness of a highly organised and stratified village healthcare system, such as the one that exists in Burma, in preventing corneal ulceration.

To describe the methodology and baseline data for the Antioxidants in Prevention of Cataracts (APC) study in South India.The APC study is a prospective, 5-year, randomized, triple-masked, placebo-controlled, field-based clinical trial to examine the effect of antioxidants (combination tablet of vitamins A, C, and E) on progression of cataract. The primary outcome variable is cataract progression (nuclear opalescence), evaluated with the slit-lamp biomicroscope by the Lens Opacification Classification System III method. Secondary outcome variables are progression in cortical and posterior subcapsular opacity and nuclear color, change in best corrected visual acuity, myopic shift, and treatment failure (progression to cataract surgery or best corrected vision worse than 20/400 in an eye). Inclusion criteria are age between 35 and 50 years and best-corrected visual acuity of 20/40 or better. Exclusion criteria are a diagnosis of diabetes mellitus or nonfasting blood glucose level7.8 mmol/L, history or presence of various ocular conditions or treatment forms, or current use of vitamin supplements. Baseline ophthalmic, demographic, and potential cataract risk factor data (such as smoking, sunlight, or alcohol exposure) were compared between groups on an intent-to-treat basis.Of 954 people screened, 798 were enrolled, a sample size which exceeded the required estimate. More than 80% of subjects had 20/20 or better vision in at least one eye, and baseline prevalence of significant cataract according to the LOCS III grading scale was high. The two treatment groups were comparable for all baseline measures except alcohol intake.The sample size and group baseline characteristics will provide sufficient power to detect a change in cataract progression within 5 years.

The importance of corneal disease as a major cause of blindness in the world today remains second only to cataract, but the epidemiology of corneal blindness is complicated and varies from country to country and even from one population to another, depending on a number of risk factors.1 The commonly cited causes of corneal blindness in developing countries include trachoma, onchocerciasis, xerophthalmia,2 and leprosy,3 but another cause, which has been frequently unrecognised, is corneal trauma.4,5 Unlike corneal injuries in the industrialised world that are usually treated as ophthalmic emergencies, minor corneal trauma in developing countries is often considered to be trivial and is frequently ignored. In the absence of appropriate prophylactic treatment the corneal stroma can quickly become infected, an ulcer develops, and the ultimate result is severe scarring and loss of vision.6 It is a documented fact that the majority of corneal ulcers in developing countries occur after minor ocular trauma sustained during agricultural work or in the home,7,8 but the incidence of corneal ulceration following these superficial corneal abrasions remains unknown because control studies are ethically inappropriate. There is evidence that several hours to, sometimes, several days are required before microbial keratitis develops following a corneal abrasion. During that time there may be a “window of opportunity” to prevent an infection from developing.7,8 The Bhaktapur Eye Study, a large well coordinated 2 year study conducted in Nepal, proved conclusively that post‐traumatic corneal ulceration can be prevented by topical application of 1% chloramphenicol ophthalmic ointment three times a day for 3 days if given in a timely fashion to the eyes of the individuals who have suffered a corneal abrasion. Local village health workers were taught to diagnose corneal abrasions with fluorescein dye and a blue torch and then to start treatment. Maximum benefit was obtained if prophylaxis was started within 18 hours of the injury.9 Success with the Bhaktapur Eye Study led logically to the development of further studies in three different countries in South East Asia (Bhutan, Burma, and India) that have different healthcare systems and a different spectrum of pathogens causing corneal ulceration. The first purpose of the three studies was to determine the effectiveness of the three different healthcare systems at the grassroots village level in preventing corneal ulceration following corneal injury. The second purpose was to determine the most effective medication or combination of medications needed to prevent corneal ulcers from developing depending on the prevalence of known pathogens causing ulceration in the community. This study in Bhutan is the first of the three studies to be reported. Bhutan is an isolated Buddhist kingdom in the eastern Himalayas with a population of 650 000 ethnic Bhutanese living in the mountains, and an unspecified number of ethnic Nepalese living in the lowlands along the border with India. The population is spread out over rugged country in isolated villages of 20–25 households. In spite of their relative isolation almost all of the villages are served by an extensive rural public health network that provides basic health services, health education, immunisations, and maternal and child health services. Basic eye care is provided in the villages by the basic health units with district hospitals functioning as the first level referral centres. In some developing countries a high proportion of corneal ulcers are caused by fungal pathogens,10 but fortunately this is not the case in Bhutan. Records at the National Microbiology Laboratory in the capital, Thimpu, indicate from hospital based data that 98% of all culture positive ulcers in Bhutan are bacterial in origin (personal communication). Because of this unique prevalence of pathogens, fungal ulcers can be effectively disregarded as a public health problem. The annual incidence of corneal ulceration in Bhutan is not known with certainty, but it is conservatively estimated by the World Health Organization that there are at least 339 ulcers per 100 000 population.11 The goal of this study was to prove that screening of corneal abrasions by volunteer village health workers (VVHWs) and treatment with topical chloramphenicol could be successfully employed at the grassroots village level in Bhutan to prevent corneal ulceration.