Risk factors for corneal abrasions in Nepal: a community-based study.

BACKGROUND: South Asia is experiencing rapid urbanization, which may be changing the risk factor profile for ocular trauma. The objective of this study was to compare risk factors for traumatic corneal abrasions in rural versus urban Nepal, and to assess if any risk factors were associated with a poor outcome. METHODS: In a prospective, cross-sectional, community-based study performed as part of a cluster-randomized trial, community health workers from Nepal were trained to diagnose and treat traumatic corneal abrasions. Participants with an abrasion were invited to complete a risk factor survey. The main exposure variable was the object of eye injury, stratified by rural-urban residence. The main outcome measure was a lack of corneal healing after a three-day course of antimicrobials. RESULTS: Of 3657 participants diagnosed with a corneal abrasion, 2265 completed a survey. Eye trauma occurred most frequently during agricultural activities. The most common object of injury was vegetative matter, accounting for approximately 40% of injuries in rural, peri-urban, and urban communities. Wood injuries were more common in rural communities (24%) compared with urban or peri-urban communities (13%). Eye injury from an animal was more likely to result in a non-healing corneal abrasion after 3 days of treatment compared with other types of trauma (prevalence ratio 2.59, 95%CI 1.16-5.76). CONCLUSIONS: Health promotion activities for prevention of corneal ulcers in Nepal should focus on agricultural trauma in both rural and urban areas. Community members experiencing eye trauma from an animal may benefit from early referral to an eye clinic.

Diagnostic accuracy of smartphone corneal photography for detection of corneal opacities in a resource-limited setting: a community-based study.

Purpose: To evaluate the diagnostic accuracy of smartphone corneal photography in detecting corneal opacities in a community-based setting. Methods: A case-control, diagnostic accuracy study was nested in a cluster-randomized trial of a corneal ulcer prevention intervention in Nepal. Smartphone corneal photography was performed annually on community members self-reporting a potential risk factor for a corneal infection. Corneal photographs were graded for the presence or absence of an opacity. All cases with an opacity on smartphone photography and an equal number of controls were invited for a comprehensive eye examination with a slit lamp biomicroscope at an eye hospital. A mobile team visited participants unable to come to the hospital, conducting a limited examination with a penlight. Results: Of 1332 study participants (666 cases and 666 controls), 1097 had a penlight examination (535 cases and 562 controls) and 191 had a slit lamp examination (120 cases and 71 controls). When penlight examination was considered the reference standard, smartphone diagnosis of a corneal opacity had a positive predictive value (PPV) of 47% (95% confidence interval 43-52%) and negative predictive value (NPV) of 95% (93-97%). When slit lamp examination was considered the reference standard, the overall PPV and NPV were 71% (62-78%) and 80% (70-88%), respectively. The NPV was greater for detection of opacities > 1mm, estimated at 95% (90-98%). Conclusions: Corneal photography performed in a resource-limited community-based setting using a smartphone coupled to an external attachment had acceptable diagnostic accuracy for detection of corneal opacities large enough to be clinically meaningful.

Relationship Between Intraocular Pressure and Age: A Population-Based Study in Nepal.

PRCIS: Intraocular pressure (IOP) decreased with age in a population-based study in Nepal, from a mean of 14.1 mm Hg among those 60-64 years old to 13.0 mm Hg among those 80 years old or older. PURPOSE: Few studies have assessed the distribution of IOP from the Indian subcontinent, despite its large population and high burden of glaucoma. The objective of this study was to assess the distribution of IOP measurements from adults living in a lowland region of Nepal. METHODS: In a population-based cross-sectional study, all individuals aged 60 years and older from an area of lowland Nepal were invited for an IOP assessment with a rebound tonometer. RESULTS: Of 160 communities (28,672 people aged ≥60 y) enrolled, 79 (13,808 people aged ≥60 y) were randomly selected for IOP testing. Of those eligible, 10,017 (72.5%) individuals underwent tonometry. Mean IOP decreased monotonically over 5-year age groups, from 14.1 mm Hg (SD: 3.6) among those aged 60-64 years to 13.0 mm Hg (SD: 4.2) among those 80 years or older. The 97.5th percentile IOP measurement was 21.0 mm Hg for all age groups. In adjusted analyses, younger age, self-reported diabetes, and higher population density were each associated with higher IOP, and self-reported cataract surgery was associated with lower IOP. CONCLUSIONS: Mean IOP was lower among older individuals in Nepal, consistent with many studies from East Asia and in contrast to many studies from western populations. These results suggest that ethnic background might be a consideration when diagnosing ocular hypertension.

Risk factors for corneal ulcers: a population-based matched case-control study in Nepal.

BACKGROUND/AIMS: We aimed to examine risk factors for corneal ulcer in a rural and peri-urban setting in Nepal. METHODS: This 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. RESULTS: Of 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. CONCLUSION: We 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.

Cutaneous melanin and glaucoma: a case control study.

Purpose: Previous studies have used subjective assessments to implicate darker skin color as a risk factor for glaucoma. This study used objective measurements to determine whether skin melanin is a risk factor for glaucoma.Methods: In a case-control study conducted at a tertiary eye hospital in Nepal, patients aged 40 years or older from the glaucoma clinic were enrolled as cases and age-matched patients without glaucoma from other clinics at the eye hospital were enrolled as controls. A colorimeter was used to capture melanin measurements in triplicate from the inner arm and forehead of each participant. The exposure variable of interest was the median skin melanin value, in arbitrary units. The outcome of interest was the presence of glaucoma.Results: 100 glaucoma cases and 100 matched controls were enrolled. Agreement between the triplicate melanin measurements was high, with an intra-class correlation of 0.99 (95% CI, 0.99-0.99) for inner arm measurements and 0.97 (95% CI 0.96-0.98) for forehead measurements. Mean inner arm melanin values were 604 units (standard deviation [SD] 177) in cases and 602 units (SD 179) in controls; forehead values were 650 (SD 146) in cases and 652 (SD 152) in controls. After adjusting for sex and country of residence, skin melanin was not associated with the presence of glaucoma (odds ratio 1.04, 95%CI 0.78-1.38 for inner arm values and 0.97, 95%CI 0.70-1.35 for forehead values).Conclusion: This study failed to find a significant association between skin pigmentation and glaucoma.

Cluster-randomised trial of community-based screening for eye disease in adults in Nepal: the Village-Integrated Eye Worker Trial II (VIEW II) trial protocol.

INTRODUCTION: The majority of blindness worldwide could be prevented or reversed with early diagnosis and treatment, yet identifying at-risk and prevalent cases of eye disease and linking them with care remain important obstacles to addressing this burden. Leading causes of blindness like glaucoma, diabetic retinopathy and age-related macular degeneration have detectable early asymptomatic phases and can cause irreversible vision loss. Mass screening for such diseases could reduce visual impairment at the population level. METHODS AND ANALYSIS: This protocol describes a parallel-group cluster-randomised trial designed to determine whether community-based screening for glaucoma, diabetic retinopathy and age-related macular degeneration reduces population-level visual impairment in Nepal. A door-to-door population census is conducted in all study communities. All adults aged ≥60 years have visual acuity tested at the census visit, and those meeting referral criteria are referred to a local eye care facility for further diagnosis and management. Communities are subsequently randomised to a community-based screening programme or to no additional intervention. The intervention consists of a single round of screening including intraocular pressure and optical coherence tomography assessment of all adults ≥60 years old with enhanced linkage to care for participants meeting referral criteria. Four years after implementation of the intervention, masked outcome assessors conduct a repeat census to collect data on the primary outcome, visual acuity. Individuals with incident visual impairment receive a comprehensive ophthalmological examination to determine the cause of visual impairment. Outcomes are compared by treatment arm according to the originally assigned intervention. ETHICS AND DISSEMINATION: The trial has received ethical approval from the University of California San Francisco Institutional Review Board, Nepal Netra Jyoti Sangh and the Nepal Health Research Council. Results of this trial will be disseminated through publication in peer-reviewed journals and presentation at local and international meetings. TRIAL REGISTRATION NUMBER: NCT03752840.

Knowledge and Practices in the Diagnosis and Treatment of Corneal Infections by Nepalese Pharmaceutical Shop Workers.

Medical shops in Nepal are a main point of treatment for many diseases including ophthalmic conditions. We sought to evaluate pharmaceutical shop worker knowledge of corneal ulcers and abrasions. A pharmaceutical shop worker from each of 117 different pharmacies surrounding Bharatpur, Nepal, was presented four different eye photographs (i.e., corneal ulcer, corneal abrasion, conjunctivitis, and a normal eye) and asked about diagnosis and management. Of 117 participants, 86 (74%) identified conjunctivitis correctly but few were able to identify corneal abrasion (50/117; 43%) or corneal infection (47/117; 40%). When presented with an illustrated diagram of potential medications to dispense, 15 (13%) participants chose a topical medication containing a corticosteroid for the corneal abrasion and 25 (21%) did so for the corneal ulcer. The appropriate use of corticosteroids for external eye infections is an important topic for additional training, given the potential for these medications to worsen corneal abrasions and ulcers.

Childhood blindness and visual impairment in the Narayani Zone of Nepal: a population-based survey.

Purpose: To estimate the prevalence and causes of blindness (BL), severe visual impairment (SVI), moderate visual impairment (ModVI) and mild visual impairment (MildVI) in children in Narayani Zone, Nepal. Methods: In 2017, 100 population clusters within the Narayani Zone of Nepal were selected using RAAB software. Children (aged 0-15 years) suspected of having visual problems were identified using Key Informants (KIs) and school teachers and were referred for ophthalmologic examination. Eye care staff actively sought children who failed to present for examination. Causes of BL/SVI/ModVI/MildVI were categorized using standard World Health Organization definitions. Results: Of 76,588 children selected, 72,900 (95%) were screened. Of 2,158 children referred for examination, 1,322 were referred by teachers and 836 by KIs. A total of 1,617 (75%) children received a detailed examination, of whom 128 children [65 girls (51%)] mean age of 9.4 (± 4.1 years) were confirmed to have BL 7 (5.5%), SVI 16 (12.5%), ModVI 19 (15%) or MildVI 86 (67%). The combined prevalence of BL/SVI/ModVI/MildVI was 175/100,000 (95% CI 172-178/100,000); BL/SVI/ModVI was 55/100,000 (95% CI 53-57/100,000) and the combined BL/SVI estimate was 30/100,000 (95% CI 29-31/100,000). The leading causes of BL/SVI/MVI were refractive error 23 (55%) and whole globe disorders 5 (12%). Total avoidable causes were 31 (74%). Conclusion: The prevalence of BL/SVI/ModVI among children in Narayani Zone was moderate and included a high proportion of avoidable and treatable cases. Pediatric ophthalmic services need improvement, mainly refractive error correction in rural areas of Nepal.

The utility of serology for elimination surveillance of trachoma.

Robust surveillance methods are needed for trachoma control and recrudescence monitoring, but existing methods have limitations. Here, we analyse data from nine trachoma-endemic populations and provide operational thresholds for interpretation of serological data in low-transmission and post-elimination settings. Analyses with sero-catalytic and antibody acquisition models provide insights into transmission history within each population. To accurately estimate sero-conversion rates (SCR) for trachoma in populations with high-seroprevalence in adults, the model accounts for secondary exposure to Chlamydia trachomatis due to urogenital infection. We estimate the population half-life of sero-reversion for anti-Pgp3 antibodies to be 26 (95% credible interval (CrI): 21-34) years. We show SCRs below 0.015 (95% confidence interval (CI): 0.0-0.049) per year correspond to a prevalence of trachomatous inflammation-follicular below 5%, the current threshold for elimination of active trachoma as a public health problem. As global trachoma prevalence declines, we may need cross-sectional serological survey data to inform programmatic decisions.

Village-Integrated Eye Worker trial (VIEW): rationale and design of a cluster-randomised trial to prevent corneal ulcers in resource-limited settings.

INTRODUCTION: Corneal 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 ANALYSIS: The 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 DISSEMINATION: The 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 NUMBER: NCT01969786; Pre-results.

Prevalence of blindness and cataract surgical coverage in Narayani Zone, Nepal: a rapid assessment of avoidable blindness (RAAB) study.

BACKGROUND: The 1981 Nepal Blindness Survey first identified the Narayani Zone as one of the regions with the highest prevalence of blindness in the country. Subseuqently, a 2006 survey of the Rautahat District of the Narayani Zone found it to have the country's highest blindness prevalence. This study examines the impact on blind avoidable and treatable eye conditions in this region after significant increase in eye care services in the past decade. METHODS: The rapid assessment of avoidable blindness (RAAB) methodology was used with mobile data collection using the mRAAB smartphone app. Data analysis was done using the standard RAAB software. Based on the 2011 census, 100 clusters of 50 participants aged 50 years or older were randomly sampled proportional to population size. RESULTS: Of the 5000 participants surveyed, 4771 (95.4%) were examined. The age-adjusted and sex-adjusted prevalence of bilateral blindness, severe visual impairment (SVI) and moderate visual impairment (MVI) were 1.2% (95% CI 0.9% to 1.5%), 2.5% (95% CI 2.0% to -3.0%) and 13.2% (95% CI 11.8% to 14.5%), respectively. Cataract remains the primary cause of blindness and SVI despite cataract surgery coverage (CSC) of 91.5% for VA<3/60. Women still account for two-thirds of blindness. CONCLUSION: The prevalence of blindness in people over the age of 50 years has decreased from 6.9% in 2006 to 1.2%, a level in keeping with the national average; however, significant gender inequity persists. CSC has improved but continues to favour men.

Prevalence of Chlamydia trachomatis-Specific Antibodies before and after Mass Drug Administration for Trachoma in Community-Wide Surveys of Four Communities in Nepal.

The target end date for the global elimination of trachoma as a public health problem is 2020. As countries begin the process for submitting their dossier for the validation of elimination of trachoma as a public health problem, strategies for post-validation surveillance must be considered. Seroprevalence of antibodies against antigens from the causative bacteria Chlamydia trachomatis (Ct) in young children has been shown to reflect trachomatous inflammation-follicular (TF) rates in both endemic and previously endemic settings. However, none of these studies has directly compared age seroprevalence in the same communities before and after mass drug administration (MDA) for trachoma. Here we report a marked shift in age seroprevalence curves in four villages in Kapilvastu District, Nepal, before and after MDA. Clinical examinations were performed and blood was taken before (N = 659) and 5 years after (N = 646) MDA. Rates of TF decreased from 17.6% in ≤ 9-year-olds before MDA (N = 52) to 0% in ≤ 9-year-olds (N = 73) after MDA. Positive antibody responses to Ct in the entire population decreased from 82.1% pre-MDA to 35.8% post-MDA, whereas those among ≤ 9-year-olds decreased from 59.6% to 4.1%. These data show that the postintervention decrease in TF was reflected in a drop in anti-Ct antibody responses, suggesting that antibody responses could be useful indicators for post-validation surveillance.

Clinical and cost impact of a pediatric cataract follow-up program in western Nepal and adjacent northern Indian States.

BACKGROUND: High-quality, comprehensive pediatric cataract surgery programs have recently developed in low-income countries, but postoperative care has lagged. This study evaluated the post-cataract surgery follow-up program implemented in March 2011 at the Lumbini Eye Institute in Bhairahawa, Nepal, which included a full-time pediatric counselor and program director, a specific database, a tracking system, and cell phone reminders. METHODS: Baseline data for all cataract surgical patients <16 years of age were obtained retrospectively from hospital administrative records for 2009, the year prior to program introduction, and prospectively for all cases between March 1, 2011, and February 28, 2012. The statistical significance of the difference in the proportion of children attending follow-up in 2009 versus 2011-12 was calculated, and the overall program costs for 2011-12 was determined based on hospital records. RESULTS: In 2011-12, 334 children (248 males [74%]) underwent cataract surgery, including 89 Nepali (27%) and 245 Indian (73%) children. The proportion of boys was significantly higher in 2011-12 compared to 2009, but there were no differences in terms of age or distance to hospital. In 2009, 87%, 60%, and 37% attended their first, second, and third follow-up visits, respectively. Follow-up rates improved significantly to 96%, 81%, and 57%, respectively, after the implementation of the postoperative follow-up program. The 2011-12 program is estimated to have cost US$17,444. CONCLUSIONS: The new post-cataract surgery program resulted in improved follow-up at relatively little additional cost.

Zoonotic Chlamydiaceae species associated with trachoma, Nepal.

Trachoma is the leading cause of preventable blindness. Commercial assays do not discriminate among all Chlamydiaceae species that might be involved in trachoma. We investigated whether a commercial Micro-ArrayTube could discriminate Chlamydiaceae species in DNA extracted directly from conjunctival samples from 101 trachoma patients in Nepal. To evaluate organism viability, we extracted RNA, reverse transcribed it, and subjected it to quantitative real-time PCR. We found that 71 (70.3%) villagers were infected. ArrayTube sensitivity was 91.7% and specificity was 100% compared with that of real-time PCR. Concordance between genotypes detected by microarray and ompA genotyping was 100%. Species distribution included 54 (76%) single infections with Chlamydia trachomatis, C. psittaci, C. suis, or C. pecorum, and 17 (24%) mixed infections that includied C. pneumoniae. Ocular infections were caused by 5 Chlamydiaceae species. Additional studies of trachoma pathogenesis involving Chlamydiaceae species other than C. trachomatis and their zoonotic origins are needed.

Cataract surgical outcome and predictors of outcome in Lumbini Zone and Chitwan District of Nepal.

PURPOSE: To evaluate visual acuity outcome from cataract surgery based on a population-based survey among people aged 50 years and older in Lumbini Zone and Chitwan District of Nepal. METHODS: A randomly selected, population-based cross sectional epidemiological study of blindness, visual impairment and cataract surgical outcome was conducted. All subjects underwent a comprehensive ocular examination by an ophthalmic assistant, while people with visual impairment (visual acuity less than 6/18) after refraction and all cataract surgical cases underwent dilated fundus examination by an ophthalmologist. RESULTS: 5,916 people were enumerated and 5,141 (86.9%) examined. Among the 359 people who had cataract surgery, 485 eyes were included in the study. First eye surgery was before 2000 in 84 (23%), between 2000 and 2003 in 130 (36%), and after 2003 in 145 (41%). A presenting visual acuity ≥ 6/18 was achieved in 298 (61.4%) eyes (10 [17.8%] and 288 [67.1%] of aphakic and pseudophakic eyes, respectively) and best corrected vision ≥ 6/18 in 411 (84.7%) in all eyes. A presenting visual acuity less than 6/60 was found in 27 (6.3%) pseudophakic eyes. There was no significant difference in visual outcome based on age, sex, literacy, or institution. Uncorrected refractive error was the main cause (72.9%) of visual impairment in pseudophakic eyes. CONCLUSIONS: Visual acuity outcome after cataract surgery requires further improvement to meet World Health Organization standards, particularly improvement in preoperative biometry and refractive services. The same quality cataract surgery was provided in and equitably distributed throughout Lumbini Zone and Chitwan District independent of age, sex, literacy or location.

Characterization of humoral immune responses to chlamydial HSP60, CPAF, and CT795 in inflammatory and severe trachoma.

PURPOSE: Chlamydia trachomatis (Ct) remains the leading global cause of preventable blindness. There are limited data on humoral immune responses in trachoma. Evaluating these responses is important for understanding host-pathogen interactions and informing vaccine design. Antibodies to chlamydial heat shock protein 60 (cHSP60) have been associated with infertility and trachomatous scarring. Other proteins, including chlamydial protease-associated factor (CPAF) and a hypothetical protein unique to the family Chlamydiaceae, CT795, elicit strong immune responses in urogenital infections, but their role in trachomatous disease is unknown. METHODS: This study was conducted to expand on previous cHSP60 findings and evaluate the association of CPAF and CT795 antibodies with ocular Ct infection and disease. Clinical trachoma grading was performed, and conjunctival samples were obtained from individuals with trachomatous trichiasis (TT; one or more inturned eyelashes) or inflammatory trachoma without trichiasis and control subjects without disease, all of whom resided in trachoma-endemic regions of Nepal. Ct infection was determined using commercial PCR. IgG and IgA tear antibodies against cHSP60, CT795, and CPAF fusion proteins were measured by quantitative ELISA. RESULTS: Significantly higher IgG antibody levels were found against cHSP60, CPAF, and CT795 in the inflammatory cases compared with levels in the controls (P < 0.005 for all three). Ct infection was independently associated with IgG antibodies against all three immunogens in the inflammatory cases but not in the controls (P = 0.025, P = 0.03 and P = 0.017, respectively). Only IgG antibodies against CPAF were significantly elevated among the TT cases (P = 0.013). CONCLUSIONS: Among individuals with trachoma, IgG antibody responses to CPAF are likely to be both a marker and risk factor for inflammatory trachoma and severe trachomatous disease.

Identification of novel single nucleotide polymorphisms in inflammatory genes as risk factors associated with trachomatous trichiasis.

BACKGROUND: Trachoma is the leading preventable cause of global blindness. A balanced Th1/Th2/Th3 immune response is critical for resolving Chlamydia trachomatis infection, the primary cause of trachoma. Despite control programs that include mass antibiotic treatment, reinfection and recurrence of trachoma are common after treatment cessation. Furthermore, a subset of infected individuals develop inflammation and are at greater risk for developing the severe sequela of trachoma known as trachomatous trichiasis (TT). While there are a number of environmental and behavioral risk factors for trachoma, genetic factors that influence inflammation and TT risk remain ill defined. METHODOLOGY/FINDINGS: We identified single nucleotide polymorphisms (SNP) in 36 candidate inflammatory genes and interactions among these SNPs that likely play a role in the overall risk for TT. We conducted a case control study of 538 individuals of Tharu ethnicity residing in an endemic region of Nepal. Trachoma was graded according to World Health Organization guidelines. A linear array was used to genotype 51 biallelic SNPs in the 36 genes. Analyses were performed using logic regression modeling, which controls for multiple comparisons. We present, to our knowledge, the first significant association of TNFA (-308GA), LTA (252A), VCAM1 (-1594TC), and IL9 (T113M) polymorphisms, synergistic SNPs and risk of TT. TT risk decreased 5 times [odds ratio = 0.2 (95% confidence interval 0.11.-0.33), p = 0.001] with the combination of TNFA (-308A), LTA (252A), VCAM1 (-1594C), SCYA 11 (23T) minor allele, and the combination of TNFA (-308A), IL9 (113M), IL1B (5'UTR-T), and VCAM1 (-1594C). However, TT risk increased 13.5 times [odds ratio = 13.5 (95% confidence interval 3.3-22), p = 0.001] with the combination of TNFA (-308G), VDR (intron G), IL4R (50V), and ICAM1 (56M) minor allele. CONCLUSIONS: Evaluating genetic risk factors for trachoma will advance our understanding of disease pathogenesis, and should be considered in the context of designing global control programs.