A novel pathogenic missense ADAMTS17 variant that impairs secretion causes Weill-Marchesani Syndrome with variably dysmorphic hand features.

Weill-Marchesani syndrome (WMS) is a rare disorder displaying short stature, brachydactyly and joint stiffness, and ocular features including microspherophakia and ectopia lentis. Brachydactyly and joint stiffness appear less commonly in patients with WMS4 caused by pathogenic ADAMTS17 variants. Here, we investigated a large family with WMS from Newfoundland, Canada. These patients displayed core WMS features, but with proportionate hands that were clinically equivocal for brachydactyly. Whole exome sequencing and autozygosity mapping unveiled a novel pathogenic missense ADAMTS17 variant (c.3068 G > A, p.C1023Y). Sanger sequencing demonstrated variant co-segregation with WMS, and absence in 150 population matched controls. Given ADAMTS17 involvement, we performed deep phenotyping of the patients' hands. Anthropometrics applied to hand roentgenograms showed that metacarpophalangeal measurements of affected patients were smaller than expected for their age and sex, and when compared to their unaffected sibling. Furthermore, we found a possible sub-clinical phenotype involving markedly shortened metacarpophalangeal bones with intrafamilial variability. Transfection of the variant ADAMTS17 into HEK293T cells revealed significantly reduced secretion into the extracellular medium compared to wild-type. This work expands understanding of the molecular pathogenesis of ADAMTS17, clarifies the variable hand phenotype, and underscores a role for anthropometrics in characterizing sub-clinical brachydactyly in these patients.

Novel 25 kb Deletion of MERTK Causes Retinitis Pigmentosa With Severe Progression.

Purpose: Retinitis pigmentosa (RP) describes a complex group of inherited retinal dystrophies with almost 300 reported genes and loci. We investigated the genetic etiology of autosomal recessive RP (arRP) in a large kindred with 5 affected family members, who reside on the island of Newfoundland, Canada. Methods: Genetic linkage analysis was performed on 12 family members (Infinium HumanOmni2.5-8 BeadChip). Whole exome sequencing analysis (Illumina HiSeq) was performed on one affected individual. A custom pipeline was applied to call, annotate, and filter variants. FishingCNV was used to scan the exome for rare copy number variants (CNVs). Candidate CNVs subsequently were visualized from microarray data (CNVPartition v.3.1.6.). MERTK breakpoints were mapped and familial cosegregation was tested using Sanger Sequencing. Results: We found strong evidence of linkage to a locus on chromosome 2 (logarithm of the odds [LOD] 4.89 [θ = 0]), at an interval encompassing the MERTK gene. Whole exome sequencing did not uncover candidate point mutations in MERTK, or other known RP genes. Subsequently, CNV analysis of the exome data and breakpoint mapping revealed a 25,218 bp deletion of MERTK, encompassing exons 6 to 8, with breakpoints in introns 5 (chr2:112,725,292) and 8 (chr2:112,750,421). A 48 bp insertion sequence was buried within the breakpoint; 18 bps shared homology to MIR4435-2HG and LINC00152, and 30 bp mapped to MERTK. The deletion cosegregated with arRP in the family. Conclusions: This study describes the molecular and clinical characterization of an arRP family segregating a novel 25 kb deletion of MERTK. These findings may assist clinicians in providing a diagnosis for other unsolved RP cases.

Molecular genetics of achromatopsia in Newfoundland reveal genetic heterogeneity, founder effects and the first cases of Jalili syndrome in North America.

Achromatopsia (ACHM) is a severe retinal disorder characterized by an inability to distinguish colors, impaired visual acuity, photophobia and nystagmus. This rare autosomal recessive disorder of the cone photoreceptors is best known for its increased frequency due to founder effect in the Pingelapese population of the Pacific islands. Sixteen patients from Newfoundland, Canada were sequenced for mutations in the four known achromatopsia genes CNGA3, CNGB3, GNAT2, and PDE6C. The majority (n = 12) of patients were either homozygotes or compound heterozygotes for known achromatopsia alleles, two in CNGB3 (p.T383fsX and p.T296YfsX9) and three in CNGA3 (p.R283Q, p.R427C and p.L527R). Haplotype reconstruction showed that recurrent mutations p.T383fsX and p.L527R were due to a founder effect. Aggregate data from exome sequencing, segregation analysis and archived medical records support a rediagnosis of Jalili syndrome in affected siblings (n = 4) from Family 0094, which to our knowledge is the first family identified with Jalili Syndrome in North America.

Primary angle closure glaucoma in East Asia: educational attainment as a protective factor.

PURPOSE: To examine the relationship between education, other risk factors and incident primary angle closure glaucoma (PACG). METHOD: Glaucoma was excluded in a group of 4597 Mongolian volunteers in 1999. After 6 years, 1892 traced participants had full ophthalmic examination, dilated disc photographs and agreed to complete a questionnaire on socio-economic status. PACG was diagnosed using both structural and functional evidence from objective grading of paired disc photographs, follow up visual fields and clinical examination. Ophthalmic examination included van Herick grading, Goldmann intraocular pressure (IOP), gonioscopy, lens opacity grading and dilated disc examination. Central anterior chamber depth, lens thickness and axial length were recorded using ultrasound A scan mounted on a slitlamp. Education level was assessed using national census categories. RESULTS: PACG was diagnosed in 29 participants (6 year incidence = 1.53%, 95% confidence interval (CI) = 1.03-2.19%). In univariate analysis, risk factors for incident PACG included presence of refractive error, narrow van Herick grading of ≤15%, narrower average Shaffer grading, higher IOP, larger cup disc ratio and lower levels of education. In multivariate analysis, adjusted for age, sex, Shaffer grading, refractive error and IOP, those with no formal education were approximately 7 times more likely to develop PACG compared to those with >8 years of formal schooling (OR = 7.27, 95% CI = 2.73-19.38). CONCLUSIONS: People with lower levels of education have a higher risk of incident PACG, independent of age, sex, IOP and axial length.

A novel, non-stop mutation in FOXE3 causes an autosomal dominant form of variable anterior segment dysgenesis including Peters anomaly.

Anterior segment dysgenesis (ASD) is a spectrum of disorders that affect the anterior ocular chamber. Clinical studies on a Newfoundland family over the past 30 years show that 11 relatives have a variable ocular phenotype ranging from microcornea to Peters anomaly, segregating as an autosomal dominant trait. To determine the molecular etiology of the variable ASD in this family, we sequenced nine functional candidate genes and identified 44 variants. A point mutation in FOXE3, which codes for a transcription factor involved in the formation of the lens and surrounding structures, co-segregated with the variable ocular phenotype. This novel mutation (c.959G>T) substitutes the stop codon for a leucine residue, predicting the addition of 72 amino acids to the C-terminus of FOXE3. Two recent reports have also identified non-stop mutations in FOXE3 in patients with variable ocular phenotypes and predict an extended protein. Although FOXE3 is a lens-specific gene, we successfully isolated complementary DNA from lymphoblasts of an affected family member, and our sequencing results show that the c.959T allele is absent, suggesting that it may be degraded at the RNA level. Though preliminary, our results challenge the notion that an extended FOXE3 protein causes ASD, and instead suggests a mechanism of haploinsufficiency in the case of non-stop mutations. This study adds to several reports that suggest that autosomal-dominant mutations within FOXE3 cause ASD and has important clinical utility, especially for the diagnosis of mildly affected patients.

Randomised controlled trial of screening and prophylactic treatment to prevent primary angle closure glaucoma.

AIMS: To determine if screening with an ultrasound A-scan and prophylactic treatment of primary angle closure (PAC) with laser peripheral iridotomy (LPI) can reduce the incidence of primary angle closure glaucoma (PACG) in Mongolia. METHODS: A single-masked randomised controlled trial was initiated in 1999. 4725 volunteer Mongolian participants ≥ 50 years old from the capital Ulaanbaatar or the rural province of Bayankhongor were recruited, of which 128 were excluded with glaucoma. 4597 were randomly allocated to the control, no-screening arm or screening with ultrasound central anterior chamber depth (cACD), with the cut-off set at < 2.53 mm. 685 screen-positive participants were examined and angle closure was identified by gonioscopy in 160, of which 156 were treated with prophylactic LPI. Primary outcome of incident PACG was determined using both structural and functional evidence from objective grading of paired disc photographs from baseline and follow-up, objective grading of follow-up visual fields and clinical examination. RESULTS: Six years later, 801 (17.42%) participants were known to have died, and a further 2047 (53.92%) were traced and underwent full ophthalmic examination. In an intention to treat analysis using available data, PACG was diagnosed in 33 participants (1.61%, 95% CI 1.11% to 2.25%), of which 19 were in the screened group and 14 in the non-screened group (OR 1.29, 95% CI 0.65 to 2.60, p = 0.47), indicating no difference between groups. CONCLUSIONS: We were not able to identify a reduction in the 6 year incidence of PACG after screening with cACD < 2.53 mm and prophylactic treatment of PAC.

Visual function and quality of life among visually impaired and cataract operated adults. The Pakistan National Blindness and Visual Impairment Survey.

PURPOSE: To assess visual functioning and quality of life in a representative sample of normally sighted, visually impaired and cataract operated individuals aged >or= 30 years in Pakistan. METHODS: As part of the Pakistan National Blindness and Visual Impairment Survey, visual functioning (VF) and quality of life (QOL) questionnaires were administered to participants with presenting visual acuity less than 6/60 in either eye, aphakes/pseudophakes and a phakic sample with normal acuity (>or= 6/12 both eyes). RESULTS: Of 16,507 adults included in the survey, 2329 questionnaires were administered. There were strong correlations between visual acuity and VF/QOL. Mean VF and median QOL scores in normally sighted phakic individuals were 81.1 and 88.9, respectively, but were only 34.8 and 64.9 in blind unoperated individuals. In the cataract operated population overall mean VF and median QOL scores were 49.3 and 75.0. Both VF and QOL scores were lower in operated individuals than unoperated individuals (p < 0.001). Among operated individuals, rural dwelling and illiteracy were associated with lower VF and QOL scores (p all < 0.02). Although in multivariable analysis bilateral pseudophakes had similar VF scores to bilateral aphakes they had significantly better QOL scores (p = 0.001). CONCLUSIONS: Cataract surgery in Pakistan has not led to VF and QOL scores equivalent to those in unoperated individuals with the same levels of visual acuity. The higher proportion of intraocular lens surgery in recent years is likely to improve QOL following cataract surgery. Further focus is needed on rural and illiterate populations, to ensure that they achieve comparable VF/QOL outcomes following surgery.

The utility of symptoms in identification of primary angle-closure in a high-risk population.

OBJECTIVE: To examine the frequency of symptoms associated with primary angle closure in an East Asian population with high rates of disease. DESIGN: Population-based survey. PARTICIPANTS: One thousand adults from rural and urban provinces of Mongolia were examined. METHODS: A standard questionnaire was used to determine a history of symptoms of angle closure. All participants underwent applanation tonometry, gonioscopy, and slit-lamp examination by the same observer. The frequency of symptoms was compared between normal subjects and those in 3 high-risk or affected groups: gonioscopically confirmed occludable angles, peripheral anterior synechiae (PAS) detected on gonioscopy, and anterior chamber depth of less than 2.5 mm. MAIN OUTCOME MEASURES: The frequency of symptoms associated with primary angle closure. RESULTS: Symptoms of visual disturbance and ocular pain traditionally linked with angle closure were reported frequently by both normal and potentially affected people. Intermittent blurring of vision at night was the only common symptom of angle closure that was significantly more frequent in people with narrow angles and PAS (P = 0.004, 48.4% vs. 31.0% narrow angles; P = 0.001, 54.3% vs. 30.6% PAS), but not in those with shallow anterior chambers (P = 0.670, 38.3% vs. 30.9%). CONCLUSIONS: Direct questioning about symptoms associated with angle closure identified high rates of positive responses in both affected and unaffected groups. Although the rate of symptoms tended to be higher in affected people, none of these symptoms were specific enough to be considered useful as a diagnostic criterion.

Refractive errors in the adult pakistani population: the national blindness and visual impairment survey.

PURPOSE: To determine the prevalence of refractive error (RE) and spectacle wear and to explore the need for spectacle correction in adults (30 years or older) in Pakistan. METHODS: Multi-stage, cluster random sampling national survey. Each subject had their medical history taken, visual acuity measured, and underwent autorefraction, biometry and fundus examination. Those that presented with visual acuity of less than 6/12 in either eye underwent more detailed examination, including corrected distance visual acuity measurement (autorefraction results placed in a trial lens frame). Myopia was defined as a spherical equivalent of worse than -0.5D, hypermetropia as greater than +0.5D, and astigmatism as greater than 0.75D. Spectacle need (i.e., those that improved from unaided VA with spectacle correction) was determined along with the spectacle coverage, defined as the proportion of need that was met (by the participant's own spectacles). RESULTS: The crude prevalence of myopia, hypermetropia and astigmatism was 36.5%, 27.1%, and 37%, respectively. The prevalence of spectacle wear in phakic participants was 4.0%, significantly lower than for those who were pseudo/aphakic (41.7%). Just over a quarter (25.8%) of spectacle wearers presenting with visual impairment (< 6/12) were able to improve their vision when retested with their autorefraction prescription. The overall spectacle coverage (6/12 cutoff) was 15.1%. CONCLUSIONS: This survey provides the first reliable national estimates. RE services are not covering the majority of the population in need and the provision of spectacle correction, as a highly cost effective treatment for visual impairment, needs addressing within the country's national eye care program.

Lens opacities in adults in Pakistan: prevalence and risk factors.

PURPOSE: To investigate the prevalence and risk factors for lens opacity (LO) amongst a nationally representative sample of the adult population of Pakistan. METHODS: This national study of blindness and visual impairment (adults > or =30 years) used multistage, stratified, cluster random sampling. Grading of LO was conducted using the Mehra/Minassian classification system. LO, partly or wholly obscuring the red reflex, or previous cataract surgery were indicators of opacity. RESULTS: 16,402 (94.7%) adults were included in this analysis (study conducted 2002-2003). A total of 4,096 (standardized prevalence 20.9%, 95%CI: 20.3, 21.5%) adults were found to have LO. The highest prevalence of LO was found in Punjab province (22.2%), the lowest in Balochistan Province (18.0%). Significant positive associations were increasing age (multivariable odds ratio (OR) 3.2: 95%CI: 3.1, 3.4), hypertension (OR 1.2, 95%CI: 1.1, 1.3), history of diabetes (OR 2.6: 95%CI 2.0, 3.2) and smoking (OR 1.3: 95%CI: 1.1, 1.5). Higher body mass index (BMI) (OR 0.8: 95%CI 0.7, 0.9, heavy vs. normal BMI) and attendance to school (OR 0.6: 95%CI: 0.5, 0.8) were associated with lower risk of LO. Individuals in districts classified as hot were at significantly increased risk (OR 1.3: 95%CI: 1.1, 1.5), and those in wet districts (> 600 mm annual rainfall) had lower odds than individuals living in dry districts (OR 0.7: 95%CI: 0.6, 0.8). CONCLUSIONS: Almost a fifth of the adult population had LO. Significant positive associations were age, smoking status, hypertension, diabetes, and increased deprivation level. Protective factors included high BMI and educational achievement. The climatic associations offer novel hypothesis for further research into cataractogenesis.

Outcomes of cataract surgery in Pakistan: results from The Pakistan National Blindness and Visual Impairment Survey.

AIM: To evaluate the outcomes of cataract surgery in Pakistan. METHODS: Cross-sectional, nationally representative sample of 16 507 adults (aged >or=30 years). Each underwent interview, logarithm of the minimum angle of resolution visual acuity (VA), autorefraction, examination of optic disc. Those with <6/12 VA on presentation underwent best-corrected VA and dilated biomicroscopic ocular examination. RESULTS: 1317 subjects (633 men) had undergone surgery in one or both eyes. Of the 1788 operated eyes, 1099 (61%) had undergone intracapsular cataract extraction (ICCE) and 607 (34%) extracapsular surgery with an intraocular lens (ECCE+IOL). Presenting VA: 275 (15.4%) eyes: 6/12 or better; 253 (14.1) <6/12 >or=6/18; 632 (35.3%) 6/18 to 6/60; 85 (4.8%): 6/60 to 3/60; 528 (29.5%): <3/60. With "best" refractive correction, these values were: 563 (31.5%), 332 (18.6%), 492 (27.5%), 61 (3.4%), 334 (18.7%), respectively. Of the 1498 eyes with VA or=4 years before the survey. CONCLUSION: Almost a third of cataract operations result in a presenting VA of <6/60, which could be halved by appropriate refractive correction. This study highlights the need for an improvement in quality of surgery with a more balanced distribution of services.

Prevalence of blindness and visual impairment in Pakistan: the Pakistan National Blindness and Visual Impairment Survey.

PURPOSE: To determine the prevalence of blindness and visual impairment in adults aged 30 years and older in Pakistan and to assess socio-demographic risk factors. METHODS: Multistage, stratified (rural/urban), cluster random sampling, with probability proportional-to-size procedures, was used to select a nationally representative, cross-sectional sample of adults 30 years of age or older. Each subject was interviewed; had visual acuity measured (logMAR; logarithm of the minimum angle of resolution); and underwent autorefraction, biometry, and fundus-optic disc examination. Those with less than 6/12 acuity in either eye underwent a detailed ophthalmic examination, including corrected distance visual acuity measurement and dilated ophthalmoscopy. RESULTS: A nationally representative sample of 16,507 adults (95.5% of those enumerated) was examined. The age- and gender-standardized prevalence of blindness was 2.7% (95% confidence interval [CI], 2.4%-2.9%). It has been estimated that there are 1,140,000 (962,000-1,330,000) blind adults in Pakistan (2003 statistics). Blindness prevalence varied throughout the country, being highest in the provinces of Punjab and Baluchistan and lowest in the North West Frontier Province. Rural areas had a higher prevalence of blindness than did urban areas (3.8% vs. 2.5%, P < 0.001). Increasing age and being female were significantly associated with presenting visual acuity of <6/60 (odds ratio [OR], 2.5; 95% CI, 2.3-2.7 and 1.3; 95% CI, 1.1-1.5, respectively). Educational status was also associated with presenting visual acuity of <6/60. Subjects who had attended primary school were 60% (P < 0.001) less likely to have acuity of <6/60 than were subjects who had never been to school. CONCLUSIONS: This comprehensive survey provides reliable estimates of the prevalence of visual impairment and blindness in Pakistan. A significant excess of visual impairment was found among the elderly and the uneducated. After adjustment for age differences, women were found to have a significant excess of severe visual impairment and blindness. Regional variations in the prevalence of blindness were also identified.

Detection of narrow angles and established angle closure in Chinese residents of Singapore: potential screening tests.

PURPOSE: To assess the performance of peripheral and central anterior chamber depth (ACD) measurements, and autorefraction, in identifying Chinese people with occludable drainage angles or established primary angle closure. DESIGN: Population-based cross-sectional analysis. METHODS: Subjects aged 40 years and older were drawn from a representative sample of Chinese Singaporean residents. Limbal chamber depth (LCD) was estimated and central ACD was measured using optical pachymetry and ultrasound. An autorefraction was taken for all subjects. Angle width and the presence of peripheral anterior synechiae were determined by gonioscopy. Receiver operating characteristic curves were generated to show the performance of these tests in detecting occludable angles. RESULTS: A total of 1090 subjects were examined. The prevalence of occludable angles was 6.5%. LCD measurement performed best in detecting occludable angles (area under the curve [AUC] 0.904, 95% confidence interval [CI] 0.870, 0.937). Optical pachymetry and ultrasound measurement of ACD performed less well (AUC 0.859 and 0.810, respectively), and autorefraction performed poorly in detecting occludable angles (AUC 0.632). LCD also gave the best performance in detecting primary angle closure (AUC 0.782, 95% CI 0.727, 0.837). CONCLUSIONS: Limbal LCD estimation outperforms other methods of measuring ACD as a screening tool for the detection of occludable drainage angles in the Chinese population of Singapore.

The long-term natural history of trachomatous trichiasis in the Gambia.

PURPOSE: Trachoma is the leading infectious cause of blindness. However, there are few data on the natural history of trachomatous trichiasis to guide program planning or that investigate its pathogenesis. METHODS: A cohort of Gambians with trichiasis in one or both eyes who had declined surgery was observed. Clinical examinations were performed at baseline and 4 years later. Conjunctival swab samples were collected for Chlamydia trachomatis PCR and bacteriology. RESULTS: One hundred fifty-four people were examined at baseline and 4 years later (241 nonsurgical eyes). At baseline 124 (52%) eyes had major trichiasis (5+ lashes), 75 (31%) minor trichiasis (1-4 lashes), and 42 (17%) no trichiasis. By 4 years, trichiasis had developed in 12 (29%) of 42 previously unaffected eyes. Minor trichiasis progressed to major in 28 (37%) of 75 eyes. New corneal opacification more commonly developed in eyes that had major (10%) compared to minor (5%) trichiasis at baseline. Bacterial infection was common (23%), becoming more frequent with increasing trichiasis. C. trachomatis infection was rare (1%). Conjunctival inflammation was common (29%) and was associated with progressive trichiasis and corneal opacification. CONCLUSIONS: Trichiasis progressed in the long-term in this environment, despite a low prevalence of C. trachomatis. Blinding corneal opacification develops infrequently, unless major trichiasis is present. Epilation and early surgery need to be formally compared for the management of minor trichiasis. The pathologic correlates and promoters of conjunctival inflammation need to be investigated.

The Pakistan national blindness and visual impairment survey--research design, eye examination methodology and results of the pilot study.

PURPOSE: To establish age- and sex-specific prevalence rates and causes of blindness and low vision in children aged 10 to 15 years and adults aged 30 years and older in Pakistan. METHODS: Multi-stage, stratified (rural/urban), cluster random sampling, with probability proportional-to-size procedures, was utilised to select a cross-sectional, nationally representative sample of adults (16,600 subjects) and children (6,000 subjects). Each subject underwent: interview, visual acuity (logMAR), autorefraction and optic disc examination. Those that saw < 6/12 in either eye underwent corrected visual acuity and dilated posterior segment examination. RESULTS: The results of a pilot survey are reported in this paper. In the two rural pilot sites, 159 subjects (including 47 children) were examined; 50% were male. Thirty seven adults (23.3%) but no children saw worse than 6/12 in either eye. Two subjects were blind (corrected visual acuity) in the better eye, and 11 were visually impaired. Refractive error was the main cause (in 22 eyes (39% of the total of 56 eyes)) of < 6/12 visual acuity, followed by cataract (12 eyes), uncorrected aphakia (6 eyes) and age-related macular disease (3 eyes). CONCLUSIONS: The pilot survey demonstrated that the proposed examination process for the main survey is feasible. Particular strengths of this survey include the use of logMAR visual acuity testing and autorefraction of all subjects, a dilated posterior segment examination, and the use of a 'less than 6/12' threshold for further examination. This lower threshold addresses the burden of refractive error, which, with cataract, are two of the diseases specifically targeted by Vision 2020.

Anterior chamber depth and the risk of primary angle closure in 2 East Asian populations.

OBJECTIVE: To evaluate the risk of peripheral anterior synechiae (PAS) and glaucomatous optic neuropathy attributable to primary angle closure at varying anterior chamber depths (ACDs) in two East Asian populations. METHODS: Participants 40 years and older were from 2 population-based glaucoma surveys in Mongolia and Singapore. Central ACD was measured by optical pachymetry. Presence of PAS was determined by dynamic gonioscopy. Cases with secondary PAS were excluded. Glaucomatous optic neuropathy was diagnosed in subjects with structural and functional evidence of glaucoma. RESULTS: A total of 2032 subjects, consisting of 942 Mongolians and 1090 Chinese Singaporeans, were included in this study. A logistic model of the relationship between ACD and PAS among Singaporeans showed a consistent, incremental increase in PAS across the entire range of ACD. In deeper anterior chambers the rate of PAS exceeded that seen in Mongolians. In Mongolians, there was a clear threshold for ACD (2.4 mm) at or above which PAS were very uncommon. With ACD less than 2.4 mm, the rate of PAS rose rapidly to overtake that seen in Singaporeans. CONCLUSIONS: Shallow anterior chambers are a significant risk factor for angle closure in East Asians, although the nature of the association is specific to the individual population. There was a trend toward higher rates of glaucomatous optic neuropathy in people with the shallowest anterior chambers.

Re-emergence of Chlamydia trachomatis infection after mass antibiotic treatment of a trachoma-endemic Gambian community: a longitudinal study.

BACKGROUND: Community-wide mass antibiotic treatment is a central component of trachoma control. The optimum frequency and duration of treatment are unknown. We measured the effect of mass treatment on the conjunctival burden of Chlamydia trachomatis in a Gambian community with low to medium trachoma prevalence and investigated the rate, route, and determinants of re-emergent infection. METHODS: 14 trachoma-endemic villages in rural Gambia were examined and conjunctival swabs obtained at baseline, 2, 6, 12, and 17 months. Mass antibiotic treatment with azithromycin was given to the community at baseline. C trachomatis was detected by qualitative PCR and individual infection load then estimated by real-time quantitative PCR. FINDINGS: C trachomatis was detected in 95 (7%) of 1319 individuals at baseline. Treatment coverage was 83% of the population (1328 of 1595 people). The effect of mass treatment was heterogeneous. In 12 villages all baseline infections (34 [3%] of 1062 individuals) resolved, and prevalence (three [0.3%]) and infection load remained low throughout the study. Two villages (baseline infection: 61 [24%] of 257 individuals) had increased infection 2 months after treatment (74 [30%]), after extensive contact with other untreated communities. Subsequently, this value reduced to less than half of that before treatment (25 [11%]). INTERPRETATION: Mass antibiotic treatment generally results in effective, longlasting control of C trachomatis in this environment. For low prevalence regions, one treatment episode might be sufficient. Infection can be reintroduced through contact with untreated populations. Communities need to be monitored for treatment failure and control measures implemented over wide geographical areas.

Prevalence of refractive error in Bangladeshi adults: results of the National Blindness and Low Vision Survey of Bangladesh.

PURPOSE: To determine the prevalence of refractive errors and to investigate factors associated with refractive error in adults 30 years of age and older in Bangladesh. DESIGN: Cross-sectional study. PARTICIPANTS: A nationally representative sample of 12 782 adults 30 years of age and older. METHODS: The sample of subjects was selected based on multistage, cluster random sampling with probability-proportional-to-size procedures. The examination protocol consisted of an interview that included measures of literacy, education, occupation, and refractive correction. Visual acuity testing (logarithm of the minimum angle of resolution [logMAR]), automated refraction, and optic disc examination were performed for all subjects. Subjects with <6/12 (0.3 logMAR) acuity in either eye were graded additionally for cataract and underwent a dilated fundal examination. Subjects for whom no refractive error was recorded (312 subjects; 2.7%) or who had undergone cataract surgery (123 subjects; 1.1%) were excluded from the analysis. MAIN OUTCOME MEASURES: Refractive error and socioeconomic variables (literacy, education, occupation). RESULTS: Eleven thousand six hundred twenty-four subjects were examined (90.9% response rate; mean age+/-standard deviation, 44+/-12.6 years). Five thousand four hundred eighty-nine subjects (49.1%) were men and 5700 subjects (50.9%) were women. Mean spherical equivalent was -0.19 diopters (D; +/-1.50 D). Six thousand four hundred twelve subjects (57.3%) were emmetropic, 2469 (22.1%) were myopic (<-0.5 D), and 2308 (20.6%) were hypermetropic (>+0.5 D). Two hundred six subjects (1.8%) were highly myopic (<-5 D). Myopia was more common in men (26.3%) than in women (21.0%), whereas hyperopia was more common in women (27.4%) than in men (15.8%). Overall, myopia increased with age (17.5% of those aged 30-39 years were myopic, compared with 65.5% of those age 70 years and older). A subanalysis of subjects without cataract showed increasing hyperopia with age and an association between myopia and higher education. Myopia was more common among the employed than in unemployed subjects. Astigmatism (>0.5 D), present in 3625 subjects (32.4%), was more common among women, illiterate subjects, and unschooled subjects. Against-the-rule astigmatism was more common (58.7%) than oblique astigmatism (29.3%), which was more common than with-the-rule (WTR) astigmatism (12.1%). Against-the-rule astigmatism and oblique astigmatism increased with age, unlike WTR astigmatism. Of 830 (7.5%) subjects, women were more commonly anisometropic (>1.0 D). Anisometropia increased with age. CONCLUSIONS: Refractive error data are described for a country and region that previously have lacked population-based data. Prevalence and factors associated with refractive error are presented, with a detailed comparison with other population-based surveys regionally and internationally.

Ocular biometry and refraction in Mongolian adults.

OBJECTIVE: To describe the variation in ocular biometry and its association with refraction in adult Mongolians. METHODS: The study included 1800 subjects, aged 40 years or more, who were selected in two Mongolian provinces-Hövsgöl and Omnögobi-to participate in this population survey. Axial length (AL) and its components, as well as noncycloplegic autorefraction and corneal power (CP), were measured. RESULTS: Of those selected, 1617 subjects (90.0%) were examined. Mean +/- SD of AL was 23.13 +/- 1.15 mm. There was a very small but significant increase in mean AL with age (0.05 mm per decade, P = 0.03). Autorefraction was performed on 620 of 675 subjects of those examined in Omnögobi. The age and gender standardized prevalences of myopia (< -0.5 D), emmetropia, hyperopia (> +0.5 D), astigmatism (< -0.5 D of cylinder) and anisometropia (>1.0 D difference between eyes) were 17.2%, 49.9%, 32.9%, 40.9%, and 10.7%, respectively. Prevalence of myopia showed no clear trend with increasing age, whereas hyperopia, astigmatism, and anisometropia all increased monotonically. Multiple regression models revealed that AL (P < 0.001) and VCD (P < 0.001) were the strongest determinants of refractive error. CONCLUSIONS: In this cross-sectional study of adult Mongolians, a much lower prevalence of myopia was found than in other East Asian populations studied to date. The mean AL differed little between age groups, in marked contrast to data on Chinese people.

Correction of refractive error in the adult population of Bangladesh: meeting the unmet need.

PURPOSE: To assess the extent of uncorrected refractive error and associated factors in Bangladesh and to suggest ways in which this need can be met. METHODS: A nationally representative sample of 12,782 adults (>/= 30 years of age) was selected. Of them, 11,624 subjects underwent a demographic interview, visual acuity (logarithm of the minimum angle of resolution [logMAR]) measurement, automated refraction, and optic disc examination. Subjects with visual acuity less than 6/12 in either eye also had a corrected refraction measurement, cataract grading, and dilated retinal examination. RESULTS: Of the 11,624 subjects examined, 2,469 (22.1%) were myopes (less than -0.5 D) and 2,308 (20.6%) hyperopes (more than +0.5 D). The spectacle coverage percentage, calculated as [met need/(met need + unmet need) x 100%] was 25.2% and 40.5%, using 6/12 and 6/18 visual acuity cutoffs, respectively, and was higher in men and urban inhabitants. Older subjects and the literate and more highly educated were more likely to wear spectacles; however, most spectacle wearers (81%) had inadequate correction. Of the 1142 subjects who would benefit from spectacles, 827 (72.4%) would be suitable for off-the-shelf spectacles. Subjects without spectacles with less than 6/12 in the better eye (n = 835), would achieve 6/12 or better with correction (unmet need). Extrapolation to the national population yields an estimate that 1.5 million (6.7%) adult men and 1.8 million (9.2%) women have an unmet need for refractive correction. CONCLUSIONS: In Bangladesh, there is low spectacle coverage with a large unmet need. This survey identified risk groups, in particular women and those living in rural areas. This description of the availability of refractive services suggests areas for improvement (e.g., off-the-shelf spectacles) that may enable Bangladesh to achieve the goals of the World Health Organization's Vision 2020 initiative.