Exceptionally Low Prevalence of Refractive Error and Visual Impairment in Schoolchildren from Lao People's Democratic Republic

Exceptionally Low Prevalence of Refractive Error and Visual Impairment in Schoolchildren from Lao People's Democratic Republic

Exceptionally Low Prevalence of Refractive Error and Visual Impairment in Schoolchildren from Lao People’s Democratic Republic Robert J. Casson, DPhil...

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Exceptionally Low Prevalence of Refractive Error and Visual Impairment in Schoolchildren from Lao People’s Democratic Republic Robert J. Casson, DPhil, FRANZCO,1 Shyalle Kahawita, MB, BS,1 Aimee Kong, BSc(Optom),1 James Muecke, FRANZCO,1 Siphetthavong Sisaleumsak, MD,2 Vithoune Visonnavong, MD2 Objective: Vientiane Province is an urbanizing region in Southeast Asia. We aimed to determine the prevalence of refractive error and visual impairment in primary school–aged children in this region. Design: Prospective, cross-sectional survey. Participants: A total of 2899 schoolchildren from Vientiane Province, Lao People’s Democratic Republic (Lao PDR). Methods: Ten districts from Vientiane were randomly selected and 2 primary schools were randomly selected from each district. All children aged 6 to 11 years at selected schools were eligible to participate. The examination included visual acuity (VA) testing, cycloplegic retinoscopy with subjective refinement if indicated, ocular motility testing, and anterior segment and fundus examinations in visually impaired children. Main Outcome Measures: Cycloplegic refraction and VA. Results: There was an estimated total of 3330 children who were eligible to participate, and data were recorded from 2899 (87%) of these children. Complete refractive data were available on 2842 children (85% of eligible population). The mean spherical equivalent (SE) in the right eyes was ⫹0.60 diopter (D) (95% confidence interval [CI], 0.49 – 0.72), and the mean SE in the left eyes was ⫹0.59 (95% CI, 0.50 – 0.68). The prevalence of hyperopia was 2.8% (95% CI, 1.9 –3.7; 88 subjects), and the prevalence of myopia was 0.8% (95% CI, 0.3–1.4; 24 subjects). The majority of children (98%; 95% CI, 97.0 –99.0) had normal unaided binocular VA (at least 20/32 in their better eye). The overall prevalence of any visual impairment (presenting VA ⬍20/32 in the better eye) was 1.9% (95% CI, 1.0 –2.9; 55 subjects). In multivariate logistic regression analysis, age (P ⫽ 0.001) was a significant predictor, and female gender (P ⫽ 0.08) and Yao ethnicity (P ⫽ 0.09) were borderline significant predictors of the presence of any visual impairment. Conclusions: Visual impairment is not a public health concern in this primary school–aged population; however, visually impaired children in the community were not studied. From this baseline, future surveys could determine the effect of increasing urbanization on myopia prevalence in this population. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Ophthalmology 2012;119:2021–2027 © 2012 by the American Academy of Ophthalmology.

Uncorrected refractive error is the leading cause of visual impairment worldwide1 and in school-aged children in both industrialized and developing regions.2–12 Cross-sectional studies report wide variations in the prevalence of myopia among different populations.3– 8,12,13 The prevalence of myopia in certain regions, particularly urban East Asian regions, is high.14 Existing evidence, albeit limited, indicates that the prevalence of myopia has dramatically increased in certain urbanized Asian regions, particularly Singapore14 and Taiwan,16 but not in Australia,17 and only weakly in the United States.18 Various hypotheses currently compete to explain the wide variation in school-age myopia prevalence, including near work during childhood,19 –21 outdoor activity,22–24 ur© 2012 by the American Academy of Ophthalmology Published by Elsevier Inc.

ban versus rural living,2,4,5,7,25 and population density.26 A predisposition to myopia seems to be particularly strong in those of Han Chinese descent, but to date, there is no convergence of evidence toward a unifying explanation, and the gene/environment interactions that underpin the development of school-age myopia remain poorly understood.27,28 Myopia has been reported to affect approximately 37% of 13-year-old children living in rural southern China.5 Whether the trend to increasing rates of myopia is occurring in other less-developed parts of neighboring East Asia remains largely unknown. Lao People’s Democratic Republic (Lao PDR) is a landlocked country in Southeast Asia. The Tai people are the major ethnic group. Historical, genetic, and linguistic eviISSN 0161-6420/12/$–see front matter http://dx.doi.org/10.1016/j.ophtha.2012.03.049

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Ophthalmology Volume 119, Number 10, October 2012 dence indicate that they migrated relatively recently into Southeast Asia from southern China.29,30 Approximately 30% of the population remains below the poverty line, and Lao PDR remains a relatively poor country with developing infrastructure and education programs. However, Lao PDR has one of the world’s highest current rates of urbanization (the projected average rate of change of the size of the urban population from 2010 to 2015).31 Its capital and major city is Vientiane, located within Vientiane Province. The prevalence of refractive error in schoolchildren in Lao PDR is currently unknown, and although the prevalence of myopia in this population may illuminate theories of myopigenesis, the study was primarily motivated by public health interests. Local ophthalmologists (S.S. and V.V.) at the Vientiane Ophthalmology Centre initiated the current study to obtain an understanding of the prevalence of refractive error in Lao schoolchildren. An understanding of the prevalence of refractive error in children in this region is important for the planning of evidence-based program delivery and the allocation of limited health care resources. If childhood refractive error was prevalent it could potentially be relatively easily managed, and if it were not prevalent then it would not be a public health issue. Negrel et al32 devised a standardized procedure, the Refractive Error Study in Children (RESC) protocol, for the collection of refractive error data in school-aged children, which was initially trialed in Nepal,9 Chile,6 and the Shunyi District, China.12 Other sites where RESC-type studies have been undertaken include rural and urban India;2,7 Malaysia;3 Guangzhou Province, China;5 and South Africa.8 In the current study, we aimed to determine the prevalence of refractive error and visual impairment in Lao children from Vientiane province using the RESC standardized protocol and definitions on a school-based sample.

Materials and Methods Study Design The study was designed as a cross-sectional, school-based survey of refractive error and visual impairment in children aged 6 to 11 years from Vientiane Province, Lao PDR.

Lao Schooling System Primary school is compulsory and free in Lao PDR, officially commences at age 6 years, and consists of 5 grades, but repetition of a grade, particularly grade 1 is common; thus, 11-year-old children comprise a considerable proportion of those still at primary school. Many rural schools do not offer the 5 grades (incomplete schools), but all schools in Vientiane Province are complete. Data from the Ministry of Education about school sizes were available, but the age distribution of the students was unknown. We estimated that approximately 15% of the children at primary school are aged 12 years or more. Textbooks are relatively scarce in all schools, and most reading is from the blackboard.

Definitions For comparability of the results with those of RESC studies, the following definitions for refractive error were used:

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Myopia was defined as spherical equivalent (SE) of ⫺0.5 diopters (D) or less. Children with myopia in 1 or both eyes were classified as myopic. Hyperopia was defined as SE of ⫹2.0 D or more. Children with hyperopia in 1 or both eyes were classified as hyperopic. Astigmatism was defined as cylindrical refraction of 0.75 D or more in at least 1 eye, recorded with a negative sign. Refractive error was defined as myopia or hyperopia in either eye. Visual impairment was categorized according to the current World Health Organization definitions of visual impairment and was consistent with other RESC studies (Table 1 available at http://aaojournal.org).

Sample Selection The sampling frame was all 6- to 11-year-old schoolchildren in Vientiane Province, Lao PDR. On the basis of data from recent surveys in rural southern China4 and Malaysia,3 the sample size was calculated to estimate an anticipated 16% prevalence of refractive error in 9-year-olds within a precision of 25%, with a 95% confidence interval (CI). The sample size requirement with simple random sampling was 324 (per year of age) assuming a binomial distribution of the dichotomous variable (refractive error: present or absent). With no oversampling at any particular age, and assuming an approximate uniform age distribution across the 6-year age interval, a total of 1944 children were required. However, after adjusting for an anticipated 15% absenteeism and nonparticipation rate, and allowing for an arbitrary 25% increase in sample size due to design effect, the sample size requirement increased to 2794 children. All children aged 6 to 11 years attending school were eligible to participate. By using data on school population sizes from the Ministry of Education, we estimated that approximately 20 schools would need to be surveyed. There are 13 geographic districts in Vientiane. From a list of the districts and schools, simple random sampling without replacement by pseudorandom number generation was used to select 10 districts; second-stage random sampling was used to select 2 schools from each district. The total number of eligible 6- to 11-year-old schoolchildren selected by this cluster sampling approach was estimated using school population information from the Ministry of Education.

Data Collection Examinations were performed by 2 teams, comprising 1 ophthalmologist, 2 optometrists, 1 orthoptist, and 1 ophthalmic nurse all experienced with childhood vision testing and refraction. All team members underwent training in the RESC protocol, equipment use, measurement methods, and data-collection forms. The examinations took place over a 4-week period in October–November 2009 at stations set up in each school. The testing and examination protocol included visual acuity (VA) measurements, cycloplegic retinoscopy, subjective refraction, ocular motility, and cover testing. The VA was measured at 4 m using a logarithm of the minimum angle of resolution chart with tumbling-E optotypes. The children were requested to indicate the direction of the E optotype by pointing with their hand or by calling the direction. The children were carefully observed to ensure that they were not squinting (using a pinhole effect). If a child presented with glasses, the power of the lenses was measured using an auto-lensometer (LM-970; Nidek Corporation, Tokyo, Japan). Acuity was measured with and without spectacle correction. Cycloplegia was induced with 2 drops of cyclopentolate 1% administered 5 minutes apart to each eye. After 20 minutes, if a

Casson et al 䡠 Refractive Error in Lao Schoolchildren pupillary light reflex was still present, a third drop was administered. The light reflex and pupil dilation were checked after an additional 15 minutes. Dilating and light reflex status were recorded between 40 and 60 minutes after the first drop. Cycloplegia was considered complete if the pupil dilated to 6 mm or greater and a light reflex was absent. Cycloplegic refraction was performed by an experienced optometrist using streak retinoscopy on all subjects and refined with subjective refraction on eyes with an uncorrected VA of ⬍20/32 (6/9.5). An experienced observer performed a cover test at 0.5 and 4.0 m, using the corneal light reflex to quantify the degree of tropia. For quality assurance, every tenth child had his or her VA and refraction measured again by a second experienced independent examiner. In keeping with other RESC studies, those eyes with a logarithm of the minimum angle of resolution VA ⬎0.2, 20/32 (6/9.5), were assigned a principal cause of visual impairment by the team ophthalmologist, based on the findings from the refraction, cover test, handheld slit-lamp, and indirect ophthalmoscopic examinations. The principal cause of visual impairment was categorized on World Health Organization datasheets. Amblyopia was considered the cause of impairment in eyes with best-corrected acuity ⱕ0.2, 20/32 (6/9.5), and no apparent organic lesion if 1 or more of the following criteria were met: (1) esotropia, exotropia, or vertical tropia at 4 m fixation or exotropia or vertical tropia at 0.5 m; (2) anisometropia of ⱖ2.00 D; or (3) bilateral ametropia of at least ⫹6.00 D.

Data Analysis All data were recorded on a standardized reporting form, and data were entered into an electronic database. The data were analyzed using a commercially available statistical package (STATA 10.0; StataCorp LP, College Station, TX). The 95% CIs of the proportion estimates and the standard errors of the regression analyses coefficients were calculated taking into account the 2-stage cluster survey design.

Ethical Considerations The study had approval from the Royal Adelaide Hospital Human Ethics Committee. It had institutional approval from the Vientiane Ophthalmology Centre, but there are no ethics committees in Laos to provide local endorsement. We were aware that the study was being conducted on a vulnerable population, but we believe that the study was conducted in adherence with the humanistic tenets of the Declaration of Helsinki. The risk/benefit ratio to the study population and the potential for direct benefit to the participating children and the target population were high. Selected schools were invited to participate and under no coercion of any form. The principal of each school approved participation. The nature of the study was explained to each child in their native language, and they were asked if they would like to take part.

Results Participation Rate There was an estimated total of 3330 children who were eligible to participate, and data were recorded from 2899 (87%) of these children (100% of those attending school). Data were recorded from an additional 246 children who were aged 12 years or more, but were not included in the analyses. No data were recorded about the absentee children.

Missing Data No age data were missing. Gender data were missing from 7 records, and ethnicity data were missing from 28 records. Visual acuity data were missing from 25 right eyes and 30 left eyes; thus, binocular visual impairment data were available on 2869 children. The VA in 3 children was unrecorded because of the children’s cognitive inability to perform the testing. The remainder of the missing acuity data was unexplained, but appeared to be random datasheet entry oversights. There were missing refraction data from 45 right eyes and 57 left eyes. Of those right eyes with missing acuity data, only 4 had missing refraction data, and of the remainder, none had a refractive error. Of those left eyes with missing acuity data, only 3 had missing refractive data and none had a refractive error. No demographic data on the absentee children were recorded. Given that the proportion of the sample with missing data was small, eyes with missing acuity or refractive data were handled as “list-wise” deletions and omitted from the analyses. Thus, after allowing for missing data, 2842 children comprised the sample size for the analyses.

Demographics Table 2 shows the age and gender distribution of the sample; 11-year-old children were relatively underrepresented. There were 4 ethnic groups represented: the Lao Loum (the majority ethnic group [“lowland” people]); the Lao Theung (“midland” people); and the Lao Soung (“highland” people), including the Yao people, comprising 68.2%, 12.2%, 18.4%, 1.2%, respectively.

Refractive Error Complete refractive data were available on 2842 children. The mean SE in the right eyes was ⫹0.60 D (95% CI, 0.49 – 0.72), and the mean SE in the left eyes was ⫹0.59 (95% CI, 0.50 – 0.68). The concordance correlation coefficients for the VA measurements and the cycloplegic refractions were high (0.94 and 0.88, respectively). There was a small but highly significant negative correlation between age and SE. For each year of increasing age, the right SE decreased by 0.057 D (P⬍0.001), and the left SE decreased by 0.06 D (P⬍0.001). Figure 1 shows box plots for the SE of the right and left eyes by age. The overall prevalence of refractive error was 3.6% (95% CI, 2.6 – 4.7; 112 subjects). The design effect for this estimate was 1.51 (the proportional increase in the standard error due to the cluster design compared with simple random sampling).

Table 2. Age and Gender Distribution of Participants Age and Gender* Distribution

Age (yrs) 6 7 8 9 10 11 Total

Male

Female

Total

265 216 223 311 252 178 1445

235 249 225 283 270 184 1446

500 465 448 594 522 362 2891

*Eight subjects had missing gender records.

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Figure 1. Boxplot of refractive error by age. Only right eye data are shown. The upper hinge of the box indicates the 75th percentile of the data set, and the lower hinge indicates the 25th percentile; whiskers extend to a maximum of 1.5 times the interquartile range. Outliers beyond ⫾3.0 diopters (D) have been excluded.

The overall prevalence of hyperopia was 2.8% (95% CI, 1.9 – 3.7; 88 subjects). The prevalence of hyperopia was 3.1% (95% CI, 1.7–5.1) in the 6-year-old children and 1.1% (95% CI, 0.3–2.9) in the 11-year-old children. The overall prevalence of myopia was 0.8% (95% CI, 0.3–1.4; 24 subjects). The prevalence of myopia was 0% (0 subjects) in the 6-year-old children and 1.6% (95% CI, 0.6 –3.6) in the 11-year-old children. Gender was not a significant predictor of myopia (P ⫽ 0.86) or hyperopia (P ⫽ 0.95). Although Yao children comprised only 1.2% of the sample, this group was 11.3 times more likely to be myopic than the majority of Lao Loum children (P ⫽ 0.006).

Visual Acuity The VA data are presented in Table 3. The majority of children (98% [95% CI, 97–99]) had normal unaided binocular VA (at least 6/9.5 in their better eye). No child presented with spectacles. On the basis of the definitions in Table 1, the overall prevalence of any visual impairment (presenting VA ⬍6/9.5 in the better eye) was 1.9% (95% CI, 1.0 –2.9; 55 subjects). The prevalence of mild Table 3. Categories of Visual Impairment Visual Acuity

VA category* Normal/near normal Mild impairment Moderate impairment Severe impairment Blind Total

Presenting Binocular VA n; % (95% CI)

Presenting Monocular VA n; % (95% CI)

2814; 98.0 (97–99) 50; 1.8 (0.9–2.6) 5; 0.2 (0.0–0.4) 0; 0 (0.0–0.0) 0; 0 (0.0–0.0) 2869

2691; 94.0 (91.6–96.4) 168; 5.8 (3.4–8.0) 9; 0.32 (0–0.62) 0; 0 (0.0–0.0) 1; 0 (0.0–0.3) 2869

CI ⫽ confidence interval; VA ⫽ visual acuity. *VA category: normal/near normal (VA ⱕ20/32), mild impairment (VA ⱕ20/60 ⬍20/32), moderate impairment (VA ⱕ20/200 ⬍20/60), severe impairment (VA ⱕ20/400 ⬍20/200), and blind (VA ⬍20/400).

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Figure 2. Distribution of prevalence of any visual impairment by age and gender. Any visual impairment is defined as presenting visual acuity (VA) ⬍20/32 (6/9.5) in the better eye.

visual impairment was 1.8% (95% CI, 0.9 –2.6; 50 subjects), and the prevalence of moderate visual impairment was 0.2% (95% CI, 0.000 – 0.4; 5 subjects). The prevalence of mild and moderate visual impairment by age and gender is shown in Table 4 (available at http://aaojournal.org) and depicted graphically in Figure 2. There were 178 children (6.0% [95% CI, 3.6 – 8.3]) with visual impairment in at least 1 eye. There were no blind children or children with severe visual impairment. Only 1 eye had ⬍3/60 acuity (from strabismic amblyopia). In multivariate logistic regression analysis, age was a significant predictor of visual impairment (odds ratio [OR], 0.61; 95% CI, 0.47– 0.79), with the OR decreasing by 0.61 for each year of increasing age. Female gender was a borderline significant (P ⫽ 0.08) predictor of visual impairment. Because of the association with uncorrected myopia, Yao ethnicity was also a borderline significant predictor of visual impairment in the multivariate analysis (P ⫽ 0.09).

Cover Testing On cover testing, there were 32 children with an exotropia for distance (1.1%; 95% CI, 0.3–1.9) and 28 children with an exotropia for near (1.0%; 95% CI, 0.3–1.8); 6 children had an esotropia for distance and near (0.2%; 95% CI, 0 – 0.4), and 3 children had vertical misalignments (0.1%; 95% CI, 0 – 0.2).

Astigmatism The cylinder from the cycloplegic refractions is shown in Table 5 (available at http://aaojournal.org). There were 262 children (9.0%; CI, 5.1–12.9) with astigmatism of at least 0.75 D in either eye. In multivariate logistic regression modeling, astigmatism was associated with increasing age (odds ratio [OR], 1.56; 95% CI, 1.20 –2.03), female gender (OR, 1.19; 95% CI, 1.10 –1.29), and ethnicity. Those of Lao Loum ethnicity were 21 times more likely (95% CI, 11.8 – 39.3) to have astigmatism than those of Lao Soung ethnicity.

Causes of Visual Impairment The majority of visual impairment was caused by refractive error. Of the 5 children with moderate visual impairment, 4 had refractive error (myopic astigmatism) and 1 had a retinal disorder (Table 6).

Casson et al 䡠 Refractive Error in Lao Schoolchildren Table 6. Causes of Visual Impairment* Uncorrected VA of <20/32 (6/9.5) Cause

Right Eye

Left Eye

Refractive error Amblyopia Corneal opacity Cataract/PCO Retinal disorder Other Total

80 3 0 1 1 0 85

86 4 1 0 1 0 92

PCO ⫽ posterior capsule opacification; VA ⫽ visual acuity. *Presenting VA ⬍20/32 (6/9.5).

Discussion The most striking finding in this study was the exceptionally low prevalence of myopia. There was an estimated 16% overall prevalence of refractive error (myopia and hyperopia combined), but the overall prevalence of refractive error was only 3.6% (95% CI, 2.6 – 4.7; 112 subjects). Correspondingly, few subjects were visually impaired, and only 5 subjects had moderate visual impairment. Because this represented only a small proportion of the sample, it was relatively easy to ensure that those children noted to have subnormal vision were accurately categorized and their visual impairment explained. A number of studies have performed refraction using both traditional cycloplegic retinoscopy and cycloplegic autorefraction.2,3,6,7,9 The agreement between these 2 techniques by Bland–Altman plot analysis has generally been reported as “good,” with 95% agreement approximately within 0.65 D in most studies.2,3,6,7,9 However, autorefraction has a tendency to minus overcorrection under noncycloplegic conditions.33 Under cycloplegia, this tendency is largely neutralized, and clinically insignificant differences have been reported in population-based studies of Caucasian children.6,8 However, a systematic tendency to more negative refraction has also been reported clinically34 and in population-based studies of East Asian children.3,12 Thus, in the current study, we have reported the cycloplegic retinoscopy results. The prevalence of myopia is considerably lower in western Asian regions2,9,35 and white Australian children,10 and at its lowest in healthy indigenous Australian children.11,36,37 A recent nationwide study found that the prevalence of “low vision” (VA ⬍20/40 but ⱕ20/200) in Australian aboriginal children aged 5 to 15 years was 1.5% (95% CI, 0.9 –2.1), and only 15 of the 1694 children in the sample had low vision due to refractive error.11 In the current study, the prevalence of low vision was slightly lower than that in indigenous Australian children (1.2% [95% CI, 0.4 – 2.0]) and was also explained by the extremely low prevalence of myopia. The age range of the children in the current study was 6 to 11 years. The upper age limit is younger than the typical 5- to 15-year age range reported in other studies; thus, we would expect the

overall prevalence of myopia and visual impairment to be lower in the current study. There are approximately 50 distinct ethnic groups recognized in Lao PDR. The groups have been divided into approximate geographic categories, and Lao people frequently self-identify as being “lowland,” “midland,” or “highland” Lao.38 The Yao ethnic group originates from southern China and generally lives in the northern highland regions of Lao PDR. Although Yao children comprised only 2.1% of the population, there was a significant association between Yao ethnicity and myopia, consistent with the possibility of genetic influences. The prevalence of astigmatism in children of East and South Asian ancestry is reportedly greater than that of European Caucasian children.39 However, the prevalence of corneal astigmatism (ⱕ0.75 D) in the current study (9.0%; CI, 5.1–12.9) was approximately half that reported in other children of East Asian extraction.3,4 The prevalence of tropia in the current population was similar to that reported in Chinese children.4 The low prevalence of visual impairment in Lao primary schoolchildren is encouraging from a public health perspective, but the reasons for the exceptionally low prevalence of ametropia in this population remain speculative. During the data-collection phase of the study, it was clear that the educational facilities in Vientiane District were limited. The majority of schools had few or no books, and most reading was from a blackboard. Although we did not attempt to collect data regarding the time children spent on near work/ reading or time spent outside, it seemed highly likely that these children engaged in considerably less near work than similarly aged children from affluent, highly educated nations. An important limitation of the study is the school-based sampling method. The initial RESC study design and accompanying studies were population-based,3,6 –9 but similar, large-scale, RESC-type studies have been school-based because of the greatly reduced cost and logistic difficulty compared with a population-based study of children.4,10 The school-based design suffers the problem of selection bias. Severely visually impaired children are unlikely to be attending school and may die at a preschool age. There is one school for the blind in Lao PDR located in Vientiane, adjacent to the Vientiane Ophthalmology Centre, but other blind and severely visually impaired children are likely to exist in the region.40 The study results can only be considered in the context of children within the schooling system. Furthermore, the results from this study can be extrapolated only to the Vientiane province. Although robust data regarding enrollment rates at school are lacking, considerable regional differences in childhood education are likely. In conclusion, the current study provides the first robust evidence of the refractive error and visual impairment prevalence in primary school-aged children in Lao PDR. Visual impairment is not a public health concern in this population. The exceptionally low prevalence of ametropia and visual impairment is consistent with current hypotheses regarding myopigenesis, but the precise underlying environmental and genetic influences driving myopia remain obscure.15

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Casson et al 䡠 Refractive Error in Lao Schoolchildren

Footnotes and Financial Disclosures Originally received: October 9, 2011. Final revision: March 5, 2012. Accepted: March 28, 2012. Available online: June 12, 2012.

Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Manuscript no. 2011-1480.

1

South Australian Institute of Ophthalmology, University of Adelaide University and Sight for All, Adelaide, South Australia, Australia.

2

Vientiane Ophthalmology Center, Vientiane, Laos.

Correspondence: Robert J. Casson, DPhil, FRANZCO, South Australian Institute of Ophthalmology, Level 8, East Wing, Royal Adelaide Hospital, South Australia, Australia 5000. E-mail: [email protected].

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