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1From the Department of Ophthalmology, Centre for Vision Research, and the Westmead Millennium Institute, University of Sydney, Westmead, Australia; the 2School of Applied Vision Sciences, Faculty of Health Sciences, University of Sydney, Sydney, Australia; the 3Research School of Biological Sciences and Centre for Visual Science, Australian National University, Canberra, Australia; the 4Centre for Clinical Epidemiology and Biostatistics, University of Newcastle, Newcastle, Australia; and the 5Department of Ophthalmology, The Children’s Hospital, Westmead, Australia.
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Abstract |
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METHODS. Noncontact methods were used to examine ocular dimensions and cycloplegic autorefraction in a stratified random cluster sample of year 1 Sydney school students (n = 1765), mean age 6.7 years (range, 5.5–8.4 years). Repeated measures of axial length, anterior chamber depth, and greatest and least corneal radius of curvature (CR1, CR2, respectively) were taken in each eye. Refraction was measured as the spherical equivalent.
RESULTS. Mean spherical equivalent refraction in right eyes was +1.26 ± 0.03 D (SEM; range, –4.88 to +8.58). The distribution was peaked (kurtosis 14.4) and slightly skewed to the right (skewness, 1.7). Prevalence of myopia, defined as spherical equivalent refraction 
–0.5 D, was 1.43% (95% CI, 0.94–2.18) in the overall population. Axial length, anterior chamber depth, and corneal radii of curvature were normally distributed. The mean axial length in right eyes was 22.61 ± 0.02 mm (SEM; range, 19.64–25.35). The mean anterior chamber depth was 3.34 ± 0.01 mm (SEM; range, 2.14–4.06). Mean CR1 was 7.85 ± 0.01 mm (SEM) and mean CR2 was 7.71 ± 0.01 mm (SEM). The distribution of axial length/mean corneal radius ratio was peaked (leptokurtic) with a mean of 2.906. Mean axial length was longer, anterior chambers were deeper, and corneas were flatter in the boys.
CONCLUSIONS. A peaked (leptokurtic) distribution of spherical equivalent refraction was present in this predominantly hyperopic 6-year-old population. The results also showed that ocular biometric measures were normally distributed, with statistically significant gender differences found in measurements.
There are some large data sets from older populations of both European19 and East Asian20 origin that provide significant data on refraction and other eye conditions, although the collection of ocular biometry is less comprehensive. A meta-analysis of the data on those of European origin has recently been published that shows, inter alia, significant regional differences between refractive errors in Europe and North America on the one hand and Australia on the other.21 In particular, Australia shows lower age-specific prevalence rates for refractive errors than Western Europe and the United States.
Despite the limitations of existing data, largely on the basis of data on adult populations and the early work on children,2 the following picture of the relationship between refractive error and ocular biometry has emerged. Most ocular biometric parameters are normally distributed, consistent with their development being controlled by a large number of independent factors, possibly both genetic and environmental. However, spherical equivalent refraction shows a peaked distribution and indicates that it is under some form of active regulation.
The Sydney Myopia Study aims to compile a systematic database on refraction, ocular biometry, and other ophthalmic and systemic measures, in school children at mean ages of 6, 9, 12, and 15 years, in a largely European population growing up in Sydney, Australia, where the prevalence of myopia appears historically to have been quite low. In this article, we report on the distributions of spherical equivalent measures and ocular biometry in the first phase of the Sydney Myopia Study, the examination of year 1 primary school students. Ocular biometry measures were obtained with noncontact laser interferometry, and cycloplegic autorefraction was performed with the use of cyclopentolate. These data provide a comprehensive age norm for this population and also provide insights into ethnic differences and development of refractive error.
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Methods |
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Procedures included a 193-item questionnaire for parents asking for estimates of time spent by each child engaging in close-up activities and distance activities. Sociodemographic information, including ethnicity, country of birth, education, occupations, age of parents, and type of current housing were collected, in addition to the mother’s obstetric history, child’s birth history, past and current medical history, and a detailed family history of eye disorders. The examination included a detailed assessment of visual acuity, identification of amblyopia and strabismus, and cycloplegic refraction with cyclopentolate. Autorefraction and keratometry (with an RK F-1 autorefractor; Canon Inc., Tokyo, Japan), ocular biometry (axial length, anterior chamber depth, and corneal radius of curvature with the IOLMaster; Carl Zeiss, Meditec AG Jena, Germany), aberrometry (with a COAS aberrometer; Wavefront Sciences, Inc., Albuquerque, NM), retinal and disc digital photography, and retinal thickness measures (with a StratusOCT3 optical coherence tomograph; Carl Zeiss Meditec Inc., Dublin, CA) were obtained.
The eye drop protocol included amethocaine hydrochloride 0.5% (Minims; Chauvin Pharmaceuticals Ltd., Romford, UK), which was instilled into each eye to provide anesthesia and enhance the absorption of the subsequent eye drops; two cycles of cyclopentolate 1% (1 drop) and tropicamide 1% (1 drop) instilled 5 minutes apart. The autorefractometer (RK-F1; Canon) was set to generate five valid readings of refraction in each eye automatically, performed 20 to 30 minutes after instillation of the eye drops. This autorefractor provides a median value of the five readings, which was used for analysis.
An ocular biometry system (IOLMaster; Carl Zeiss Meditec) was used to obtain five valid readings of axial length and anterior chamber depth and three keratometry readings. The measures were taken on the entire cohort before the instillation of eye drops and on a subsample after pupil dilation. Predilation measurements for ocular biometry were used in this study. Postcycloplegia anterior chamber depth measurements are also reported.
Definitions
Signals from the tear film and retinal pigment epithelium (RPE) are used by the biometry system (IOLMaster; Carl Zeiss Meditec) for axial length measurements. The system automatically adjusts for the distance difference between the inner limiting membrane and the RPE, so that the displayed axial lengths are directly comparable to those obtained by immersion ultrasound. Light is relatively often reflected at the inner limiting membrane producing an interference signal. In this event, the measuring cursor was moved to the RPE peak.23 Anterior chamber depth was defined as the distance from the anterior corneal surface to the anterior lens surface. Corneal curvature was measured in two meridians, the greatest corneal radius of curvature (CR1) and the least corneal radius of curvature (CR2). The axial length-corneal radius (AL/CR) ratio was defined as the axial length divided by the mean corneal radius. Myopia was defined as the spherical equivalent –0.5D, hyperopia as 
+0.5D and emmetropia as between –0.5 and +0.5D.
Data Analysis
Data were analyzed on computer (Statistical Analysis System software, ver. 8.2; SAS Institute, Cary, NC). Measures of spread, including kurtosis and skewness, were derived. Distributions for refraction and ocular biometric parameters were tested for normality with the Kolmogorov-Smirnov test and were considered significantly different from normal when P 0.05. Linear regression models were constructed to assess the effect of age and gender. Mixed models were used to adjust for clustering within schools. Where cluster effects were not significant, t-tests and normal linear regression were used. Correlations between refractive error and the biometrical measures were calculated with Spearman correlation coefficients. Measures are presented as the mean ± SEM. All confidence intervals (CI) are 95%.
Population Characteristics
Of 2238 eligible children, 1765 (79%) were given parental permission to participate in the study, and questionnaire data were provided by parents. Of the 473 nonparticipants, 53.7% were boys and 46.3% were girls. Of the 1765 children who participated, 24 were not examined (but had questionnaire data), as they were absent from school during the examination period, and one 9-year-old child was excluded from the analysis. Missing data were also excluded from the analysis, leaving right eye data available in: 1724 (refraction), 1716 (axial length), 1726 (anterior chamber depth), and 1727 (corneal radius) children. Because right eye and left eye data correlated highly, only data from right eyes are reported. Mean age was 6.68 years in the girls and 6.74 years in the boys; this small difference was statistically significant, P < 0.0001. Sixty-seven children aged 5 years and 3 children aged 8 years were included in the analysis. The ethnic distribution of this sample included 64.5% white (European), 17.2% East Asian, 4.9% Middle Eastern, 2.3% South Asian, 2.0% Oceanic and Indigenous Australian, 7.9% mixed, and 1.2% other ethnic groups.
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Results |
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Figure 4A shows the distribution of CR1 (greatest corneal radius of curvature) in the right eyes of all participants. This curve was also normally distributed. There was very high correlation in CR1 between right and left eyes, with a coefficient of 0.98. The mean CR1 in the right eyes was 7.85 ± 0.01 mm. Figure 4B shows the distribution of CR2 (least corneal radius of curvature) in the right eyes. This curve was normally distributed. There was very high correlation in CR2 between right and left eyes, with a coefficient of 0.97. The mean CR2 in the right eyes was 7.71 ± 0.01 mm. Mean CR1 and CR2 in the girls was significantly lower than in the boys (P < 0.0001). Height- and age-adjusted mean CR1 and CR2 in the girls were 7.79 mm (CI, 7.77–7.81) and 7.64 mm (CI, 7.63–7.66), respectively. In the boys they were 7.91 mm (CI, 7.90–7.93) and 7.77 mm (CI, 7.75–7.78), respectively. There was no significant difference in CR1 or CR2 between children aged 6 years and those aged 7 years.
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Discussion |
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Methodology in Biometry
In early studies, investigators measured axial length either indirectly3 4 or directly with radiography,5 6 but these methods have now been replaced by ultrasound biometry,7 8 9 10 11 12 13 16 17 24 25 or optical coherence approaches (IOLMaster; Carl Zeiss Meditec). When comparing biometry data from ultrasound and laser interferometry, certain differences in measurement should be pointed out. First, lens thickness is not measured directly with the IOLMaster. Second, anterior chamber depth using ultrasound were found to be significantly shorter than noncontact measures, because of indentation.26 Studies have also found axial length measures by interferometry to be slightly longer than those obtained by ultrasound, possibly because the IOLMaster measurement is noncontact and is assessed along the visual axis with the aid of a fixation beam.27
Spherical Equivalent
Early work on refraction after cycloplegia (with atropine), generally in adult populations, found that the distributions significantly deviates from a normal distribution, with a marked excess at emmetropia and a positive skewness toward myopia.1 On the basis of these data, an emmetropization effect was postulated as early as the 19th century,28 in which ocular components were actively modulated and adjusted to minimize refractive error. Other investigators suggested that optical components were randomly associated, but this idea is not consistent with the narrow distributions of refractive error observed. Still others argued that a peaked distribution simply results from the geometric expansion of the eye, but this ignored the fact that the distribution of refractive errors becomes more peaked with age, from a very broad distribution in neonates.29 More recent data have strongly supported this concept or idea of active modulation of ocular components to produce a peaked distribution.30 31
Our data showing a marked leptokurtosis in spherical equivalent refraction demonstrate that substantial remodeling of the optical components of the eye had already taken place in this sample of 6-year-old children, although the refractions were far from emmetropic, with a mean spherical equivalent in the hyperopic range. The refractions in this sample were very different from those in a population in Singapore, where the prevalence of myopia was already high in children aged 7 to 9 years, and the mean spherical equivalent was in the myopic range. However, one would expect less hyperopia in the slightly older Singaporean sample.
Axial Length
Early work on the refractive components of the human eye demonstrated binomial distribution curves for each optical component, except axial length.2 These data must be interpreted prudently, because of limitations of study design and technical difficulties. Tron3 4 demonstrated a distribution curve that became normal after subjects with high myopia were eliminated. Stenstrom5 found axial length to distribute with a peak and positive skew. Separation of eyes into those with and without optic disc crescents eliminated the skewing, but the peak excess persisted. Deller et al.6 also examined vertical and transverse diameters of the eye and found that highly myopic eyes deviated from normal spherical shape.
Our data show that the axial length distribution in this mostly 6-year-old sample is statistically indistinguishable from a normal distribution, but there were few children with myopia (and only one with high myopia), to contribute to a non-normal distribution. The mean axial length in a Singaporean population aged 7 years with a much higher myopia prevalence9 was 23.1 mm compared with 22.67 mm in our 7-year-old children. Their reported distribution appears to be essentially normal but is slightly skewed to the right. A large study in Taiwan found a 20% myopia rate in their 7-year-old population with axial length in the boys and girls significantly longer than in our population.8 The baseline Orinda Study reported comparable mean axial length measurements in a sample with a similar ethnic distribution, but with less hyperopic refraction, possibly due to the use of a different method of cycloplegia (tropicamide).16 In contrast to both the Singapore and Taiwan findings, axial length in our sample of 6-year-old Australian children is normally distributed, with a narrower range. It is possible that compensatory interactions between refractive components act as a buffer to counter the optical effect of axial lengthening.
Corneal Curvature and Anterior Chamber Depth
The distributions of corneal radius of curvature and anterior chamber depth were also essentially normal in this sample. The mean corneal radius of curvature in our 7-year-old sample was quite similar to that in other 7-year-old populations in Singapore (7.7 mm)9 and Taiwan (
7.7 mm).7 8 We found no increase in corneal radius between 6- and 7-year-old children, in keeping with data from Taiwan7 8 that cover ages 7 to 18 years. Anterior chamber depth was greater in 7-year-old Singaporean children (3.6 mm)9 than in our Australian sample (3.36 mm), consistent with their longer axial length. Mean anterior chamber depth in the Orinda Study (3.57 mm)16 was measured after cycloplegia and was quite similar to that found in this study (3.54 mm). There was a deepening of 0.18 mm in anterior chamber depth in our study after cycloplegia, which could be due to changes in lenticular shape and position.32 The Orinda Study investigators also measured lens power and found a decreasing power with age.16
Axial Length/Corneal Radius Ratio
Much of the compensatory adjustment of the optical components of the eye seems to involve interactions between axial length and corneal curvature.33 The AL/CR ratio has therefore been used to give a better correlation with refractive error than is obtained with axial length alone.33 The distribution of the AL/CR ratio was leptokurtic, although not as clearly as spherical equivalent refraction, and the mean AL/CR ratio was 2.906. The AL/CR ratio in this Australian sample is, on average, well below 3.0, the level associated with the development of myopia.34 This result is consistent with the predominantly hyperopic refraction observed in the population. AL/CR ratios in the Singapore data were over 3.0, levels that are associated with increasingly myopic refraction.35 The COMET study of myopic children reported a mean AL/CR ratio (horizontal meridian) at baseline of 3.18.
Refractive Error and Ethnic Differences in Biometry
The prevalence of myopia found in this population of Australian children at 1.43% is among the lowest reported, slightly higher than the rate in Nepal.36 More than 90% of children in this study had hyperopic spherical equivalent refractions. The lower prevalence of myopia and higher prevalence of hyperopia found in white children of European origin compared with other ethnicities is interesting, given that the children are growing up in the same city and are educated at the same schools. The axial length was shorter and the anterior chamber depth deeper in whites (European), but both groups had comparable AL/CR ratios.
Correlations between Optical Components
Axial length, AL/CR ratio, and anterior chamber depth correlated negatively with refractive error. These correlations indicate that longer eyes, and those in which axial elongation has outpaced changes in corneal curvature are more likely to be myopic, or in this sample, less hyperopic. The higher correlation observed for the AL/CR ratio and refractive error may indicate the extent to which an imbalance between axial elongation and corneal curvature contributes to progression toward myopia. The correlation of anterior chamber depth with refraction could be due to a tendency for longer eyes to have a deeper anterior chamber depth or could represent some form of more active modulation, because the refractive effect of a deeper anterior chamber is away from myopia.
Previous workers have suggested that corneal curvature may be actively modulated to regulate the development of refractive error, and indeed some have suggested that myopia results from a failure of corneal compensation for increasing axial length.37 Our findings show that there is almost no correlation between refractive error and corneal curvature, in contrast to the significant correlations seen between refractive error and either axial length, or more strikingly, AL/CR ratio. This suggests that the mechanisms that regulate axial elongation are able to produce a given pattern of refractive error—predominantly hyperopic in the 6- to 7-year-olds in our Sydney sample and significantly myopic in the 7-year-olds in Singapore, irrespective of corneal curvature.
Implications for the Development of Refractive Error
Ocular growth and refraction are dynamic and change during childhood. Decreasing hyperopia during the transition from infancy to adulthood has been widely documented. The longitudinal data of Sorsby et al.30 demonstrated eye growth to consist of a rapid infantile phase, wherein the eye had to compensate by 20 D for an increase in axial length of 5 mm, with adult dimensions almost reached by 2 years of age. A slower phase followed when the eye had to compensate for 3 D, attributable to a 1-mm increase in axial length. One childhood study reported that corneal curvature varied little from ages 5 to 12 years.16 Another recent large study of ocular biometric components reported no change in corneal curvature with age.17 The study in Taiwan, where myopia rates are high, also reported no change in corneal radius with age.7 8 Past studies suggested anterior chamber deepening after the age of 5 to be caused by lens thinning.11 In our study, the AL/CR ratio distribution was leptokurtic, with a mean value of 2.906. A high ratio (i.e., >3.0) has been suggested to be a predictor or correlate of myopia.34
This study provides definitive refraction and ocular biometric data in a representative population of Sydney schoolchildren. Although our study was able to confirm many well-described patterns, we also found that axial length was normally distributed and that the distribution of axial length/corneal radius ratio peaked in children with hyperopic refraction. We are planning a 3-year follow-up of these children, which should help further inform the topic of refractive error development and concomitantly assess changes in ocular biometry.
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Footnotes |
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Submitted for publication November 11, 2004; revised December 15, 2004, and January 4, 2005; accepted January 11, 2005.
Disclosure: E. Ojaimi, None; K.A. Rose, None; I.G. Morgan, None; W. Smith, None; F.J. Martin, None; A. Kifley, None; D. Robaei, None; P. Mitchell, None
The publication costs of this article were defrayed in part by page charge payment. This article must therefore be marked "advertisement" in accordance with 18 U.S.C. 
1734 solely to indicate this fact.
Corresponding author: Paul Mitchell, Department of Ophthalmology, Centre for Vision Research, University of Sydney, Westmead Hospital, Hawkesbury Road, Westmead, NSW, Australia 2145; paul_mitchell{at}wmi.usyd.edu.au.
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