Distribution of Macular Thickness by Optical

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Distribution of Macular Thickness by Optical Coherence Tomography: Findings from a Population-Based Study of 6-Year-Old Children Son C. Huynh,1,2 Xiu Ying Wang,1,2,3 Elena Rochtchina,1 and Paul Mitchell1 PURPOSE. To study the distribution of macular thickness by ocular and demographic variables in a population-based study of young children. METHODS. The Sydney Childhood Eye Study examined 1765 6-year-old children from 34 randomly selected Sydney schools during 2003 and 2004 (78.9% response). A comprehensive eye examination included cycloplegic autorefraction and optical biometry. Fast macular thickness scans were performed over a 6-mm diameter central retinal region with optical coherence tomography. Multivariate analyses were performed. Macular thickness is presented on a modified Early Treatment Diabetic Retinopathy Study (ETDRS) macular grid, with outer radii for the central, inner, and outer macular regions being 0.5, 1.5, and 3 mm, respectively. RESULTS. In the study, 1543 children (88.7% of participants; 51.1% boys) had high-quality scan data (mean age, 6.7 years). The mean (SD) minimum foveal thickness was 161.1 (19.4) ␮m. The thickness of the central, inner, and outer macula was normally distributed, with means (SD) of 193.6 (17.9), 264.3 (15.2), and 236.9 (13.6) ␮m, respectively. Total macular volume was also normally distributed, with a mean (SD) of 6.9 (0.4) mm3. The temporal quadrant was thinner than other quadrants for both inner and outer macular regions. The foveal minimum, central, and inner macula was generally significantly thicker in boys than in girls, and in white than in East Asian children. Outer macular thickness showed no significant gender– ethnic differences. Sectoral macular thickness variations were preserved in both gender and ethnic groups. The inner and outer macula, but not the central macula, showed significant thinning with increasing axial length. These corresponding areas were significantly thicker with more hyperopic spherical equivalent refractions. CONCLUSIONS. Macular thickness and volume were normally distributed in this young childhood population. Significant gender and ethnic differences were demonstrated. Axial length

From the 1Department of Ophthalmology, the University of Sydney and the Centre for Vision Research, Westmead Millennium Institute, Westmead Hospital, Sydney, Australia; and 3Vision Co-operative Research Centre, School of Optometry and Vision Science, University of New South Wales, Sydney, Australia. 2 Contributed equally to the work and therefore should be considered equivalent authors. Supported by Grant 253732 from the Australian National Health and Medical Research Council, Canberra, Australia, and the Vision Co-operative Research Centre. Submitted for publication October 28, 2005; revised December 22, 2005; accepted March 15, 2006. Disclosure: S.C. Huynh, None; X.Y. Wang, None; E. Rochtchina, 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, Centre for Vision Research, Department of Ophthalmology, University of Sydney, Hawkesbury Road, Westmead, NSW 2145, Australia; [email protected]. Investigative Ophthalmology & Visual Science, June 2006, Vol. 47, No. 6 Copyright © Association for Research in Vision and Ophthalmology

and refraction were important ocular biometric determinants of macular thickness. (Invest Ophthalmol Vis Sci. 2006;47: 2351–2357) DOI:10.1167/iovs.05-1396

P

athologic processes involving the macula, such as glaucoma, macular hole, and macular edema, can profoundly influence vision. In many clinical situations, knowledge of the thickness of the macula in comparison to population or normal values and their variation with demographic and ocular variables is an essential aid in the diagnosis and monitoring of disease severity or progression. Data on normal macular thickness in adults have been reported,1–3 but to our knowledge, limited normative data are available,4 and no population data have been reported for children. Optical coherence tomography (OCT) is a noninvasive technology that provides in vivo high-resolution measurements of the retina, nerve fiber layer, and optic disc. OCT is a valuable new clinical tool that is emerging as highly useful in the diagnosis and monitoring of diseases such as diabetic retinopathy1,5 and glaucoma.4,6 – 8 Increasingly, it is also being used to study the effects of refractive error and elongation of the globe on retinal parameters.2,9 –11 We sought in the present study to examine the distribution of macular thickness and its variation with demographic and ocular variables in a population-based sample of predominantly 6-year-old Australian school children.

METHODS Study Participants The Sydney Myopia Study is a population-based survey of eye health in school children resident in the metropolitan area of Sydney, Australia. This project forms part of the Sydney Childhood Eye Study, which is examining childhood eye conditions across a range of ages. The study was approved by the Human Research Ethics Committee, University of Sydney, and the Department of Education and Training, New South Wales, Australia. The study adhered to the tenets of the Declaration of Helsinki. We obtained informed written consent from at least one parent, as well as verbal assent from each child. Detailed study methods have been described elsewhere.12,13 In brief, 34 primary schools in Sydney were identified through a random stratified sampling process. Stratification of the city used socioeconomic status data from the Australian Bureau of Statistics 2001 national census. A proportionate mix of government-funded and private–religious schools were included. All children in first grade (mostly aged 6 years) were eligible. Examinations were conducted during 2003 and 2004, and data from this sample are presented.

Demographic Data Demographic data were obtained from a comprehensive questionnaire sent to parents. The child’s ethnicity was determined from the ethnicity and country of birth of both parents. Ethnic groups represented were European white, East Asian, South Asian (Indian, Pakistani, or Sri Lankan), African, Melanesian/Polynesian, Middle Eastern, Indigenous Australian, and South American.

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FIGURE 1. Components of the optical coherence tomography (OCT) output for the right eye of a child, showing (A) an infrared video image of the scan; (B) a retinal cross-sectional profile for one of the scans with positions of the foveal minimum (F), central macula (CM), inner macula (IM), and outer macula (OM) indicated; (C) a topographic map of retinal thickness; and (D) the average thickness of the nine regions defined.

Ocular Examination Axial length was measured before cycloplegia with an optical biometer (IOLMaster; Carl Zeiss Meditec, Inc., Jena, Germany) using dual-beam partial coherence interferometry (PCI) technology.14,15 Low-coherence laser light (wavelength 780 nm) emitted by a superluminescent diode was passed through a Michelson interferometer, where it was split into two beams: a reference beam and a second beam directed into the eye. The echo time delay between the reference beam and the second beam, which reflected back from the retinal pigment epithelium, was used to calculate axial length. The average of five such measurements was used in analysis. After corneal anesthesia with amethocaine 1% (1 drop), cycloplegia was induced by instilling cyclopentolate 1% and tropicamide 1% (2 drops each), separated by 5 minutes. Phenylephrine 2.5% was also instilled in a small proportion of children, to achieve adequate mydriasis (ⱖ6 mm). Autorefraction (RK-F1 autorefractor/keratometer; Canon, Tokyo, Japan) was performed 25 to 30 minutes after the last drop. Five autorefractions were performed automatically. The median value given by the instrument was used for analyses. Mydriatic digital retinal photography was also performed to detect any retinal conditions.

OCT Measurements Macular thickness scans were performed through dilated pupils with a commercially available optical coherence tomograph (StratusOCT, software ver. 4.0.4; Carl Zeiss Meditec, Inc.). The instrument used PCI technology (wavelength 820 nm) to obtain cross-sectional retinal images (equivalent to B-scan ultrasound), with axial resolution less than 10 ␮m.14,16 Previous studies have demonstrated the reproducibility of

this instrument in measuring macular thickness.16 –18 In our study, the coefficient of variation was used as a measure of intrasubject reproducibility and was calculated as the ratio of the standard deviation of the mean of all measurements performed in one individual, expressed as a percentage. Median coefficients of variation for measurements in the central, inner, and outer macular regions were 3.7%, 1.9%, and 1.8%, respectively. There were no significant differences between ethnic and refractive subgroups. Macular measurements were performed with the fast protocol (fast macular scan). This consists of six individual line scans regularly arranged in a radial pattern with default scan lengths of 6-mm. Each line scan was composed of 128 individual A-scans, so that a 6-mm diameter macular area was sampled at 768 separate points. Total acquisition time for each fast macula scan was 1.92 seconds. Five scans were performed and the average used in analysis. More than 90% of scans were performed by a single operator (XYW). An internal-fixation target was used in all scans, with the location of each scan on the retina monitored using an infrared-sensitive video camera. Scans were performed using default axial length (24.46 mm) and refractive error (0 D) for consistency with usual clinical practice. Scans were accepted if free of artifacts (boundary errors and decentration) and complete cross-sectional images were seen for all individual line scans. Only scans with signal strengths of at least five were used. Retinal thickness was automatically determined by the instrument software as the distance between the internal limiting membrane and retinal pigment epithelium. Measurements were provided for three concentric regions (Fig. 1). The central disc, hereafter called the central macula, was a region with a radius of 0.5 mm. The inner and outer rings had outer radii of 1.5 and 3 mm, respectively, and

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TABLE 1. Characteristics of Children with and without OCT Measurement of the Macula Children with OCT (n ⴝ 1543) Age (y), n (%) ⬍6 6–⬍7 7⫹ Gender, n (%) Boys Girls Ethnicity, n (%)* White East Asian Age (y) Visual acuity (letters)† Axial length (mm) Spherical equivalent (D) Height (cm) Weight (kg) Body mass index (kg/m2)

Children without OCT (n ⴝ 197)

P

58 (3.8) 1068 (69.2) 417 (27.0)

6 (3.1) 162 (82.2) 29 (14.7)

0.0006

789 (51.1) 754 (48.9)

92 (46.7) 105 (53.3)

0.2

1009 (65.4) 245 (15.9) 6.7 (0.4) 49.8 (3.9) 22.61 (0.69) 1.29 (0.89) 120.7 (5.7) 23.73 (4.48) 16.2 (2.1)

99 (50.3) 54 (27.4) 6.6 (0.3) 49.8 (4.4) 22.61 (0.69) 1.12 (0.76) 119.4 (5.0) 23.32 (4.63) 16.3 (2.4)

⬍0.0001 0.01 ⬎0.9 ⬎0.9 0.006 0.0006 0.2 0.6

Data not marked otherwise are the mean ⫾ SD. * Data on other ethnic groups not presented. † Logarithm of the minimum angle of resolution visual acuity.

were divided into four quadrants. Average retinal thickness was provided for each of the nine regions.

Statistical Analysis Analyses were performed on computer (SAS, ver. 9.1; SAS Institute, Cary, NC). Mixed models and generalized estimating equations (GEEs) adjusted for cluster sampling effects. The ␹2 test and paired t-test were used to compare measurements between eyes. Comparisons between subgroups were determined by multivariable-adjusted regression analyses.

RESULTS Population Characteristics Of 2238 eligible children, 1765 (78.9%) participated in the study; 25 children were not included due to absence from school during the examination period. A further 197 children had poor-quality scans, leaving data available for 1543 (88.7%) children. Table 1 shows characteristics of children with and without OCT macular thickness measurements. These groups were significantly different in age, refraction, height, and ratio of East Asian to white children. However, absolute differences in age, refraction, and height were small. There were no significant differences between the two groups in gender, visual acuity, axial length, weight, and body mass index. The ethnic composition of this population was predominantly European white (n ⫽ 1009, 65.4%) and East Asian (n ⫽ 245, 15.9%). There were also 63 Middle Eastern children (4.1%). Other ethnic groups comprised the remaining 226 (14.6%) children. Data for these groups are not presented because of the small sample size.

Distribution Results are shown for right eyes only, as there were no significant differences in measurements between right and left eyes (P ⬎ 0.06) except for marginal differences in the thickness of the outer superior (0.9 ␮m, P ⫽ 0.004), outer temporal (0.9 ␮m, P ⫽ 0.04), and inner temporal (1.0 ␮m, P ⫽ 0.03) macula. The right–left eye correlation of central macular thickness was 0.81 (P ⬍ 0.0001); the average inner macula thickness, 0.60

(P ⬍ 0.0001); and the average outer macula thickness, 0.68 (P ⬍ 0.0001). The thickness measurements of the central, inner, and outer macular regions, as well as the central macular volume were normally distributed (Fig. 2). The central macula was thinnest, followed by the outer macula (P ⬍ 0.0001). The inner macula was thicker than both the central (P ⬍ 0.0001) and outer macula (P ⬍ 0.0001). This tendency for the outer macula to be thinner than the inner macula was also found in all quadrants. Table 2 shows that the inner temporal macula was also thinner than the inner superior, inner nasal, and inner inferior macula (P ⬍ 0.0001). Findings were similar for the outer macula (P ⬍ 0.0001). There were significant positive correlations between central macular thickness and age (0.09, P ⫽ 0.0006), height (0.15, P ⬍ 0.0001), weight (0.12, P ⬍ 0.0001), body mass index (0.06, P ⫽ 0.02), spherical equivalent (SE) refraction (0.13, P ⬍ 0.0001), and axial length (0.06, P ⫽ 0.03). After adjustment for age, gender, height, ethnicity, and cluster-sampling effects, retinal thinning with increasing axial length (Table 3) was significant in the inner and outer macula (both P ⬍ 0.0001) but not in the central macula (P ⫽ 0.14). Increased thickness of the central, inner, and outer macula was significantly associated (P ⬍ 0.0001) with more hyperopic SE refraction (Table 3). Gender differences in macular thickness and volume were statistically significant after adjustment for age, spherical equivalent refraction, height, ethnicity, and cluster-sampling (Table 4). Results were similar when adjusted for axial length instead of spherical equivalent refraction. The central and inner macula were generally thicker in boys than in girls. Only the outer inferior quadrant, however, was significantly thicker in boys. Gender differences in macular thickness were greater in the central than in the inner macula. Central, but not total, macular volume was significantly greater in boys than in girls, although the difference was marginal. Differences in macular thickness between white and East Asian children were statistically significant after adjustment for age, gender, height, spherical equivalent refraction, and cluster sampling (Table 5). Results were similar when adjusted for axial length instead of spherical equivalent refraction. The central and inner macula were generally significantly thicker in

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FIGURE 2. 1543).

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Distribution of the mean (A) central, inner, and outer macular thicknesses and (B) central macular volume in the entire group (n ⫽

white than in East Asian children. The magnitude of the central macular difference in thickness was approximately two to four times the magnitude of the difference for the inner macula. There were no significant differences in outer macular thickness between these two ethnic groups. White and Middle Eastern children also showed no significant differences in retinal thickness for all macular regions (all P ⬎ 0.2) except the outer temporal region, where retinal thickness was 4.9 ␮m (95% confidence interval 0.9 –9.0 ␮m) thicker in Middle Eastern children (P ⫽ 0.02). There was a tendency, in both ethnic groups and also in both boys and girls, for the outer macula to be thinner than the inner macula and for the temporal quadrant to be thinner than all other quadrants. Differences in central macular and total macular volumes between white and East Asian children were small but statistically significant.

DISCUSSION In this population-based study of predominantly 6-year-old children, macular thickness and volume measured using OCT were normally distributed. Macular thickness varied with retinal location, axial length, refraction, gender, and ethnicity. The normal distribution of macular thickness and volume is not unexpected, as most biological variables are normally dis-

tributed. The mean foveal minimum and central macular thickness obtained in our study, however, was comparatively thicker than values obtained histologically. For the central 0.35-mm diameter area, the average thickness was reported to be 130 ␮m,19 although this was likely to have been an adult thickness. Further, histologic preparation may cause some tissue shrinkage, resulting in underestimation of retinal thickness in vivo. In a sample of 104 normal children (mean age, 9.5 ⫾ 3.5 years) examined by Hess et al.,4 with the StratusOCT, the reported outer macular thickness was greater than in our sample by approximately 6 ␮m. Macular thickness at other locations was not reported. In a small sample of adults (n ⫽ 73), Hee et al.1 reported the central and inner macular regions to be thinner by approximately 10 to 20 and 3 to 8 ␮m, respectively, whereas outer macular thickness was similar. Also in adults, Chan and Duker19 reported mean foveal minimum thickness of 182 ␮m. Our finding of 163 ␮m in white children represents 90% of the adult thickness found in their study. There are very few reports of the distribution of macular volume, with one childhood study of normal eyes4 reporting a mean total macular volume of 7.01 ⫾ 0.42 mm3, very close to our finding of 6.85 ⫾ 0.38 mm3. Several points also deserve mention in consideration of the data in Figure 2A and Tables 2, 3, and 4. First, there was a relatively wide range of thicknesses for the central, inner, and

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TABLE 2. Overall Distribution of Macular Thickness and Volume in Right Eyes

Thickness (␮m) Foveal minimum Central macula Inner macula Average Temporal Superior Nasal Inferior Outer macula Average Temporal Superior Nasal Inferior Volume (mm3) Total macula Central macula

Mean (SD)

Median

Minimum

Maximum

Kurtosis

Skew

K-S

161.1 (19.4) 193.6 (17.9)

159.0 193.0

107.8 130.8

250.3 260.0

1.5 0.5

0.9 0.4

⬍0.01 ⬍0.01

264.3 (15.2) 256.2 (16.5) 269.7 (15.1) 264.8 (18.7) 266.7 (15.1)

265.1 257.8 270.2 266.2 267.3

179.6 137.4 211.5 152.0 192.5

313.1 307.8 319.0 317.6 317.0

1.1 3.0 0.5 1.9 0.9

⫺0.4 ⫺0.8 ⫺0.1 ⫺0.7 ⫺0.3

0.01 ⬍0.01 ⬎0.15 ⬍0.01 0.06

236.9 (13.6) 223.1 (15.2) 239.5 (13.9) 254.1 (17.9) 230.9 (14.1)

236.7 223.1 238.8 254.1 230.9

173.2 146.6 174.5 146.4 173.2

283.7 295.0 287.0 310.2 287.4

0.5 1.9 0.4 1.8 0.6

⫺0.03 0.08 0.2 ⫺0.5 0.1

⬎0.15 ⬍0.01 0.03 ⬍0.01 ⬎0.15

4.9 0.1

8.1 0.2

0.8 0.5

⫺0.1 0.4

⬎0.15 ⬍0.01

6.85 (0.38) 0.15 (0.01)

6.85 0.15

n ⫽ 1543. K-S, Kolmogorov-Smirnov test for normality.

outer macula. At all three locations, the maximum and minimum thickness measurements differed by just over 100 ␮m. In the central macula, the difference was almost twofold. Second, there was considerable overlap in the distribution of thickness of the three concentric regions, particularly in the inner and outer macula. This suggests that the cross-sectional retinal profile in the pediatric population can be accentuated with a deep foveal depression, a relatively thick inner macula, and a thinner outer macula, or it can be relatively flat. Topographically, we also showed that the temporal macula was thinnest. Both the superior inner and outer macula were thicker than the inferior. In the inner macula, the nasal quadrant was thinner than the superior and inferior quadrants, but in the outer macula, the nasal quadrant was thicker near the optic nerve head. This pattern was present in both gender and ethnic groups. These findings are consistent with reports from previous studies in which a retinal thickness analyzer11,20,21 or OCT1,4 was used. The variations in thickness were suggested to be due to crowding of nerve fibers along the superior and inferior arcuate bundles as well as along the papillomacular bundle. In the present study, we found that all macular regions were thicker with increasing hyperopia. To our knowledge,

this is the first report of the effect of hyperopia on macular thickness. Previous studies mainly explored the effect of myopia on macular thickness, with variable results.2,3,9,11 These studies were based on different methods of measuring retinal thickness, but generally found that retinal thinning occurred with increasing myopia3 and that thinning of the retina mainly occurred in the parafovea rather than at more central locations.2,9,11 In several studies, central macular thickness did not change9 or actually became thicker2 with myopia. It has been postulated that the peripheral retina becomes thinner as a compensatory mechanism to preserve central macular thickness, which is more critical to vision.9 Unfortunately, this has the effect of reducing peripheral visual resolution by reducing neural sampling density.22 It is not known what effect central foveal thickening has on visual function in hyperopic subjects. One possibility is that it reduces visual acuity, as acuity has been found to worsen with increasing central macular thickness in otherwise normal adult eyes.1 Our finding of an effect of axial length on the thickness of the inner and outer macula, but not on the central macula, compares favorably with the study by Lim et al.,2 which found that the foveal maximum thickness, which is located in the

TABLE 3. Relationship of Axial Length and Refraction with Central, Inner and Outer Macular Thickness Retinal Thickness (␮m) Central Macula Mean (95% CI) Quintile of axial length (range in mm) 1: 19.64–⬍22.04 191.9 (194.4–189.3) 2: 22.04–⬍22.44 192.3 (194.6–190.0) 3: 22.44–⬍22.78 192.1 (194.3–189.8) 4: 22.78–⬍23.17 190.8 (193.1–188.6) 5: 23.18–⬍25.35 189.9 (192.2–187.5) P for trend 0.1 Quintile of refraction (range in D) 1: ⫺4.88–0.75 189.3 (187.2–191.4) 2: 0.76–1.08 191.1 (188.8–193.5) 3: 1.08–1.27 190.7 (188.2–193.3) 4: 1.27–1.63 191.3 (189.0–193.6) 5: 1.66–8.58 195.9 (193.7–198.2) P for trend ⬍0.0001

Inner Macula Mean (95% CI)

Outer Macula Mean (95% CI)

266.9 (265.3–268.5) 265.7 (264.0–267.3) 263.1 (260.9–265.4) 263.6 (261.7–265.5) 258.4 (256.2–260.5) ⬍0.0001

241.4 (239.6–243.3) 238.2 (236.6–239.7) 235.7 (233.7–237.6) 234.7 (232.5–236.9) 229.9 (227.7–232.1) ⬍0.0001

262.1 (260.4–263.7) 263.7 (261.7–265.6) 261.8 (259.6–263.9) 263.0 (260.4–265.6) 267.3 (265.8–268.9) ⬍0.0001

233.2 (231.6–234.8) 235.6 (234.0–237.1) 234.8 (232.9–236.8) 236.5 (234.3–238.6) 240.3 (238.6–242.0) ⬍0.0001

Data are adjusted for age, gender, height, ethnicity, and cluster-sampling.

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TABLE 4. Gender-Specific Distribution of Macular Thickness and Volume

Thickness (␮m) Foveal minimum Central macula Inner macula Average Temporal Superior Nasal Inferior Outer macula Average Temporal Superior Nasal Inferior Volume (mm3) Total macula Central macula

Boys (n ⴝ 789) Mean (95% CI)

Girls (n ⴝ 754) Mean (95% CI)

161.2 (159.3–163.1) 194.2 (192.3–196.1)

158.6 (157.1–160.2) 189.3 (187.9–190.8)

2.6 (0.9–4.3) 4.9 (3.4–6.4)

0.003 ⬍0.0001

264.9 (263.3–266.5) 256.7 (255.0–258.3) 270.3 (268.5–272.0) 265.5 (263.4–267.5) 267.3 (265.9–268.7)

262.5 (261.4–263.7) 254.2 (252.7–255.6) 269.0 (267.7–270.3) 262.7 (261.3–264.0) 264.5 (263.4–265.7)

2.3 (0.8–3.9) 2.5 (0.9–4.1) 1.3 (0.4–2.9) 2.8 (0.9–4.7) 2.8 (1.4–4.1)

⬍0.003 ⬍0.002 0.1 0.003 ⬍0.0001

235.6 (234.1–237.2) 222.0 (220.4–223.7) 238.9 (237.4–240.4) 252.7 (250.6–254.9) 229.0 (224.4–230.5)

236.8 (235.4–238.1) 221.3 (220.1–222.5) 239.6 (238.1–241.1) 254.7 (252.8–256.7) 231.5 (230.1–233.0)

⫺1.1 (⫺2.6–0.3) 0.7 (⫺1.0–2.4) ⫺0.7 (2.1–0.7) ⫺2.0 (⫺4.0–0.001) 2.6 (1.1–4.1)

0.1 0.4 0.3 0.05 0.0009

6.83 (6.78–6.87) 0.152 (0.151–0.154)

6.83 (6.8–6.9) 0.149 (0.147–0.150)

0.005 (⫺0.05–0.03) 0.004 (0.003–0.005)

0.8 ⬍0.0001

Difference Mean (95% CI)

P

Data are adjusted for age, spherical equivalent refraction, height, ethnicity and cluster-sampling.

inner macula, became thinner with increasing axial length. However, both these authors and Wong et al.23 reported that foveal minimum thickness increased with axial length. In contrast, Wakitani et al.9 reported no difference in the thickness of the central, inner, and outer macular regions between three groups of axially myopic subjects (age range, 12–74 years) and an emmetropic group. Garcia-Valenzuela et al.10 also found no association between axial length and thickness of the temporal peripapillary retina, an area in close proximity to the nasal outer macula. Differences between our results and those of other investigators could be partly explained by differences in instrumentation, subject age, and differences in definition of the size of various macular regions. It is also possible that part of the differences resulted from the actual scan lengths being slightly different, due to refraction- and axial length–related magnification. Researchers have consistently reported gender differences in macular thickness, with males having slightly thicker retinas

than females.1,9,23 In our study, these gender differences were evident even in young children. To our knowledge, ethnic differences in the macular thickness of children have not been reported. Essentially, we found that retinal thickness in East Asian children was significantly greater than in white children, with larger differences in the central than inner macula, and no significant differences in the outer macula. This is consistent with a slight difference in central macular volume. We believe that this finding may be useful in management and further research in diseases of the macula. There are several potential sources of error in our study, although the similarity between our findings and those of previous studies suggests that these limitations were not major. First, we used the default axial length (24.46 mm) and refraction (0.0 D) when scans were being performed. Although this choice does not directly affect thickness measurements itself,17 the scan lengths were likely to have been less than 6 mm in most children, as the mean axial length in our study population

TABLE 5. Ethnicity-Specific Distribution of Macular Thickness and Volume

Thickness (␮m) Foveal minimum Central macula Inner macula Average Temporal Superior Nasal Inferior Outer macula Average Temporal Superior Nasal Inferior Volume (mm3) Total macula Central macula

White (n ⴝ 1009) Mean (95% CI)

East Asian (n ⴝ 245) Mean (95% CI)

Difference Mean (95% CI)

P

163.0 (161.8–164.3) 196.0 (194.9–197.1)

154.9 (152.6–157.1) 186.7 (184.7–188.7)

8.2 (5.6–10.7) 9.3 (6.9–11.6)

⬍0.0001 ⬍0.0001

265.2 (264.3–266.0) 257.0 (256.2–257.9) 270.2 (269.3–271.0) 265.6 (264.6–266.6) 267.9 (266.9–268.9)

262.3 (260.9–263.8) 254.8 (253.7–256.0) 268.6 (267.0–270.2) 263.1 (260.7–265.4) 263.3 (261.7–264.8)

2.8 (1.2–4.5) 2.2 (0.7–3.7) 1.5 (⫺0.2–3.2) 2.6 (0.1–5.0) 4.6 (2.8–6.4)

0.0005 0.0004 0.08 0.04 ⬍0.0001

237.5 (236.6–238.3) 224.1 (223.1–225.1) 239.8 (238.8–240.7) 254.4 (253.2–255.5) 231.6 (230.6–232.6)

237.0 (235.4–238.6) 222.7 (221.0–224.3) 241.0 (238.7–243.2) 254.5 (252.5–256.5) 230.1 (228.7–231.5)

0.5 (⫺1.3–2.2) 1.4 (⫺0.6–3.4) ⫺1.2 (⫺3.6–1.1) ⫺0.1 (⫺2.3–2.1) 1.5 (⫺0.2–3.2)

0.6 0.2 0.3 0.9 0.08

6.87 (6.85–6.89) 0.154 (0.153–0.155)

6.83 (6.79–6.88) 0.147 (0.145–0.15)

0.04 (⫺0.01–0.1) 0.007 (0.005–0.01)

0.1 ⬍0.0001

Data are adjusted for age, gender, height, spherical equivalent refraction and cluster-sampling.

IOVS, June 2006, Vol. 47, No. 6 was 22.61 mm. This method may have produced slight overestimates of retinal thickness in the outer macula, but not in the central macula or the foveal minimum. Another possible source of error is the variable reflectivity of the internal limiting membrane, which has been found to affect retinal nerve fiber layer measurement in advanced glaucoma,24 although its effect in normal children’s eyes is not known. In summary, in this population-based study of predominantly 6-year-old children, with a standardized clinical protocol used to perform OCT measurements, we found that macular thickness and volume were normally distributed with characteristic regional variations. Most notably, the temporal quadrant was markedly thinner than all other quadrants. Macular thickness and volume were greater in boys than in girls, and in white than East Asian children, with differences in thickness being greatest in the central macula, followed by the inner macula. Increasing axial length was associated with a thinner inner and outer macula, but not a thinner central macula, whereas more hyperopic refractions were associated with increased thickness of all three regions. Future research should explore differences in other ethnic groups and also should seek to investigate the significance of these gender and ethnic differences and their influence on visual function.

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