myopia, axial length, and oct characteristics

7/27/2019 Myopia, Axial Length, And OCT Characteristics

1/9

Myopia, Axial Length, and OCT Characteristicsof the Macula in Singaporean Children

Hai-Dong Luo,1,2 Gus Gazzard,3 Allan Fong,4 Tin Aung,1,5 Sek Tien Hoh,4

Seng-Chee Loon,1,5 Paul Healey,6 Donald T. H. Tan,1,4 Tien-Yin Wong,1,7

and Seang-Mei Saw1,2

PURPOSE. The purpose of this study was to evaluate the associ-ations between macular volume and thickness, as assessed byoptic coherence tomography (OCT), with refraction and axiallength (AL) in children.

METHODS. A total of 104 Chinese school children (51 girls and53 boys) 11 to 12 years of age were randomly selected fromone school during the 2005 examination in the SingaporeCohort Study of the Risk Factors for Myopia (SCORM). Cyclo-plegic autorefraction was performed to obtain refraction (de-fined as spherical equivalent [SE]) and ultrasound biometryperformed to obtain the AL. Macular volume and thicknesswere then measured (StratusOCT3; Carl Zeiss Meditec, Dublin,CA).

RESULTS. Children with moderate myopia (SE at least 3.0 D)tended to have smaller total macular volume and thinner quad-rant-specific macular thickness (except in the inferior andsuperior inner quadrants), followed by children with low my-opia (0.5 SE 3.0 D), compared with children with nomyopia (SE 0.5 D). Total macular volume was positivelyassociated with SE ( 1.58, 95% CI, 0.84 to 2.32, standard-ized 0.14, P 0.001) and negatively associated with AL( 1.20, 95% CI, 1.62 to 0.79, standardized 0.45,

P 0.001) in multiple linear regression models controlling forage and gender.

CONCLUSIONS. In children, increasing axial myopia was associ-ated with reduced macular volume and thickness. These find-

ings suggest that early anatomic changes may be present in theretinas of children with axial myopia. (Invest Ophthalmol VisSci. 2006;47:27732781) DOI:10.1167/iovs.05-1380

Myopia is a common condition affecting a significant pro-portion of the population, particularly in East Asian coun-tries. In Singapore, Hong Kong, and Taiwan, the prevalence ofhigh myopia (at least 6.0 D) appears to be rising and may leadto a future increase in the incidence of potentially blindingocular morbidity such as glaucoma, cataract, retinal detach-ment, and myopic neovascular macular degeneration.15 Reti-nal changes in persons with high myopia include peripapillaryatrophy, peripheral lattice degeneration, tilting or malinsertionof the optic disc, posterior staphyloma, and breaks in Bruchsmembrane.1,6

Few studies have evaluated possible structural retinalchanges in individuals with low to moderate myopia without

evidence of clinically overt retinal disease. In adults, studiesbased on the use of optical coherence tomography (OCT) todetect subtle macular changes have shown inconsistent re-sults.7,8 In two Asian adult OCT studies in Japan and Singapore,the average macular retinal thickness did not vary with refrac-tion.9,10 However, in the Singapore study, minimum (foveal)macular thickness was greater in adults with longer axiallengths (ALs), whereas the parafoveal macular layers in thesuperior and inferior quadrants were thinner. Macular thick-ness of the nasal and superior quadrants were greater than thetemporal and inferior parts.9,10

There are few studies in children in which early macularanatomic features have been examined in myopic eyes. In astudy using OCT among Polish adolescents 14 to 18 years ofage, macular thickness decreased with increasing myopic re-

fraction, with a mean macular retinal thickness of 231.0 m ineyes with low myopia, 218.0 m in moderate myopia, and178.0 m in high myopia.11

To our knowledge, however, there are no reports of thecorrelations of OCT-defined parameters with ocular biometryin children. The purpose of this study was to investigate theassociations of OCT measurements of macular volume andmacular thickness with refractive error and AL in Singaporeanchildren.

METHODS

Study Population

The methodology of the Singapore Cohort Study of the Risk Factors ofMyopia (SCORM) has been described previously.12,13 The study com-

menced in 1999, and schoolchildren in grades 1 to 3 (ages 79 years),

attending three schools (located in the Eastern, Northern, and Western

Singapore) were recruited. Subjects with media opacity, pseudoexfo-

liation, uveitis, or pigment dispersion syndrome and a history of in-

traocular surgery or refractive surgery, glaucoma, or retinal disease

were excluded from the study.

This cohort was examined yearly. During the 2005 (fourth year)

examination, 104 Chinese children randomly selected from 561 chil-

dren in the Western school who were in grades 5 and 6 (ages 11 and

12 years) had OCT measurements. The mean age of this sample was

11.5 0.5 years (51 girls and 53 boys). The mean spherical equivalent

From the 1Singapore Eye Research Institute, Republic of Singa-pore; the 2Department of Community, Occupational and Family Med-icine, National University of Singapore, Republic of Singapore; 3TheInstitute of Ophthalmology, London, United Kingdom; the 4SingaporeNational Eye Center, Republic of Singapore; the 5Department of Oph-thalmology, National University Hospital, Republic of Singapore; the6University of Sydney, Center for Vision Research, Westmead Millen-nium Institute, Westmead, New South Wales, Australia; and the 7Cen-ter for Eye Research Australia, University of Melbourne, Melbourne,

Australia.

Supported by Singapore National Medical Research Council GrantNMRC/0695/2002.

Submitted for publication October 24, 2005; revised December29, 2005, and January 26, 2006; accepted April 26, 2006.

Disclosure: H.-D. Luo, None; G. Gazzard, None; A. Fong, None;T. Aung, None; S.T. Hoh, None; S.-C. Loon, None; P. Healey, None;D.T.H. Tan, None; T.-Y. Wong, None; S.-M. Saw, None

The publication costs of this article were defrayed in part by pagecharge payment. This article must therefore be marked advertise-ment in accordance with 18 U.S.C. 1734 solely to indicate this fact.

Corresponding author: Seang-Mei Saw, Associate Professor, De-partment of Community, Occupational and Family Medicine, NationalUniversity of Singapore, 16 Medical Drive, Singapore 117597, Republicof Singapore; [email protected].

Investigative Ophthalmology & Visual Science, July 2006, Vol. 47, No. 7

Copyright Association for Research in Vision and Ophthalmology 2773


2/9

(SE) refraction was 1.38 1.58 D (range, 4.5 to 1.10). Compar-

ison of this random sample with those not selected for this study

showed that it was similar by age (P 0.42) and gender (P 0.91), but

the mean SE of this group was less myopic (1.38 D vs. 2.20 D) and

they had shorter ALs (23.87 mm vs. 24.23 mm) compared with those

not selected.

This research followed the tenets of the Declaration of Helsinki.

Informed written consent was obtained from parents of each subject,

and each procedure was performed with the subjects consent. The

study was approved by the ethics committee of the Singapore Eye

Research Institute.

Eye Examinations

All children had a standardized examination as follows. Cycloplegic

refraction was performed after instillation of 3 drops of 1% cyclopen-

tolate 5 minutes apart. At least 30 minutes after the last drop, five

consecutive refraction and keratometry readings were obtained with

one of two calibrated autokeratorefractometers (model RK5; Canon,

Inc. Ltd., Tochigiken, Japan). AL measurements were obtained using

one of two contact ultrasound biometry machines (Echoscan model

US-800, probe frequency of 10 mHz; Nidek Co., Ltd., Tokyo, Japan),

after 1 drop of 0.5% proparacaine was administered. The average of six

measurements was taken if the standard deviation was 0.12 mm. If

the standard deviation was0.12 mm, the data were not included, andthe measurements were repeated until the standard deviation reached

0.12 mm.

The OCT measurements (StratusOCT3; Carl Zeiss Meditec, Dublin,

CA) were performed in a dim room after cycloplegia. The pupils were

dilated to at least 5 mm diameter before the measurements. The

measurements of AL and refractive error were entered into the OCT

software. The OCT examination was performed by the same ophthal-

mologist (AF) and analyzed (ver. 4.1 software; Carl Zeiss Meditec,

Dublin, CA). Scans were performed using the Fast Macular Thickness

protocol and were repeated six times until three good-quality horizon-

tal and three good-quality vertical scans were achieved for each child.

Twenty-three parameters were measured by the Fast Macular Thick-

ness scan protocol: the volume and average retinal thickness of the

macula, the thickness of four quadrants of the inner and outer maculain the parafoveal area; the minimum macular thickness in the foveal

area; and ratios of superiorinferior outer macular thickness and tem-

poralnasal inner and outer macular thickness by horizontal and ver-

tical 6-mm scans centered against the point of fixation of each eye.

Definitions and Data Analysis

Spherical equivalent was defined as spherical power plus half-negative

cylinder power. Myopia was defined as an SE of at least 0.5 D. Levels

of myopia included low myopia, defined as SE 0.5 D and 3 D,

and moderate myopia, defined as SE of at least 3 D.12 The OCT

measurements of macular volume and macular thickness were nor-

mally distributed. The ANOVA procedure was used to compare the

differences in OCT parameters among groups of children with no

myopia, low myopia, and moderate myopia and among groups with AL

in the highest, middle, and lowest tertiles. Multiple linear regression

models were conducted with OCT parameters as the dependent vari-

able, with SE, AL, age, and gender as the covariates. All data were

analyzed with statistical software (SPSS ver. 12.0; SPSS Inc., Chicago,

IL), and statistical significance was assumed at P 0.05. However, for

multiple comparisons among the 23 parameters measured by the OCT

Fast Macular Thickness scan protocol, a Bonferroni correction was

applied with resultant significance of P 0.0022.

RESULTS

The mean SE was 1.38 1.57 D (median, 1.28; range,4.57 to 1.10). There were 39 (38%) subjects without myo-pia (1.10 to 0.49 D), 43 (41%) with low myopia (0.50 D

to 2.99 D), and 22 (21%) with moderate myopia (3.00 D to

4.57 D). The mean (SD) AL was 23.87 1.00 mm (median,23.91; range, 21.2226.59).

The average total macular volume, average foveal volume,overall average macula thickness (overall), and foveal mini-mum thickness, were 6.65 0.39 mm3 (median, 6.57; range,5.997.67), 0.15 0.01 mm3, 171.4 35.8 m (median,169.8; range, 101.3241.3), and 157.0 19.2 m (median,155.8; range, 122.0208.7), respectively. The boys had higher

foveal minimum thickness (162.1

17.5 m vs. 151.4

19.6m) than did the girls. Inner and outer macular thicknesseswere significantly positively correlated with inner and outermacular volume in all quadrants (linear regression, P 0.001).The average inner macular thicknesses of the superior, inferior,temporal, and nasal quadrants were 271.4 14.3, 261.8 13.2, 255.4 13.4, and 266.2 16.2 m, respectively, and theaverage outer macular thicknesses were 234.5 13.2, 230.2 14.1, 214.6 13.5, and 254.6 14.9 m, respectively.

Comparisons of differences in macular volume and thick-ness among the children with moderate myopia, low myopia,and no myopia are shown in Table 1. The children withmoderate and mild myopia had significantly lower total macu-lar volume and superior inner, temporal inner, nasal inner,temporal outer, nasal outer, and inferior outer macular vol-

umes than did the children with no myopia. The children withmoderate and mild myopia also had higher minimum macularthickness and lower quadrant-specific macular thickness (ex-cept inferior inner) than did those with low myopia and nomyopia. After the application of the Bonferroni correction formultiple comparisons, only the differences in total macularvolume, temporal outer, nasal outer, and inferior outer macularvolumes and macular thicknesses remained statistically signif-icant among the three groups.

Comparisons of the differences in macular volume andthickness among children with highest, middle, and lowesttertiles of AL are shown in Table 2. The children in the highesttertile had a smaller total macular volume and all outer andinner macular volumes in the four quadrants than did the

children in the middle and lowest tertiles. Those in the highesttertile also showed thicker minimum macular thickness andthinner quadrant-specific macular thickness than did the otherchildren. The children in the middle tertile had smaller totalmacular volume, and all outer and inner macular volumes infour quadrants than did those in the lowest and also hadthicker minimum macular thickness and thinner quadrant-spe-cific macular thickness. After the application of the Bonferronicorrection, only the differences in total macular volume, allouter macular volumes and outer macular thicknesses, tempo-ral inner macular volume and thickness, nasal inner macularvolume, and superior inner macular thickness remained statis-tically significant among the three groups.

The changes in total macular volume and foveal minimummacular thickness among different SE and AL groups weresmall but highly consistent and statistically significant, and thedifferences in SE and AL among the groups were relativelysmall as well. The mean total macular volumes in the moderatemyopia, low myopia, and nonmyopia groups were 6.48, 6.56,and 6.84 mm3, respectively. The foveal minimum macularthicknesses in the moderate myopia, low myopia, and nonmyo-pia groups were 167.2, 156.3, and 152.3 m, respectively(Tables 1, 2). It should be pointed out that the foveal changewas in the opposite direction to the rest of the macula in thisstudy (Tables 1, 2).

Figure 1 depicts scatterplots of SE with selected OCT mea-surements, and Figure 2 depicts scatterplots of AL with se-lected OCT measurements. The Pearson correlation coeffi-cients were 0.44 for total macular volume and SE, 0.07 for

average macular thickness versus SE, and 0.26 for minimum

2774 Luo et al. IOVS, July 2006, Vol. 47, No. 7


3/9

macular thickness versus SE. The Pearson correlation coeffi-cients were 0.48 for total macular volume and AL, 0.02 foraverage macular thickness versus AL, and 0.30 for minimummacular thickness versus AL.

Table 3 shows the results of multiple linear regressionmodels with macular estimates as the dependent variables, andSE and AL as the independent variables, adjusting for age andgender. Figure 3 demonstrates a schematic diagram of the OCTmacular scan area. The regression coefficients are given forquadrant-specific macular volumes and thicknesses for spheri-cal equivalent in the multiple linear regression model, withmacular estimates as the dependent variables and spherical

equivalent, axial length, age, and gender as the independent

variables. Total macular volume correlated positively with SEregression coefficients were 1.58 (95% CI, 0.84 2.32, P 0.0005)and correlated negatively with ALregression coef-ficient 1.20 (95% CI, 1.62 to 0.79, P 0.0001). Thestandardized coefficients of AL and SE in a model with totalmacular volume as the dependent variable were 0.45 and0.14, respectively. Moreover, outer and inner macular volumeand thickness measurements were significantly positively cor-related with SE and negatively with AL, though inner macularvolumes and thicknesses were not statistically significant afterthe application of the Bonferroni correction. There was nolinear relationship between average macular thickness with SE

(P 0.80) or AL (P 0.53).

TABLE 1. Macular Volume and Thickness in All Subjects, and in Those with Moderate Myopia,Low Myopia, or No Myopia

OCT Measurements All SubjectsModerate

MyopiaLow

MyopiaNo

Myopia P

Macular volume (mm3)Fovea 0.15 0.01 0.16 0.01 0.15 0.01 0.15 0.02 0.13

(0.130.17) (0.130.18) (0.130.19) (0.120.18)Temporal inner 0.40 0.02 0.39 0.02 0.40 0.02 0.41 0.02 0.03

(0.360.44) (0.360.42) (0.350.46) (0.380.46)Superior inner 0.42 0.03 0.41 0.04 0.42 0.02 0.43 0.02 0.01

(0.360.48) (0.300.46) (0.360.47) (0.400.51)Nasal inner 0.42 0.03 0.41 0.02 0.42 0.03 0.43 0.02 0.03

(0.360.48) (0.350.44) (0.340.49) (0.380.50)Inferior inner 0.41 0.02 0.41 0.02 0.41 0.02 0.42 0.02 0.11

(0.370.45) (0.380.44) (0.370.45) (0.370.48)Temporal outer 1.14 0.07 1.10 0.07 1.13 0.07 1.17 0.07 0.001

(1.001.28) (0.961.21) (1.001.32) (1.061.29)Superior outer 1.25 0.07 1.22 0.07 1.24 0.06 1.27 0.07 0.10

(1.111.39) (1.101.32) (1.131.36) (1.111.50)Nasal outer 1.36 0.08 1.32 0.07 1.35 0.08 1.39 0.08 0.002

(1.201.52) (1.141.42) (1.131.54) (1.251.67)Inferior outer 1.22 0.07 1.19 0.07 1.20 0.06 1.27 0.07 0.0003

(1.081.36) (1.031.31) (1.101.35) (1.141.43)Total 6.65 0.39 6.48 0.32 6.56 0.37 6.84 0.37 0.0002

(5.897.41) (5.997.03) (6.017.53) (6.247.67)Macular thickness (m)

Foveal minimum 157.0 19.2 167.2 17.3 156.3 18.8 152.3 19.1 0.02(119.4194.6) (134.0206.7) (124.7208.7) (122.0196.0)

Overall average 171.4 35.8 178.8 39.2 170.9 35.9 168.1 34.3 0.56(101.2241.6) (102.3226.0) (101.3241.3) (102.7232.0)

Temporal inner 255.4 13.4 250.0 11.4 254.5 14.8 259.4 11.9 0.03(229.1281.7) (228.3268.7) (222.7290.3) (240.7291.3)

Superior inner 271.4 14.3 266.0 12.8 270.3 14.8 275.3 13.7 0.05(243.4299.4) (243.3293.3) (239.0310.7) (252.7321.7)

Nasal inner 266.2 16.2 259.0 15.3 265.8 16.8 270.5 14.8 0.03(234.4298.0) (221.3 279.3) (218.0312.0) (240.3319.3)

Inferior inner 261.8 13.2 257.7 11.3 260.8 13.3 265.1 13.7 0.12(236.0287.7) (241.3279.7) (237.3287.3) (236.0304.0)

Temporal outer 214.6 13.5 207.6 12.7 212.5 13.0 220.7 12.3 0.001(188.1241.1) (180.7227.7) (188.7248.7) (199.3242.3)

Superior outer 234.5 13.2 228.7 12.8 233.1 11.8 239.0 13.6 0.01(208.6260.4) (206.7249.0) (212.7256.3) (210.0281.7)

Nasal outer 254.6 14.9 247.9 13.6 251.8 12.9 261.2 15.4 0.001(225.4283.8) (212.7264.3) (212.7273.0) (235.3314.7)

Inferior outer 230.2 14.1 223.2 13.4 225.8 11.0 238.7 13.4 0.0003(202.6257.8) (193.7245.7) (206.3253.7) (214.3269.0)

Thickness ratioSuperior/inferior

outer 1.02 0.04 1.03 0.04 1.03 0.04 1.00 0.03 0.002(0.941.10) (0.941.10) (0.971.18) (0.921.08)

Temporal/nasal inner 0.96 0.03 0.97 0.05 0.96 0.03 0.96 0.03 0.53(0.901.02) (0.901.11) (0.901.08) (0.881.03)

Temporal/nasal outer 0.83 0.07 0.84 0.05 0.83 0.09 0.84 0.04 0.54(0.690.97) (0.740.96) (0.290.98) (0.760.92)

Data are the mean standard deviation (range). Low myopia was defined as SE 0.5 D and 3

D, and moderate myopia was defined as SE at least 3 D.

IOVS, July 2006, Vol. 47, No. 7 Macular Parameters and Refraction in Singaporean Children 2775


4/9

The relationships between absolute cylinder and OCT esti-mates of macular volume and macular thickness were alsoexamined in multiple linear regression models. No OCT mea-surements significantly correlated with absolute cylinder (P 0.05).

DISCUSSION

Our study demonstrated that, in these Singaporean Chinesechildren aged 11 and 12 years, axial myopia was associatedwith lower total macular volume and reduced quadrant-spe-cific macular thickness (excepting in the inferior inner andsuperior inner quadrants). We found significant correlations

between total macular volume, quadrant-specific macular vol-

ume, and quadrant-specific macular thickness with both SE andAL, after controlling for age and gender. These findings high-light anatomic differences in the macula between the childrenwith moderate myopia, mild myopia, and no myopia.

One of the key findings of our study is that three-dimen-sional OCT macular measurement parameters such as totalmacular volume and outer and inner macular volume de-creased with more myopic refraction and increasing AL. Thedifference in total macular volume among the nonmyopic, lowmyopic, and high myopic children was small but statisticallysignificant (6.84 0.37 mm3 vs. 6.56 0.37 mm3 vs. 6.48 0.32 mm3, P 0.0002). To our knowledge, there have been noprevious reports regarding differences in macular volume mea-

sured by OCT between myopic and nonmyopic subjects. Hess

TABLE 2. Macular Volume and Thickness in All Subjects, and in Those in the Highest, Middle, andLowest Tertile of AL

OCT MeasurementsHighest Tertile

(21.2223.23 mm)Middle Tertile

(23.2424.30 mm)Lowest Tertile

(24.3126.59 mm) P

Macular volume (mm3)Fovea 0.15 0.01 0.15 0.01 0.15 0.02 0.28

(0.130.18) (0.130.17) (0.120.19)Temporal inner 0.39 0.02 0.40 0.02 0.41 0.02 0.001

(0.350.42) (0.350.44) (0.380.46)Superior inner 0.42 0.02 0.42 0.03 0.43 0.02 0.007

(0.330.46) (0.300.46) (0.400.51)Nasal inner 0.41 0.02 0.42 0.02 0.43 0.03 0.002

(0.340.45) (0.350.45) (0.380.50)Inferior inner 0.40 0.02 0.41 0.02 0.42 0.02 0.007

(0.370.45) (0.380.45) (0.370.48)Temporal outer 1.10 0.06 1.14 0.06 1.18 0.07 0.0002

(0.961.24) (1.041.23) (1.061.32)Superior outer 1.21 0.07 1.24 0.05 1.29 0.07 0.0008

(1.101.32) (1.151.33) (1.151.50)Nasal outer 1.31 0.08 1.35 0.05 1.41 0.08 0.0001

(1.131.45) (1.231.44) (1.281.67)Inferior outer 1.18 0.07 1.21 0.05 1.27 0.07 0.0007

(1.031.35) (1.101.31) (0.961.24)Total 6.49 0.30 6.52 0.32 6.94 0.38 0.0001

(5.997.21) (6.017.17) (6.037.67)Macular thickness (m)

Foveal minimum 163.3 16.8 156.0 18.5 151.6 20.9 0.04(127.3206.7) (129.0208.7) (122.0208.0)

Overall average 173.5 40.2 170.2 33.3 170.6 34.8 0.92(101.3232.7) (102.7223.0) (104.3241.3)

Temporal inner 249.6 11.9 255.2 13.0 261.5 13.0 0.001(222.7268.7) (224.3282.3) (240.7291.3)

Superior inner 265.8 12.3 270.1 13.0 278.2 15.1 0.001(239.0293.3) (240.0292.7) (252.7321.7)

Nasal inner 260.4 15.8 264.7 13.9 273.6 16.3 0.003(218.0284.3) (224.3288.3) (240.3319.3)

Inferior inner 257.3 12.5 260.9 11.4 267.2 14.2 0.008(237.3284.7) (241.7286.3) (236.0304.0)

Temporal outer 206.9 12.0 213.9 10.8 223.1 12.9 0.0002(180.7234.0) (195.0231.0) (199.3248.7)

Superior outer 228.0 12.3 232.8 9.5 242.6 13.3 0.0009(206.7249.0) (217.0251.0) (216.3281.7)

Nasal outer 246.8 14.5 252.9 9.7 264.1 14.9 0.0003(212.7272.7) (231.7270.7) (242.0314.7)

Inferior outer 222.4 13.2 228.6 9.3 239.5 13.8 0.0007(193.7254.3) (206.3246.7) (214.7269.0)

Thickness ratioSuperior/inferior

outer 1.02 0.04 1.02 0.03 1.01 0.04 0.42(0.941.18) (0.941.11) (0.921.11)

Temporal/nasal inner 0.96 0.04 0.97 0.03 0.96 0.03 0.57(0.901.11) (0.881.02) (0.911.03)

Temporal/nasal outer 0.84 0.05 0.82 0.10 0.84 0.03 0.55(0.740.98) (0.290.91) (0.760.92)

Data are the mean standard deviation (range).



5/9

et al. 14 showed that macular volume was smaller in glaucoma-tous (6.57 0.85 mm3) than in normal (7.01 0.42 mm3) eyesin white children (P 0.001).

The two-dimensional OCT measurements of macular thick-

ness and its correlation with myopia in our study are in agree-

ment with previous reports.9,10 Our findings should be com-pared with findings from a recent OCT study in a Singaporeanadult population.10 Both studies show that the thickest point atthe parafoveal region decreased with myopia, whereas foveal

thickness increased. The reduction in the difference in thick-

FIGURE 1. Scatterplots of SE and OCT mea-surements.



6/9

FIGURE 2. Scatterplots of AL and OCT measure-ments.



7/9

TABLE 3. Relationship of Macular Volume and Thickness with SE and AL

OCT Measurements

Spherical EquivalentRegression Coefficient

(95% CI) P

Axial LengthRegression Coefficient

(95% CI) P

Macular volume (mm3)Fovea 28.11 (52.70 to 3.52) 0.03 10.30 ( 4.63 to 25.23) 0.17Temporal inner 20.66 (6.37 to 34.94) 0.005 18.22 (26.30 to 10.13) 0.0002Superior inner 16.71 (5.32 to 28.10) 0.004 12.38 (19.01 to 5.74) 0.0004Nasal inner 17.24 (5.16 to 29.32) 0.006 13.26 (20.27 to 6.25) 0.0003Inferior inner 17.89 (2.89 to 32.88) 0.02 15.96 (24.59 to 7.34) 0.0004Temporal outer 8.31 (4.26 to 12.36) 0.001 6.86 (9.08 to 4.64) 0.0002Superior outer 7.35 (3.03 to 11.67) 0.001 6.11 (0.54 to 3.68) 0.0003Nasal outer 6.82 (3.17 to 10.47) 0.0004 5.26 (7.33 to 3.19) 0.0002Inferior outer 9.40 (5.60 to 13.20) 0.0004 6.64 (8.79 to 4.48) 0.0002Total 1.58 (0.84 to 2.32) 0.0005 1.20 (1.62 to 0.79) 0.0001

Macular thickness (m)Overall average 0.03 (0.01 to 0.006) 0.53 0.0007 (0.006 to 0.005) 0.80Foveal minimum 0.02 (0.04 to 0.007) 0.006 0.01 (0.002 to 0.022) 0.02Temporal inner 0.03 (0.01 to 0.05) 0.005 0.03 (0.04 to 0.02) 0.0002Superior inner 0.03 (0.01 to 0.05) 0.005 0.03 (0.04 to 0.01) 0.0006Nasal inner 0.03 (0.008 to 0.046) 0.006 0.02 (0.03 to 0.01) 0.0003Inferior inner 0.03 (0.004 to 0.05) 0.02 0.02 (0.04 to 0.01) 0.0005Temporal outer 0.04 (0.02 to 0.07) 0.001 0.04 (0.05 to 0.02) 0.0002Superior outer 0.04 (0.02 to 0.06) 0.001 0.03 (0.05 to 0.02) 0.0003

Nasal outer 0.04 (0.02 to 0.06) 0.0002 0.03 (0.04 to 0.02) 0.0002Inferior outer 0.05 (0.03 to 0.07) 0.0003 0.04 (0.05 to 0.02) 0.0002

Thickness ratioSuperior/inferior outer 8.46 (15.80 to 1.11) 0.03 3.99 ( 0.44 to 8.43) 0.08Temporal/nasal inner 4.20 (13.77 to 5.38) 0.39 0.28 ( 5.46 to 6.02) 0.92Temporal/nasal outer 0.36 ( 4.42 to 5.15) 0.88 1.11 (3.96 to 1.74) 0.44

FIGURE 3. Map of the fovea and fourquadrants of the inner and outermacula. *Regression coefficient ofmacular volume; **regression coeffi-cient of macular thickness as for SEin the multiple linear regressionmodel with macular estimates as thedependent variables and SE, axiallength, age, and gender as the inde-

pendent variables.



8/9

ness between the foveal pit and parafoveal crest with increas-ing myopic refraction in adults10 was also observed in ourstudy.

An interesting observation in our study is that the minimummacular thickness at the foveal region increased, whereas over-all macular thickness decreased with increasing myopic refrac-tion and AL. This somewhat paradoxical finding is not easilyexplainable. Thinner maculae could be due to the stretching ofa similar volume of retina over a larger area or a decreasednumber of photoreceptors. Even early chorioretinal atrophy inhigh myopia, which had been described in the posterior polein eyes, has been associated with longer AL and increasedretinal thinning with myopia.6,15,16 However, there were fewhighly myopic children in our study, and it would be surprisingif chorioretinal atrophy were present in children with suchsmall amounts of myopia. In contrast, the increased macularthickness in the foveal region may be related to other mecha-nisms. In a form-deprivation model of myopia of tree shrews,17

subfoveal blood-retinal barrier permeability in form-deprivedmyopic animals was significantly higher than in the controlgroup. It is possible that the increase in minimum macularthickness (in the foveal area), which was associated with in-creasing myopic SE and AL in our study, may be due to patho-

logic subfoveal chorioretinal changes.18

An alternative expla-nation for the decreased macular crest thickness along withincreased foveal thickness was suggested by Springer and Hen-drickson in their experiments of macular modeling during aperiod of experimentally induced myopia progression in younganimals. The absence of vasculature in the foveal area may leadto foveal pits that are very deformable in response to intraoc-ular pressure, and ocular growth-induced retinal stretch maycontribute to the formation of foveal pits in primates.1921 Thesignificance of these OCT findings may require further re-search.

The similar pattern of associations of OCT measurementswith SE and AL in our study was, of course, related to the closecorrelation between SE and AL (Pearson coefficient 0.6, P 0.001),12,22 and indicates that the OCT findings reflect axial

myopia. The standardized coefficient of AL was higher thanthat of SE (0.45 vs. 0.14) in the multiple linear regression modelfor the prediction of total macular volume. It is well knownthat more highly myopic eyes have longer AL, which is largelycontributed by a greater vitreous chamber depth.23 Thus, ALpossibly contributes to a relatively larger variation of totalmacular volume than does just the SE. The stretch effect fromthe elongation of AL in myopic progression may thus in partexplain the reduction of macular retinal thickness and macularvolume, aspects of an overall stretching process of ocularstructures in both myopic human subjects and animal mod-els.23,24

We did not find significant correlation between the absolutecylinder reading and the OCT measurements (both macular

volume and macular thickness), indicating that the major factoraffecting variations in OCT parameters is axial refraction. Theoverall average macular thickness did not show a significantrelationship with refractive error. The measurements were notinfluenced by the refractive state of the eye. The counteractingeffects of the decrease of parafoveal thickness and the increaseof foveal thickness with increasing myopic SE and AL mayexplain the insignificant changes in overall average macularthickness in our study. It should be stated that magnificationerror may be present in transverse measurements in this Stra-tusOCT study, as the manufacturer (Carl Zeiss Meditec, Inc.)did not control for error in the current version of the instru-ment. The StratusOCT does not provide correction of theactual scan itself. Future refinement of the instrument shouldinclude some estimation of this error introduced by refractive

error. Despite this, OCT provided quantification of retinal

thickness with the excellent reliability reported in previousstudies.7,8,10,25,26 In one study, coefficients of variation of mac-ular thickness measurements by OCT within the same subjectswere 10%, decreasing to 9% when scans were repeated fivetimes.26

Early macular changes such as peripapillary atrophy havebeen documented in young myopic children in an Asian coun-try in which high myopia (SE at least 6 D) develops even inyoung children.12 To our knowledge, this is the first report ofmyopia-related variations in macular anatomy in young chil-dren determined by OCT measurement. Because high myopiahas been reported to be associated with ocular disease includ-ing myopic macular degeneration, macular retinoschisis, andmacular holes, the early identification of children with possiblemyopia-related macular changes is important.3,27,28 It has beenshown that kinetics of cone pigments become abnormal pre-ceding the loss of cone cells or chorioretinal degeneration inhigh myopia.28 It is uncertain whether there are any directlinks between reductions in macular thickness and the subse-quent onset of clinically significant macular disease.

The OCT is a commonly used method in the documentationof retinal diseases. It provides detailed measurements of theoptic disc and retinal nerve fiber layer and the detection of

decreased macular thickness may provide a sensitive methodfor the detection and monitoring of early glaucomatous tissueloss in the posterior pole.29 Our study shows that becausemacular thickness is influenced by the degree of refractiveerror, any interpretations of retinal changes should be madeonly after the refractive error of the individual is considered.Possible limitations of this study include the small number ofchildren with high myopia, the unknown effect of the trans-verse magnification error, and the possible lack of generaliz-ability of our study to other non-Asian or adult populations.

In summary, the myopic children in our study had reducedmacular volumes and parafoveal thickness. The findings sug-gest that the three-dimensional OCT may serve as a useful toolin the evaluation of early macular changes in myopic children,although the ultimate clinical significances of these changes

require further evaluation. Nonetheless, the degree of refrac-tive error should be considered in all OCT assessments ofmacular changes in children with other eye diseases.

Acknowledgments

The authors thank Angela Cheng for coordinating the SCORM study.

References

1. Saw SM, Katz J, Schein OD, Chew SJ, Chan TK. Epidemiology ofmyopia. Epidemiol Rev. 1996;18:175187.

2. Wong TY, Foster PJ, Hee J, et al. Prevalence and risk factors forrefractive errors in adult Chinese in Singapore. Invest Ophthalmol

Vis Sci. 2000;41:24862494.3. Saw SM, Gazzard G, Chan SY, Chua WH. Myopia and associated

pathological complications. Ophthalmic Physiol Opt. 2005;25:111.

4. Fan DSP, Lam DSC, Lam RF, et al. Prevalence, incidence, andprogression of myopia of school children in Hong Kong. InvestOphthalmol Vis Sci. 2004;45:10711075.

5. Lin LL, Shih YF, Tsai CB, et al. Epidemiology study of refractionamong schoolchildren in Taiwan in 1995. Optom Vis Sci. 1999;76:275281.

6. Curtin BJ. The Myopias: Basic Science and Clinical Management.Philadelphia: Harper & Row; 1985.

7. Hee MR, Izatt JA, Swanson EA, et al. Optical coherence tomogra-phy of human retina. Arch Ophthalmol. 1995;113:325332.

8. Panozzo G, Mercanti A. Optical coherence tomography findings inmyopic traction maculopathy. Arch Ophthalmol. 2004;122:1455

1460.



9/9

9. Wakitani Y, Sasoh M, Sugimoto M, Ito Y, Ido M, Uji Y. Macularthickness measurements in healthy subjects with different axiallengths using optical coherence tomography. Retina. 2003;23:177182.

10. Lim MC, Hoh ST, Foster PJ, et al. Use of optical coherence tomog-raphy to assess variations in macular retinal thickness in myopia.Invest Ophthalmol Vis Sci. 2005;46:974978.

11. Mrugacz M, Bakunowicz-Lazarczyk A, Sredzinska-Kita D. Use ofoptical coherence tomography in myopia. J Pediatr Ophthalmol

Strabismus. 2004;41:159162.12. Saw SM, Tong L, Chua WH, et al. Incidence and progression of

myopia in Singaporean school children. Invest Ophthalmol VisSci. 2005;46:5157.

13. Tong L, Saw SM, Siak JK, Gazzard G, Tan D. Corneal thicknessdetermination and correlates in Singapore schoolchildren. InvestOphthalmol Vis Sci. 2004;45:4004 4009.

14. Hess DB, Asrani SG, Bhide MG, Enyedi LB, Stinnett SS, FreedmanSF. Macular and retinal nerve fiber layer analysis of normal andglaucomatous eyes in children using optical coherence tomogra-phy. Am J Ophthalmol. 2005;139:509517.

15. Curtin BJ, Karlin DB. Axial length measurements and funduschanges of myopic eye. Am J Ophthalmol. 1971;1:4253.

16. Yanoff M, Fine BS. Ocular Pathology: A Text and Atlas. 3rd ed.Philadelphia: JB Lippincott; 1989:408.

17. Kitaya N, Ishiko S, Abiko T, et al. Changes in blood-retinal barrierpermeability in form deprivation myopia in tree shrews. VisionRes. 2000;40:23692377.

18. Montero JA, Ruiz-Moreno JM. Macular thickness in patients withchoroidal neovascularization determined by RTA and OCT3: com-parative results. Eye. 2005;19:7276.

19. Springer AD, Hendrickson AE. Development of the primate area ofhigh acuity. 1. Use of finite element analysis models to identify

mechanical variables affecting pit formation. Vis Neurosci. 2004;21:5362.

20. Springer AD, Hendrickson AE. Development of the primate area ofhigh acuity. 2. Quantitative morphological changes associated

with retinal and pars plana growth. Vis Neurosci. 2004;21:775790.

21. Springer AD, Hendrickson AE. Development of the primate area ofhigh acuity. 3. Temporal relationships between pit formation,retinal elongation and cone packing. Vis Neurosci. 2005;22:171

185.22. Mallen EA, Gammoh Y, Al-Bdour M, Sayegh FN. Refractive errorand ocular biometry in Jordanian adults. Ophthalmic Physiol Opt.2005;25:302309.

23. Saw SM, Chua WH, Hong CY, Wu HM, et al. Nearwork in early-onset myopia. Invest Ophthalmol Vis Sci. 2002;43:332339.

24. Hirata A, Negi A. Lacquer crack lesions in experimental chickmyopia. Graefes Arch Clin Exp Ophthalmol. 1998;236:138 145.

25. Goebel W, Kretzchmar-Gross T. Retinal thickness in diabeticretinopathy: a study using optical coherence tomography (OCT).Retina. 2002;22:759767.

26. Neubauer AS, Priglinger S, Ullrich S, et al. Comparison of fovealthickness measured with the retinal thickness analyzer and opticalcoherence tomography. Retina. 2001;21:596601.

27. Benhamou N, Massin P, Haouchine B, Erginay A, Gaudric A. Mac-ular retinoschisis in highly myopic eyes. Am J Ophthalmol. 2002;

133:794800.28. Horio N, Miyake Y, Horiguchi M. Kinetics of foveal cone photopig-

ment in myopia without chorioretinal degeneration. Jpn J Oph-thalmol. 1999;43:4447.

29. Zeimer R, Asrani S, Zou S, Quigley H, Jampel H. Quantitativedetection of glaucomatous damage at the posterior pole by retinalthickness mapping: a pilot study. Ophthalmology. 1998;105:224231.


myopia, axial length, and oct characteristics

Documents