October 2014
Volume 55, Issue 10
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Retina  |   October 2014
Macular Choroidal Thicknesses in Healthy Adults—Relationship With Ocular and Demographic Factors
Author Affiliations & Notes
  • Colin S. H. Tan
    National Healthcare Group Eye Institute, Tan Tock Seng Hospital, Singapore
    Fundus Image Reading Center, National Healthcare Group Eye Institute, Singapore
  • Kai Xiong Cheong
    National Healthcare Group Eye Institute, Tan Tock Seng Hospital, Singapore
  • Correspondence: Colin S. H. Tan, National Healthcare Group Eye Institute, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, Singapore 308433; Colintan_eye@yahoo.com.sg
Investigative Ophthalmology & Visual Science October 2014, Vol.55, 6452-6458. doi:10.1167/iovs.13-13771
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      Colin S. H. Tan, Kai Xiong Cheong; Macular Choroidal Thicknesses in Healthy Adults—Relationship With Ocular and Demographic Factors. Invest. Ophthalmol. Vis. Sci. 2014;55(10):6452-6458. doi: 10.1167/iovs.13-13771.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose.: To determine the differences in choroidal thickness (CT) among different groups of refractive errors and axial lengths, and to describe the rates of change of CT with ocular and demographic factors in various regions of the macula.

Methods.: Prospective cohort study of 150 healthy volunteers. Spectral-domain optical coherence tomography was performed on both eyes using a standardized imaging protocol. Manual grading of the choroidal boundaries was independently performed by trained graders to determine Early Treatment Diabetic Retinopathy Study (ETDRS) subfield choroidal thickness. Multiple linear regression analyses were performed to determine the effects of spherical equivalent, axial length and age on choroidal thickness in each subfield.

Results.: The mean central subfield CT was 324.9 μm (range, 123–566 μm) and varied significantly with both spherical equivalent (P < 0.001) and axial length (P < 0.001), but not age or sex. On multiple linear regression analysis using spherical equivalent, the coefficients were 20.0 for the central subfield, ranged from 16.9 to 19.9 for the inner subfields, and decreased to 13.9 to 16.2 for the outer subfields. Performing regression analysis using axial length, the coefficients were −36.4 for the central subfield, −30.5 to −34.5 for the inner subfields, and −24.6 to −27.3 for the outer subfields.

Conclusions.: Choroidal thickness varies significantly with spherical equivalent and axial length in all regions of the macula, but exhibits different rates of change among different subfields. The rates of change were greater in the central and inner subfields compared with the outer subfields.

Introduction
Besides playing an essential role in the normal physiology of the eye, the choroid has also been shown to be of importance in the pathophysiology of various retinal diseases. Using spectral domain optical coherence tomography (SD-OCT), investigators have reported relative thinning or thickening of the choroid in patients with diseases such as AMD, 1,2 polypoidal choroidal vasculopathy, 2 diabetic retinopathy, 3 central serous chorioretinopathy, 4,5 and pathologic myopia. 6,7 Indeed, it has been suggested that variations in choroidal thickness may indicate the presence of a disease, or affect its prognosis and progression. In these studies, choroidal thickness in the diseased eye was compared with either the patient's contralateral eye or with a control group. 
However, any attempt to compare choroidal thickness in eyes with diseases with what is considered “normal” must be tempered by the knowledge that there exists considerable variation of normal choroidal thicknesses reported in the literature. Mean subfoveal choroidal thickness ranges from 264.15 to 354.00 μm. 814 To fully appreciate the relationship between choroidal thickness and retinal diseases, it is essential to have normative values for choroidal thicknesses among different populations, and to understand the demographic and ocular factors that affect these parameters. 
Earlier studies have reported that choroidal thickness varies with spherical equivalent (6.205–25.4 μm per diopter), 10,1522 axial length (−17.031 to −58.2 μm per mm), 10,17,20,21,2325 or age (−0.899 to −5.4 μm per year). 9,10,1518,20,2224,26,27 Most of these studies, however, analyzed the change of point thickness measurements (subfoveal choroidal thickness) or, less commonly, central subfield choroidal thicknesses. 15,23,24 Because the choroid is a three-dimensional structure, with a highly anastomosed network of blood vessels, and has been shown to exhibit considerable topographic variation, 14,15,23,24 a key gap in our current knowledge is whether ocular parameters affect choroidal thickness uniformly throughout the macula or at different rates in various regions of the macula. Retinal and choroidal diseases are not confined to the fovea, and may involve other regions of the macula. Therefore, it is essential to understand how choroidal thicknesses in different regions of the macula vary with spherical equivalent, axial length, or age so as to fully appreciate the effects of the disease process on the choroid. 
Our objectives were to determine the differences in choroidal thickness among different groups of refractive error and axial lengths. We also aimed to describe the rates of change of choroidal thickness with ocular and demographic factors, and to compare the rates of change among various regions of the macula. 
Methods
In a prospective cohort study performed at the National Healthcare Group Eye Institute, Tan Tock Seng Hospital, Singapore, 150 consecutive healthy volunteers of Chinese ethnicity underwent ocular imaging with SD-OCT. This study was approved by the Institutional Review Board of the National Healthcare Group, and conformed to the tenets of the Declaration of Helsinki. Written, informed consent was obtained from all participants. Participants were examined by a trained ophthalmologist (CSHT) to exclude ocular pathology. Participants with ocular disease or previous ocular surgery were excluded. Due to the small number of hyperopes among the young volunteers, participants with spherical equivalent greater than +0.50 diopters (D) were also excluded. 
Ocular Imaging Protocol
Using a standardized imaging protocol, SD-OCT with enhanced depth imaging 8 was performed on both eyes using the Spectralis OCT (Heidelberg Engineering, Heidelberg, Germany). 
The same experienced operator performed all OCT scans under standardized mesopic lighting conditions, first on the right eye, followed by the left eye. A 31-line horizontal raster scan (30° × 25°, 9.2 × 7.6 mm) centered on the fovea was performed, with 25 to 35 frames averaged in each OCT B scan to improve the image quality. Each OCT scan was reviewed by a Fellowship-trained retinal specialist (CSHT) to ensure that the scan was of sufficient clarity to adequately visualize the choroid–scleral boundary on every B scan. If any scan was of insufficient quality, it was immediately repeated and reviewed until the image was satisfactory. 
All OCT scans were performed within a standardized 2-hour period from 12 PM to 2 PM to account for the effects of diurnal variation of choroidal thickness. 14,28,29  
Axial length was measured using the IOL Master (Carl Zeiss Meditec, Dublin, CA, USA), and refractive error and keratometry were measuring using the Canon RK-F1 full autorefractor-keratometer (Canon, Inc., Tokyo, Japan). 
Emmetropia was defined as spherical equivalent between −0.49 D and +0.50 D, and myopia was defined as spherical equivalent of −0.5 D or more. High myopia was defined as spherical equivalent of −6.0 D or more. 
Manual Segmentation of the Choroid
The segmentation lines of all 31 horizontal B scans from each of the 300 eyes were manually adjusted by two trained and experienced graders using the Heidelberg Eye Explorer software (version 1.7.0.0); (Heidelberg Engineering). The OCT scans were first centered over the fovea. The lower segmentation line, originally drawn automatically at the lower border of the RPE, was moved to the choroid–scleral junction. In regions where the choroid–scleral boundary could not be seen distinctly (between 500 and 1000 μm in length), reference was made to the adjacent areas of the choroid–scleral interface as well as to OCT sections superior and inferior to that B scan to give an indication of the variation of the choroidal topography both horizontally and vertically in that region. Subsequently, the upper segmentation line (originally corresponding to the internal limiting membrane) was moved down to the lower border of the RPE. 
The mean choroidal thicknesses in all sectors of the Early Treatment Diabetic Retinopathy Study (ETDRS) grid were calculated by the software and displayed. Subfoveal choroidal point thickness was measured from the lower border of the RPE to the choroid–sclera junction. 
Statistical Analysis
Statistical analysis was performed using SPSS version 16.0 (SPSS, Inc., Chicago, IL, USA). The differences between the spherical equivalent groups were analyzed using ANOVA with Bonferroni correction. Multiple linear regression analyses were performed to determine the effects of spherical equivalent, axial length, and age on choroidal thickness in each sector of the ETDRS grid. Intraclass correlation was used to assess the agreement between the two graders for choroidal thickness measurements. 
Results
The mean spherical equivalent of the 300 eyes was −4.0 D (range, −11.5 D to +0.50 D, SD ±1.9), and the axial length ranged from 22.0 to 29.3 mm (mean 25.4 mm, SD ±1.4 mm). Of the 150 participants, 83 (55.3%) were males and 67 (44.7%) were females, with a mean age of 23.0 years (range, 21–33, SD ±1.9). Intraclass correlation for choroidal thickness measurements between the graders was 0.989 (95% confidence interval [CI] 0.976–0.995). No participants were excluded from this study because of inadequate imaging quality. 
Choroidal thickness in the central subfield correlated well with both spherical equivalent and axial length (Pearson correlation coefficient R = 0.57 and −0.54, respectively, both P < 0.001). In all ETDRS subfields, the correlation coefficient for choroidal thickness with spherical equivalent was marginally stronger compared with the correlation with axial length. Analyzing separately, spherical equivalent was found to correlate strongly with axial length (R = −0.77, P < 0.001). The Kolmogorov-Smirnov tests and Q-Q plots for choroidal thicknesses showed normal distributions in all subfields. 
The mean central subfield choroidal thickness was 324.9 μm (SD ± 94.3), and demonstrated a considerable range (443 μm), with a minimum of 123 μm and a maximum of 566 μm. Analyzing by spherical equivalent, mean central subfield choroidal thickness decreased progressively with increasingly severity of myopia, ranging from 438.5 μm among emmetropes to 238.9 μm among myopes with spherical equivalent greater than or equal to −8.0 D (Fig. 1A). The differences in choroidal thickness among all spherical equivalent groups were statistically significant (ANOVA P < 0.001). Similarly, the mean central subfield choroidal thickness decreased progressively with increasing axial length (Fig. 1B), with the differences among groups also being statistically significant. 
Figure 1
 
(A) Variation of central subfield choroidal thickness with spherical equivalent. (B) Variation of central subfield choroidal thickness with axial length.
Figure 1
 
(A) Variation of central subfield choroidal thickness with spherical equivalent. (B) Variation of central subfield choroidal thickness with axial length.
Table 1 summarizes the mean choroidal thickness in each subfield of the ETDRS grid and its variation with spherical equivalent. Analyzing for all participants, the choroid was thickest in either the temporal or superior sectors, and thinnest in the nasal sectors. Among those with spherical equivalent −1.99 D to +0.50 D, the choroid was thickest in the inner temporal and central subfields, whereas in all other groups, the central subfield was thinner than the corresponding temporal or superior sectors. The variation of choroidal thickness with axial length in each subfield of the ETDRS grid is summarized in Table 2, and shows a decrease in choroidal thickness with increasing axial length. Among participants with axial length 22.0 to 23.99 mm, the choroid was thickest in the central subfield and inner temporal sectors. For those with axial length of 24 mm or more, the temporal and/or superior subfields were thicker than the central subfield. 
Table 1
 
Variation of Choroidal Thicknesses With Spherical Equivalent (Diopter)
Table 1
 
Variation of Choroidal Thicknesses With Spherical Equivalent (Diopter)
+0.50 to −0.49 −0.50 to −1.99 −2.00 to −3.99 −4.00 to −5.99 −6.00 to −7.99 ≥−8.00 All Participants P Value
Central subfield 438.5 (69.2) 381.1 (81.3) 329.0 (80.9) 307.1 (84.2) 267.0 (69.8) 238.9 (53.0) 324.9 (94.3) <0.001
Central (point thickness) 438.0 (66.0) 381.8 (87.3) 332.2 (79.7) 309.7 (84.2) 267.7 (73.1) 238.5 (54.6) 326.4 (95.2) <0.001
Inner superior 430.9 (66.7) 377.7 (71.4) 327.0 (78.9) 311.9 (74.3) 283.4 (65.7) 252.9 (53.4) 328.5 (85.7) <0.001
Inner inferior 427.4 (65.8) 381.8 (83.3) 328.1 (82.3) 307.7 (86.3) 262.9 (67.1) 238.7 (60.2) 322.9 (94.2) <0.001
Inner nasal 398.0 (70.1) 351.0 (81.6) 295.0 (75.9) 280.0 (81.7) 239.1 (63.6) 212.4 (52.5) 294.0 (90.0) <0.001
Inner temporal 441.0 (70.4) 387.7 (74.2) 345.4 (81.5) 316.4 (82.5) 287.0 (66.0) 257.6 (53.5) 337.9 (89.7) <0.001
Outer superior 421.9 (68.2) 373.6 (61.5) 331.7 (76.3) 323.0 (66.2) 293.6 (61.8) 275.7 (51.9) 334.0 (77.5) <0.001
Outer inferior 393.5 (54.0) 365.1 (74.7) 316.6 (77.5) 303.4 (85.2) 265.2 (62.7) 245.1 (62.9) 313.8 (84.3) <0.001
Outer nasal 317.4 (71.9) 285.9 (68.6) 242.9 (70.2) 231.0 (72.9) 198.2 (55.1) 174.6 (46.5) 240.9 (77.1) <0.001
Outer temporal 412.4 (69.2) 373.1 (68.7) 347.2 (76.2) 316.9 (71.4) 298.3 (57.6) 274.2 (54.5) 336.8 (77.8) <0.001
Table 2
 
Variation of Choroidal Thicknesses With Axial Length (Millimeter)
Table 2
 
Variation of Choroidal Thicknesses With Axial Length (Millimeter)
22.00–22.99 23.00–23.99 24.00–24.99 25.00–25.99 26.00–26.99 ≥27.00 All Participants P Value
Central subfield 433.0 (65.0) 413.4 (82.2) 346.8 (77.9) 304.5 (90.0) 288.5 (79.3) 248.5 (49.7) 324.9 (94.3) <0.001
Central (point thickness) 440.0 (81.2) 413.9 (81.6) 349.2 (77.4) 307.1 (88.7) 289.5 (80.9) 245.8 (53.3) 326.4 (95.2) <0.001
Inner superior 426.3 (73.5) 405.8 (79.0) 344.3 (72.2) 308.3 (84.4) 299.7 (72.0) 267.7 (51.1) 328.5 (85.7) <0.001
Inner inferior 409.7 (54.1) 404.1 (90.7) 345.3 (77.4) 308.5 (94.1) 285.5 (74.8) 243.7 (56.8) 322.9 (94.2) <0.001
Inner nasal 390.3 (61.0) 382.3 (85.6) 312.6 (76.1) 277.0 (84.8) 257.0 (73.3) 223.8 (46.8) 294.0 (90.0) <0.001
Inner temporal 429.0 (68.2) 415.6 (77.5) 361.8 (76.3) 317.4 (91.2) 308.4 (73.3) 263.4 (48.4) 337.9 (89.7) <0.001
Outer superior 418.8 (77.2) 396.6 (67.3) 344.2 (66.4) 312.7 (78.0) 313.5 (66.7) 289.2 (49.6) 334.0 (77.5) <0.001
Outer inferior 378.8 (45.2) 374.1 (71.9) 330.0 (74.1) 303.9 (88.9) 286.6 (69.5) 247.4 (53.5) 313.8 (84.3) <0.001
Outer nasal 313.5 (62.3) 312.1 (73.8) 255.4 (67.6) 229.1 (73.8) 209.9 (60.2) 182.2 (41.0) 240.9 (77.1) <0.001
Outer temporal 402.5 (67.7) 395.8 (69.8) 354.1 (71.8) 321.4 (84.3) 319.6 (60.6) 274.3 (46.2) 336.8 (77.8) <0.001
Comparing by sex, there were no significant differences in choroidal thickness in any ETDRS subfield (all P > 0.05). These results were seen when the entire cohort was analyzed, and when the cohort was subdivided by spherical equivalent or axial length groups. Analyzing for age, there was no significant correlation between age and choroidal thickness (P > 0.05 for all sectors) and no significant difference in choroidal thickness among older participants compared with younger participants. 
Linear Regression Analysis
Performing linear regression analysis, spherical equivalent was a significant factor in determining central subfield choroidal thickness, with a coefficient of 20.0 (95% CI 16.4–23.6, P < 0.001) and R 2 of 0.328. Using axial length as the independent variable instead, the coefficient was −36.4 (95% CI −43.6 to −29.3, P < 0.001) with R 2 of 0.292. The coefficient for age was −3.0 (95% CI −9.2 to 3.2, P = 0.339). 
Two separate linear regression models were constructed: the first using spherical equivalent as the independent variable (Table 3), and the second using axial length (Table 4). 
Table 3
 
Relationship Between Choroidal Thickness and Spherical Equivalent
Table 3
 
Relationship Between Choroidal Thickness and Spherical Equivalent
Spherical Equivalent Intercept R 2
Coefficient (95% CI) P Value Coefficient (95% CI) P Value
Central subfield 20.0 (16.4–23.6) <0.001 469.4 (351.9–587.0) <0.001 0.328
Central (point thickness) 20.1 (16.4–23.7) <0.001 469.6 (350.5–588.8) <0.001 0.323
Inner superior 16.9 (13.5–20.2) <0.001 465.4 (355.0–575.7) <0.001 0.282
Inner inferior 19.9 (16.3–23.5) <0.001 458.1 (340.3–576.0) <0.001 0.323
Inner nasal 18.9 (15.4–22.3) <0.001 427.3 (314.3–540.2) <0.001 0.319
Inner temporal 18.3 (14.8–21.7) <0.001 502.5 (388.8–616.2) <0.001 0.306
Outer superior 14.2 (11.0–17.3) <0.001 465.1 (362.6–567.6) <0.001 0.244
Outer inferior 16.2 (12.8–19.5) <0.001 436.2 (326.4–546.0) <0.001 0.266
Outer nasal 14.7 (11.7–17.8) <0.001 363.2 (262.8–463.7) <0.001 0.267
Outer temporal 13.9 (10.8–17.0) <0.001 513.1 (410.2–615.9) <0.001 0.245
Table 4
 
Relationship Between Choroidal Thickness and Axial Length
Table 4
 
Relationship Between Choroidal Thickness and Axial Length
Axial Length Intercept R 2
Coefficient (95% CI) P Value Coefficient (95% CI) P Value
Central subfield −36.4 (−43.6 to −29.3) <0.001 1247.4 (1065.1–1429.8) <0.001 0.292
Central (point thickness) −37.3 (−44.5 to −30.1) <0.001 1271.4 (1087.5–1455.2) <0.001 0.298
Inner superior −30.5 (−37.3 to −23.7) <0.001 1101.1 (928.4–1273.9) <0.001 0.243
Inner inferior −34.5 (−41.8 to −27.3) <0.001 1196.6 (1012.4–1380.7) <0.001 0.266
Inner nasal −34.0 (−40.8 to −27.1) <0.001 1153.9 (978.9–1328.8) <0.001 0.280
Inner temporal −33.4 (−40.3 to −26.4) <0.001 1182.8 (1005.1–1360.5) <0.001 0.267
Outer superior −24.6 (−30.9 to −18.3) <0.001 957.1 (797.1–1117.1) <0.001 0.196
Outer inferior −27.1 (−33.8 to −20.4) <0.001 998.2 (828.0–1169.0) <0.001 0.206
Outer nasal −27.3 (−33.3 to −21.3) <0.001 931.4 (779.3–1083.4) <0.001 0.249
Outer temporal −25.3 (−31.7 to −19.0) <0.001 978.9 (816.6–1141.2) <0.001 0.200
Analyzing the effects of spherical equivalent on choroidal thickness, the coefficient was greatest in the central subfield (20.0), ranged from 16.9 to 19.9 for the inner ETDRS subfields, and decreased to 13.9 to 16.2 for the outer subfields (Table 3). As a result, the rate of change of choroidal thickness with spherical equivalent was greatest in the central subfield, followed by the inner subfields, and was more gradual in the outer subfields (Fig. 2A). The difference in mean choroidal thicknesses among the central, inner, and outer subfields was greatest for emmetropes, and progressively decreased with myopia severity (Fig. 2A). Among high myopes (spherical equivalent −6 D or higher), the mean central, inner, and outer ETDRS subfields were of similar thickness. 
Figure 2
 
(A) Variation of choroidal thicknesses in the central subfield, mean inner subfields, and mean outer subfields with spherical equivalent. The mean choroidal thicknesses among the three regions are similar for spherical equivalent −6 D or more. (B) Variation of choroidal thicknesses in the central subfield, mean inner subfields, and mean outer subfields with axial length. The mean choroidal thicknesses among the three regions are similar for axial length of 26.0 mm or more. Mean inner subfield is the mean choroidal thickness of the inner superior, inferior, nasal, and temporal subfields. Mean outer subfield is the mean choroidal thickness of the outer superior, inferior, nasal, and temporal subfields.
Figure 2
 
(A) Variation of choroidal thicknesses in the central subfield, mean inner subfields, and mean outer subfields with spherical equivalent. The mean choroidal thicknesses among the three regions are similar for spherical equivalent −6 D or more. (B) Variation of choroidal thicknesses in the central subfield, mean inner subfields, and mean outer subfields with axial length. The mean choroidal thicknesses among the three regions are similar for axial length of 26.0 mm or more. Mean inner subfield is the mean choroidal thickness of the inner superior, inferior, nasal, and temporal subfields. Mean outer subfield is the mean choroidal thickness of the outer superior, inferior, nasal, and temporal subfields.
Similar patterns were observed for linear regression using axial length, with higher rates of change in the central and inner subfields, and lower rates in the outer subfields (Table 4; Fig. 2B). 
Spherical equivalent was a significant factor affecting choroidal thickness for those with spherical equivalent less than −6 D (coefficient 23.3, R 2 = 0.20, P < 0.001) but not for high myopes (spherical equivalent −6D or higher; coefficient 13.4, R 2 = 0.04, P > 0.05). Performing linear regression separately for participants with axial length less than 26 mm and axial length of 26.0 mm or more, the coefficients were −45.4 (R 2 = 0.15, P < 0.001) and −36.4 (R 2 = 0.11, P < 0.0001), respectively. 
Central point choroidal thickness was similar to central subfield choroidal thickness (Tables 1, 2), and it has similar rates of change with spherical equivalent and axial length compared with central subfield choroidal thickness (Tables 3, 4). 
Discussion
In this prospective cohort study, we found progressive changes in mean choroidal thicknesses in all ETDRS subfields across a wide range of spherical equivalents and axial lengths. The rate of change of choroidal thickness varies in different regions of the macula, being largest in the central subfield, followed closely by the inner ETDRS subfields, and smallest in the outer ETDRS subfields. 
Although some earlier studies have described the effects of spherical equivalent or axial length on central point thickness measurements, 9,10,1621 central ETDRS subfield thickness, 24 or for mean choroidal thickness of the entire 6-mm ETDRS zone 15,23,24 as summarized in Table 5, we are not aware of any comprehensive analysis and comparison of the variation of choroidal thicknesses and their actual rates of change among different regions of the macula in healthy adults. Because choroidal thickness is postulated to influence the course of a disease, and some authors have reported measurements of choroidal thicknesses under the active lesion (which may occur outside of the central subfield), 5 it is essential to have normative values for choroidal thicknesses in all regions of the macula and to understand how these change with ocular parameters. For example, we have shown that choroidal thickness decreases with more severe myopia and longer axial length at a slower rate in the outer subfields; hence, it would not be appropriate to assume that spherical equivalent or axial length affect choroidal thickness to the same extent in the outer subfields compared with the central subfield. 
Table 5
 
Relationship Between Choroidal Thickness With Various Ocular and Demographic Factors
Table 5
 
Relationship Between Choroidal Thickness With Various Ocular and Demographic Factors
Study No. of Eyes Ethnicity Mean Age Spherical Equivalent, D (±SD) Axial Length, mm (±SD) Change of Variable per Diopter of Spherical Equivalent Change of Variable per Millimeter of Axial Length Change of Variable per Year of Age
Central subfield choroidal thickness
 Current 300 Chinese 23.0 −4.0 (1.9) 25.42 (1.38) 20.0  −36.1 −3.01*
 Ouyang24 59 Mixed 32.85 −0.50 (median) 23.83 (1.33) −31.96 −1.95
Mean total choroidal thickness (6 mm area in macula)
 Hirata23 31 Japanese 64.6 −1.67 (5.1) 24.6 (2.1) NS −24.95 −3.04
 Shin15 80 Korean 46.2 −0.68 (2.0)  9.55 −0.97
 Ouyang24 59 Mixed 32.85 −0.50 (median) 23.83 (1.33) −28.44 −1.85
Point central choroidal thickness
 Current 300 Chinese 23.0 −4.0 (1.9) 25.42 (1.38) 20.1  −37.0 −2.94*
 Margolis9 54 50.4 −1.3 (2.1) −1.56
 Ikuno10 79 Japanese 39.4 −1.9 (2.3) 24.40 (1.24) 29.13 −22* 4.32
 Fujiwara16 55 58.1 −11.1 (3.3)  7.84 −1.25
 Flores-Moreno17 120 54.4 −14.34 (5.46) 29.17 (2.43)  9.39* −25.166 −1.795
 Ding18 420 Chinese 49.7 10.871 (<60 y) −5.403 (>60 y)
NS (>60 y) NS (<60 y)
 Fujiwara19 145 Japanese 45.7 >−6 (range) 7.9 −20.1* −2.0
 Wei20 3233 Chinese 64.3 −0.18 (1.98) 23.2 (1.11) 15* (<−1D) −44.7 −4.12
NS (≥−1D)
 Li21 93 Danish 24.9 −1.43 24.0 25.4 −58.2
 Ozdogan Erkul30 123 Turkish 47.47 −0.24 NS −3.14
In a review of the literature, we are not aware of any studies reporting regression analysis for central subfield choroidal thickness against spherical equivalent in healthy adults. Among the studies using central point thickness measurements, the rate of change of choroidal thickness per diopter ranges from 6.205 μm to 29.13 μm, 10,1522 which is consistent with our results for both central subfield and central point thickness. These variations could be due to differences among the cohorts, or the effects of diurnal variation of choroidal thickness. 14,28,29  
Some studies have reported that spherical equivalent did not affect choroidal thickness in their study population or a specific subgroup in their study. 17,20,23,30 Flores-Moreno et al. 17 reported that spherical equivalent was significantly correlated with choroidal thickness only among high myopes (−6 D or higher) and Wei et al. 20 reported that the relationship between choroidal thickness and refractive error was not statistically significant for a spherical equivalent range of −1 D through hyperopia. When we subdivided our cohort by refractive error, spherical equivalent was a significant factor for those with emmetropia or lower severity of myopia (23.3 μm per diopter), whereas axial length was significant for those with shorter or longer axial lengths. 
The reported variations of choroidal thickness with axial length ranges from −20.1 μm to −58.2 μm per mm of axial length, which is consistent with our findings. In this study, we constructed regression models for spherical equivalent and axial length separately (Tables 3, 4) due to the strong correlation and collinearity between the two variables. Both factors demonstrated strong correlations with choroidal thickness, although the model fit was slightly better using spherical equivalent compared with axial length. 
Although some earlier studies have reported that the choroid is thickest in the central subfield, 15 or subfoveally using central point thickness, 9,31,32 others have described the choroid to be thicker in either the superior or temporal regions. 14,15,23,24,26,27 We found important differences in the location of the thickest sector based on the spherical equivalent and axial length of the participant. For those with spherical equivalent −1.99 D to +0.50 D, the central and temporal subfields were of similar thickness. In contrast, among myopes with spherical equivalent of −2.00 D or more, the choroid was thicker in the superior and temporal sectors compared with the central subfield. A similar pattern was observed based on the effects of axial length, suggesting that ocular parameters have an important impact on the region where the choroid is thickest. A paper by Flores-Moreno et al. 17 reported that in the control group (without myopia), the choroid was thickest centrally. In contrast, among high myopes, the temporal choroid was thicker than the central choroid. 
Several studies have reported significant decreases in choroidal thickness with age. 9,10,1520,2224,33 In this study, age did not significantly affect choroidal thickness, and it is likely due to the relatively smaller age range of our cohort. 
The strengths of this study include a large number of participants (300 eyes), which is larger than in many earlier studies. We also included participants with a wide range of spherical equivalent (−11.5 to +0.50 D) and axial lengths (22.0–29.3 mm). This improves the accuracy of regression analyses and allows us to examine the effects of these parameters across a large range of refractive errors. We also accounted for possible confounders by including a group of participants with relatively uniform demographics. All OCT scans were performed at standardized time so as to minimize the effect of diurnal variation on choroidal thickness, as earlier studies have described diurnal variation with mean amplitudes of more than 30 μm. 14,28,29  
In this study, 31 horizontal sections were performed for each OCT scan, which is consistent with the imaging protocols in earlier studies using Spectralis OCT. 27 A paper by Chhablani et al. 34 reported that with the Spectralis OCT, 16 OCT B scans over the macula with an interscan distance of 480 μm was sufficient to provide a clinically relevant and reliable choroidal volume map for both eyes with and without chorioretinal diseases. 
This study is not without limitations. We included participants within the ages of 21 to 33 years and hence cannot comment on the factors affecting choroidal thickness among older patients. However, we feel that this actually confers an advantage: Because the age is restricted to a smaller range, any variation in choroidal thicknesses observed is more likely due to factors such as spherical equivalent or axial length, and this eliminates the need to account for the effects of age statistically. Furthermore, the relative impact of factors such as spherical equivalent, age, or retinal diseases on variation of choroidal thickness over the decades remain unknown. Could one factor such as spherical equivalent assume a greater importance earlier on in life, only to play a relatively smaller role in later years? We demonstrated that spherical equivalent affects choroidal thickness among those with spherical equivalent less than −6.0 D, but not among high myopes, whereas axial length affects both groups. Ding et al. 18 reported that spherical equivalent was significantly correlated with choroidal thickness only in participants 60 years and younger and not in their older participants. This study establishes a baseline range of choroidal thickness among young adults on which to base future comparisons with studies on the effect of age and disease. It is for this same reason that we chose to limit our study to participants of Chinese ethnicity, although we do feel that it would be interesting to examine the roles of age and ethnicity on choroidal thickness variation in future studies. 
In conclusion, we demonstrated that choroidal thicknesses vary significantly with spherical equivalent and axial length in all ETRDS sectors. The rates of change of choroidal thicknesses vary based on the region of the macula involved, with choroidal thicknesses changing more rapidly in the central and inner subfields. 
Acknowledgments
Supported by a National Healthcare Group Clinician Scientist Career Scheme Grant (Code: CSCS/12005) (CSHT). The authors have no financial or proprietary interests in the subject of this manuscript. 
Disclosure: C.S.H. Tan, Bayer (South East Asia) Pte., Ltd. (R), Heidelberg Engineering (R), Novartis (R); K.X. Cheong, None 
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Figure 1
 
(A) Variation of central subfield choroidal thickness with spherical equivalent. (B) Variation of central subfield choroidal thickness with axial length.
Figure 1
 
(A) Variation of central subfield choroidal thickness with spherical equivalent. (B) Variation of central subfield choroidal thickness with axial length.
Figure 2
 
(A) Variation of choroidal thicknesses in the central subfield, mean inner subfields, and mean outer subfields with spherical equivalent. The mean choroidal thicknesses among the three regions are similar for spherical equivalent −6 D or more. (B) Variation of choroidal thicknesses in the central subfield, mean inner subfields, and mean outer subfields with axial length. The mean choroidal thicknesses among the three regions are similar for axial length of 26.0 mm or more. Mean inner subfield is the mean choroidal thickness of the inner superior, inferior, nasal, and temporal subfields. Mean outer subfield is the mean choroidal thickness of the outer superior, inferior, nasal, and temporal subfields.
Figure 2
 
(A) Variation of choroidal thicknesses in the central subfield, mean inner subfields, and mean outer subfields with spherical equivalent. The mean choroidal thicknesses among the three regions are similar for spherical equivalent −6 D or more. (B) Variation of choroidal thicknesses in the central subfield, mean inner subfields, and mean outer subfields with axial length. The mean choroidal thicknesses among the three regions are similar for axial length of 26.0 mm or more. Mean inner subfield is the mean choroidal thickness of the inner superior, inferior, nasal, and temporal subfields. Mean outer subfield is the mean choroidal thickness of the outer superior, inferior, nasal, and temporal subfields.
Table 1
 
Variation of Choroidal Thicknesses With Spherical Equivalent (Diopter)
Table 1
 
Variation of Choroidal Thicknesses With Spherical Equivalent (Diopter)
+0.50 to −0.49 −0.50 to −1.99 −2.00 to −3.99 −4.00 to −5.99 −6.00 to −7.99 ≥−8.00 All Participants P Value
Central subfield 438.5 (69.2) 381.1 (81.3) 329.0 (80.9) 307.1 (84.2) 267.0 (69.8) 238.9 (53.0) 324.9 (94.3) <0.001
Central (point thickness) 438.0 (66.0) 381.8 (87.3) 332.2 (79.7) 309.7 (84.2) 267.7 (73.1) 238.5 (54.6) 326.4 (95.2) <0.001
Inner superior 430.9 (66.7) 377.7 (71.4) 327.0 (78.9) 311.9 (74.3) 283.4 (65.7) 252.9 (53.4) 328.5 (85.7) <0.001
Inner inferior 427.4 (65.8) 381.8 (83.3) 328.1 (82.3) 307.7 (86.3) 262.9 (67.1) 238.7 (60.2) 322.9 (94.2) <0.001
Inner nasal 398.0 (70.1) 351.0 (81.6) 295.0 (75.9) 280.0 (81.7) 239.1 (63.6) 212.4 (52.5) 294.0 (90.0) <0.001
Inner temporal 441.0 (70.4) 387.7 (74.2) 345.4 (81.5) 316.4 (82.5) 287.0 (66.0) 257.6 (53.5) 337.9 (89.7) <0.001
Outer superior 421.9 (68.2) 373.6 (61.5) 331.7 (76.3) 323.0 (66.2) 293.6 (61.8) 275.7 (51.9) 334.0 (77.5) <0.001
Outer inferior 393.5 (54.0) 365.1 (74.7) 316.6 (77.5) 303.4 (85.2) 265.2 (62.7) 245.1 (62.9) 313.8 (84.3) <0.001
Outer nasal 317.4 (71.9) 285.9 (68.6) 242.9 (70.2) 231.0 (72.9) 198.2 (55.1) 174.6 (46.5) 240.9 (77.1) <0.001
Outer temporal 412.4 (69.2) 373.1 (68.7) 347.2 (76.2) 316.9 (71.4) 298.3 (57.6) 274.2 (54.5) 336.8 (77.8) <0.001
Table 2
 
Variation of Choroidal Thicknesses With Axial Length (Millimeter)
Table 2
 
Variation of Choroidal Thicknesses With Axial Length (Millimeter)
22.00–22.99 23.00–23.99 24.00–24.99 25.00–25.99 26.00–26.99 ≥27.00 All Participants P Value
Central subfield 433.0 (65.0) 413.4 (82.2) 346.8 (77.9) 304.5 (90.0) 288.5 (79.3) 248.5 (49.7) 324.9 (94.3) <0.001
Central (point thickness) 440.0 (81.2) 413.9 (81.6) 349.2 (77.4) 307.1 (88.7) 289.5 (80.9) 245.8 (53.3) 326.4 (95.2) <0.001
Inner superior 426.3 (73.5) 405.8 (79.0) 344.3 (72.2) 308.3 (84.4) 299.7 (72.0) 267.7 (51.1) 328.5 (85.7) <0.001
Inner inferior 409.7 (54.1) 404.1 (90.7) 345.3 (77.4) 308.5 (94.1) 285.5 (74.8) 243.7 (56.8) 322.9 (94.2) <0.001
Inner nasal 390.3 (61.0) 382.3 (85.6) 312.6 (76.1) 277.0 (84.8) 257.0 (73.3) 223.8 (46.8) 294.0 (90.0) <0.001
Inner temporal 429.0 (68.2) 415.6 (77.5) 361.8 (76.3) 317.4 (91.2) 308.4 (73.3) 263.4 (48.4) 337.9 (89.7) <0.001
Outer superior 418.8 (77.2) 396.6 (67.3) 344.2 (66.4) 312.7 (78.0) 313.5 (66.7) 289.2 (49.6) 334.0 (77.5) <0.001
Outer inferior 378.8 (45.2) 374.1 (71.9) 330.0 (74.1) 303.9 (88.9) 286.6 (69.5) 247.4 (53.5) 313.8 (84.3) <0.001
Outer nasal 313.5 (62.3) 312.1 (73.8) 255.4 (67.6) 229.1 (73.8) 209.9 (60.2) 182.2 (41.0) 240.9 (77.1) <0.001
Outer temporal 402.5 (67.7) 395.8 (69.8) 354.1 (71.8) 321.4 (84.3) 319.6 (60.6) 274.3 (46.2) 336.8 (77.8) <0.001
Table 3
 
Relationship Between Choroidal Thickness and Spherical Equivalent
Table 3
 
Relationship Between Choroidal Thickness and Spherical Equivalent
Spherical Equivalent Intercept R 2
Coefficient (95% CI) P Value Coefficient (95% CI) P Value
Central subfield 20.0 (16.4–23.6) <0.001 469.4 (351.9–587.0) <0.001 0.328
Central (point thickness) 20.1 (16.4–23.7) <0.001 469.6 (350.5–588.8) <0.001 0.323
Inner superior 16.9 (13.5–20.2) <0.001 465.4 (355.0–575.7) <0.001 0.282
Inner inferior 19.9 (16.3–23.5) <0.001 458.1 (340.3–576.0) <0.001 0.323
Inner nasal 18.9 (15.4–22.3) <0.001 427.3 (314.3–540.2) <0.001 0.319
Inner temporal 18.3 (14.8–21.7) <0.001 502.5 (388.8–616.2) <0.001 0.306
Outer superior 14.2 (11.0–17.3) <0.001 465.1 (362.6–567.6) <0.001 0.244
Outer inferior 16.2 (12.8–19.5) <0.001 436.2 (326.4–546.0) <0.001 0.266
Outer nasal 14.7 (11.7–17.8) <0.001 363.2 (262.8–463.7) <0.001 0.267
Outer temporal 13.9 (10.8–17.0) <0.001 513.1 (410.2–615.9) <0.001 0.245
Table 4
 
Relationship Between Choroidal Thickness and Axial Length
Table 4
 
Relationship Between Choroidal Thickness and Axial Length
Axial Length Intercept R 2
Coefficient (95% CI) P Value Coefficient (95% CI) P Value
Central subfield −36.4 (−43.6 to −29.3) <0.001 1247.4 (1065.1–1429.8) <0.001 0.292
Central (point thickness) −37.3 (−44.5 to −30.1) <0.001 1271.4 (1087.5–1455.2) <0.001 0.298
Inner superior −30.5 (−37.3 to −23.7) <0.001 1101.1 (928.4–1273.9) <0.001 0.243
Inner inferior −34.5 (−41.8 to −27.3) <0.001 1196.6 (1012.4–1380.7) <0.001 0.266
Inner nasal −34.0 (−40.8 to −27.1) <0.001 1153.9 (978.9–1328.8) <0.001 0.280
Inner temporal −33.4 (−40.3 to −26.4) <0.001 1182.8 (1005.1–1360.5) <0.001 0.267
Outer superior −24.6 (−30.9 to −18.3) <0.001 957.1 (797.1–1117.1) <0.001 0.196
Outer inferior −27.1 (−33.8 to −20.4) <0.001 998.2 (828.0–1169.0) <0.001 0.206
Outer nasal −27.3 (−33.3 to −21.3) <0.001 931.4 (779.3–1083.4) <0.001 0.249
Outer temporal −25.3 (−31.7 to −19.0) <0.001 978.9 (816.6–1141.2) <0.001 0.200
Table 5
 
Relationship Between Choroidal Thickness With Various Ocular and Demographic Factors
Table 5
 
Relationship Between Choroidal Thickness With Various Ocular and Demographic Factors
Study No. of Eyes Ethnicity Mean Age Spherical Equivalent, D (±SD) Axial Length, mm (±SD) Change of Variable per Diopter of Spherical Equivalent Change of Variable per Millimeter of Axial Length Change of Variable per Year of Age
Central subfield choroidal thickness
 Current 300 Chinese 23.0 −4.0 (1.9) 25.42 (1.38) 20.0  −36.1 −3.01*
 Ouyang24 59 Mixed 32.85 −0.50 (median) 23.83 (1.33) −31.96 −1.95
Mean total choroidal thickness (6 mm area in macula)
 Hirata23 31 Japanese 64.6 −1.67 (5.1) 24.6 (2.1) NS −24.95 −3.04
 Shin15 80 Korean 46.2 −0.68 (2.0)  9.55 −0.97
 Ouyang24 59 Mixed 32.85 −0.50 (median) 23.83 (1.33) −28.44 −1.85
Point central choroidal thickness
 Current 300 Chinese 23.0 −4.0 (1.9) 25.42 (1.38) 20.1  −37.0 −2.94*
 Margolis9 54 50.4 −1.3 (2.1) −1.56
 Ikuno10 79 Japanese 39.4 −1.9 (2.3) 24.40 (1.24) 29.13 −22* 4.32
 Fujiwara16 55 58.1 −11.1 (3.3)  7.84 −1.25
 Flores-Moreno17 120 54.4 −14.34 (5.46) 29.17 (2.43)  9.39* −25.166 −1.795
 Ding18 420 Chinese 49.7 10.871 (<60 y) −5.403 (>60 y)
NS (>60 y) NS (<60 y)
 Fujiwara19 145 Japanese 45.7 >−6 (range) 7.9 −20.1* −2.0
 Wei20 3233 Chinese 64.3 −0.18 (1.98) 23.2 (1.11) 15* (<−1D) −44.7 −4.12
NS (≥−1D)
 Li21 93 Danish 24.9 −1.43 24.0 25.4 −58.2
 Ozdogan Erkul30 123 Turkish 47.47 −0.24 NS −3.14
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