The choroid accounts for most ocular blood flow.1 Its main functions include blood supply to the outer layers of the retina and the photoreceptors2 and absorption of excess light and heat from the retina.3,4 Severe choroidal thinning may result in photoreceptor damage and visual loss.2 The choroid is involved in many vision-threatening ocular diseases, such as age-related macular degeneration, idiopathic polypoidal choroidal vasculopathy, central serous chorioretinopathy, and myopic chorioretinal atrophy.5
Histologic studies have shown the choroid to be approximately 220 μm thick.6,7 These studies were performed decades ago and their accuracy has been questioned because they were performed in vitro and did not describe the living functioning choroid.8,9 Until recently, choroidal thickness could not be accurately measured by any imaging modality. However, with new advances in optical coherence tomography (OCT) technology and the development of spectral-domain OCT (SD-OCT), several studies have focused on measuring choroidal thickness in healthy participants and several pathologies.4,5,8–12
OCT is based on a broad band light source that illuminates the eye. Backscattered light is combined with light reflected from a reference arm to generate an interference signal. The frequency of the reflected light is correlated to the depth of its origin, whereby the greater the depth the higher the frequency. Because increased depth is associated with reduced signal intensity and resolution, both the retina and the retinal pigment epithelium prevent clear demonstration of the choroid by OCT.4,9 It has been shown that increased wavelength allows greater tissue penetration by OCT.13 SD-OCT uses a wavelength of 840 nm and a technique where the light source is brought closer to the eye can produce an inverted image focusing on the choroid and inner sclera,4 allowing an accurate image of the choroid. This technique that enables high-resolution visualization of the choroid is termed “enhanced depth imaging.”4,9,10 It has also been performed with OCT prototypes using a 1,060-nm wavelength.5,11
Recent studies have shown the average choroidal thickness to be approximately 300 μm.4,5,8,9 A correlation of choroidal thickness with age and refraction has been found, so that increasing age and myopia are associated with choroidal thinning.4,5,9–11 In addition, the choroid was shown to be thickest in the subfoveal region and thinner in the nasal and inferior regions compared to the temporal and superior regions, respectively.5,9,11,12
Choroidal thickness is important for understanding and evaluating various choroidal pathologies. With increasing knowledge and technological advances, it may become an important imaging modality used in future routine practice. Choroidal pathology has been shown to be part of some common diseases in ophthalmology, such as diabetic retinopathy and age-related macular degeneration, which is the leading cause of irreversible severe central visual acuity loss in people older than 50 years in the developed world.14 Choroidal oxidative stress, chronic inflammation, atrophy, and extracellular matrix changes have all been implicated in the pathogenesis of age-related macular degeneration,15,16 and choroidal abnormalities have been demonstrated to be common in nonproliferative diabetic retinopathy17 and diabetic macular edema.18
Previously published series were smaller than ours and most were retrospective in nature. The purpose of this study was to measure the choroidal thickness in a larger cohort of healthy adult volunteers, and thus contribute to the growing knowledge of choroidal thickness and its correlation with age, refractive error, and axial length. With the growing importance of choroidal pathology diagnosed by high-resolution OCT, it is of utmost importance to establish a normative database including variations according to the above mentioned parameters.
Patients and Methods
This study was performed at the ophthalmology department in our institution. All participants were healthy white volunteers, with no ophthalmic or systemic diseases. Both eyes of each participant were included. All participants underwent a complete biomicroscopic examination, including dilated fundus examination, Goldmann applanation tonometry, and Snellen visual acuity testing. Volunteers with any ocular abnormality were excluded. Specifically, no participant had any retinal abnormality, cataract, unclear cornea, media opacities, or glaucoma. The only ocular finding that was not an exclusion criterion in our study was the presence of peripapillary atrophy (PPA). Any participant who had previously undergone ocular surgery, including cataract removal or laser refractive surgery, was excluded.
Additionally, participants were examined by an autorefractometer (KR-8000PA Supra; Topcon, Itabashi, Japan) to determine the spherical equivalent refractive error. Participants with astigmatism of 2.00 diopters (D) or more were excluded. Participants were also examined by an IOLMaster (Carl Zeiss Meditec AG, Jena, Germany) to determine axial length.
All participants were examined by Heidelberg Spectralis SD-OCT (Heidelberg Engineering, Heidelberg, Germany), with an 840-nm wavelength. The retina was first scanned by a horizontal fast raster scanning protocol of a 30° × 30° area to determine that no retinal abnormalities were present. Participants were examined through dilated pupils.
Choroidal thickness was then measured by the enhanced depth imaging technique.4,9 This technique consists of positioning the OCT device close to the eye until an inverted image is obtained. This image captures the choroid from the retinal pigment epithelium to the inner border of the sclera. The choroid was imaged by 20° horizontal and vertical single cross-sections at the macula, centered at the fovea. Obtained images were inverted according to the enhanced depth imaging technique. To ensure high quality and noise reduction, we used the eye tracking system and averaging technique. Each scan consisted of 100 averaged high-resolution OCT frames. Images were converted to white on black grayscale to sharpen the contrast and allow more accurate measurement. Choroidal thickness was then measured using Image J software, version 1.43u, a Java-based image processing program developed by the National Institutes of Health ( http://rsb.info.nih.gov/ij). Choroidal thickness was measured at five locations: subfoveal, 3 mm nasal to the fovea, 3 mm temporal to the fovea, 3 mm inferior to the fovea, and 3 mm superior to the fovea. Thickness was measured as the vertical distance between the outer margin of the hyperreflective retinal pigment epithelium layer and the chorioscleral interface. All OCT examinations and measurements were performed by a single examiner (DG) and made to the nearest 1 μm.
An analysis of variance with repeated measures was performed to assess the correlation between choroidal thickness at each location and age, spherical equivalent refractive error, and axial length. Paired t tests were used to compare the choroidal thickness between locations. Statistical significance was defined as a P value of .05. Data were analyzed using SPSS for Windows, version 17.0 (SPPS, Inc., Chicago, IL). Both eyes of each participant were included in this study. Every eye has its own refractive error, axial length, and choroidal thickness, and our data indicate that there may be a significant difference between both eyes of the same participant. Inclusion of both eyes was also done in previous studies.3,10
Eighty-four eyes from 42 healthy participants with no preexisting systemic or ophthalmic conditions were included in the study. The participants included 16 men (38%) and 26 women (62%). Mean age was 42.31 years ± 16.31 (range: 19 to 86 years). Mean visual acuity was 0.045 logarithm of the minimum angle of resolution, equivalent to 20/22 (range: 20/20 to 20/30). Mean intraocular pressure was 13.66 ± 1.65 mm Hg (range: 11 to 18 mm Hg).
Mean spherical equivalent refractive error was −1.31 ± 1.90 D (range: −8.00 to +1.50). Fifteen eyes (17.8%) had peripapillary atrophy. Mean axial length was 23.72 ± 0.99 mm (range: 22.07 to 27.12 mm).
An example of an enhanced depth image used in this study is presented in Figure 1. Mean choroidal thicknesses at the subfoveal, superior, inferior, temporal, and nasal locations were 293, 308, 264, 263, and 174 μm, respectively (Table 1). Choroidal thickness was found to be greatest at the superior location, followed closely by the subfoveal location, then by the inferior and temporal locations (which were similar), and thinnest at the nasal location. The correlation between choroidal thicknesses at the various locations is presented in Figure 2. Mean choroidal thickness at each location was significantly correlated with all other locations, except between the inferior and temporal locations (Table 2).
Figure 1. A horizontal enhanced depth image of the left eye of a 32-year-old participant with emmetropia had an axial length of 23.31 mm. Choroidal thickness (indicated by the yellow lines) is 165, 360, and 312 μm at the nasal, subfoveal, and temporal locations, respectively.
Table 1: Mean Choroidal Thickness at the Five Studied Macular Locations
Figure 2. The relations measured between choroidal thicknesses in the five studied locations.
Table 2: Comparison of Choroidal Thickness Between All Possible Pairs of Macular Locations
The study included 15 eyes with PPA; all were myopic with a mean spherical equivalent refractive error of −3.50 D and a mean axial length of 24.66 mm. The presence of PPA was correlated with choroidal thickness at four of the five studied locations (all but the temporal location). Comparison between these eyes and the remaining 69 eyes without PPA demonstrated that choroidal thickness was significantly lower at the subfoveal, nasal, superior, and inferior locations (P = .002, .003, .002, and .007, respectively) in eyes with PPA. Choroidal thickness temporal to the fovea was not significantly different between eyes with and without PPA (P = .164).
Choroidal thickness was significantly inversely correlated with age in all locations except nasal to the fovea. It was significantly inversely correlated with axial length and positively correlated with spherical equivalent refractive error in all locations. These results and the levels of their statistical significance are presented in Table 3.
Table 3: Correlations Between Measured Choroidal Thickness in All Locations and Age, Axial Length (AL), and Spherical Equivalent (SE) Refractive Error
In our study, mean subfoveal choroidal thickness was 293 μm, which is within the range of previous studies that reported a mean thickness of 272 to 354 μm.4,5,9–12 The differences in mean choroidal thickness between the different studies may reflect differences in age and refractive error between the studied cohorts. Measurements of choroidal thickness have been made using other modalities, such as partial coherence inferometry8 and high-resolution ultrasound.19 These methods found mean choroidal thickness to be 293 to 320 μm.8,19 The studies have rendered the histologic measured value of 220 μm obsolete, and we conclude it is reasonable to assume that the average subfoveal choroidal thickness in healthy adults is approximately 300 μm.
Previous studies have demonstrated correlations between choroidal thicknesses at various locations in the macula. It has been established that the choroid is thicker subfoveally than either temporally or nasally to the fovea.5,9,12 Similar to our findings, all studies of choroidal thickness have demonstrated the thinnest location being nasal to the fovea,4,5,9,11,12 especially in eyes with peripapillary atrophy. Few studies have investigated the relations between choroidal thickness in the subfoveal and superior and inferior locations. In their study of healthy Japanese participants, Ikuno et al.5 found similar mean choroidal thicknesses in three locations, the greatest being superiorly, followed by subfoveally and inferiorly (364, 354, and 345 μm, respectively). Esmaeelpour et al.11 reported that choroidal thickness 1.5 mm superior to the fovea was significantly greater than subfoveally in myopic eyes.
Our results are consistent with the previous findings and serve to corroborate them. In our study, the choroidal thickness was greater subfoveally than temporal to it and thinnest at the nasal location. We also found the choroid to be significantly thicker superior to the fovea than subfoveally, which is a new finding as a general correlation not limited only to myopic eyes.
In an analysis of eyes with PPA, its presence was correlated with a significant decrease in choroidal thickness at the subfoveal, nasal, superior, and inferior locations. The choroidal thickness temporal to the fovea was not affected by PPA. This is reasonable due to the distance of this location from the PPA.
Based on our results, we provide a comprehensive description of the choroidal thickness in the macula. Horizontally, it is thickest at the fovea, then temporally and nasally. Vertically, it is thickest superior to the fovea, then subfoveally and inferiorly. The superior location is the thickest of all locations, the nasal location is the thinnest, and the temporal and inferior locations are similar (Table 1 and Fig. 1).
Choroidal thickness has previously been correlated to age and refractive error. Increased age and myopia were demonstrated to be associated with a significantly thinner choroid.5,9–12 For example, Fujiwara et al.10 reported a series of 55 eyes with a mean refractive error of −11.90 D and a mean subfoveal choroidal thickness of 93.2 μm. Our results demonstrate a significant inverse correlation between choroidal thickness and axial length and a positive correlation between it and spherical equivalent refractive error in all studied locations (Table 3). This strengthens the association between increasing myopia and decreased choroidal thickness. Our results indicate that this association holds true not only subfoveally, but in all other macular locations.
Our study included 15 eyes with PPA and a mean spherical equivalent refractive error of −3.50 D. It is possible that the higher myopic error may be responsible for the thinner choroids measured in them. However, the correlation between increased myopia and decreased choroidal thickness was significant at the temporal location when analyzed in all eyes, whereas it was not significant in the subgroup of eyes with PPA. This discrepancy may indicate that although eyes with PPA are generally myopic, there are two separate causes for choroidal thinning and they have different patterns; myopia is associated with global thinning of the choroid in the macular region, whereas PPA is associated with a “sloping” pattern of choroidal thinning that is more significant nasally and gradually lessens temporally. This pattern is demonstrated in Figure 3.
Figure 3. A horizontal enhanced depth image of the left eye of a 30-year-old participant with peripapillary atrophy had myopia of −6.00 diopters and an axial length of 25.65 mm. Choroidal thickness (indicated by the yellow lines) is 97, 195, and 164 μm at the nasal, subfoveal, and temporal locations, respectively. Note the slope of the choroidal thickness from the nasal location toward the fovea.
Our results also demonstrate an inverse correlation between age and choroidal thinning, which is consistent with the results of previous studies.5,9,11,12 This correlation was found to be statistically significant in all studied locations except nasal to the fovea (Table 3). It is possible that eyes with PPA confound this effect at the nasal location.
The prospective nature of this study allowed us to thoroughly examine all participants and verify they had no previous ocular conditions. This was a major limitation in previous retrospective studies. Our study was also larger than most previously published series of choroidal thickness in healthy adults. Inclusion of eyes with PPA and participants with a wide range of age, refractive error, and axial length may be regarded as a limitation because mean choroidal thickness is influenced by these factors. However, their inclusion served to elucidate the correlations demonstrated in this study. The inclusion of both eyes from each participant may also be regarded as a limitation; however, we chose to do so because it does not confound the correlations found between choroidal thickness and axial length or spherical equivalent refractive error.
Enhanced depth imaging OCT is becoming an accurate method for measuring choroidal thickness. In the future, it may become a useful clinical tool for the diagnosis and monitoring of various ocular diseases that involve choroidal pathology. It has already made meaningful contributions in research and clinical practice.4,20,21 The results of this study unite and ascertain previous knowledge of choroidal thickness, aid in establishing normal values of choroidal thickness in healthy adults, and describe its relations between different macular locations. The results strengthen the correlation between increased age and myopia, decrease choroidal thickness, and demonstrate the pattern of thinning associated with PPA. We present a new correlation that choroidal thickness is significantly greater superior to the fovea than subfoveally and inferior to it. Further research is needed to focus on documenting the progression over time of choroidal thickness in eyes with ocular conditions, or comparing choroidal thickness between eyes of patients with unilateral conditions.
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Mean Choroidal Thickness at the Five Studied Macular Locations
|Location||Mean (μm)||SD (μm)||Range (μm)|
|Nasal (3 mm nasal to fovea)||174.84||67.21||42–318|
|Temporal (3 mm temporal to fovea)||263.02||68.47||103–441|
|Superior (3 mm superior to fovea)||308.56||80.02||128–492|
|Inferior (3 mm inferior to fovea)||264.20||81.04||104–430|
Comparison of Choroidal Thickness Between All Possible Pairs of Macular Locations
|Compared Location Pairs (and Their Relations)||Mean Difference in Choroidal Thickness (μm)||P|
|Subfoveal > Nasal||118.69||< .001|
|Subfoveal > Temporal||30.51||< .001|
|Subfoveal < Superior||15.02||.021|
|Subfoveal > Inferior||29.33||< .001|
|Nasal < Temporal||88.17||< .001|
|Nasal < Superior||133.71||<.001|
|Nasal < Inferior||89.35||< .001|
|Superior > Inferior||44.35||< .001|
|Superior > Temporal||45.53||< .001|
|Temporal ∼ Inferior||1.17||.877|
Correlations Between Measured Choroidal Thickness in All Locations and Age, Axial Length (AL), and Spherical Equivalent (SE) Refractive Errora
|Location||Correlation With Age||Correlation With AL||Correlation With SE|
|Subfoveal||< .001||< .001||.02|
|Nasal||.231||< .001||< .001|
|Temporal||< .001||< .001||.05|
|Superior||< .001||< .001||.009|