September 2012
Volume 53, Issue 10
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Glaucoma  |   September 2012
Choroidal Thickness in Unilateral Advanced Glaucoma
Author Notes
  • From the Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida. 
  • Current affiliation: *Department of Ophthalmology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina. 
  • Corresponding author: Jean-Claude Mwanza, Department of Ophthalmology, University of North Carolina at Chapel Hill, 130 Mason Farm Road, 5151 Bioinformatics Bldg CB# 7040, Chapel Hill, NC 27599; jean-claude_mwanza@med.unc.edu
Investigative Ophthalmology & Visual Science September 2012, Vol.53, 6695-6701. doi:10.1167/iovs.12-10388
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      Jean-Claude Mwanza, Fouad E. Sayyad, Donald L. Budenz; Choroidal Thickness in Unilateral Advanced Glaucoma. Invest. Ophthalmol. Vis. Sci. 2012;53(10):6695-6701. doi: 10.1167/iovs.12-10388.

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      © 2017 Association for Research in Vision and Ophthalmology.

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Abstract

Purpose.: To investigate whether choroidal thickness measured using optical coherence tomography (OCT) in eyes with advanced glaucoma differs from that of fellow eyes with no or mild glaucoma.

Methods.: Thirty-six patients with advanced glaucoma in one eye and with no glaucoma or mild glaucoma in the fellow eye underwent macular scanning using enhanced depth imaging OCT. Average, subfoveal, nasal, and temporal choroidal thicknesses were compared between severely affected and fellow eyes after adjusting for axial length and intraocular pressure.

Results.: There were no significant differences between choroidal thickness measurements in eyes with advanced glaucoma and those in fellow eyes (P = 0.78 to 0.99). Based on average and subfoveal choroidal thicknesses, the choroid of eyes with advanced glaucoma was thicker than that of fellow eyes in 2.8% and 2.8% of the patients, whereas the choroid of fellow eyes was thicker than that of eyes with advanced glaucoma in 5.6% and 8.3% of the patients (P = 0.55 and 0.30, respectively). Neither eye had a consistently thinner or thicker choroid. Stepwise multiple regression analysis also showed no differences between choroidal thicknesses of severely affected eyes and those of fellow eyes (all P > 0.05). Factors associated with a thinner choroid were aging (28.6 μm per decade, P < 0.001) and increasing axial length (21.4 μm/mm, P < 0.001). Visual field mean deviation did not correlate with choroidal thickness measurements.

Conclusions.: There was no significant change in choroidal thickness of eyes with advanced open-angle glaucoma compared to that of fellow eyes with no glaucoma or with mild glaucoma. A thinner choroid does not necessarily indicate the presence of glaucoma, nor is a thicker choroid necessarily a surrogate for the absence of glaucoma. These observations further suggest a lack of relationship between open-angle glaucoma and choroidal thickness.

Introduction
Glaucoma is an neurodegenerative optic neuropathy caused by injury to retinal ganglion cells and their axons. 1 The clinical correlates of this cellular damage are progressive changes to the optic disc, the retinal nerve fiber layer, the ganglion cell-inner plexiform layer, and the peripheral visual field, followed by the central field. Elevated intraocular pressure (IOP) is the major risk factor for glaucoma, and its reduction can slow the progression of vision loss even in normal tension glaucoma (NTG). 24 On the other hand, loss of visual function may continue even with medically or surgically controlled IOP, 5,6 indicating that IOP-independent factors such as worsened choroidal blood flow parameters may play a role in ocular hypertension, NTG, or POAG. 79 Other studies have reported that patients experiencing glaucoma progression have worse ocular hemodynamics than nonprogressors. 10,11  
Despite being a bilateral disease, open-angle glaucoma is often asymmetric at presentation and can progress at different rates in the two eyes. From an ocular hemodynamic standpoint, significant differences have been reported between asymmetric and unilateral glaucoma. 12,13 However, it not well established whether unilateral advanced open-angle glaucoma is associated with choroidal thinning compared to that in fellow eyes with no glaucoma or mild glaucoma. Histological and imaging (i.e., ultrasonography) studies evaluating choroidal thickness in glaucomatous eyes as a marker of choroidal blood flow have produced inconsistent findings. 1418 The advent of high-resolution imaging modalities such as spectral domain optical coherence tomography (SDOCT) has led to a renewed interest in investigating the relationship between choroidal thickness and various retinochoroidal pathologies. We and others have recently shown, using SDOCT, that there are no differences between macular 1922 or peripapillary 23 choroidal thicknesses in patients with open-angle glaucoma and normal individuals. In addition, in a recent study by Maul et al., 24 patients with glaucoma and those suspected of having glaucoma had comparable macular and peripapillary choroidal thicknesses. However, a review of all current reports of the association between choroidal thickness and open-angle glaucoma yields conflicting results, which justifies the need for more studies in this area. Thus, demonstrating the lack or presence of difference in choroidal thickness between eyes with unilateral severe open-angle glaucoma and contralateral eyes without glaucoma or with early glaucoma would further corroborate or refute the above-mentioned recent findings. In the present study, the choroid was imaged in patients with unilateral advanced open-angle glaucoma using SDOCT, and the choroidal thickness was measured and compared with that of the fellow eye without glaucoma or with early glaucoma. 
Subjects and Methods
Subjects
Following approval of the study by the Institutional Review Board of the University of Miami Miller School of Medicine and after consent was obtained from each participant, 36 patients aged 18 years or older with advanced glaucoma (POAG or NTG) in one eye and with mild or no glaucoma in the fellow eye were consecutively enrolled in the study. The study followed Declaration of Helsinki principles for research involving human subjects and the Health Insurance Portability and Accountability Act. Selection criteria were unilateral advanced glaucomatous optic neuropathy (mean deviation of <−12 dB), a fellow eye that was normal or had mild glaucoma (mean deviation >−6 dB). POAG was diagnosed in the presence of open iridocorneal angle accompanied by glaucomatous optic disc changes and visual field defects and in the absence of any other identifiable cause. NTG was diagnosed if repeatable IOP measurements of ≤21 mm Hg were associated with optic disc changes and visual field deficits consistent with glaucoma. At least two reliable, consecutive visual field test results using a Swedish interactive thresholding algorithm (SITA) standard 24-2 Humphrey visual field analyzer (Carl Zeiss, Inc., Dublin, CA) were required, with the most recent test performed within 1 year of enrollment. An abnormal visual field test result was defined as a typical pattern of glaucomatous changes accompanied by a pattern standard deviation of <5% and/or a glaucoma hemifield test result outside limits of normal. 
An eye was considered normal if it had an IOP of ≤21 mm Hg, an optic disc with normal ophthalmoscopic appearance (cup-to-disc ratio <0.5, absence of hemorrhage, and absence of localized or diffuse rim thinning), and normal visual field test results. Both normal and glaucomatous eyes were required to have a refractive error of less than −6 diopters of sphere or 3 diopters of cylinder, clear media, no history of retinal disease (i.e., diabetic retinopathy, retinal detachment, or macular degeneration) or laser therapy, choroidal pathology, nonglaucomatous optic neuropathy, or ocular surgery within 1 month of enrollment. 
Image Acquisition, Choroidal Segmentation, and Thickness Measurement
All scans were acquired after pupil dilation by the same experienced operator (FES), using an OCT device (Spectralis 4.0; Heidelberg Engineering, Heidelberg, Germany). A single horizontal B-scan centered on the fovea was used (number of A-scans/number of B-scans = 1536; scan angle = 30°; scan length = 9 mm). The automatic real time (ART = 100 frames) averaging mode was used to ensure good quality images. Images were acquired using enhanced depth imaging OCT in semiautomatic segmentation mode. Unlike the original technique where the image was acquired in an inverted position, 25 the semiautomatic segmentation mode allows image acquisition with the instrument kept away from the eye, as in conventional SDOCT scanning, and the image is captured in an upright position. It automatically detects the Bruch's membrane and draws the segmentation line. The sclerochoroidal boundary of all images was visually located, and, using the manual segmentation option provided by the internal software, one reader (JCM), who was masked to the subjects' identity and diagnosis, manually placed the segmentation line. Any error in the inner choroidal border segmentation was corrected manually prior to measuring choroidal thickness. The retinal thickness algorithm function was used to automatically generate subfoveal, nasal average, temporal average, and overall average choroidal thicknesses. All eyes also underwent axial length measurement with an IOLMaster (Carl Zeiss Meditec, Dublin, CA). 
Statistical Analysis
Based on data from our previous study, 21 we estimated that 12 pairs of eyes would be required to detect a significant difference in thickness of at least 63 μm between severely diseased eyes and fellow eyes at a significance level of 0.05 and a power of 0.85, for a standard deviation of 72 μm. The difference in thickness of at least 63 μm as a statistically significant difference, as recently reported by Cennamo et al., 26 was used to determine whether the choroid was thinner or thicker in either eye of each patient or whether it was similar in both eyes (equal to or less than 62 μm). Choroidal thicknesses of eyes with severe glaucoma were compared to those of fellow eyes using multivariate general linear model after adjusting for axial length and IOP. The same test was used to compare choroidal thicknesses of fellow normal eyes and eyes with mild glaucoma after adjusting for age, axial length, and IOP. Correlation between choroidal thickness and visual field mean deviation was assessed with Pearson correlation. Multivariate regression analyses were performed that included each choroidal thickness parameter as dependent variable and ethnicity, sex, eye laterality, history of cataract surgery or glaucoma surgery, current use of IOP-lowering medication, age, axial length, IOP, and visual field mean deviation as independent variables. Eyes with advanced glaucoma were considered references with which to compare eyes with no or mild glaucoma. All data were analyzed using Statistical Package for Social Sciences version 19.0 software (SPSS Inc., Chicago, IL). A P value of <0.05 was considered statistically significant. 
Results
Subject Characteristics
Of the 36 eyes with severe glaucoma, 23 had POAG, and 13 had NTG. Among fellow eyes, 24 were normal, and 12 had mild glaucoma. Patients' mean age was 69.6 ± 12.9 years (range, 36–93 years). Study and fellow eyes did not differ in axial length (23.97 ± 1.29 μm and 24.07 ± 1.28 μm, respectively, P = 0.11) or in IOP (13.52 ± 3.85 mm Hg and 15.00 ± 5.60 mm Hg, respectively, P = 0.16). Eyes with severe glaucoma had significantly reduced best-corrected visual acuity, expressed in decimals (0.60 ± 0.33), visual field mean deviation (−19.82 ± 6.4 dB), and higher visual field pattern standard deviation (10.30 ± 2.60 dB) than fellow eyes (0.85 ± 0.20, −2.28 ± 1.93 dB, and 2.75 ± 1.80 dB, respectively), all P = 0.001. 
Interocular Choroidal Thickness Comparison
The sclerochoroidal junction was visualized in both eyes of all 36 patients, and no image was excluded due to inability to delineate the posterior border of the choroid. The results shown in Table 1 indicate there were no statistically significant differences between subfoveal, nasal, temporal, and average choroidal thickness measurements in eyes with advanced glaucoma and those of fellow eyes after adjusting for axial length and IOP (all P > 0.05). In an effort to confirm that combining normal eyes with those with mild glaucoma in one group did not account for the observed lack of difference in choroidal thickness, an additional analysis was performed comparing eyes with severe glaucoma relative to fellow normal eyes (n = 24 pairs) only. Again, no significant differences were observed (P = 0.75 to 0.95) (Table 2). Additionally, when only the group of fellow eyes was considered for analysis, choroidal thicknesses of eyes with mild glaucoma (n = 12) did not differ from those of normal eyes (n = 24; P = 0.18 to 0.25), although the choroid tended to be thicker in eyes with mild glaucoma compared to that in normal eyes after adjusting for age, axial length, and IOP (Table 3). Similar results were obtained after comparing unadjusted measurements. To determine whether there was a trend toward an increase or decrease in choroidal thickness in either eyes with advanced glaucoma or fellow eyes, individual differences between the two eyes were calculated by subtracting measurements obtained in fellow eyes from those obtained in eyes with advanced glaucoma. No consistent or specific trend toward thinner or thicker subfoveal, nasal, temporal, and average choroid was observed (Figs. 1, 2). In other words, a thinner choroid did not necessarily indicate the presence of glaucoma, nor did a thicker choroid necessarily indicate the absence of glaucoma. Based on average choroidal thickness (Fig. 2), the choroids of eyes with advanced glaucoma were at least 63 μm thicker than those of fellow eyes in 1 patient (2.8%), whereas the choroids of fellow eyes were at least 63 μm thicker than those of eyes with advanced glaucoma in 2 patients (5.6%); the difference was not significant (P = 0.55). Similarly, such differences in proportions based on subfoveal (2.8% vs. 8.3%, respectively, P = 0.30), temporal (2.8% vs. 2.8%, respectively, P = 1) or nasal (0% vs. 5.6%, respectively, P = 0.15) choroidal thickness were not all significant. The difference between the two eyes was within 62 μm in 33 (91.6%) patients for average, 32 (88.9%) patients for subfoveal, 34 (94.4%) patients for temporal, and 34 (94.4%) patients for nasal choroidal thicknesses. 
Figure 1. 
 
Plots of differences in subfoveal (top left), average (top right), nasal (bottom left), and temporal (bottom right) choroidal thicknesses between the eye with advanced glaucoma and the fellow eye. Each bar represents the difference in thicknesses in a single patient. A positive difference indicates that the choroid is thicker in the eye with advanced glaucoma, whereas a negative difference indicates that the choroid is thicker in the fellow eye.
Figure 1. 
 
Plots of differences in subfoveal (top left), average (top right), nasal (bottom left), and temporal (bottom right) choroidal thicknesses between the eye with advanced glaucoma and the fellow eye. Each bar represents the difference in thicknesses in a single patient. A positive difference indicates that the choroid is thicker in the eye with advanced glaucoma, whereas a negative difference indicates that the choroid is thicker in the fellow eye.
Figure 2. 
 
Macular enhanced-depth imaging OCT scans of three selected study patients. The top panel shows a thicker choroid (subfoveal thickness = 342 μm, average thickness = 302 μm) in a right eye with advanced glaucoma and a thinner choroid (subfoveal thickness = 211 μm, average thickness = 184 μm) in a normal left eye; the middle panel shows a thicker choroid (subfoveal thickness = 347 μm, average thickness = 292 μm) in a normal right eye and a thinner choroid (subfoveal thickness = 207 μm, average thickness = 159 μm) in a severely diseased left eye; the lower panel shows similar choroidal thicknesses in a normal right eye (subfoveal thickness = 167 μm, average thickness = 143 μm) and in a severely affected left eye (subfoveal thickness = 175 μm, average thickness = 148 μm). Downward and upward arrows indicate Bruch's membrane and sclerochoroidal boundaries, respectively. Corresponding visual field pattern deviation plots are shown next to choroidal images.
Figure 2. 
 
Macular enhanced-depth imaging OCT scans of three selected study patients. The top panel shows a thicker choroid (subfoveal thickness = 342 μm, average thickness = 302 μm) in a right eye with advanced glaucoma and a thinner choroid (subfoveal thickness = 211 μm, average thickness = 184 μm) in a normal left eye; the middle panel shows a thicker choroid (subfoveal thickness = 347 μm, average thickness = 292 μm) in a normal right eye and a thinner choroid (subfoveal thickness = 207 μm, average thickness = 159 μm) in a severely diseased left eye; the lower panel shows similar choroidal thicknesses in a normal right eye (subfoveal thickness = 167 μm, average thickness = 143 μm) and in a severely affected left eye (subfoveal thickness = 175 μm, average thickness = 148 μm). Downward and upward arrows indicate Bruch's membrane and sclerochoroidal boundaries, respectively. Corresponding visual field pattern deviation plots are shown next to choroidal images.
Table 1. 
 
Adjusted Choroidal Thickness in Eyes with Unilaterally Severe Glaucoma and Fellow Eyes (n = 36 pairs)
Table 1. 
 
Adjusted Choroidal Thickness in Eyes with Unilaterally Severe Glaucoma and Fellow Eyes (n = 36 pairs)
Parameter Mean (±SEM) [95% CI] Thickness, μm P
Advanced Glaucoma Eyes Fellow Eyes
Subfoveal 224.40 (14.07) [196.30–252.50] 223.79 (14.49) [194.86–252.71] 0.97
Nasal 182.31 (13.27) [155.80–208.81] 182.18 (13.66) [154.90–209.46] 0.99
Temporal 214.40 (10.71) [193.01–235.80] 210.07 (11.03) [188.05–232.09] 0.78
Average 200.89 (11.35) [178.22–223.55] 198.24 (11.68) [174.91–221.57] 0.87
Table 2. 
 
Choroidal Thickness in Eyes with Unilaterally Severe Glaucoma and Fellow Normal Eyes (n = 24 pairs)
Table 2. 
 
Choroidal Thickness in Eyes with Unilaterally Severe Glaucoma and Fellow Normal Eyes (n = 24 pairs)
Parameter Mean (±SEM) [95% CI] Thickness, μm P
Advanced Glaucoma Eyes Normal Fellow Eyes
Subfoveal 212.91 (15.57) [181.54–244.29] 220.09 (15.57) [188.71–251.47] 0.75
Nasal 175.27 (15.74) [143.48–207.06] 177.90 (15.77) [146.11–209.69] 0.91
Temporal 208.60 (11.88) [184.67–234.54] 205.90 (11.87) [181.96–229.83] 0.87
Average 194.64 (13.00) [168.45–220.84] 193.69 (12.99) [167.50–219.89] 0.95
Table 3. 
 
Adjusted Choroidal Thickness in Fellow Eyes with Early Glaucoma (n = 12) and Normal Eyes (n = 24)
Table 3. 
 
Adjusted Choroidal Thickness in Fellow Eyes with Early Glaucoma (n = 12) and Normal Eyes (n = 24)
Parameter Mean (±SEM) [95% CI] Thickness, μm P
Early Glaucoma Eyes Normal Eyes
Subfoveal 250.05 (22.59) [204.04–296.06] 214.98 (15.87) [182.65–247.300] 0.22
Nasal 206.96 (20.65) [164.90–249.02] 171.98 (14.51) [142.43–201.53] 0.18
Temporal 228.05 (17.52) [192.36–263.74] 202.96 (12.31) [177.90–228.05] 0.25
Average 219.69 (18.36) [182.29–257.08] 189.49 (12.90) [163.22–215.76] 0.19
In stepwise multivariate regression analysis (Table 4), eyes with advanced glaucoma used as reference and those with no or less advanced disease had comparable subfoveal (P = 0.89), average (P = 0.77), nasal (P = 0.59; not in Table), and temporal (P = 0.83; not in Table) choroidal thickness. Aging and increase in axial length significantly decreased subfoveal (31.3 μm per decade and 26.0 μm/mm of elongation; all P < 0.001) and average choroidal thickness (28.6 μm per decade and 21.4 μm/mm; all P < 0.001), respectively. Nasal (31.0 μm per decade, P < 0.001; and 29.1 μm/mm, P = 0.003) and temporal (29.4 μm per decade, P = 0.002; and 27.2 μm/mm, P = 0.004) choroidal thicknesses also decreased as a result of aging and eye elongation (not in Table). 
Table 4. 
 
Stepwise Multivariate Regression for Associations with Subfoveal and Average Choroidal Thicknesses
Table 4. 
 
Stepwise Multivariate Regression for Associations with Subfoveal and Average Choroidal Thicknesses
Parameter Subfoveal Thickness Average Thickness
MV Beta Value P MV Beta Value P
Advanced vs. fellow eye* −5.43 0.89 −9.64 0.77
Caucasian vs. non-Caucasian* −2.14 0.41 −4.37 0.32
Male vs. female sex* 10.59 0.51 17.95 0.57
Age, y −3.12 <0.001 −2.86 <0.001
Axial length, mm −26.00 <0.001 −21.40 <0.001
Intraocular pressure, mm Hg 3.37 0.41 1.06 0.56
Previous glaucoma surgery −21.45 0.42 −17.33 0.42
Currently receiving glaucoma medication −30.17 0.19 −25.78 0.18
Correlations between choroidal thicknesses and visual field mean deviations in eyes with advanced glaucoma were not significant (r 2 = 0.014 and P = 0.50 for subfoveal; r 2 = 0.0003 and P = 0.98 for nasal; r 2 = 0.024 and P = 0.37 for temporal; and r 2 = 0.008 and P = 0.61 for average thickness). The correlations remained insignificant after increasing the range of visual field mean deviation by merging data of eyes with advanced glaucoma with those of fellow eyes into one data set (r 2 = 0.012 and P = 0.36 for subfoveal; r 2 = 0.0043 and P = 0.61 for nasal; r 2 = 0.0057 and P = 0.55 for temporal; and r 2 = 0.0055 and P = 0.56 for average thickness). Adjusting for axial length and IOP did not change the outcome (r 2 = 0.0027–0.01; P = 0.43 to 0.69). 
Discussion
Lately there has been a renewed interest in investigating the association between open-angle glaucoma and choroidal thickness by using SDOCT, and all currently available studies have compared eyes with glaucoma with normal eyes from different groups of subjects. This association was assessed in the present study by using an intraindividual rather than interindividual comparison approach. To date, only one study has used this approach and has reported a lack of association between choroidal thickness and glaucoma. 24 Using eyes with unilateral advanced glaucoma and fellow eyes of the same subjects as controls seems to be the ideal model for testing the hypothesis that choroidal thickness is not reduced in severely affected eyes compared to that in fellow normal eyes or in eyes with less severe open-angle glaucoma. This model is advantageous in that the results are not affected by factors that are known as underlying causes of large interindividual variability in choroidal thickness such as age and systemic blood pressure. Eyes with advanced glaucoma and fellow eyes in the present study were comparable with regard to axial length and IOP. 
Knowing whether choroidal thickness of eyes with advanced glaucoma is different from that of fellow normal eyes alone or from that with less severe glaucoma is very important in elucidating the association between choroidal thickness and glaucomatous optic neuropathy. The results presented herein show that all choroidal thickness measurements in eyes with advanced glaucoma were not significantly different from those of fellow eyes, including normal and eyes with mild glaucoma. Hence, when the analysis was restricted to eyes with advanced glaucoma and fellow normal eyes, the differences remained nonsignificant. Thus, these results suggest that choroidal thinning is not an important component of glaucomatous optic neuropathy. This is consistent with the findings recently reported by Maul et al. 24 and with our previous finding that patients with open-angle glaucoma and normal individuals have comparable choroidal thicknesses and that there is no association between severity of glaucomatous optic neuropathy and choroidal thickness. 21 Other recent SDOCT-based studies have reported similar results. 19,20,22,23 Also in agreement with these studies is the lack of difference in macular and peripapillary choroidal thickness between patients with glaucoma and those suspected of having glaucoma. 24 In contrast, Usui et al. 27 found a statistically significant thinner choroid in highly myopic subjects with NTG than that in normal subjects. However, their finding may have been affected by the fact that highly myopic eyes have preexisting thinner choroids. A recent study by Roberts et al. 28 reported finding a choroid that was thinner in patients with sclerotic glaucomatous optic discs than that in healthy controls. Interestingly, in the same study, the choroidal thickness of patients with localized or diffuse disc damage did not differ from that of controls, suggesting that the choroid of patients with advanced glaucoma was as thick as that of healthy subjects. Also, in two separate, recent studies, Hirooka et al. 29,30 found choroids that were significantly thinner in eyes with NTG than those in normal eyes. One previous histologic study 18 reported thinner choroid, whereas another histologic 16 and two ultrasonographic studies 14,17 found thicker choroids in glaucomatous eyes relative to those in normal eyes. Thicker choroids in eyes with glaucoma was also recently reported by Cennamo et al. 26 It is important to note that none of these histologic studies has mentioned correcting for axial length or age, and their results may not be representative of in vivo choroidal thickness for various technical reasons. Indeed, there are pitfalls associated with examining histological slides with light microscopy for choroidal thickness measurement. The tissue must first be removed and subsequently fixated, sectioned, and stained. All of these steps may result in artifacts that can influence the measurements. 31,32 Additionally, fixation using formalin may shrink ocular tissues compared to freshly excised specimens. Further manipulation for histologic preparation such as embedding and sectioning may also result in additional reduction in size of the tissue to be examined. Moreover, different tissue locations may differ in the extent to which they are affected by these manipulations, leading to tissue distortion and subsequently to artifactual measurements. 33 As for ultrasonography, although it has long been the gold standard for determining the thickness of the retina and choroid in vivo, it is less accurate than SDOCT due to its lower resolution resulting from lower signal-to-noise ratio. Also, the use of ultrasonography often involves directly contacting the eye with the probe, which can sufficiently change the ocular axial length and subsequently the thickness of the choroid and the retina even with minimal pressures on the eyeball. Unfortunately, previous ultrasonography-based studies failed to estimate the amplitude of pressures exerted by the probe. Thus, choroidal thickness values obtained with SDOCT are likely to most closely reflect the real thickness in vivo. 
Age and axial length were associated with choroidal thickness, which agrees with findings in most previous studies. The magnitude of the effect of age (28.6-μm decrease per decade of aging) and axial length (21.4-μm decrease per each millimeter of eye elongation) on average choroidal thickness was comparable with other recent estimates. 24 Factors such as central corneal thickness and diastolic perfusion pressure were not analyzed in this study, but they have been reported to be inversely related with choroidal thickness. 24  
A widely discussed question is whether choroidal thickness correlates with glaucomatous damage. In other words, it is not known whether elevated IOP injures the choroid at the same time as it damages the optic nerve head or whether eyes with preexisting thinner choroid are more vulnerable to elevation of IOP and suffer glaucomatous damage more easily than eyes with thicker choroid. Again, the results of our analyses do not support the view that thinner choroid is associated with glaucoma, even in severely affected eyes. Because of large interindividual variability in normal choroidal thickness, our results may suggest that the thickness of the choroid is nothing other than an inborn ocular feature, as it has been found in chickens, 34 and that glaucomatous damage can occur without measurable differences in choroidal thickness. This view is further supported by the lack of correlation between choroidal thickness and visual field deficit, as also recently reported by Maul and colleagues. 24 Another supporting finding is the lack of correlation between choroidal thickness and retinal nerve fiber layer thickness. 23,24 Briefly, although additional studies will be needed, most currently available SDOCT data do not support the link between choroidal thickness and open-angle glaucoma. 
One of the theories behind glaucomatous optic neuropathy is that structural damage leading to functional deficit is the result of impaired choroidal blood flow to the optic nerve head. 35,36 Due to the lack or limited amount of information on the relationship between choroidal blood flow and choroidal thickness in humans, we are unable to conclude based on our results whether choroidal blood flow was normal in eyes with advanced glaucoma despite having choroidal thickness within normal range. Interestingly, in favor of our finding is the fact that subfoveal choroidal blood flow of patients with open-angle glaucoma was not different from that of normal subjects in one study 37 and did not correlated with either functional or structural parameters of glaucomatous damage in another study. 36 Clearly, even due to the vascular nature of the choroid, assuming that a thin choroid corresponds to less or thin choroidal vessels and therefore to reduced blood flow may not be true. Future studies are needed that will attempt to correlate choroidal thickness and ocular blood blow, that is, by measuring both parameters in the macular and peripapillary regions of normal eyes and eyes with open-angle glaucoma. This is particularly true based on observation in chicks recovering from experimentally induced myopia that increase in choroidal thickness is preceded by increase in choroidal blood flow. 38,39 Similarly, young pigeons have been shown to have thicker choroid and higher choroidal blood flow than older ones. 40 However, evidence has also been presented that in birds, changes in choroidal thickness predominantly affect the suprachoroid, 40 which is closest to the sclera and contains lymphatic vessels that act as reservoirs for fluid movements into and out of the choroidal vessels prior to choroidal thickening and thinning, respectively. In other words, changes in choroidal blood flow barely affect the thickness of choroidal vascular layers (the outer Haller's layer of large blood vessels and the inner Sattler's layer of medium and small arteries and arterioles). This view is supported by the lack of correlation between choroidal thickness and ocular blood flow in healthy humans. 41  
Statistically, the present study was designed to detect a difference of at least 63 μm in choroidal thickness between eyes with severe glaucoma and fellow eyes. On this basis, a sample size of 36 pairs of eyes was used in the analysis, even though it was estimated that 12 pairs of eyes were sufficient to detect a significant difference with an 85% power. However, as shown in Tables 1 and 2, the mean choroidal thicknesses were identical in eyes with advanced glaucoma and fellow eyes, the confidence intervals around the means were approximately ±30 μm, and the standard deviations were approximately 70 μm in both groups of eyes. This suggests that increasing the sample size would have had no effect on the outcome because any further difference between eyes with advanced glaucoma and fellow eyes would have been lower than the variability of measurement in either group of eyes. 
In conclusion, this study provides additional evidence that in vivo choroidal thickness measured with SDOCT in eyes with advanced open-angle glaucoma is not reduced in comparison with that in fellow normal eyes or that in eyes with mild glaucoma. It also confirms the lack of association between choroidal thickness and functional deficit in open-angle glaucoma. 
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Footnotes
 Supported by an unrestricted grant from Research to Prevent Blindness, New York, New York.
Footnotes
 Disclosure: J.-C. Mwanza, None; F.E. Sayyad, None; D.L. Budenz, None
Figure 1. 
 
Plots of differences in subfoveal (top left), average (top right), nasal (bottom left), and temporal (bottom right) choroidal thicknesses between the eye with advanced glaucoma and the fellow eye. Each bar represents the difference in thicknesses in a single patient. A positive difference indicates that the choroid is thicker in the eye with advanced glaucoma, whereas a negative difference indicates that the choroid is thicker in the fellow eye.
Figure 1. 
 
Plots of differences in subfoveal (top left), average (top right), nasal (bottom left), and temporal (bottom right) choroidal thicknesses between the eye with advanced glaucoma and the fellow eye. Each bar represents the difference in thicknesses in a single patient. A positive difference indicates that the choroid is thicker in the eye with advanced glaucoma, whereas a negative difference indicates that the choroid is thicker in the fellow eye.
Figure 2. 
 
Macular enhanced-depth imaging OCT scans of three selected study patients. The top panel shows a thicker choroid (subfoveal thickness = 342 μm, average thickness = 302 μm) in a right eye with advanced glaucoma and a thinner choroid (subfoveal thickness = 211 μm, average thickness = 184 μm) in a normal left eye; the middle panel shows a thicker choroid (subfoveal thickness = 347 μm, average thickness = 292 μm) in a normal right eye and a thinner choroid (subfoveal thickness = 207 μm, average thickness = 159 μm) in a severely diseased left eye; the lower panel shows similar choroidal thicknesses in a normal right eye (subfoveal thickness = 167 μm, average thickness = 143 μm) and in a severely affected left eye (subfoveal thickness = 175 μm, average thickness = 148 μm). Downward and upward arrows indicate Bruch's membrane and sclerochoroidal boundaries, respectively. Corresponding visual field pattern deviation plots are shown next to choroidal images.
Figure 2. 
 
Macular enhanced-depth imaging OCT scans of three selected study patients. The top panel shows a thicker choroid (subfoveal thickness = 342 μm, average thickness = 302 μm) in a right eye with advanced glaucoma and a thinner choroid (subfoveal thickness = 211 μm, average thickness = 184 μm) in a normal left eye; the middle panel shows a thicker choroid (subfoveal thickness = 347 μm, average thickness = 292 μm) in a normal right eye and a thinner choroid (subfoveal thickness = 207 μm, average thickness = 159 μm) in a severely diseased left eye; the lower panel shows similar choroidal thicknesses in a normal right eye (subfoveal thickness = 167 μm, average thickness = 143 μm) and in a severely affected left eye (subfoveal thickness = 175 μm, average thickness = 148 μm). Downward and upward arrows indicate Bruch's membrane and sclerochoroidal boundaries, respectively. Corresponding visual field pattern deviation plots are shown next to choroidal images.
Table 1. 
 
Adjusted Choroidal Thickness in Eyes with Unilaterally Severe Glaucoma and Fellow Eyes (n = 36 pairs)
Table 1. 
 
Adjusted Choroidal Thickness in Eyes with Unilaterally Severe Glaucoma and Fellow Eyes (n = 36 pairs)
Parameter Mean (±SEM) [95% CI] Thickness, μm P
Advanced Glaucoma Eyes Fellow Eyes
Subfoveal 224.40 (14.07) [196.30–252.50] 223.79 (14.49) [194.86–252.71] 0.97
Nasal 182.31 (13.27) [155.80–208.81] 182.18 (13.66) [154.90–209.46] 0.99
Temporal 214.40 (10.71) [193.01–235.80] 210.07 (11.03) [188.05–232.09] 0.78
Average 200.89 (11.35) [178.22–223.55] 198.24 (11.68) [174.91–221.57] 0.87
Table 2. 
 
Choroidal Thickness in Eyes with Unilaterally Severe Glaucoma and Fellow Normal Eyes (n = 24 pairs)
Table 2. 
 
Choroidal Thickness in Eyes with Unilaterally Severe Glaucoma and Fellow Normal Eyes (n = 24 pairs)
Parameter Mean (±SEM) [95% CI] Thickness, μm P
Advanced Glaucoma Eyes Normal Fellow Eyes
Subfoveal 212.91 (15.57) [181.54–244.29] 220.09 (15.57) [188.71–251.47] 0.75
Nasal 175.27 (15.74) [143.48–207.06] 177.90 (15.77) [146.11–209.69] 0.91
Temporal 208.60 (11.88) [184.67–234.54] 205.90 (11.87) [181.96–229.83] 0.87
Average 194.64 (13.00) [168.45–220.84] 193.69 (12.99) [167.50–219.89] 0.95
Table 3. 
 
Adjusted Choroidal Thickness in Fellow Eyes with Early Glaucoma (n = 12) and Normal Eyes (n = 24)
Table 3. 
 
Adjusted Choroidal Thickness in Fellow Eyes with Early Glaucoma (n = 12) and Normal Eyes (n = 24)
Parameter Mean (±SEM) [95% CI] Thickness, μm P
Early Glaucoma Eyes Normal Eyes
Subfoveal 250.05 (22.59) [204.04–296.06] 214.98 (15.87) [182.65–247.300] 0.22
Nasal 206.96 (20.65) [164.90–249.02] 171.98 (14.51) [142.43–201.53] 0.18
Temporal 228.05 (17.52) [192.36–263.74] 202.96 (12.31) [177.90–228.05] 0.25
Average 219.69 (18.36) [182.29–257.08] 189.49 (12.90) [163.22–215.76] 0.19
Table 4. 
 
Stepwise Multivariate Regression for Associations with Subfoveal and Average Choroidal Thicknesses
Table 4. 
 
Stepwise Multivariate Regression for Associations with Subfoveal and Average Choroidal Thicknesses
Parameter Subfoveal Thickness Average Thickness
MV Beta Value P MV Beta Value P
Advanced vs. fellow eye* −5.43 0.89 −9.64 0.77
Caucasian vs. non-Caucasian* −2.14 0.41 −4.37 0.32
Male vs. female sex* 10.59 0.51 17.95 0.57
Age, y −3.12 <0.001 −2.86 <0.001
Axial length, mm −26.00 <0.001 −21.40 <0.001
Intraocular pressure, mm Hg 3.37 0.41 1.06 0.56
Previous glaucoma surgery −21.45 0.42 −17.33 0.42
Currently receiving glaucoma medication −30.17 0.19 −25.78 0.18
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