|Year : 2016 | Volume
| Issue : 3 | Page : 143-150
Spectralis optical coherence tomography normal macular thickness in Egyptians
Mohammad A.M. El-Hifnawy, Amir R Gomaa, Ahmed M Abd El-Hady, Hassan E Elkayal MD
Department of Ophthalmology, Faculty of Medicine, Alexandria University, Alexandria, Egypt
|Date of Submission||27-Apr-2016|
|Date of Acceptance||02-Sep-2016|
|Date of Web Publication||6-Dec-2016|
Hassan E Elkayal
119 Ahmed Shawky Street, Mostafa Kamel, Alexandria 21523
Source of Support: None, Conflict of Interest: None
The aim of this study was to determine the normative data of macular thickness in the Egyptian population and to assess the effect of different demographic data and ocular parameters on it using spectral-domain optical coherence tomography (SD-OCT).
Patients and methods
This cross-sectional study included 105 healthy Egyptian patients who underwent a comprehensive ophthalmic examination, including Spectralis SD-OCT scanning, at Alexandria Main University Hospital. One eye from each patient was chosen randomly to be included in the study. Macular thickness was calculated based on center thickness and nine areas that corresponded to the Early Treatment Diabetes Retinopathy Study map using OCT mapping software. The relationships between macular thickness and sex, age, axial length (AL), spherical equivalent, keratometry readings, intraocular pressure, BMI, parity, and use of oral contraceptive pills were analyzed.
The study included 49 male and 56 female patients. The mean age of the patients was 40.41±14.17 years. The mean central subfield thickness was 262.70±19.64 μm. The mean macular thickness values in all areas of the Early Treatment Diabetes Retinopathy Study map were significantly greater in men than in women. As age increased, outer macular thickness decreased significantly in the overall group and in female but not in male patients (partial correlation). The AL correlated negatively with inner and outer macular thickness (partial correlation). However, spherical equivalent had no significant influence on multiple linear regression analysis. Central subfield thickness did not correlate significantly with keratometry readings, intraocular pressure, BMI, parity, or use of oral contraceptive pill.
The mean macular thickness values in the Egyptian population were found to be less than those seen in the Spectralis SD-OCT studies published previously on Caucasians but more than those seen in Blacks. Sex had the most significant effect on macular thickness in all regions. Age and AL showed a significant negative correlation with outer macular thickness.
Keywords: Egyptian, macular thickness, normal, spectral-domain optical coherence tomography
|How to cite this article:|
El-Hifnawy MA, Gomaa AR, Abd El-Hady AM, Elkayal HE. Spectralis optical coherence tomography normal macular thickness in Egyptians. Delta J Ophthalmol 2016;17:143-50
|How to cite this URL:|
El-Hifnawy MA, Gomaa AR, Abd El-Hady AM, Elkayal HE. Spectralis optical coherence tomography normal macular thickness in Egyptians. Delta J Ophthalmol [serial online] 2016 [cited 2020 Apr 5];17:143-50. Available from: http://www.djo.eg.net/text.asp?2016/17/3/143/195269
| Introduction|| |
Optical coherence tomography (OCT) generates cross-sectional images of the retina by measuring the echo time delay and magnitude of backscattered light . With the development of high-speed OCT using spectral-domain/Fourier domain detection (SD-OCT), devices have achieved axial resolutions in the 5–7 μm range and image acquisition speeds greater than 20 000 axial scans per second ,,. The Spectralis SD-OCT combines a scanning laser ophthalmoscope with OCT to produce tracking laser tomography that scans at 40 000 A-scans per second . Real-time eye tracking allows acquisition of 1–100 B-scans at the same location  and through frame averaging; it improves image quality by removing motion error . Spectralis OCT macular thickness measurements in healthy individuals show good interchangeability for the different macular volume scan protocols (fast, dense, and detail) .
Normal macular thickness measurements have been studied extensively in the past for Stratus time domain OCT (TD-OCT) ,,,,. Many studies have demonstrated that macular thickness measurements obtained using various SD-OCTs were consistently greater than those obtained using Stratus TD-OCT ,,,.
Discrepancies in retinal thickness measurements between instruments may be partially accounted for by the varying segmentation algorithms. OCT instruments differ in defining the outer retinal boundary. Stratus OCT measures retinal thickness to the inner segment/outer segment junction of photoreceptors, whereas SD instruments include the outer segments and measure closer to the retinal pigment epithelium (RPE) .
It has also been shown that even different SD-OCT instruments have slightly different segmentation capabilities. One study measured the average normal central retinal thickness as 289 µm with Spectralis, which was 77 µm greater than Stratus, 12 µm greater than Cirrus, and 42 µm greater than RTVue ,. Spectralis measures to the outermost of the three hyper-reflective OCT retinal bands, which includes measurement of the RPE and Bruch membrane .
Several authors have demonstrated normative data for macular thickness as measured using Spectralis SD-OCT ,,,,,. However, there is a significant variation in the published normative macular thickness values of different ethnic groups ,,,,,.
Macular aging involves alterations in its function, structure, and blood supply ,. Sex-related differences exist in both healthy and diseased eyes . Recent studies in which the third-generation Stratus OCT was used have shown macular thickness to be related to refractive error/axial length (AL) in normal individuals ,.
The aim of this cross-sectional study was to collect normative macular thickness data in the Egyptian population using the Spectralis SD-OCT and to assess its correlations with demographic data and ocular parameters that can possibly affect the macular thickness.
| Patients and methods|| |
The present study included 105 healthy eyes of normal adult individuals who were recruited from the Ophthalmology Outpatient Clinic at Alexandria Main University Hospital, Alexandria, Egypt. The study protocol adhered to the tenets of the Declaration of Helsinki and was approved by the local Institutional Review Board. Written informed consent was obtained from each subject prior to the examination procedure.
Inclusion criteria were as follows: an age of 18 years or more, best-corrected visual acuity of 6/12 or better, intraocular pressure (IOP) of 21 mmHg or less, cup-disc ratio of 0.5 or less with no optic disc changes suggestive of glaucoma, and normal macular examination.
Exclusion criteria were as follows: presence of diabetes mellitus or systemic inflammatory diseases, clinical evidence of ocular abnormalities, ocular trauma, previous intraocular or retinal surgery or laser therapy to the retina, refractive error of spherical power more than −6.00 or +6.00 D, as well as cylindrical power more than 2.50 D, and significant media opacities.
In patients with two eligible eyes, only one eye was randomly selected for macular thickness analysis.
The study protocol adhered to the tenets of the Declaration of Helsinki and was approved by the local Institutional Review Board.
All patients were subjected to the following: best-corrected visual acuity measurement; body mass index calculation; autorefraction and keratometric recordings using autokerato-refractometer (Topcon KR-8100PA; Topcon Corporation, Tokyo, Japan); slit lamp biomicroscopy including dilated fundus examination; IOP measurements using Goldmann applanation tonometry (Goldmann; Haag-Streit diagnostics, Switzerland); AL measurement using A-scan ultrasound (E-Z Scan AB5500+, Sonomed Escalon, New York, New York, USA); and macular thickness measurement using SD-OCT (Spectralis OCT; Heidelberg Engineering, Heidelberg, Germany).
OCT images were generated by the fast volume scan: 20°×20° (6×6 mm) raster scans consisting of 25 horizontal lines. For each horizontal line, nine B-scans were averaged with the automatic real-time mode to reduce speckle noise. Only the scans with a numerical quality score of more than 16/40 db and in the blue range of the quality bar were collected, whereas scans with significant image artifacts were excluded.
The retinal thickness in each frame was calculated as the distance between the first signal from the vitreoretinal interface and the signal from the outer border of the RPE.
Spectralis OCT provides a circular map analysis in which the average thickness is displayed as a color code or numeric values in the nine Early Treatment Diabetes Retinopathy Study (ETDRS) areas . The ETDRS map consists of three concentric rings with diameters of 1 mm (central), 3 mm (inner), and 6 mm (outer) ([Figure 1]). The inner and outer rings are divided into four areas. The retinal thickness within the inner circle is defined as the central subfield (CSF) thickness. The Spectralis volume scanning also displays a center point thickness (CPT) calculated at the midpoint of the central horizontal line scan. The mean retinal thickness of the four areas in the inner ring was defined as the mean inner macula thickness. The mean retinal thickness of the four areas in the outer ring was defined as the mean outer macula (MOM) thickness ([Figure 1]b). The centering of the measurements at the fovea was checked. If necessary, the ETDRS grid was shifted to compensate for minor fixation errors.
|Figure 1 (a) Depiction of the standard nine Early Treatment Diabetes Retinopathy Study subfields. CSF, central subfield; IIM, inferior inner macula; IOM, inferior outer macula; NIM, nasal inner macula; NOM, nasal outer macula; SIM, superior inner macula; SOM, superior outer macula; TIM, temporal inner macula; TOM, temporal outer macula; (b) MIM, mean inner macula; MOM, mean outer macula .|
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All data were analyzed with SPSS software (version 16, SPSS; Microsoft Corporation, Chicago, Illinois, USA).
Global and pair-wise comparisons of the mean macular thicknesses in the different sectors of the ETDRS map were made using the analysis of variance test with Bonferroni correction for multiple comparisons. Comparisons of means between male and female patients were made with Student’s t-test and were repeated after adjusting for covariates using the analysis of covariance test.
Pearson correlation was used to analyze correlations of mean macular thicknesses with age, AL, and spherical equivalent (SE). The analysis was repeated after adjusting for the other factors being tested using partial correlation. Factors with the most significant effect on macular thickness in the previous analyses were analyzed again using multiple linear regression analysis in an attempt to isolate the effect of each factor alone using the β coefficient. A P-value of less than and equal to 0.05 was considered statistically significant.
| Results|| |
The study included 105 normal eyes from 105 healthy individuals. The study comprised 53 right eyes and 52 left eyes. There were 49 men and 56 women. The mean age of all participants was 40.41±14.17 years (range: 18–70 years).
The mean AL was 23.13±0.76 mm (range: 21.0–25.69 mm). The mean SE was −0.26±1.50 D (range: −5.0 to +4.0 D). The mean keratometry was 44.06±1.75 D (range: 39.25–48.50 D). The mean IOP was 15.27±3.39 mmHg (range: 9.0–21.0 mmHg). The mean BMI was 32.0±7.70 kg/m2 (range: 19.98–55.06 kg/m2).
The mean macular thickness of each ETDRS sector is shown in [Figure 2]. The mean CSF thickness was 262.70±19.64 μm (range: 221–315 μm). The macular thickness was least at the center point, followed by the CSF and outer macular ring. The inner ring was the thickest macular region (all P<0.001). Global and pair-wise comparison for the inner ring showed that the inner temporal region was significantly thinner than all other inner macular regions (all P<0.001). Similarly, comparison for the outer ring showed that the outer temporal region was the thinnest of all outer regions and the nasal outer region was the thickest (all P<0.001).
|Figure 2 The mean macular thickness of each Early Treatment Diabetes Retinopathy Study sector.|
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Men showed statistically significantly greater mean macular thicknesses compared with women in all areas. The mean CSF thickness was 274.55±15.52 μm in men and 252.34±16.87 μm in women (P<0.001). Sex differences in macular thickness were still statistically significant after adjusting for age, AL, SE, BMI, keratometry readings, and IOP (analysis of covariance test) ([Table 1]).
Age was not found to correlate significantly with CPT, CSF, or inner macular thicknesses. However, the macular thicknesses of each of the four outer regions showed a significant negative correlation with age.
The same relations were found after repeating the analysis in women and adjusting for the other factors (P<0.05, partial correlation). However, in men, the macular thicknesses of none of the ETDRS regions demonstrated significant correlations with age (P>0.05, partial correlation) ([Table 2]).
|Table 2 Partial correlation between age and macular thickness in men and women|
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The macular thickness of none of the ETDRS sectors significantly correlated with AL. However, after adjusting for the other factors, macular thickness of all areas of the ETDRS map, except CPT and CSF, showed a significant negative correlation with the AL (P-values were <0.001–0.024, partial correlation) ([Table 3]).
|Table 3 Correlation and partial correlation between axial length and macular thickness in the different Early Treatment Diabetes Retinopathy Study sectors|
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The SE showed a significant positive correlation only with the CSF thickness. Nevertheless, after adjusting for the other factors, SE no longer correlated significantly with CSF thickness but showed a significant negative correlation with macular thickness in the nasal, inferior, and temporal inner macular sectors, as well as the inferior and temporal outer macular sectors (P-values were 0.001–0.034, partial correlation).
From the previous results it can be concluded that age, sex, AL, and SE are important factors that might influence macular thickness measurements. The effect of these factors was reanalyzed using multiple linear regression analysis ([Table 4]). Sex was found to be the statistically significant factor related to all macular thickness values, whereas SE showed no significant relationship with any macular thickness values. Age and AL were only significantly associated with MOM thickness. In addition to the significant effect of AL on MOM thickness, a trend was seen in the relation of AL with the mean inner macula thickness (β coefficient=−3.087, P<0.1).
MOM thickness was found to be the region influenced by the largest number of factors. When the AL increased by 1 mm, the MOM thickness decreased by 5.426 μm (β coefficient=−5.426, P<0.001). When the age increased by 1 year, the MOM thickness decreased by 0.240 μm (β coefficient=−0.240, P=0.001). The MOM was thicker in men than in women by 11.675 μm (β coefficient=−11.675, P<0.001).
On the basis of the results of multiple regression analysis, which show that sex had the most significant effect on macular thickness, separate cutoff values for normal macular thickness in men and women are proposed ([Figure 3]).
|Figure 3 Cutoff values (upper limit) for normal macular thickness in (a) men and (b) women|
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| Discussion|| |
SD-OCT uses a greater number of sampling points compared with TD-OCT and has a faster scanning speed and better image quality, allowing more precise retinal thickness measurements. However, the definition of the posterior boundary differs according to the SD-OCT instrument used, and hence the normative value of retinal thickness needs to be determined in an instrument-specific manner ,,.
Differences in retinal thickness among various ethnic groups were previously reported. Among Spectralis SD-OCT studies, Grover et al.  reported a mean CSF thickness of 270.2±22.5 μm. The thickest CSF (279.5±27.4 μm) was found in Asians, followed by Whites (272.7±20.8 μm) and Blacks (256.5±16.9 μm). Choovuthayakorn et al.  reported the mean CSF thickness of the Thai population to be 259.18±19.08 μm. In the present study, the mean CSF thickness of the Egyptian population (262.70±19.64 μm) was less than that seen in the Spectralis SD-OCT studies published previously on Caucasians but more than those seen in Blacks. This is a reasonable finding, given that the Egyptian population is a mixed race. It has been hypothesized that this racial difference is because of attenuation of incident optical radiation by the increased pigment in the apical portion of the RPE cells, leading to a decreased signal of the posterior retinal segments and concomitant underassessment of retinal thickness in darkly pigmented individuals .
Topographically, the foveal center was the thinnest. Macular thickness increased gradually to reach its maximum in the inner ring and then decreased again in the outer ring. The thickness in the nasal sector was much greater than that in the other three sectors within the outer ring, whereas there were no large differences between the inner ring sectors. This is consistent with previous OCT studies ,,,,,,. Greater asymmetry of the macular thickness of the outer ring compared with that of the inner ring may be due to the horizontally asymmetric anatomic nature of the retinal nerve fiber layer (RNFL), in which the retinal nerve fibers from the superior and inferior arcuate bundles and the papillomacular bundle converge toward the optic disc. In contrast, the inner ring corresponds to regions with the thickest total retina and ganglion cell layer and a relatively thin RNFL .
In the present study, the mean retinal thicknesses in all regions of the ETDRS grid were significantly thicker in men than in women. This is consistent with previous studies of healthy populations ,,. As regards the CSF, the current study showed that the CSF thickness was 22.21 μm greater in men than in women. Choovuthayakorn et al.  reported a difference of 12.21 μm (P<0.001) obtained with a Spectralis SD-OCT, whereas Song et al.  reported a difference of 11.47 μm (P=0.009) with a Cirrus SD-OCT. Only few studies did not find sex differences in macular thickness ,,. Chan et al.  and Oshitari et al.  both found no correlation between sex and CSF thickness using Stratus OCT, but both studies had a small sample size with an uneven distribution of sex.
The layer responsible for the intersex difference in retinal thickness is yet unknown . Most previous studies reported no intersex difference in mean circumpapillary RNFL thickness ,,, but a recent study by Ooto et al.  using a 3D SD-OCT (Topcon Corporation) with the automated retinal layer segmentation algorithm  found that the inner nuclear layer thickness and thickness of the outer plexiform layer and outer nuclear layer complex were significantly thicker in men than in women.
The CSF thickness did not show statistically significant changes with advancing age in either sex, which was similar to the results obtained in many previous studies. Using SD-OCT, Ooto et al. , Grover et al. , and Choovuthayakorn et al.  reported that there was no correlation of CSF thickness with age in either sex. The same results were reported by Neuville et al.  and Manassakorn et al.  using TD-OCT. In contrast to these results, Eriksson and Alm  reported a negative correlation of CSF thickness with age.
As regards the parafoveal areas, in the present study, the retinal thickness in the outer ring decreased significantly with advancing age. When the analysis was repeated in each sex alone with adjustment for the effect of other factors, the same significant correlation was found in women only. In agreement with the present study, Ooto et al.  and Choovuthayakorn et al.  using SD-OCT reported a significant thinning of the nonfoveal retina with age. In contrast, Grover et al.  found no relationship between retinal thickness and age in any ETDRS area, but most of the participants were less than 60 years old, and the sizes of the ETDRS rings differed.
Various histological studies have reported substantial axon fiber loss per year ,. Consistent with these studies, most OCT studies indicate a significant decrease in the mean peripapillary RNFL thickness with age ,. The retinal thickness in the temporal quadrant with the thinnest RNFL was the most resistant to age-dependent decay. Furthermore, age did not correlate with the mean foveal thickness at a 1-mm diameter where the RNFL thickness is negligible. Thus, age-related decay of extrafoveal macular retinal thickness seems to be partly due to the age-related decay of RNFL thickness.
In the present study, CSF thickness did not correlate with AL, which is in agreement with studies by Ooto et al.  and Song et al. . However, Duan et al.  and Choovuthayakorn et al.  found that the CSF thickness increases significantly with increasing AL. The differences in the findings may be partly due to limiting the refractive errors of the participants in the present study to between −6 and +6 D.
As regards the extrafoveal regions, it was shown in the present study that, as the AL increased, the thickness of the inner and outer macular regions decreased significantly. This negative correlation was only detected after adjusting for the effect of other factors. This finding affirms histopathological studies that have demonstrated retinal thinning with myopia , and a clinical study that demonstrated more frequent chorioretinal atrophy in the posterior pole in eyes with longer AL . Recent studies using SD-OCT showed similar results as in the studies of Song et al.  and Choovuthayakorn et al. .
The present study did not show a statistically significant correlation between SE and CSF thickness after adjusting for other factors. This is in accordance with the studies by Duan et al. , Manassakorn et al. , Kelty et al. , Song et al. , and Choovuthayakorn et al. .
As regards the extrafoveal regions, after using multiple linear regression analysis SE showed no significant relationship with any macular thickness values. The results as regards extrafoveal regions and SE were identical to those shown by Choovuthayakorn et al. .
Diabetic retinopathy studies have used TD-OCT to monitor macular thickness for the effect of various treatment protocols. They have used a mean CSF thickness of 250 μm as the cutoff value to represent the upper limit of normal macular thickness, based on 2 SDs above the mean CSF thickness ,. Using similar criteria, based on the present study, we propose 302 μm as the cutoff value for normal CSF thickness in the Egyptian population using the Spectralis SD-OCT. On the other hand, retinal thinning can be suspected if CSF thickness is less than 223 μm when measured with the Spectralis OCT.
In conclusion, this study has demonstrated normative values for retinal thickness in the adult Egyptian population as obtained with the Spectralis SD-OCT. Men have a thicker CSF compared with women. Age, sex, and AL should be taken into consideration for extrafoveal retinal thickness. The diagnosis and monitoring of retinal diseases in clinical practice should be adjusted to account for differences among ethnic groups in baseline retinal thicknesses.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4]