|Year : 2013 | Volume
| Issue : 1 | Page : 11-16
Determinants of macular thickness in normal Indian eyes
Zia S Pradhan, Andrew Braganza, Lekha M Abraham
Department of Ophthalmology, Christian Medical College, Schell Eye Hospital, Arni Road, Vellore, Tamil Nadu, India
|Date of Submission||17-Sep-2012|
|Date of Acceptance||08-Nov-2012|
|Date of Web Publication||22-Jan-2013|
Zia S Pradhan
Department of Ophthalmology, Christian Medical College, Schell Eye Hospital, Arni Road, Vellore, Tamil Nadu
Source of Support: None, Conflict of Interest: None
Purpose: To generate normative data for optical coherence tomography (OCT) estimated macular thickness in Indian eyes and to establish its determinants. Materials and Methods: In this cross-sectional, observational, hospital-based study, 189 healthy Indian individuals underwent a fast macula OCT scan. Macular thickness was measured in nine ETDRS (Early Treatment Diabetic Retinopathy Study) regions, and the effect of gender, age, laterality, diabetes, and hypertension status on it was determined. Results: Females had a significantly thinner fovea (176.71 ± 23.32 μm v/s. 193.24 ± 20.95 μm) and inner macula (p < 0.001) as compared to males. With advancing age, foveal thickness increases (p = 0.012) while the superior and inferior outer macula thins (p = 0.018-0.027). Diabetes in the absence of any clinical retinopathy did not affect macular thickness. Hypertensive individuals had a thinner macula in all regions except the fovea and nasal macula. Conclusions: The thinner macula in females and age-related thinning should be considered when interpreting OCT scans of the macula. Diabetics with good visual acuity and no evidence of clinical retinopathy had normal macular thickness. Sub-clinical attenuation of vessels might account for the thinner macula in individuals with hypertension.
Keywords: Age-related decline, diabetic macula, hypertensive maculopathy, macular thickness, optical coherence tomography
|How to cite this article:|
Pradhan ZS, Braganza A, Abraham LM. Determinants of macular thickness in normal Indian eyes. J Clin Ophthalmol Res 2013;1:11-6
|How to cite this URL:|
Pradhan ZS, Braganza A, Abraham LM. Determinants of macular thickness in normal Indian eyes. J Clin Ophthalmol Res [serial online] 2013 [cited 2022 Jul 4];1:11-6. Available from: https://www.jcor.in/text.asp?2013/1/1/11/106273
Macular thickness as determined by optical coherence tomography (OCT) is being used in the management of several ophthalmic conditions. Prior to labeling the macula as abnormal, it is important to determine the range of normal macular thickness and the factors on which it depends. Ethnic variation has been shown. , There has been only one study of macular thickness in normal Indian eyes  whose conclusions regarding some of its determinants differ from other reports. ,, Therefore, this study was carried out to establish the normal macular thickness in Indians and to determine factors affecting it.
| Materials and Methods|| |
This was an observational study of the macular thickness in normal Indian eyes as measured by optical coherence tomography. One hundred and eighty nine healthy volunteers were recruited from the out-patient department from June 2007 to June 2009. Informed consent was obtained from all participants using a consent form approved by the Institutional Review Board and the methods described adhered to the tenets of the Declaration of Helsinki. All patients underwent a complete ophthalmic examination including best-corrected visual acuity estimation, slit-lamp examination, Goldmann applanation tonometry, dilated stereoscopic fundus examination, Standard automated perimetry (Humphrey's Field Analyzer 30-2 SITA standard protocol), and ultrasound pachymetry measuring the central corneal thickness. The following exclusion criteria were laid down:
All participants were subjected to macular imaging using Stratus OCT version 4.0.7 following pupillary dilatation. The OCT images were taken ensuring good centration and signal strength of ≥6. The fast macula thickness map was used, which comprises 3 concentric circles centered at the fovea that divide the macula into 3 zones; the fovea (less than 1 mm diameter), the inner macula (1 to 3 mm) and the outer macula (3 to 6 mm). These zones were further divided into 9 ETDRS (Early Treatment Diabetic Retinopathy Study) regions  as depicted in [Figure 1]. Only one eye of each participant was included in the study. If both eyes were eligible, one eye was chosen using block randomization.
- Age <25 years
- Best-corrected visual acuity worse than 6/9 using Snellen's visual acuity chart for patients with a clear lens or pseudophakia and worse than 6/12 for patients with cataract
- Refractive error >6.00 diopters sphere and/or 3.00 diopters cylinder
- Eyes with severe media opacities preventing fundus assessment
- Intra-ocular pressure (IOP) > 21 mmHg
- Eyes with retinopathy due to any cause (diabetes /hypertension/macular hole/age-related macular degeneration etc.)
- Patients on medications known to cause maculopathy (e.g. chloroquine, hydroxychloroquine)
- Patients with known neuro-ophthalmological disease
- Patients with any one characteristic glaucomatous disc change on clinical examination by a glaucoma consultant (vertical cup/disc ratio asymmetry of more than 0.2, vertical cup/disc ratio of more than 0.6 with thinning of neuro-retinal rim, notching, retinal nerve fiber layer defects or disc hemorrhages)
- Patients with any 2 of the following visual field changes
- A Glaucoma hemifield test outside normal limits
- A cluster of 3 or more contiguous non-edge points in a pattern deviation probability plot that have sensitivities occurring in fewer than 5% of the normal population, and one of the points has a sensitivity that occurs in fewer than 1% of the population (p < 1%) in the arcuate area
- A pattern standard deviation depressed to an extent found in less than 0.5% of the population
|Figure 1: ETDRS regions of the macula as measured by fast macula program of OCT|
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For the purpose of this study, hypertension was defined as blood pressure ≥140/90 mmHg as measured manually using a mercury sphygmomanometeror those on anti-hypertensive medication.  Irrespective of the duration or control of hypertension, all those with absence of hypertensive retinopathy were included in the study. Diabetics were identified from self-reported use of diabetic medication or physician-diagnosed diabetes. Clinical experience has shown that several patients (>40%) do not develop diabetic retinopathy for several years inspite of poor glycemic control.  On the other hand, some patients (10%) develop microvascular complications despite good glycemic control.  Besides duration of diabetes, glycemic control, HbA 1C levels, and body mass index, other undefined factors are believed to play a role in determining the risk of microvascular changes in the retina. Therefore, irrespective of the duration or control of diabetes, any individual without diabetic retinopathy was included in this study.
Statistical analysis was performed by SPSS version 11.0.1. Analysis of variance (ANOVA) and Chi-square test were used to determine if the macular thickness differed between the population baseline variables. Correlation between macular thickness and age was evaluated using partial correlation (after controlling for diabetes and hypertension). Where indicated, linear regression was used to describe parametric associations and to generate graphic representations of the same.
| Results|| |
One hundred and eighty nine eyes of 189 subjects aged between 25 to 79 years were evaluated. The baseline parameters are shown in [Table 1]. The visual acuity of 180 patients was 6/9 or better. Nine patients had visual acuity of 6/12, which was due to the presence of cataract. Preliminary statistical analysis showed no difference in macular thickness between right and left eyes in any of the ETDRS regions (P ranging from 0.404 to 0.949). Therefore, for all subsequent analysis, only one randomly chosen eye of each patient was used.
The macular thickness was determined in 9 ETDRS regions. The means, standard deviations, and ranges are shown in [Table 2].As expected, the fovea was the thinnest area (186.07 ± 23.44 μm). The inner macula was the thickest,and the retina thinned towards the periphery. The nasal macula (inner and outer) was found to be significantly thicker (p<0.001) than the temporal macula.
|Table 2: Macular thickness measurements/μm in 189 healthy subjects using OCT|
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Females were found to have a significantly thinner fovea (176.71 ± 23.32 μm v/s. 193.24 ± 20.95 μm with p< 0.001) and inner macula in all quadrants (P< 0.001) than males as depicted in [Figure 2]. The outer macular thickness did not show significant variation between men and women (P = 0.093-0.914).
|Figure 2: Comparison of macular thickness (nearest μm) in men and women as for the right eye|
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Foveal thickness was found to have a weak positive correlation with age as shown in [Table 3] when analyzed using partial correlation after controlling for diabetes and hypertension. The rest of the macula was found to have a negative correlation with age, which was statistically significant in superior and inferior outer macula as shown in [Table 3]. Linear regression analysis plotted to determine the age-related changes of macular thickness also showed that all areas except the fovea [Figure 3] had a decline with advancing age. The inner nasal sector had the least decline (0.165μm per year) compared to its corresponding regions in the inner macula (0.225-0.277μm per year) as shown in [Figure 4]. The ETDRS area with the greatest age-related decline was the outer inferior sector (0.339μm per year) as depicted in [Figure 5].
|Table 3: Correlation between macular thickness and age using partial correlation after controlling for diabetes and hypertension|
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Different levels of normal IOP (≤21mm Hg) were not associated with significantly different macular thickness using ANOVA (p=0.273-0.984). A similar analysis was performed for the corrected IOP (based on the assumption that the Goldmann applanation tonometer was calibrated for a corneal thickness of 520μm and every 14 μm difference resulted in a change of 1 mmHg), which also were not significantly associated with macular thickness (p=0.605-0.988). The corneal pachymetry measured in all participants varied from 433 to 632 μm (Mean ±SD = 528.10 ±32.35). We found no correlation between the central corneal thickness and the retinal thickness of the macula using Pearson's correlation (P= 0.08-0.558).
The mean duration of diabetes amongst the study participants was 6.12 (SD = 4.89) years. The mean fasting blood sugar was 128.05 (SD = 41.38) mg/dl, and median was 115 mg/dl. The mean post-prandial blood glucose was 185.59 (SD = 93.74) mg/dl. Therefore, the study participants showed a varied level of control of diabetes, but none of them had any diabetic retinopathy. The minimum foveal thickness was initially found to be significantly greater in diabetics when compared to non-diabetics (168.38 ± 31.93 μm CI = 157.24-179.52 μm v/s. 155.07 ± 24.48 μm CI = 151.19-158.95 μm with a P=0.007). The rest of the macula did not show any difference in thickness between diabetics and non-diabetics. Since diabetes is more common in an older population and we have already recorded an age-related foveal thickening, age was an obvious confounding factor in this analysis. Therefore, we reanalyzed this data using only age-matched non-diabetics. This included participants over age 50 years,and no significant age difference was noticed between the two groups (p=0.52). Analysis of these 58 non-diabetic and 28 diabetic eyes did not show any difference in the average macular thickness of the ETDRS areas (p>0.20) or the minimum foveal thickness (p=0.25).
The mean duration of hypertension amongst the study patients was 4.97 (SD=2.92) years. The mean systolic blood pressure was 130.71 (SD=12.07) mm of Hg with a range of 110 to 150 mm of Hg. The mean diastolic blood pressure was 81.43 (SD = 8.64) mm of Hg with a range of 70 to 100 mm of Hg. Therefore, the hypertensive subjects showed varying degrees of control of their blood pressure, but none of them had any signs of hypertensive retinopathy. Hypertensive patients were found to have a significantly thinner macula when compared to patients without hypertension (p= 0.002-0.05) in all areas except the fovea (p=0.843). However, given that hypertension tends to occur in the elderly and we have already established an age-related macular thinning, age was a confounding factor. Therefore, were-examined only patients aged ≥47 years (n=99) where the difference in age between hypertensives and non-hypertensives was not significant (p=0.056). This showed that the macula remained significantly thinner in hypertensive patients in all areas, except the fovea and nasal macula as shown in [Table 4]. Although we did not find diabetes to be a confounding factor in our analysis, since diabetes and hypertension often co-exist, we also analyzed our data in patients with hypertension alone and not diabetes and found similar results where all areas showed a significantly thinner macula (p=0.003-0.041), except the fovea (p=0.898) and nasal macula (p= 0.065-0.094) as shown in [Figure 6].
|Figure 6: Comparison of macular thickness (nearest μm) in hypertensives and non-hypertensives as for the right eye|
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|Table 4: Association between macular thickness and hypertension (HT) in individuals of age ≥47 years|
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| Discussion|| |
OCT is an established, reproducible tool to objectively measure macular thickness. The various models of OCT differ in their measurement of macular thickness due to different retinal segmentation algorithms used (Fourier-domain OCT shows higher values than Time-domain OCT). , Macular thickness measurements are not interchangeable among different instruments. , Since a time-domain OCT was used in the study, for the purpose of this discussion, only those studies which used 3 rd generation Stratus OCThave been referred to.
OCT-estimated macular thickness has shown variations between different ethnic groups. ,,,, Asians and African-Americans have thinner maculae when compared to Caucasians. , The mean thickness in the central 1mm diameter area was found to be 176.4 ± 17.5 μm in Chinese,  181.2 ± 18.4 μm in Indians,  183.2 ± 1.3 μm in Thai,  209.5 ± 26.7 μm in Japanese,  and 212 ± 20 μm in Caucasians.  In addition, factors affecting macular thickness differed in these various study groups. Our literature review showed only one study of macular thickness in normal Indian eyes whose conclusions regarding its determinants differ from other studies.  We examined our data in the background of these same determinants and more, to study the factors upon which macular thickness depends.[Table 5] shows the normal values of macular thickness as measured in our population compared to other studies.
On evaluating the macular thickness in the 9 ETDRS regions in our population, the nasal macula (inner and outer areas) was significantly thicker than the temporal macula (P<0.001), a finding consistent with previous studies. ,, This could be because of the thicker papillo-macular bundle of the retinal nerve fiber layer (RNFL) in this region.
We found that women had a significantly thinner fovea and inner macula compared to men. These findings are similar to those of Manassakorn et al.,  Kelty et al.,  and Huang et al.  Few reports , do not agree with this observation, but these were relatively small studies. A large population-based study done on Chinese eyes found that in addition to the fovea and inner macula, the outer macula was also significantly thicker in men.  Tewari et al.,  in their study on Indian eyes,concluded that macular thickness did not vary with gender. However, a careful examination of their published data shows that 3 of the 4 sectors in the inner macula (superior, inferior, and nasal) differed significantly between the sexes. In fact, on scrutiny of the volumetric data, there was also a statistically significant difference in the inner temporal sector (p<0.035). Though this study  stated that there is no difference in macular thickness between males and females, its data is not very different from our study as well as others. ,
We included patients whose ages ranged from 25 to 79 years and observed that the foveal thickness increased with age. This may be due to the absence of ganglion cells in this area (whose decay is believed to be responsible for normal age-related thinning). Also, there may be sub-clinical retinal pigment epithelial (RPE) changes undetectable on slit-lamp biomicroscopy, which may result in an inefficient RPE pump, causing an increase in foveal thickness.Although many authors found a positive correlation between age and foveal thickness, ,,,,, this was not statistically significant in most studies. This may be due to inadequate correction for confounding factors. Contrary to all the above results, Eriksson et al.  found a significant decline in foveal thickness with age (r=-0.25; p=0.042), and others , found no correlation between age and foveal thickness (p=0.8).
We observed that all ETDRS regions except the fovea had an age-related decline in macular thickness, which was most significant in the superior and inferior outer macula. This can be attributed to the age-related decay of ganglion cells and RNFL, which is responsible for an overall retinal thinning. These findings have been mirrored by others. ,,, However, the rate of decline varied in different regions among these studies. In our study, the area with the least decline was the inner nasal macula (0.165 μm per year). The reason for this may be due to a preferential loss of neurons in other areas of the macula with relative preservation of the fovea and papillo-macular bundle to maintain vision.  Also, the nerve fibers in the papillo-macular bundle are thinner than other areas as reported in histological sections.  Therefore, even if the same number of axons are lost simultaneously around the fovea, the retinal thickness will decrease slowly in these areas with thinner fibers. The outer inferior macula had the greatest decline (0.339 μm per year).
Similar to our study, most authors , have observed a slower age-related decline in retinal thickness of the inner sectors when compared to the outer macula. Manassakorn et al.  observed a reduction which ranged from 0.2 μm per year in the inner nasal area to 0.42 μm per year in the outer nasal area. Sung et al.  also found the steepest decline in the outer nasal sector. Neuville et al.  found that the macula thins with increasing age in all areas outside the fovea,and this was greatest and statistically significant in the nasal sector (0.41 μm per year). Eriksson et al.  found a reduction of 0.26-0.46 μm per year of the total retinal thickness. Contrary to all the above, a study done in Chinese eyes  demonstrated a positive correlation between age and macular thickness (r=0.05-0.46), and another done on Japanese eyes  did not show any significant correlation (r =-0.26; p=0.05).
We also examined the effect of diabetes and hypertension on macular thickness in patients with no clinical evidence of retinopathy. The macular thickness of diabetic eyes did not differ from age-matched normal eyes. An earlier study showed that neither duration of diabetes nor control of blood sugar affected the foveal thickness in eyes without retinopathy.  Sanchez-Tocino et al.  found a statistically significant increase in average foveal thickness between normal eyes and eyes of diabetics without any retinopathy (p=0.043). However, they included patients from a wide range of ages (21-79 years), and the effect of age on these results cannot be ruled out. Shaudig et al.  found significant differences between these two groups only in the superior quadrant. Massin et al.  did not detect any difference between these two groups. Verma et al.  found a contrasting decrease in foveal thickness in diabetics as compared to controls when analyzed using spectral-domain OCT and attributed this to diabetes causing early neuronal degeneration before clinical microvascular changes. However, patients included had vision almost as low as 20/200 who may have had macular ischemia accounting for the poor vision and thinner macula. In that study, a fundus fluorescein angiogram may have been useful. Therefore, the foveal thickness in diabetics without clinical retinopathy has been variable in different studies; but, if the visual acuity is preserved, the foveal thickness is usually normal. Hypertensives had thinner inner and outer maculaein all regions, except nasal to the fovea, when compared to non-hypertensives. This thinning of the macula may be due to sub-clinical arteriolar attenuation. This may also explain why the central fovea remained unaffected by hypertension since it is an avascular zone. We could not find any other report on the effect of hypertension on retinal thickness.
The main limitation of our study was that it was a hospital-based rather than population-based. Another drawback is that the age-related changes documented were based on cross-sectional data, as this is more feasible, rather than longitudinal data.
In conclusion, since ethnicity is known to affect macular thickness, we established the largest normative database of Indian eyes. We also studied the determinants of macular thickness and found that gender, age,and presence of systemic hypertension affect various regions of the macula in normal eyes. These should be considered when interpreting an OCT of the macula.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]