Normative Values of The Retinal Macular Thickness in a Middle Eastern Population.

doi:10.21203/rs.2.91/v1

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Normative Values of The Retinal Macular Thickness in a Middle Eastern Population.

https://doi.org/10.21203/rs.2.91/v1

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published 06 Apr, 2020

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Background: Since the normative value of the retinal macular thickness is undocumented in the Middle East, the aim of this work is to assess the normative values of the macular thickness in healthy eyes in a Middle Eastern population and its relationship with age, sex, and laterality.

Methods: 98 individuals were randomly selected from volunteers visiting the Jordan University Hospital in Amman, Jordan. Measurements were obtained using the Fourier domain optical coherence tomography (OCT). Multivariable regression models were developed to obtain predicted normative values with adjustment to candidate variables. In addition, the effect of age, sex and laterality were evaluated.

Results: The average central fovea macular thickness was 232.1 (±30.85) um. The quadratic value of the retinal macular thickness decreased from the superior value of 299.71 (±23.67) um to the inferior value of 296.46 (±28.85) um and a nasal figure of 93.63 (±26.86) um. The temporal area has the thinnest value of 293.43 (±30.78) um. Central thickness was higher in males with a mean variation of 11.67 um (95% CI: 2.41 to 20.93) (p= 0.003). The thickness was highest within 3mm diameter from the center and decreased towards the periphery Eye sidedness didn’t contribute to variability of the macular thickness.

Conclusion: Our set of predicted normative data may be used to interrupt measurement of the macular thickness in Middle Eastern population. The average fovea macular thickness among Jordanians is consistent with previously reported values. Normative values from additional Middle Eastern populations are required to appraise our module.

Internal Medicine Specialties

Macular thickness

OCT

Macula

Gender

Middle Eastern population

Fluid accumulation in the macula or macular edema is a common cause of visual loss. However, the amount of edema does not always correlate with visual acuity [1, Macular thickness; OCT; Macula; Gender; Middle Eastern population Macular thickness; OCT; Macula; Gender; Middle Eastern population [2]. This accretion is caused by a break of the blood-retinal barrier. It is imperative to note that various diseases cause fluid accumulation within the macula with examples being diabetes, branch and central retinal vein occlusion, age-related macular degeneration, as well as central serous chorioretinopathy. Essentially, the macula is the central area of the retina. Therefore, a healthy macula is responsible for good visual acuity [3]. This point implies that various diseases can affect the macula and lead to a decrease in visual acuity [1, 2].

The OCT is a well-known method used for accurately detecting macular thickness and any early subtle changes [4]. Since Diabetes is a common disease, diabetic retinopathy is a leading cause of blindness in the adult population. Therefore, regular screening of the retina is recommended for every diabetic patient with the frequency of the check-ups depending on the retinal status. This routine should be maintained throughout the patient’s life [4].

Optical Coherence Tomography (OCT) is a non-invasive imaging technique that measures internal structures of biological systems. Specifically, it is useful for high resolution reproducible in-vivo imaging of the retinal structure; this ocular technology is a useful tool to ophthalmologists. For instance, high resolutions in vivo retinal images are essential for diagnosis and follow up of patients with macular edema [1, 4, and 5]. The outcome of OCT based imaging is constantly developing with further iterations on the technology. In fact the latest iterations include Gabor-domain optical coherence microscopy which can be useful in assessment of the cornea [6, 7]. Based on this understanding, the aforementioned changes can be detected early by imaging the macula using an Ocular Coherence Tomography that facilitates both thicknesses and morphology detection before these changes are clinically apparent. In effect, early detection may favorably affect the visual outcome [8]. In the clinic, Fourier-domain OCT is used in standard commercial systems and offers superior sensitivity compared to the conventional time-domain approach [8, 9].

Retinal macular thickness is naturally subject to anatomic variation. Therefore, measurements are interpreted against a backdrop of normative reference values. Normative values are readily available, albeit for no more than a select number of ethnic groups [9]. The preceding fact is problematic as normative values may be highly variable between populations. Thus, their documentation in additional populations is necessary [9].Therefore, detecting the normal value of the macular retinal thickness in a Middle Eastern population helps in early diagnosis of diabetic changes. Currently, data concerning the normal value of the adult Middle Eastern population, and the effect of age, sex, as well as the refractive error of the macular retinal thickness, is unavailable. As such, it is important to note that this aspect may be confused with early changes related to diabetic retinopathy [5]. The heterogeneity of Middle Eastern populations calls for a series of investigations to determine robust normative values of retinal macular thickness. Herein we present a preliminary investigation of these values using Fourier-domain OCT.

For this retrospective cross-sectional study, patients who were evaluated in the ophthalmology clinic in the Jordan University Hospital were included. Data was collected from July 2017 to July 2018 after obtaining approval from our institutional review board. Written informed consent was obtained from all participants. The sampled subjects were adults aged above 18 years who underwent a complete ophthalmic assessment at the Jordan University hospital and whose data regarding macular OCT was available. The study’s exclusion criteria disqualified individuals with any history of ocular pathology, abnormal ocular exam comprising abnormally looking macula or diabetic retinopathy, a recent history of trauma or ocular surgery (in the last 12 months), a high degree myopia (more than 6 diopters) or poor quality images.

Retinal macular thickness was measured using Fournier domain OCT. A Macular cross line Emm5 protocol was used. These measurements were taken by the same operator in all cases. Measurements of the central fovea area and the macular scan were covered by an area of 6 mm2. The automated Optivue (RTVue, Optivue, Inc., Fremont, Canada) software derived a 6mm diameter macular retinal thickness map centered on the fovea to cover the 9 Early Treatment Diabetic Retinopathy Study (ETDRS) areas (`Figure 1).

The areas are located in three rings of 1, 3, and 6mm diameters. The 1mm ring covers the central fovea and the para-foveal area. In contrast, the other rings are located 3 and 6 mm from the 1 mm diameter ring. Each ring is divided into four quadrants that are described as superior, inferior, temporal, and nasal. Furthermore, age, sex, eye laterality and spherical equivalent were recorded.

The IBM SPSS version 21.0 (Chicago, USA) is used in the present analysis. Similarly, the mean (± standard deviation) was applied in describing the continuous variables, which are age and measurements. Count (frequency) was used to describe other nominal variables that comprised the participants’ gender and eyes. On the other hand, numerical data was presented according to the recommendations of TJ Cole [10]. Furthermore, a sample T-test was used to perform the analysis of the mean difference between measurements and each gender as well as laterality. The obtained data was presented in an average of 95% confidence intervals (CI). The correlations between central thickness and thickness at each quadrant at 3mm and at 6mm were studied using Pearson’s correlation. Moreover, Pearson’s correlation was used to study the correlation between age and each measurement. It should be noted that all underlying assumptions were met unless otherwise indicated. Lastly, a p-value of 0.05 was adopted as a significant threshold.

A total of 98 patients were included in the present study; eighteen eyes were excluded due to poor quality scans. One hundred seventy eight eyes entered statistical analysis. The age range was between 18 and 83 years with a mean age of 59.57 (±12.48) years. The median spherical equivalent was 0.5diopters (ranged from -4.5 to 2.5 diopters). The participants comprised 41 men and 57 women.

As such, a total of 178 eyes were included in the present study, including 90 right-sided eyes that translate to 50.6 percent of the tot

l number studied, and 88 left-side ones equivalent to 49.4 percent. The mean central macular thickness for the included sample was 232.1 um (±30.85). The average central fovea macular thickness was 232.1 (±30.85) um. The quadratic value of the retina macular thickness decreased from the superior value of 299.71 (±23.67) um to the inferior value of 296.46 (±28.85) um to the nasal figure of 293.63 (±26.86) um. Finally, the temporal has the thinnest value with a figure of 293.43 (±30.78) um. Table 1 presents the central macular thickness of 1mm from the ring and thicknesses at 3mm and 6mm from the central ring.

The present study indicated significant gender differences for macular thickness at the following locations:

1. Central thickness (p= 0.003), higher in males with a mean difference of 11.67 um (95% CI: 2.41 to 20.93 um).

1. Superior at 3mm (p= 0.001), higher in females with a mean difference of 0.88 (95% CI: -7.79 to 6.67 um).

1. Nasal at 3mm: (p= 0.002), higher in males with a mean difference of 0.56 (95% CI: -5.67 to 10.71 um).

1. Temporal at 3mm: (p= 0.001), higher in males with a mean difference of 0.30 (95% CI: -4.41 to 14.33 um).

No gender differences were found for other measurements. Upon comparing thickness differences between right and left eyes, the present study did not find any significant difference with any performed measurement.

Central thickness significantly and positively correlated:

1. With nasal at 3mm (p< 0.001; correlation coefficient of 0.60).

1. With temporal at 3mm (p< 0.001; correlation coefficient of 0.52).

1. With inferior at 3mm (p< 0.001; correlation coefficient of 0.38).

1. With superior at 3mm (p< 0.001; correlation coefficient of 0.29).

The present study did not find a significant correlation between age and any investigated measurement. Refractive error didn’t statistically add to the prediction model.

Predicted normative data are based on the regression model. The prediction assumes a negative history of systemic hypertension and a negative history of diabetes mellitus and a spherical equivalent of zero.

Optical Coherence Tomography is a new technique that can accurately measure the macular thickness in-vivo with high reproducibility [2]. Essentially, knowledge of the normal value of the macular thickness helps in early detection of any abnormalities [8].

We developed regression models to predict the normative values of retinal macular thickness in a Middle Eastern population. During model development, we examined retinal macular thickness measurements for sexual dimorphism, binocular asymmetry, age-related changes, and clinical association with refractive error.

Ethnic variability, the effect of age, sex, distance from the fovea and laterality has been reported by various studies [9, 11-18]. Furthermore, the current work is consistent with the findings of most previous investigations.

Based on a study conducted on the Caucasian population [9] the central fovea’s macular thickness was 278.2um (range 266-291um) using spectral domain OCT on Caucasian population. This inquiry is consistent with the present findings. Furthermore, male participants have a higher macular thickness in all areas except for the temporal superior and the outer segment after adjusting the age.

In the present study, the mean value of the central fovea area was obtained as 232.1 (±30.85) um. This value is consistent with that of the previous studies on the Caucasian population using the Spectrally OCT 270+/-22.5 um [5, 11]. This investigative inquiry reveals that age is negatively correlated with macular thickness. This result is consistent with a previous work [12], which demonstrated that age had a negative correlation with all ETRDS macular areas except those found in the central fovea areas.

The retinal thickness values of the present inquiry were thinnest in the fovea area and thickest in the para-foveal area. These values decrease as the distance from the fovea increases. This finding is consistent with previous investigations [13], whose analysis concluded that irrespective of age or sex, macular thickness increased when moving from the central fovea area to the 3mm area. Eventually, it was thinnest in the 6mm area. However, in that study, the central thickness was 245.44+/-20.39um, which is thinner compared to the results obtained in this investigation.

Concerning eye sidedness, previous investigative inquiries indicated that the average macular thickness had no significant difference between the right and the left eye [14]. This finding is consistent with the results of the current study.

Various studies have evaluated the demographic variations in macular thickness [14-19]. A value of 181.1+/_ 3.7 as the normal figure for mean foveal thickness.in African-Americans and 200.27+/-27um was suggested in whites [16]. Additionally it was concluded that blacks tend to have thinner retinas compared to whites using Stratus OCTs [17]. In addition a significant difference in mean foveal thickness between Blacks and whites using Spectralis SD-OCT was documented [11].

Moreover, a thinner mean foveal thickness was observed in healthy Indians compared to other populations that were found to have a value of 149.19+\- 21.15um using Stratus OCT [19]. In contrast, it was observed that Japanese have thicker retinas compared to the US population using Stratus OCT [18].

Concerning the distribution of macular thickness in Iranian population, results show that the central foveal was 255.4 um, while the average inner thickness was 316.5 um. The average outer thickness was found to be 275.3 um, whereas the overall thickness was 278.6 um. All the obtained results from this study indicated a thicker central foveal in males compared to women. The central area of the fovea increased with age while the thickness in the other areas decreased. Another areas of the retina was evaluated in the Middle Eastern population namely, the peri-papillary nerve fiber layer, this analysis concluded that the thickness in various areas is consistent with previous studies [20 ],

Essentially, the African-American race was a predictor of decreased mean foveal thickness when compared to Caucasians and Hispanics. Furthermore, males were associated with increased mean foveal thickness. Similarly, a negative correlation between age and thickness was reported [5], while other investigators concluded that there is no effect of age and gender on macular thickness.

It appears, then, that adjustments need not be made to the retinal macular thickness measurements in Middle Easterners. However, the Middle Eastern population comprises a heterogeneous admixture of peoples. Therefore, normative data from additional Middle Eastern populations are required to confirm this finding.

The results of the current research inquiry indicate that in the Jordanian population, a Middle Eastern country, it is possible to interpret the macular thickness with increased accuracy.

This study’s set of predicted normative data may be used to interpret measurements of retinal macular thickness within the 6mm, 3mm areas and at the center of the fovea from Middle Eastern patients. This inquiry’s findings suggest that males have higher values. However, normative data from other Middle Eastern populations are required to appraise the models employed in this experiment.

Ethical Approval and consent to participate: this work has been approved by Institutional review board at the Jordan University Hospital.

Consent to publish: Not applicable

Authors Contributions: MS, AS and SR have examined and collected the data. MS performed the tomography. All authors analyzed and interrupted the patients’ data regarding the demographic criteria and the thickness on the tomography. All authors contributed in writing the manuscript. All authors read and approved the final manuscript.

Competing Interests: The authors declare that they have no conflict of interest.

Funding: This work was not supported by a grant.

Availability of Data and Materials: The data that support the findings of this study are available from the corresponding author upon reasonable request.

Acknowledgement: Not applicable.

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Table1: Central macular thickness (1mm ring) and thicknesses at 3 and 6mm from the central ring.

	Total		Sex				Eye
	Total		Male		Female		Right		Left
	Mean	SD	Mean	SD	Mean	SD	Mean	SD	Mean	SD
Central Thickness	232.11	30.85	239.32	35.68	227.65	26.66	235.58	31.80	228.57	29.61
Superior 3mm	299.71	23.67	299.37	29.13	299.93	19.70	301.86	25.60	297.52	21.44
Nasal 3mm	293.63	26.86	295.19	32.50	292.67	22.79	300.43	28.94	286.68	22.67
Inferior 3mm	296.46	29.85	302.96	29.33	292.45	29.58	296.77	33.86	296.15	25.28
Temporal 3mm	293.43	30.78	296.50	38.12	291.54	25.22	289.36	34.90	297.60	25.44
Superior 6mm	279.89	30.04	278.46	29.33	280.77	30.57	280.89	31.53	278.86	28.58
Nasal 6mm	281.75	35.01	282.97	33.81	280.99	35.86	292.68	37.87	270.57	27.86
Inferior 6mm	271.98	32.41	271.26	32.69	272.42	32.38	270.14	35.65	273.85	28.81
Temporal 6mm	284.17	31.20	285.79	33.77	283.17	29.62	274.82	31.52	293.74	27.95

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Normative Values of The Retinal Macular Thickness in a Middle Eastern Population.

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Abstract

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Background

Methods

Results

Discussion

Conclusion

Declarations

Competing Interests: The authors declare that they have no conflict of interest.

Funding: This work was not supported by a grant.

Availability of Data and Materials: The data that support the findings of this study are available from the corresponding author upon reasonable request.

References

Tables

Status:

Journal Publication

Version 1