Macular and Retinal Nerve Fiber Layer Analysis by Optical Coherence Tomography in Normal Children
Asmaa N. Ali1, Rania K. Farag1, Tarek A. Abd El Wahab1, Asaad A. Ghanem1*
Copyright : © 2018 . This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Aim: This study aims to evaluate macular and peripapillary retinal nerve fiber layer measurements in normal children and their correlation with age, gender, laterality, refraction and axial length.
Methods: This was an observational cross sectional study among 100 eyes of 50 child (25 boys, 25 girls) aged between 6 and 17 years. After detailed eye examination and axial length measurements, the children were scanned using swept source optical coherence tomography (3D DRI OCT Triton [plus], Topcon Corporation, Tokyo, Japan) to measure macular thickness, macular volume, peripapillary RNFL thickness and optic disc parameters.
Results: Both eyes of fifty child were included in the study. Mean age was 10.96 ± 2.75 years, average spherical equivalent refraction (SE) was 0.78±1.65 (−4.50 to +5.00) diopters and average axial length was 22.87 ± 0.90 (20.99 to 24.67) mm. Average macular thickness was 276.41±17.8 μm, central macular thickness was 225.26±20.79 μm, mean macular volume was 7.84±0.48 mm3 and mean peripapillary RNFL thickness was 111.26±20.46 μm. Axial length showed positive correlation with age unlike negative correlation with spherical equivalent. It also showed negative correlation with mean average RNFL thickness. Most of the parafoveal region quadrants correlated positively with age unlike RNFL measurements that correlated negatively. Central macular thickness values were significantly higher in males (p=0.001) but there was no difference between male and female as regard RNFL thickness. Spherical equivalent didn’t show significant effect on studied parameters. Concerning the side of the eye, it had no statistically significant difference between both eyes but good correlation.
Conclusion: Normative paediatric SS-OCT data might facilitate use of SS -OCT for assessing childhood ophthalmic diseases. This study provides a paediatric normative database of SS -OCT peripapillary RNFL and macular data.
1. Introduction
2. Patients And Methods
Peripapillary RNFL measurements, average of three measurements was taken, measurements were expressed as an average over four quadrants, 12 clock hours and mean thickness of the total circumpapillary scan. Optic nerve head parameters included disc area, cup volume, horizontal and vertical cup disc ratio and rim area.
3. Statis Tical Analys Is
4. Results
Pearson correlation was used, *Significant p-value Inner circle values were significantly increased as compared to the outer macular thicknesses (p< 0.0001) (Figure . 2).
In the correlation analysis (Table . 2) of macular parameters with age there was no significant effect on macular volume, average macular thickness and central macular thickness while there was significant positive correlation between age and inner circle quadrants apart from the nasal highly significant p-value < 0.001. quadrant. The p-value was 0.016 for the superior and inferior quadrants and 0.006 for the temporal quadrant. Also age showed significant negative correlation only with the nasal quadrant of the outer circle (p-value = 0.034).
By correlating axial length with macular parameters there was no significant effect on macular volume, central macular thickness and average macular volume while it showed statistically significant positive correlation with the temporal quadrant of the parafoveal area (p-value = 0.029) and statistically significant negative correlation with the superior quadrant of perifoveal area (p-value =0.038) and the inferior quadrant of the perifoveal area (p-value=0.023).
Regarding correlation between spherical equivalent and macular parameters, macular volume and temporal quadrant of the outer circle showed significant positive correlation with spherical equivalent but other parameters did not shoe statistically significant correlation.
By studying the difference between male and female as regard macular parameters, male showed statistically significant higher values for macular volume, central macular thickness, inferior quadrant of the inner circle and inferior and temporal quadrant of the outer circle. However the side of the eye did not show statistically significant effect on studied parameters (Table 3).
The average thickness of the RNFL was 111.26 ± 20.46 μm ranging from 87.00μm to 243.00 μm while the mean thickness of the optic disc quadrants was 137.38 ± 24.62 μm for the superior quadrant with range from 103.00 μm - 291.00 μm, 140.71 ± 28.48 μm for the lower quadrant with range from 105.00 μm to 313.00 μm, 90.39 ± 21.90 μm for the nasal quadrant with range from 57.00 μm to 220.00 μm and 76.29 ± 17.68 μm for the temporal quadrant with range from 52.00 μm to 180.00μm(Table .4).
RNFL distribution among studied group followed ISNT rule (inferior ˃ superior ˃ nasal ˃ temporal) (Figure . 3).
Regarding optic disc measurements, the mean of the disc area of examined children was 2.38 ± 0.44 with range from 1.57 mm² to 3.94 mm² with the mean cup volume 0.11 ± 0.14 ranging from 0.00 mm³ to 0.70 mm³. The mean of the rim area was 1.86 ± 0.47 with range from 0.85 mm² to 3.21 mm² while the mean of the vertical cup disc ratio was 0.42 ± 0.13 ranging from 0.10 to 0.66 and the mean linear cup disc ratio was 0.43 ± 0.14, which range from 0.00-0.64 By correlating RNFL thickness and optic disc parameters with age, axial length and spherical equivalent, average RNFL thickness and four quadrants thickness showed significant negative correlation with age. Linear and vertical cup disc ratio showed highly significant positive correlation with age as the p-value for both < 0.001 while the rim area shows significant negative correlation age (p-value = 0.003). Axial length there revealed significant negative correlation with total thickness (p-value = 0.014) and with the inferior sector (p-value = 0.005). It also shows significant negative correlation with rim area (p-value= 0.001), positive correlation with vertical cup disc ratio (p-value = 0.003) and cup volume (p-value = 0.002) and highly significant positive correlation with linear cup disc ratio (p-value < 0.001). Spherical equivalent showed non-significant effect on RNFL thickness and optic disc parameters (Table .5).
Regarding gender differences and interocular differences, there was no statistically significant difference between male and female and also between both sides of the eye (Table .6).
5. Discussion
Foveal thickness in the current study was the thinnest compared by all nine quadrants. Also the nasal quadrant of the outer macular circle was the thickest which consists with convergence of retinal nerve fibers in the optic disc while the temporal quadrant was the thinnest like similar studies [1,10].
Comparison between inner and outer macular thickness values in all quadrants revealed highly statistically significant difference between both similar to results detected by Eriksson et al, and AL-Haddad et al [11].Regarding correlation of macular parameters with age in the current study we found that there was no significant correlation between age and central macular thickness. This coordinates with that reported by Molnar et al [14].In contrast to this result, AL-Haddad et al, 11reported positive correlation between age and central macular thickness.
The present study found that there was significant positive correlation between inner macular circle quadrants and age except for the nasal quadrant (did not reach statistical significance) which is similar to results given by AL-Haddad et al, [11] which also reported positive correlation between age and the thickness of inner macular circle. Katiyar et al, [12] also reported significant positive correlation between age and thickness of inner macular circle quadrants.
Regarding outer macular thickness, all quadrants showed negative correlation with age except for the temporal quadrant. But only the nasal quadrant reached statistical significance.
Katiyar et al,[12] reported positive correlation between nasal and inferior quadrants of the outer macula with age while negative correlation between superior and temporal quadrants of the outer macula with age. This does not coordinate with current study may be due to different mean of age which was 12.59 ± 3.5 yrs., different version of OCT used (Cirrus) and different refraction as they excluded any child with refractive error more than ± 0.5 D (sphere or cylinder).
Concerning correlation between gender and macular parameters, there was statistically significant increase in central thickness measurements in male over female. This result matches with that reported by Huynh et al, [15] AL-Haddad et al, [11] and Barrio-Barrio et al, 6 whom applied gender differences only on central macular thickness. Katiyar et al, [12] also found that male had higher values for central thickness than female.
In addition to that, the present study also compared between male and female from macular volume and found that male children had higher values for macular volume which correlates with that found by Qian et al, [16] whom examined Chinese children of school age.
Pokharel et al,[17] reported a study on normal eyes of Nepalese population aging from (10-37) yrs. and concluded that males have higher values for macular volume than females which coordinates with our result.
The current study also studied the correlation between axial length and average macular thickness and found no statistically significant association. This coordinates with that reported by Barrio-Barrio et al, [6]. Gürağaç et al, 1iffer from the current study as they reported that AL negatively correlates with average macular thickness.
Several studies[14] correlated spherical equivalent with central macular thickness and reported non-significant association and in the current study we also found similar result. However, macular volume in the current study showed significant positive correlation with SE. This result coordinated with that reported by AL-Haddad et al,[11] and et al, Gürağaç et al, [1] Exclusion of high refractive error might have limited our ability to assess the effect of axial length and spherical equivalent on macular parameters.
By studying the interocular difference regarding macular parameters there was no statistically significant difference between both eyes similar to results reported by Altemir et al, 4 Peripapillary RNFL Thickness Several studies have evaluated the RNFL thickness in normal children. Earlier studies used TD-OCT (OCT3-Stratus) , later SD- OCT used in measurement of RNFL thickness [1,5,11] (Table .8).
In the current study SS-OCT (Topcon) was used and it was found that the mean RNFL thickness was 111.26±20.46 μm which is similar to Qian et al, 16 (112.3±9.2 μm) , Tsai et al, [5] (109.4±10.0 μm) and Nigam et al, [19] (110.79±13) who used Stratus , RTVue and Cirrus respectively.
Turk et al,[13] and Yanni et al,[20]evaluated children between 5–16 years of age with Heidelberg Spectralis SD-OCT and reported that the mean RNFL thickness was 106.45±9.47 μm and 107.6±1.2 μm, respectively. Tsai et al, ]] evaluated 470 children aged 4 to 17 using RTVue and reported that the mean RNFL thickness was 109.4±10.0 μm. These results are slightly lower than present results.
Elía et al, [21] Barrio-Barrio et al 6 and Rao et al,[7] used cirrus and reported that the mean RNFL thickness was 98.5±10.8 μm, 95.0±10.9 μm and 97.4±9.0 μm respectively. AL-Haddad et al, [11] and Gürağaç et al, [1] also used Cirrus and reported that the mean RNFL thickness was 95. 6±8.7 μm and 96.49±10.10 μm respectively. These results are lower than current results.
The average-quadrant-wise RNFL thickness values in the current study followed the ISNT rule, it was not so for the individual eyes. The ISNT rule on the RNFL was followed by 52 eyes (52%). this result was quiet similar to another study where the ISNT rule on the NRR was followed in 30 eyes (56 %) of children between 5 and 16 years of age Larsson et al, [22]. However, this study was done on Heidelberg retinal tomography, and hence cannot be directly compared to current study.
This result is higher than Dave et al, [23] who examined children using SD-OCT and found that ISNT rule was only applicable on 30 eyes (23.8%).
The IST rule was better followed in the current study with 64 eyes (64%) obeying it. Similar results have also been found in children by Dave et al, [23] who found that 66 eyes (52.4%) obeying IST rule compared to 30 eyes (23.8%) only obeying the ISNT rule. This means that the ISNT and the IST rules for RNFL are not universally followed by all normal eyes in children. All deviations should therefore not be considered pathological.
The RNFL thickness has been considered dependent on factors such as age, AL and refraction so, the current study correlated RNFL thickness with these factors.
Regarding age, it was found that average RNFL thickness and the thickness for the four quadrants negatively correlated with age especially the average thickness as the p-value was < 0.001 unlike other studies which found that RNFL values not affected by age[6,11]. Mwanza et al, [24] have reported that the RNFL thickness decreases with age over the fifth decade in adults.
The RNFL thickness in the current study was not affected by gender similar to several studies[1,6,11,19] and different from Rao et al,[7] who reported that RNFL is thinner in female than male this may be due to different race.
Turk et al, [13]reported that significant difference between males and females only found in the temporal inferior segment (thicker in female) and no significant differences were detected in other RNFL parameters.
Axil length was negatively correlated with RNFL thickness in the present study and reached statistical significance for the average thickness and inferior quadrant thickness, this finding supported that RNFL was thinner in eyes with longer axial length. This consisted with that concluded by Savini et al, [25]. Barrio-Barrio et al,6 and Rao et al, [7]also confirmed this in their studies which evaluated children aged 4 to 17 years using Cirrus OCT. Gürağaç et al, [1] also found that negative correlation was strongest for the inferior RNFL.
On the other hand, Turk et al, [13] reported non-significant correlation between AL and RNFL thickness this may be due to different spherical equivalent, race and OCT used.
Regarding correlation between spherical equivalent and RNFL parameters we found no significant correlation between both which consisted with that concluded by Turk et al,[13] in their study on healthy Turkish children and different from AL-Haddad et al, [11] who reported strong positive correlation between SE and average RNFL but they didn’t find significant correlation with quadrant thickness similar to the current study. This may be attributed to different race and difference of SE of the excluded cases which was more than ±7D unlike more than ±6D in current study.
Regarding the side of the eye, no significant difference was detected in mean RNFL thickness of the four quadrants between right and left eyes. This results consistent with several studies[7,9,26].
Altemir et al, [4] also reported that there is no statistically significant difference between right and left eye in optic disc parameters but they reported statistically significant difference for superior, nasal and temporal quadrants of the RNFL.
Budenz et al,[27] also found no relationship between RNFL thickness and eye side in his study on 328 subjects aged 18 to 85 years. However, Gherghel et al, [28] reported that the eye side had significant influence on RNFL thickness. Difference may be attributed to using confocal scanning laser ophthalmoscopy.
Strengths of the current study include the large age range (6–17 years) of enrolled children, the use of the new generation Topcon SS-OCT, the recording of both normative RNFL and macular parameters, and the biometric correlations.
Limitations of the current study include the mostly uniform ethnic group so the effect of race and ethnicity could not be tested. We also excluded patients with high refractive errors and increased cup to disc ratios; normative data for these groups were not established. Additionally, our study was hospital based and not population-based. However, patients in this setting received a comprehensive examination and biometric data were recorded.
OCT, time domain optical coherence tomography; SD-OCT, spectral domain optical coherence tomography; SS-OCT, swept source optical coherence tomography; N, number; AL, axial length; SE, spherical equivalent.
6. Conclusion
References