In groups of healthy pediatric subjects, we collected quantitative data on macular microvascular structure changes. FAZ and VD of SCP and DCP are unaffected by age or contralaterality. FAZ was greater in boys and could be impacted adversely by SCP-fovea and CC perfusion.
DCP-Fovea was found to be influenced by SCP-Fovea (and vice versa), SCP-perifovea, FAZ, and VD of CC. The fovea has the highest mean of VD at CC, and the age groups have more VD in the inferior hemifield of CC at the macular region. The only variables that were correlated with VD of foveal CC were WI-inf-hemi-CC and SCP-parafovea. Retinal and choroidal vascular changes may occur before structural changes. Many aspects of the microscopic and physiologic characteristics of the retina and choroid are now well understood in normal subjects thanks to OCTA. OCTA was used to explore pathophysiologic features of certain diseases [[12–16]]. Most previous studies using OCTA, however, mainly have evaluated normal adult patients [1, 4, 5, 9].
FAZ was reported to be 0.26–0.47 mm using different kinds of OCTA machines at 3 × 3-mm enface AngioScans in the kids between mean age of 8–12 years in different capillary layers. Hsu et al. recorded an FAZ of 0.35 ± 0.17 mm2 in their 89 eyes (mean age, 8.5 ± 5.3 years-Heidelberg OCTA instrument and MATLAB program by unknow size of evaluated field) [7]. Comparingly, Yilmaz et al reported the SCP-FAZ area to be 0.28 ± 0.09 mm2 and DCP-FAZ to be 0.38 ± 0.09 in 15 eyes from 15 normal children (a mean age of 8.6 ± 2.2 years- Nidek's RS-3000 in 3 × 3-mm) [17]. İçel et al stated SCP-FAZ as 0.3 ± 0.09 mm2 in 146 children eyes (the mean age of 11.27 ± 3 years- Nidek RS-3000 AngioScan in 3×3-mm) [18]. In our study, the mean FAZ area was 0.38 ± 0.60 mm2, considering a single layer measurement on 3×3-mm enface image (automatedly derived data from software).
The observed differences may be attributed to ethnic differences, sample size, different OCTA machine use, and different capillary layer FAZ measurements. While the estimation techniques were not equivalent, we could conclude that the FAZ areas of healthy children and adults are comparable. The FAZ area of adults has been found to be from 0.24–0.46 mm and more in DCP than SCP [4, 19–21].
The effect of aging on the size and shape of the FAZ is a hotly debated subject. OCTA has demonstrated in many studies that the scale and form of the FAZ in healthy adult populations increases with age [6, 22, 23]. Since our and other studies only included children, the aging impact on FAZ could not be detected in this age range [7, 19, 24].
The impact of sex on the FAZ area remains inconclusive. Some research results indicated that adult females had higher FAZ than males, which can also be seen in children [8, 19, 23, 25, 25, 26]. Other studies reported no significant difference between the sexes [18, 25, 26]. In our study, accounting our smaller number of female subjects, the median of FAZ was 0.24 mm (range 0.104–5.05) in male and 0.33 mm (range 0.035–1.083) in female. Population-based studies are needed to determine the true effect of sex on FAZ area in the future.
Unlike previous studies [6–8, 18, 26], our research found no correlation between FAZ and CMT. The difference may be attributed to unadjusted results to certain major confounders in previous studies.
Our multivariate analysis showed that FAZ was only correlated with VD of fovea-SCP and CC, especially perifoveal CC. Any 0.4 percent reduction in SCP-fovea and 1.81 percent reduction in CC-WI VD result in a 1mm increase in FAZ. Zhang et al disclosed the impact of sex, foveal retinal thickness, parafoveal retinal thickness, axial length, and SSI on FAZ in their cohort [8].
Using the Optovue Angioretina program, several researchers have tested the SCP and DCP in healthy adult subjects. In line with our results, some of these studies revealed no variations in VD between genders [7] whereas increased SCP-VD in males was reported in other studies [6].
In our study, the foveal region CC had the most VD compared to the other parts' VD in SCP, DCP, and CC. At the foveal part of CC, the VD increased up to age 10 and from 11 to 18 years a decreasing trend started. The parafoveal area of CC and mostly perifoveal area had increasing order up to 13 years of age and then mild decrease in each part was noted (P < 0.05). Similar to our results, Zhang et al showed that in the parafoveal region, the CC had the densest vascular flow compared to DCP and SCP (P < 0.001) [[8]]. Other studies have shown that as the FAZ area increases, the VD of SCP, DCP, and CMT decreases dramatically during aging [18].
Our study used 6×6-mm enface images for measurements to evaluate the macular region as a whole, while their study used 3×3-mm enface images, so the quantities are not equivalent. In a pediatric study, they found that neither retinal perfusion nor VD were affected by age [[6]]. They reported that CC perfusion density not retinal VD inversely is correlated with age, even after accounting for potentially confounding factors such as refractive error and race, but not adjusting for sex and the BMI of the children [6].
Iafe et al [22] analyzed adult macular VD in 70 subjects (mean 48 ± 20 years of age, range 9–88 years), Wang et al [27] in 105 Chinese healthy participants (age: 35.9 ± 13.8 years, range 17–64 years), Coscas et al [20] in 70 subjects (age: 48 ± 18 years, range 20–79 years), and Ghassemi et al [5] in 112 healthy cases (age: 36.39 ± 11.31 years, range 12–67 years). VD of SCP and DCP decreased with age in these and other similar studies on healthy adult eyes [28, 29]. However, only the CC-fovea was affected by age in our pediatric series, and aging changes could be observed in children aged 11 to 18 years. Our study was confined to pediatric patients, and hence we were unable to determine whether VD continues to decline throughout young adulthood or stabilizes.
Although we did not note any gender differences in VD of retina and CC at macular area, some significant differences were reported in the SCP between sexes in healthy children in other study [[25]]. On the other hand in adults, Coscas et al uncovered a higher retinal VD in females than in males > 60 years of age and attributed this difference to a slower vascular aging in females [20]. Other studies stated no gender-based variance in VD of retina in macular area [5].
The primary limitation of our study was the cross-sectional nature of the analysis and relatively small samples in age groups. Furthermore, we did not perform axial length measurements in our study that may have weakened our analysis. Although, we limited our cases to those with a small amount of refractive error and a spherical equivalent between − 0.5 and + 0.5 diopter, in which it does not seem to affect significantly the image magnification. The effect of ethnic variation on VD is not evaluated in this study. The flow projection artifact of the large vessels of the SCP onto deeper retinal layers may have been a concern and may have influenced the quantitative analysis of VD values in the DCP.