Microvascular parameters evaluated with optical coherence tomography‐angiography in children: comparison between preterm and full‐term patients

Mechanisms leading to anomalous retinal vessel formation underlying retinopathy of prematurity (ROP) are of great interest (Quazi et al. 2009; Tasman 2011) and not fully understood. Optical coherence tomography angiography (OCT-A) is a recent noninvasive retinal imaging technique that could be useful in the study of retinal vascularization of former preterm infants. The aim of this study was to quantitatively evaluate and compare macular microvascular parameters, foveal avascular zone (FAZ) area and perfusion density (PD), in full-term and preterm children by means of swept-source (SS) OCT-A. Two hundred fifty eyes of 133 children were prospectively enrolled. One hundred sixty-seven eyes were of full-term children (gestational age, GA ≥ 37 weeks, group A), 52 eyes of preterm children without ROP (group B), 11 eyes of preterm patients with spontaneously regressed ROP (group C), 20 eyes of preterm patients with laser-treated ROP (group D). The study adhered to the tenets of the Declaration of Helsinki and was approved by the institutional Ethics Committee; all parents signed a written informed consent before examination. Optical coherence tomography angiography (OCT-A) images were acquired with Dri SS-OCT-A Triton plus (Topcon Medical Systems Europe, Milano, Italy), and a 4.5 × 4.5 mm macular map was captured for all patients. Foveal avascular zone (FAZ) area was manually delineated using Topcon's intrinsic tool, and PD was evaluated at the superficial and deep capillary plexus using image j (https://imagej.nih.gov/ij/). Mean FAZ area was 241.3 ± 129.7 μm, divided as follows: group A 288.4 ± 109.6 μm, group B 173 ± 114 μm, group C 48 ± 42.1 μm, group D 132.3 ± 116 μm. Foveal avascular zone (FAZ) area was significantly different among subgroups (p < 0.0001). Group A had a significantly larger FAZ compared to all other groups (p < 0.0001). Group D had a significantly larger FAZ compared to group C (p < 0.05; Fig. 1). A linear correlation between FAZ area and birthweight (r = 0.46) and between FAZ area and GA (r = 0.53) was found. Foveal avascular zone (FAZ) area analysis after stratification by age range showed that average FAZ area between the tenth and ninetieth percentile did not change significantly with increasing age. No significant differences were found in PD among subgroups, except for a slight trend for a higher PD in group C. Age was not significantly different among subgroups. Summing up, we found a significantly smaller FAZ area in preterm compared to full-term children. Interestingly, patients with spontaneously regressed ROP had smaller FAZ than children with laser-treated ROP. In a recent study performed with OCT-A, Falavarjiani et al. (2017) reported that FAZ profile was clearly identifiable in all full-term children examined and not in many preterm ones. In the present study as well as in Falavarjani's, a small or absent FAZ proved to be an hallmark of prematurity. Our results are also consistent with data obtained by Nonobe et al. They found that FAZ of premature laser-treated patients was smaller than FAZ of healthy controls (Nonobe et al. 2019). These results seem to strengthen the hypothesis that foveal vascular development may be altered in premature patients. Furthermore, in the present study, laser-treated patients had significantly larger FAZ than patients with spontaneously regressed ROP. Therefore, we could hypothesize that laser may stop the angiogenetic factors cascade, playing a protective role against abnormal retinal vascularization. A debate could be raised on the utility of photocoagulation not only as a necessary treatment to prevent complications, but also as a potentially protective treatment against what may seem an excessive capillary vessels growth in the foveal region maybe due to high Vascular Endothelial Growth Factor (VEGF) levels leading to relative hypoxia. Consequently, another interesting point of discussion should be the role of anti-VEGF (an off-label treatment for ROP) on foveal vascularization. The strength of the present study is the large size of the initial population; however, the asymmetry of the subgroups is a major limitation, in particular when looking at the results of PD. On the other hand, FAZ area differences are so explicit that conclusions can be drawn despite discrepancies among group numbers. Results are consistent with the two main published studies on OCT-A in paediatric patients; further, longitudinal studies are needed to confirm these preliminary data.

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