At the early developmental stage, the demarcation line between vascular and avascular areas is the characteristic feature of ROP. However, are there any other vascular differences between the ROP and corresponding group besides this typical feature?
To the best of our knowledge, this is the first study revealing the morphological and developmental differences between preterm infants with and without ROP. The main findings of this study are as follows: (1) The vascular tortuosity, vascular width and vascular branch angle of preterm infants with ROP but without plus disease are significantly larger than those of without ROP. (2) There was no significant difference in vascular density and vascular fractal dimension between preterm infants with ROP and without ROP. (3) Compared with preterm infants without ROP, the vascular development in preterm infants with ROP was slower. All results had excluded the effects of plus disease and pre-plus disease.
Mao et al. found that the vascular curvature, vascular width, vascular density and fractal dimension of preterm infants with ROP with pre-plus and plus disease were significantly higher than preterm infants without ROP. Similarly, we found that the vascular tortuosity and vascular caliber of preterm infants with ROP without plus or pre-plus were significantly larger than those of without ROP. These results suggested that the changes in vascular tortuosity and caliber in the posterior pole region of the retinal are continuous dynamic process in the evolution from the normal state toward ROP, eventually into plus disease, which is consistent with the views of Chiang and other scholars.
We found that vascular density and vascular fractal dimension were significantly different between preterm infants with ROP and without ROP before correcting the effects of gestational age and weight. But after correcting the effect of gestational age and weight, the difference disappeared. This indicates that in the absence of plus or pre-plus diseases, ROP does not bring about changes in density and fractal dimension. But Mao et al. has demonstrated the significant difference between preterm infants with plus diseases and without ROP. This indicated that during development of ROP, the vascular density and vascular fractal dimension of the posterior pole region may not change continuously.
The results of Gupta et al.[10, 18] showed that after anti-VEGF treatment, the severity of vessel alteration in preterm infants with ROP was significantly lower than that before treatment. These findings suggested that hypoxia-induced up-regulation of neovascular factors such as VEGF is one of the main causes of tortuousness and dilation of vessels in the posterior pole region of the preterm infant’s retinal. In addition, hypoxia of the retinal leads to block of retinal vessels, which increases the circulatory resistance of the retinal vascular network, and is also one of the reasons for the tortuousness and expansion of retinal vessels. In the process of retinal vascularization in preterm infants, with the retinal hypoxia and the increase of hypoxia-induced neovascularization factors, the vascular tortuosity and vascular caliber in the posterior pole region continue to increase, and patients with severe diseases develop plus disease.
Retinal vascular branch angles become larger, suggesting decreased retinal blood perfusion[19, 20], which could lead to retinal ischemia. Statistical analysis of retinal vascular branch angle showed that the vascular branch angle of preterm infants with ROP but without plus disease was significantly larger than that of preterm infants without ROP, which indicated that retinal blood perfusion in preterm infants with ROP was less than that of preterm infants without ROP. This is consistent with the mechanism of ROP that hypoxia-induced retinal vessel occlusion and vessel-growth-factor-mediated neovascularization can hinder normal retinal vascularization, resulting in less retinal blood perfusion in preterm infants with ROP than in preterm infants without ROP[7, 21].
ROP is a fibrovascular proliferative disorder that affects preterm infants and is characterized by arrest or disruption of normal retinal vascular development[7, 21]. Postnatal hypoxia forms retinal avascular areas. And hypoxia causes spasmodic occlusion of retinal arterioles, which in turn aggravates retinal hypoxia, resulting in retinopathy and delayed retinal vascular development[10, 18]. This fact is consistent with the results of our study, which showed that compared with normal preterm infants, the retinal vascular density of the preterm infants with ROP without plus changed more slowly. That is, the retinal vessel developed more slowly in the preterm infants with ROP. Slower retinal vessel development further aggravates retinal hypoxia, which further promotes the occurrence of ROP.
In summary, during the evolution of normal preterm infants to ROP, the vascular tortuosity and vascular caliber of the retinal posterior pole region continue to increase. When there is a visible tortuousness and expansion, it often indicates that ROP is more serious. When ROP occurs in preterm infants, retinal vascular development is delayed, which further hinders the normal retinal vascularization process. This study is a retrospective study, and no further study was made on the vascular morphological changes with the disease development in the same patient over time. The research subjects we selected were preterm infants with ROP and without ROP at 4–6 weeks after birth. The vascular development dynamics revealed in this study can only reflect the situation at 4–6 weeks after birth. Next, we will further explore the dynamic changes of retinal morphology over time in preterm infants with ROP and without ROP in order to predict the occurrence of ROP and monitor the progress of the disease through changes in the morphological vessels of the vessels in posterior pole region.