Retinopathy of prematurity (ROP) is a retinal vascular disease in preterm or low birth weight infants and a leading cause of childhood blindness. Anti-vascular endothelial growth factor (VEGF) therapy offers advantages such as minimal invasiveness and convenient intervention; however, it carries a relatively high risk of disease reactivation, necessitating long-term follow-up due to the potential for severe outcomes. Studies indicate that post-anti-VEGF reactivation rates vary regionally and are related with birth status, ROP severity, and the specific anti-VEGF agent used. Most reactivations occur 6-16 weeks after initial treatment, at a postmenstrual age of 37-60 weeks. Reactivated lesions often develop at the original ridge or the junction of vascularized and avascular retina, and may present with dilation and tortuosity of the posterior retinal vessels, peripheral vascular leakage, neovascularization, or retinal detachment. Fundus fluorescein angiography may reveal Plus disease, posterior arterial tortuosity, abnormal nondichotomous retinal vessel branching at the junction of vascularized and avascular retina, irregular circumferential vessels, vasoobliteration with capillary nonperfusion, neovascularization, and fluorescein leakage. The choice of retreatment (such as retinal laser photocoagulation, intravitreal anti-VEGF injection, or vitrectomy) should be decided by the timing and severity of reactivation, along with prognostic considerations. It is recommended to establish a standardized management protocol for reactivation after anti-VEGF treatment in ROP to enable early detection and intervention, thereby preventing severe visual impairment. Future studies should focus on the mechanisms underlying ROP reactivation, differences in reactivation rates and timing among various anti-VEGF agents, predictive models for reactivation risk, and long-term management of reactivated disease.
ObjectiveTo investigate the fundus fluorescein angiography (FFA) characteristics of spontaneous regression in retinopathy of prematurity (ROP) and the range of retinal vascularization. MethodsA clinical retrospective study. A total of 82 eyes of 41 infants with ROP, who underwent FFA from January 2019 to December 2021 in Department of Ophthalmology of Xijing Hospital after completion of ROP regression, were included. There were 25 males (50 eyes) and 16 females (32 eyes). ROP was diagnosed in Zone Ⅱ in 44 eyes, with 38 eyes in stage 2 and 6 eyes in stage 3, and in zone Ⅲ in 38 eyes of stage 2. All patients underwent FFA examination under general anesthesia, at postmenstrual age of 70.70±12.25 weeks, after the natural regression of ROP was completed. Focus on the retinal vascular development, as well as choroid circulation and macular abnormalities, and compare and observe the differences between zone Ⅱ and Ⅲ after spontaneous regression. The extent of retinal vascularization was determined by the ratio between the distance of the center of the disc to the border of the vascularized zone (DB) and the center of the disc to the fovea distance (DF). The width of avascular area, recorded as the distance from the ora serrata to the vascular termination, was counted by disc diameters (DD). The measurement data between zone Ⅱ and zone Ⅲ ROP were compared by the independent sample t-test, and the count data were compared by χ2 test or Fisher exact probability test. ResultsThe linear choroidal pattern was present in 9 eyes (21.95%, 9/41), and the tortuous arteries in the posterior retina were detected in 32 eyes (39.02%, 32/82). It was noted that increased branching of vessels presented in 45 eyes (54.88%, 45/82), straight shape of vessels shown in 27 eyes (32.93%, 27/82), circumferential vessels arisen in 45 eyes (54.88%, 45/82), arteriovenous shunt appeared in 18 eyes (21.95%, 18/82), and capillary bed lost in 46 eyes (56.10%, 46/82) in areas from initial ridge to vascular termini. Punctate or linear dye leakage was observed in 23 eyes (28.05%, 23/82) during the late phase of FFA. Macular abnormalities, such as the absence of foveal avascular zone and hypoperfusion, were observed in 28 eyes (34.15%, 28/82), of which the macular ectopia presented in 1 eye. The mean DB/DF ratio of all the 82 eyes on the temporal side was 4.63±0.29 and 3.77±0.23 in the nasal. The mean avascular area on the temporal retina was 1.74±1.00 DD. Compared with ROP in zone Ⅲ, increased branching of vessels and dye leakage were more common (χ2=9.303, 10.774; P=0.002, 0.001), the extent of temporal retinal vascularization was smaller (t=－2.285, P=0.026), and the avascular area of the retina was more significant (t=5.491, P＜0.001) in zone Ⅱ ROP. ConclusionsEven after completion of spontaneous regression in ROP, incomplete retinal vascularization and vascular abnormalities may exist permanently in FFA, including those such as the tortuous arteries in the posterior retina, increased branching and straight shape of vessels, circumferential vessels, capillary bed lost and macular abnormality. Further appropriate follow-up is needed for long-term safety.