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Purpose: To evaluate the serum levels of vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF-1) after intravitreal injection of aflibercept (IVA) and the transition of aflibercept into systemic circulation in infants with severe retinopathy of prematurity (ROP)., Study Design: Prospective study., Methods: This single-centered prospective cohort study included infants who received IVA for the treatment of type 1 ROP in zone I and posterior zone II. Blood samples were collected before IVA and at 1 day and 1, 2, 4, and 8 weeks after IVA. VEGF, IGF-1 and aflibercept levels were measured., Results: Thirty eyes of 15 infants received IVA of 1 mg/0.025 mL. Serum VEGF levels decreased significantly at 1 day and 1, 2, 4, and 8 weeks after IVA compared with baseline (P < 0.05). Serum aflibercept levels decreased significantly 1, 2, 4, and 8 weeks after IVA compared with the level at 1 day after IVA (P < 0.05) and increased significantly at 1 day, 1, 2, and 4 weeks after IVA compared with the baseline level (P < 0.05). No significant difference was detected between serum IGF-1 levels any time in any infant (P > 0.05)., Conclusion: Serum VEGF levels are suppressed for at least 8 weeks, and aflibercept could be detected in the systemic circulation at 4 weeks after injection. Clinicians should be cautious about changes in systemic VEGF levels and passage of the agent into systemic circulation after IVA in infants., (© 2021. Japanese Ophthalmological Society.)

Objective: Evaluation of vascular leakage and retinal vascular development with fundus fluorescein angiography for infants diagnosed with aggressive posterior retinopathy of prematurity who underwent intravitreal anti-VEGF treatment., Method: Medical recordings of 30 patients who received RetCam fluorescein angiography during follow-up and had been treated with anti-VEGF on diagnosis of aggressive posterior ROP in the zone I or zone II between the dates of April 2014-January 2017 were evaluated retrospectively., Results: Fifty-nine eyes of 30 patients were included in the study. Mean birth weight was 1145 g; gestation week was 28.4. Recurrence occurred in 30.5% of the patients, and 10.1% of them were given a second dose of injection of anti-VEGF. Leakage was detected in 15.3% of the eyes during angiography, and all of these eyes were treated with laser photocoagulation. Evaluation of vascular development revealed that in the temporal, complete retinal vascular development was achieved in only 8% of the eyes. It was detected that complete retinal vascularization was not observed in any of the cases which were given second dose of injection due to recurrence. The patients were distributed into groups according to postmenstrual week taken to angiography as 32 eyes of 16 patients in group 1, 17 eyes of 9 patients in group 2 and 10 eyes of 5 patients in group 3. The vascular leakage rate of group 3 patients was statistically significantly higher (p < 0.05) and vascular development between groups was not statistically significant (p > 0.05)., Discussion: With the initiation of FFA usage in pediatric cases, especially treated with anti-VEGF due to retinopathy of prematurity (ROP), more findings (vascular arrest, leakage, and abnormalities, etc.) are obtained than those achieved via ophthalmoscopic examination. In the light of these findings, early intervention with laser photocoagulation in early stages becomes possible enabling prevention of possible blindness.

Purpose: To investigate the extent of vascularization of the peripheral retina and vascular development patterns in patients with type 1 retinopathy of prematurity (ROP) treated with intravitreal injection of bevacizumab (IVB) and compare fluorescein angiography (FA) findings of them to those seen in patients with type 2 ROP who have recovered spontaneously., Methods: Between May 2014 and September 2016, patients with type 1 ROP who had a single 0.025 ml (0.625 mg) IVB were evaluated as study group. On the other hand, type 2 ROP patients with stage 2 or stage 3 ROP in zone II without plus disease on indirect ophthalmoscopy were not treated and included as a control group. The progression of ROP and vascularization of retina were evaluated by FA under sedation analgesia in all patients., Results: Sixty-two eyes of 31 premature infants were included in the study: 36 eyes/18 patients were treated for type 1 ROP and 26 eyes/13 patients were followed conservatively with the diagnoses of type 2 ROP. In the last FA examination among the study group, vascular terminal was in zone II in 8 eyes/4 patients (22.22%) and in zone III in 28 eyes/14 patients (77.78%). Vascular terminal was in zone III in all eyes of the control group (100%). We noted circumferential vessels in 12 eyes/8 patients (33.3%) and 7 eyes/5 patients (26.92%) in the study and control groups, respectively. Abnormal branching was noticed in 13 eyes/7 patients (46.42%) in the control group, whereas it was not detected in the study group. Arteriovenous shunts were noted in 1 eye of a patient in the study group and in 5 eyes/4 patients in the control group. In 6 eyes/3 patients among the study group, we performed laser photocoagulation to the avascular retina because of profound vascular leakage., Conclusion: Peripheral vascular abnormalities probably occur as a result of ROP itself because similar FA findings were detected both in type 1 and type 2 ROP patients with or without treatment, although significantly less in IVB-treated group. Retinal vascularization usually reaches the farthermost limits with time even though it slows down in eyes treated with IVB, indicating the importance of a longer follow-up.

Purpose: To evaluate the efficacy of intravitreal aflibercept (IVA) in vascular and macular maturation in neonates with type 1 retinopathy of prematurity (ROP) and aggressive posterior retinopathy of prematurity (APROP)., Materials and Methods: Thirty-six eyes of 18 patients with type 1 ROP or APROP in zone I or posterior zone II were enrolled in our study. At baseline, only fluorescein angiography (FA) was performed. After IVA injection, both FA and optical coherence tomography (OCT) were performed after 6.8 ± 0.8 (range 6-8) and 19 ± 0.9 (range 18-20) weeks to follow vascular and macular changes., Results: Both diffuse flat neovascularization with leakage and abnormal vascular branching at the small arteriolar level were detected in all eyes (100%) at baseline FA. Regression of the disease was observed in 34 eyes (94.4%) in the first week with binocular indirect ophthalmoscopy. Early unresponsiveness in remaining two eyes of an infant required an IVA re-treatment. Late reactivation was detected only in 19.4% of eyes, none of which required treatment during 12 months of follow-up. The most common feature after IVA injection was abnormal branching at capillary level, which was noted in 100% in the first post-injection FA and 50.0% of all eyes in the second FA. Meanwhile, the end limit of vascularization was observed in zone III in 83.3% of eyes. No vascular abnormality was also detected in 27.3% of eyes. The OCT examination at a mean postmenstrual age of 43.4 weeks revealed cystoid macular changes in four eyes of two infants (11.1%), normal foveal contour in 30 eyes of 15 infants (83.3%) and matured ellipsoid zone at the foveal center in 28 eyes of 14 infants (77.8%). Macular maturation was complete in all eyes in the last OCT analyses., Conclusion: Intravitreal aflibercept monotherapy has been an effective treatment in type I ROP and APROP with much lower early and late re-treatment rates because of early unresponsiveness and late reactivation, respectively. In most of the eyes, rapid vascular outgrowth beyond zone III together with normal macular maturation was observed more precisely by periodic FA and OCT.

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