This study evaluates the vascular development of premature infants at 50 weeks postconception after treatment with intravitreal bevacizumab for type 1 retinopathy of prematurity (ROP).
Methods:
A retrospective case series was conducted on type 1 ROP neonates with a high risk of general anesthesia complications. Patients were treated with bevacizumab between February 2013 and February 2016. At 50 weeks’ gestational age, all patients were imaged with RetCam (Clarity Medical Systems, Inc) fundus photographs and widefield fluorescein angiography (FA).
Results:
There were 4 boys and 7 girls with an average gestational age of 24.8 weeks and weight of 734.3 grams at birth. The estimated gestational age at injection was 37.1 weeks. Examination under anesthesia with FA was performed at a mean of 61 weeks posttreatment. Nineteen of 20 eyes (95%) of 11 infants had incomplete vascularization and peripheral nonperfusion on imaging. FA showed new vessels with increased tortuosity, microvascular abnormalities, and leakage past the original ridge. These 19 patients were treated with confluent ablative photocoagulation to the peripheral nonperfused retina. Patients were followed for a mean of 73.3 weeks after birth. None required incisional surgery.
Conclusions:
Patients with type 1 ROP treated with bevacizumab may have delayed vascularization of the peripheral retina and even late recurrence of active disease. Clinicians should regularly monitor patients after bevacizumab for potential neovascular complications.
BlencoweHLawnJEVazquezTFielderAGilbertC. Preterm-associated visual impairment and estimates of retinopathy of prematurity at regional and global levels for 2010. Pediatr Res. 2013;74(suppl 1):35–49. doi:10.1038/pr.2013.205
3.
GoodWVPalmerEA. Bevacizumab for retinopathy of prematurity. N Engl J Med. 2011;364(24):2359; author reply 2361-2362. doi:10.1056/NEJMc1103460
4.
YonekawaYThomasBJThanosA, et al.The cutting edge of retinopathy of prematurity care: expanding the boundaries of diagnosis and treatment. Retina. 2017;37(12):2208–2225. doi:10.1097/IAE.0000000000001719
5.
Mintz-HittnerHAKennedyKAChuangAZ. Efficacy of intravitreal bevacizumab for stage 3+ retinopathy of prematurity. N Engl J Med. 2011;364(7):603–615. doi:10.1056/NEJMoa1007374
6.
ChenWBinenbaumGKarpK, et al.Late recurrence of retinopathy of prematurity after treatment with both intravitreal bevacizumab and laser. J AAPOS. 2014;18(4):402–404. doi:10.1016/j.jaapos.2014.03.011
7.
MehtaSHubbardGBIII. Delayed recurrent neovascularization and persistent avascular retina following intravitreal bevacizumab for retinopathy of prematurity. Retin Cases Brief Rep. 2013;7(3):206–209. doi:10.1097/ICB.0b013e318285238e
8.
Mintz-HittnerHAGeloneckMMChuangAZ. Clinical management of recurrent retinopathy of prematurity after intravitreal bevacizumab monotherapy. Ophthalmology. 2016;123(9):1845–1855. doi:10.1016/j.ophtha.2016.04.028
9.
SankarMJSankarJChandraP. Anti-vascular endothelial growth factor (VEGF) drugs for treatment of retinopathy of prematurity. Cochrane Database Syst Rev. 2018;1:CD009734. doi:10.1002/14651858.CD009734.pub3
10.
HwangCKHubbardGBHutchinsonAKLambertSR. Outcomes after intravitreal bevacizumab versus laser photocoagulation for retinopathy of prematurity: a 5-year retrospective analysis. Ophthalmology. 2015;122(5):1008–1015. doi:10.1016/j.ophtha.2014.12.017
11.
HarderBCvon BaltzSJonasJBSchlichtenbredeFC. Intravitreal low-dosage bevacizumab for retinopathy of prematurity. Acta Ophthalmol. 2014;92(6):577–581. doi:10.1111/aos.12266
12.
WuWCKuoHKYehPTYangCMLaiCCChenSN. An updated study of the use of bevacizumab in the treatment of patients with prethreshold retinopathy of prematurity in Taiwan. Am J Ophthalmol. 2013;155(1):150–158.e1. doi:10.1016/j.ajo.2012.06.010
13.
YetikHGunayMSiropSSalihogluZ. Intravitreal bevacizumab monotherapy for type-1 prethreshold, threshold, and aggressive posterior retinopathy of prematurity—27 month follow-up results from Turkey. Graefes Arch Clin Exp Ophthalmol. 2015;253(10):1677–1683. doi:10.1007/s00417-014-2867-0
14.
TahijaSGHersetyatiRLamGCKusakaSMcMenaminPG. Fluorescein angiographic observations of peripheral retinal vessel growth in infants after intravitreal injection of bevacizumab as sole therapy for zone I and posterior zone II retinopathy of prematurity. Br J Ophthalmol. 2014;98(4):507–512. doi:10.1136/bjophthalmol-2013-304109
LeporeDQuinnGEMolleF, et al.Intravitreal bevacizumab versus laser treatment in type 1 retinopathy of prematurity: report on fluorescein angiographic findings. Ophthalmology. 2014;121(11):2212–2219. doi:10.1016/j.ophtha.2014.05.015
17.
ChenTAShieldsRABodnarZHCallawayNFSchacharIHMoshfeghiDM. A spectrum of regression following intravitreal bevacizumab in retinopathy of prematurity. Am J Ophthalmol. 2019;198:63–69. doi:10.1016/j.ajo.2018.09.039
18.
SnyderLLGarcia-GonzalezJMShapiroMJBlairMP. Very late reactivation of retinopathy of prematurity after monotherapy with intravitreal bevacizumab. Ophthalmic Surg Lasers Imaging Retina. 2016;47(3):280–283. doi:10.3928/23258160-20160229-12
19.
ToyBCSchacharIHTanGSMoshfeghiDM. Chronic vascular arrest as a predictor of bevacizumab treatment failure in retinopathy of prematurity. Ophthalmology. 2016;123(10):2166–2175. doi:10.1016/j.ophtha.2016.06.055
20.
HuJBlairMPShapiroMJLichtensteinSJGalassoJMKapurR. Reactivation of retinopathy of prematurity after bevacizumab injection. Arch Ophthalmol. 2012;130(8):1000–1006. doi:10.1001/archophthalmol.2012.592
21.
PerenteIErisESeymenZCevikSGBekmezS. Aggressive posterior retinopathy of prematurity treated with intravitreal bevacizumab: late period fluorescein angiographic findings [published online March 20, 2019]. Graefes Arch Clin Exp Ophthalmol. doi:10.1007/s00417-019-04292-4
22.
LeeBJKimJHHeoHYuYS. Delayed onset atypical vitreoretinal traction band formation after an intravitreal injection of bevacizumab in stage 3 retinopathy of prematurity. Eye (Lond). 2012;26(7):903–909; quiz 910. doi:10.1038/eye.2012.111
23.
IttiaraSBlairMPShapiroMJLichtensteinSJ. Exudative retinopathy and detachment: a late reactivation of retinopathy of prematurity after intravitreal bevacizumab. J AAPOS. 2013;17(3):323–325. doi:10.1016/j.jaapos.2013.01.004
24.
WallaceDKDeanTWHartnettME, et al.A dosing study of bevacizumab for retinopathy of prematurity: late recurrences and additional treatments. Ophthalmology. 2018;125(12):1961–1966. doi:10.1016/j.ophtha.2018.05.001
25.
HarperCAIIIWrightLMYoungRCReadSPChangEY. Fluorescein angiographic evaluation of peripheral retinal vasculature after primary intravitreal ranibizumab for retinopathy of prematurity. Retina. 2019;39(4):700–705. doi:10.1097/IAE.0000000000001996
26.
HondaSHirabayashiHTsukaharaYNegiA. Acute contraction of the proliferative membrane after an intravitreal injection of bevacizumab for advanced retinopathy of prematurity. Graefes Arch Clin Exp Ophthalmol. 2008;246(7):1061–1063. doi:10.1007/s00417-008-0786-7
27.
JangSYChoiKSLeeSJ. Delayed-onset retinal detachment after an intravitreal injection of ranibizumab for zone 1 plus retinopathy of prematurity. J AAPOS. 2010;14(5):457–459. doi:10.1016/j.jaapos.2010.05.011
28.
YonekawaYWuWCNitulescuCE, et al.Progressive retinal detachment in infants with retinopathy of prematurity treated with intravitreal bevacizumab or ranibizumab. Retina. 2018;38(6):1079–1083. doi:10.1097/IAE.0000000000001685
29.
LienRYuMHHsuKH, et al.Neurodevelopmental outcomes in infants with retinopathy of prematurity and bevacizumab treatment. PloS One. 2016;11(1):e0148019. doi:10.1371/journal.pone.0148019
30.
MorinJLuuTMSupersteinR, et al.Neurodevelopmental outcomes following bevacizumab injections for retinopathy of prematurity. Pediatrics. 2016;137(4):e20153218. doi:10.1542/peds.2015-3218
31.
Araz-ErsanBKirNTuncerS, et al.Preliminary anatomical and neurodevelopmental outcomes of intravitreal bevacizumab as adjunctive treatment for retinopathy of prematurity. Curr Eye Res. 2015;40(6):585–591. doi:10.3109/02713683.2014.941070
32.
ClinicalTrials.gov. RAINBOW Study: RAnibizumab Compared With Laser Therapy for the Treatment of INfants BOrn Prematurely With Retinopathy of Prematurity—Study Results. 2018. https://clinicaltrials.gov/ct2/show/results/NCT02375971. Results posted July 31, 2018. Last updated November 14, 2018. Accessed June 18, 2019.
33.
BeckKYoungRReadSHarperHDesireddiJHarperCA. The severity and associated comorbidities of retinopathy of prematurity among micro-premature infants with birth weights less than 750 grams. J Neonatal Perinatal Med. 2019;12(1):41–45. doi:10.3233/NPM-17158
