Assessment of vascular leakage and its development with FFA among patients treated with intravitreal anti-VEGF due to aggressive posterior ROP

  • Dilbade Yıldız EkinciEmail author
  • Asli Deger Vural
  • Sadik Etka Bayramoglu
  • Ismail Umut Onur
  • Gulsum Oya Hergunsel
Original Paper



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.


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.


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).


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.


Intravitreal anti-VEGF Aggressive posterior ROP Vascular leakage Fundus fluorescein angiography 



  1. 1.
    Blencowe H, Lawn JE, Vazquez T et al (2013) Preterm-associated visual impairment and estimates of retinopathy of prematurity at regional and global levels for 2010. Pediatr Res 74(1):35–49CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Early Treatment for Retinopathy of Prematurity Cooperative Group (2003) Revised indications for the treatment of retinopathy of prematurity: results of the early treatment for retinopathy of prematurity randomized trial. Arch Ophthalmol 121:1684–1694CrossRefGoogle Scholar
  3. 3.
    Cryotherapy for Retinopathy of Prematurity Cooperative Group (1988) Multicenter trial of cryotherapy for retinopathy: preliminary results. Arch Ophthalmol 106:471–479CrossRefGoogle Scholar
  4. 4.
    Bakri SJ, Snyder MR, Reid JM et al (2007) Pharmacokinetics of intravitreal bevacizumab (Avastin). Ophthalmology 114:855–859CrossRefPubMedGoogle Scholar
  5. 5.
    Shah PK, Narendran V, Tawansy KA et al (2007) Intravitreal bevacizumab (Avastin) for post laser anterior segment ischemia in aggressive posterior retinopathy of prematurity. Indian J Ophthalmol 55:75–76CrossRefPubMedGoogle Scholar
  6. 6.
    Travassos A, Teixeira S, Ferreira P et al (2007) Intravitreal bevacizumab in aggressive posterior retinopathy of prematurity. Ophthalmic Surg Lasers Imaging 38:233–237PubMedGoogle Scholar
  7. 7.
    Mintz-Hittner HA, Kuffel RR Jr (2008) Intravitreal injection of bevacizumab (Avastin) for treatment of stage 3 retinopathy of prematurity in zone I or posterior zone II. Retina 28:831–838CrossRefPubMedGoogle Scholar
  8. 8.
    Chung EJ, Kim JH, Ahn HS, Koh HJ (2007) Combination of laser photocoagulation and intravitreal bevacizumab (Avastin) for aggressive zone I retinopathy of prematurity. Graefes Arch Clin Exp Ophthalmol 245:1727–1730CrossRefPubMedGoogle Scholar
  9. 9.
    Law JC, Recchia FM, Morrison DG et al (2010) Intravitreal bevacizumab as adjunctive treatment for retinopathy of prematurity. J AAPOS 14:6–10CrossRefPubMedGoogle Scholar
  10. 10.
    Lalwani GA, Berrocal AM, Murray TG et al (2008) Off-label use of intravitreal bevacizumab (Avastin) for salvage treatment in progressive threshold retinopathy of prematurity. Retina 28:S13–S18CrossRefPubMedGoogle Scholar
  11. 11.
    Larraiaga-Fragoso P, Peralta J, Bravo-Ljubetic L, Pastora N, Abelairas Gomez J (2016) Intravitreal bevacizumab for zone II retinopathy of prematurity. J Pediatr Ophthalmol Strabismus 53(6):375–382CrossRefGoogle Scholar
  12. 12.
    Mintz-Hittner HA, Kennedy KA, Chuang AZ (2011) Efficacy of intravitreal bevacizumab for stage 3 + retinopathy of prematurity. N Engl J Med 364:603–615CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Nicoara SD, Ştefanuţ AC, Nascutzy C, Zaharie GC, Toader LE, Drugan TC (2016) Regression rates following the treatment of aggressive posterior retinopathy of prematurity with bevacizumab versus laser: 8-year retrospective analysis. Med Sci Monit 22:1192–1209CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Tahija SG, Hersetyati R, Lam GC, Kusaka S, McMenamin PG (2014) 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 98:507–512CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Lepore D, Quinn GE, Molle F et al (2014) Intravitreal bevacizumab versus laser treatment in type 1 retinopathy of prematurity: report on fluorescein angiographic findings. Ophthalmology 121:2212–2219CrossRefPubMedGoogle Scholar
  16. 16.
    Klufas MA, Patel SN, Ryan MC, Patel Gupta M, Jonas KE et al (2015) Influence of fluorescein angiography on the diagnosis and management of retinopathy of prematurity. Ophthalmology 122(8):1601–1608CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    The Committee for the Classification of Retinopathy of Prematurity (2005) The international classification of retinopathy of prematurity revisited. Arch Ophthalmol 123:991–999CrossRefGoogle Scholar
  18. 18.
    Lorenz B, Stieger K, Jager M, Mais C, Stieger S, Andrassi-Darida M (2017) Retinal vascular development with 0.312 mg intravitreal bevacizumab to treat severe posterior retinopathy of prematurity. A longitudinal fluorescein angiographic study. Retina 37(1):97–111CrossRefPubMedGoogle Scholar
  19. 19.
    Lorenz B, Stieger K (2015) Retinopathy of prematurity-recent developments in diagnosis and treatment. Expert Rev Ophthalmol 10:167–182CrossRefGoogle Scholar
  20. 20.
    Hittner HM, Rhodes LM, McPherson AR (1979) Anterior segment abnormalities in cicatricial retinopathy of prematurity. Ophthalmology 86:803–816CrossRefPubMedGoogle Scholar
  21. 21.
    Trigler L, Weaver RG Jr, O’Neil JW et al (2005) Case series of angle-closure glaucoma after laser treatment for retinopathy of prematurity. J AAPOS 9:17–21CrossRefPubMedGoogle Scholar
  22. 22.
    Early Treatment for Retinopathy of Prematurity Cooperative Group, Quinn GE, Dobson V et al (2011) Visual field extent at 6 years of age in children who had high-risk prethreshold retinopathy of prematurity. Arch Ophthalmol 129:127–132CrossRefGoogle Scholar
  23. 23.
    Early Treatment for Retinopathy of Prematurity Cooperative Group, Quinn GE, Dobson V et al (2013) Progression of myopia and high myopia in the early treatment for retinopathy of prematurity study: findings at 4 to 6 years of age. J AAPOS 17:124–128CrossRefGoogle Scholar
  24. 24.
    Geloneck MM, Chuang AZ, Clark WL et al (2014) Refractive outcomes following bevacizumab monotherapy compared with conventional laser treatment: a randomized clinical trial. JAMA Ophthalmol 132:1327–1333CrossRefPubMedGoogle Scholar
  25. 25.
    Snyder LL, Garcia-Gonzalez JM, Shapiro MJ, Blair MP (2016) Very late reactivation of retinopathy of prematurity after monotherapy with intravitreal bevacizumab. Ophthalmic Surg Lasers Imaging Retina 47:280–283CrossRefPubMedGoogle Scholar
  26. 26.
    Hu J, Blair MP, Shapiro MJ et al (2012) Reactivation of retinopathy of prematurity after bevacizumab injection. Arch Ophthalmol 130:1000–1006CrossRefPubMedGoogle Scholar
  27. 27.
    Wu WC, Kuo HK, Yeh PT et al (2013) An updated study of the use of bevacizumab in the treatment of patients with prethreshold retinopathy of prematurity in Taiwan. Am J Ophthalmol 155:150.e1–158.e1CrossRefGoogle Scholar
  28. 28.
    Garcia Gonzalez JM, Snyder L, Blair M, Rohr A, Shapiro M, Greenwald M (2018) Prophylactic peripheral laser and fluorescein angiography after bevacizumab for retinopathy of prematurity. Retina 38(4):764–772CrossRefPubMedGoogle Scholar
  29. 29.
    Purcaro V, Baldascino A, Papacci P et al (2012) Fluorescein angiography and retinal vascular development in premature infants. J Matern Fetal Neonatal Med 25(3):53–56PubMedGoogle Scholar
  30. 30.
    Lepore D, Quinn GE, Molle F et al (2017) Follow-up to age 4 years of treatment of type 1 retinopathy of prematurity intravitreal bevacizumab injection versus laser: fluorescein angiographic findings. Ophthalmology 125(2):218–226CrossRefPubMedGoogle Scholar
  31. 31.
    Toy BC, Schachar IH, Tan GS, Moshfeghi DM (2016) Chronic vascular arrest as a predictor of bevacizumab treatment failure in retinopathy of prematurity. Ophthalmology 123(10):2166–2175CrossRefPubMedGoogle Scholar
  32. 32.
    Zepeda-Romero LC, Oregon-Miranda AA, Lizarraga-Barron DS, Gutierrez-Camarena O, Meza-Anguiano A, Gutierrez-Padilla JA (2013) Early retinopathy of prematurity findings identified with fluorescein angiography. Graefes Arch Clin Exp Ophthalmol 251:2093–2097CrossRefPubMedGoogle Scholar

Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Gazi Yaşargil Eğitim ve Araştırma HastanesiDiyarbakirTurkey

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