Clinical Management of Recurrent Retinopathy of Prematurity after Intravitreal Bevacizumab Monotherapy

Ophthalmology. 2016 Sep;123(9):1845-55. doi: 10.1016/j.ophtha.2016.04.028. Epub 2016 May 27.


Purpose: To determine incidence, risk factors, risk period, and characteristics of recurrent retinopathy of prematurity (ROP) treated by intravitreal bevacizumab (IVB) monotherapy.

Design: Retrospective case series.

Participants: Premature infants with type 1 ROP (subdivided into stage 3+ ROP and aggressive posterior ROP [APROP]) in zone I or zone II posterior who received IVB monotherapy and were followed up for at least 65 weeks adjusted age (AA).

Methods: Retrospective review of infants who demonstrated recurrence of type 1 ROP after IVB monotherapy, including examination of RetCam fundus photographs and fluorescein angiograms.

Main outcomes measures: Incidence, risk factors, risk period, and characteristics of recurrent ROP.

Results: Intravitreal bevacizumab monotherapy in 241 infants (471 eyes) was reviewed. Recurrence incidence was 8.3% (20/241) for infants and 7.2% (34/471) for eyes. Recurrence risk factors of greatest significance were appearance of neovascularization as APROP (P = 0.006), extended duration of hospitalization (P = 0.01), and lower birth weight (P = 0.024). Recurrence risk period was between approximately 45 and 55 weeks AA (90.0% [18/20] for infants and 94.1% [32/34] for eyes), with mean recurrence of 51.2 weeks AA (±4.6 weeks; range, 45.7-64.9 weeks) and mean interval of 16.2 weeks (±4.4 weeks) between treatments. Recurrence characteristics included plus disease (20/20 infants [100%]) and neovascularization, which appeared at the following sites: stage 3+ ROP with confluent neovascularization recurred both at the advancing edge and at the initial ridge and extraretinal fibrovascular proliferative complex (12/14 infants [85.7%]). However, APROP (6/6 infants [100%]) and stage 3+ ROP with nonconfluent neovascularization (2/14 infants [14.3%]) recurred only at the advancing edge. Also, the anterior extent of retinal vascularization was decreased (mean, 1.76 disc diameters [DD] vs. 4.48 DD), and the rate of retinal vascularization was delayed (mean, 0.11 DD/week vs. 0.23 DD/week) in those with versus without recurrence, respectively. After retreatment with IVB, retinal vascularization proceeded minimally and slowly.

Conclusions: Premature children with severe ROP are being treated successfully with IVB monotherapy. However, recurrence is not uncommon, so vigilant follow-up is necessary to ensure timely re-treatment. Knowledge of recurrence incidence, risk factors, risk period, and characteristics allows for tailored clinical management.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / administration & dosage*
  • Bevacizumab / administration & dosage*
  • Female
  • Fluorescein Angiography
  • Gestational Age
  • Humans
  • Incidence
  • Infant, Newborn
  • Infant, Premature
  • Intravitreal Injections
  • Male
  • Recurrence
  • Retinal Neovascularization / drug therapy
  • Retinopathy of Prematurity / drug therapy*
  • Retinopathy of Prematurity / epidemiology
  • Retinopathy of Prematurity / etiology
  • Retrospective Studies
  • Risk Factors
  • Texas / epidemiology


  • Angiogenesis Inhibitors
  • Bevacizumab