Elsevier

Ophthalmology

Volume 118, Issue 1, January 2011, Pages 176-183
Ophthalmology

Original article
Effects and Complications of Bevacizumab Use in Patients with Retinopathy of Prematurity: A Multicenter Study in Taiwan

https://doi.org/10.1016/j.ophtha.2010.04.018Get rights and content

Purpose

To investigate the effects and complications of the anti-vascular endothelial growth factor agent bevacizumab in the treatment of retinopathy of prematurity (ROP) in Taiwanese patients.

Design

A multicenter, retrospective case series study.

Participants

Twenty-seven patients (49 eyes) from 4 medical centers across Taiwan.

Methods

This study included patients receiving intravitreal injections of bevacizumab (IVB) (0.625 mg) for the treatment of ROP between 2007 and 2009 at 4 major medical centers in Taiwan. The effects and complications associated with this treatment were analyzed. Patients were followed for at least 6 months after bevacizumab injection.

Main Outcome Measures

Regression of ROP and the complications associated with the injection of bevacizumab.

Results

Forty-nine eyes of 27 patients (18 male and 9 female) were included in the study. Mean gestational age and birth weight were 26.0±2.4 weeks and 971.6±589.6 g, respectively. There were 41 eyes (23 patients) with stage 3 ROP, 6 eyes (3 patients) with stage 4A ROP, and 2 eyes (1 patient) with stage 5 ROP. All of the eyes received only a single injection of IVB. The mean injection time was 36.8±2.6 weeks postmenstrual age for eyes with stage 3 ROP. A total of 37 of 41 eyes (90%) with stage 3 ROP regressed after bevacizumab injection only. Four eyes (10%) required additional laser treatment to regress the ROP. Of 6 eyes (3 patients) with stage 4A ROP, 2 eyes (1 patient; 33%) regressed after bevacizumab injection and 4 eyes (67%) regressed after bevacizumab injection and subsequent vitrectomy. The 2 eyes with stage 5 ROP exhibited decreased vascular tortuosity after bevacizumab injection, but the retina failed to reattach after vitrectomy surgeries. Major complications included vitreous or pre-retinal hemorrhage in 4 eyes (8%) and transient vascular sheathing in 2 eyes (4%).

Conclusions

Bevacizumab injection seems effective and well tolerated in some cases of ROP, especially in stage 3 ROP. Ocular complications could result from the injection of bevacizumab in pediatric eyes.

Financial Disclosure(s)

The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Section snippets

Patients and Methods

This is a multicenter, retrospective study of bevacizumab use in patients with ROP. The data were collected from medical centers in 4 cities across Taiwan. These centers included National Taiwan University Hospital in Taipei, Changhua Christian Hospital in Changhua, Chang Gung Memorial Hospital in Kaohsiung, and Chang Gung Memorial Hospital in Taoyuan. The study was approved by the institutional review board for each hospital. Each patient's parent or legal guardian signed a consent form before

Results

During the study period, 40 patients received a single bevacizumab injection. Thirteen patients were excluded from the study because of a follow-up time of less than 6 months. In the end, 49 eyes of 27 patients (18 male and 9 female) were included in the study. Six patients were from National Taiwan University Hospital in Taipei, 5 patients were from Changhua Christian Hospital in Changhua, 10 patients were from Chang Gung Memorial Hospital in Kaohsiung, and 6 patients were from Chang Gung

Discussion

This study found that IVB (0.625 mg), used either as a primary treatment or salvage treatment after laser treatment, caused neovascularization to regress and resulted in full retinal vascularization in the majority of patients with stage 3 ROP. In advanced ROP with retinal detachment, the treatment benefits of bevacizumab are less evident than in stage 3 ROP. The plus sign decreased after injection, and no active bleeding was noted during vitrectomy surgery. However, fibrotic traction on the

Study Limitations

The limitations of this study include its retrospective nature and the lack of a concomitant control group. Also, fundus photographs were not available in all study centers. Finally, laser treatment was allowed if a response was not observed in 2 to 3 weeks. Nonetheless, to our knowledge, this study is the largest case series of bevacizumab use in the treatment of ROP ever reported. Data were collected from multiple centers all over the country, and all of the patients were followed up for at

References (46)

  • T. Alon et al.

    Vascular endothelial growth factor acts as a survival factor for newly formed retinal vessels and has implications for retinopathy of prematurity

    Nat Med

    (1995)

  • Revised indications for the treatment of retinopathy of prematurity: results of the Early Treatment for Retinopathy of Prematurity randomized trial

    Arch Ophthalmol

    (2003)
  • M.X. Repka et al.

    Outcome of eyes developing retinal detachment during the Early Treatment for Retinopathy of Prematurity Study (ETROP)

    Arch Ophthalmol

    (2006)
  • W.S. Gilbert et al.

    Partial retinal detachment at 3 months after threshold retinopathy of prematurity: long-term structural and functional outcome

    Arch Ophthalmol

    (1996)
  • W.C. Wu et al.

    Plasmin enzyme-assisted vitrectomy for primary and reoperated eyes with stage 5 retinopathy of prematurity

    Retina

    (2008)
  • H. Hurwitz et al.

    Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer

    N Engl J Med

    (2004)
  • Z.F. Bashshur et al.

    Intravitreal bevacizumab for treatment of neovascular age-related macular degeneration: the second year of a prospective study

    Am J Ophthalmol

    (2009)
  • R.F. Spaide et al.

    Intravitreal bevacizumab treatment of choroidal neovascularization secondary to age-related macular degeneration

    Retina

    (2006)
  • R.L. Avery et al.

    Intravitreal bevacizumab (Avastin) in the treatment of proliferative diabetic retinopathy

    Ophthalmology

    (2006)
  • J.O. Mason et al.

    Intravitreal injection of bevacizumab (Avastin) as adjunctive treatment of proliferative diabetic retinopathy

    Am J Ophthalmol

    (2006)
  • R.F. Spaide et al.

    Intravitreal bevacizumab (Avastin) treatment of proliferative diabetic retinopathy complicated by vitreous hemorrhage

    Retina

    (2006)
  • J.B. Jonas et al.

    Intravitreal bevacizumab for vitreous haemorrhage [letter]

    Acta Ophthalmol

    (2008)
  • J.M. Ruiz-Moreno et al.

    Intravitreal bevacizumab in recurrent diabetic vitreous haemorrhage after vitrectomy [letter]

    Acta Ophthalmol

    (2008)
  • M.E. Iliev et al.

    Intravitreal bevacizumab (Avastin) in the treatment of neovascular glaucoma

    Am J Ophthalmol

    (2006)
  • K. Kriechbaum et al.

    Intravitreal Avastin for macular oedema secondary to retinal vein occlusion: a prospective study

    Br J Ophthalmol

    (2008)
  • F. Prager et al.

    Intravitreal bevacizumab (Avastin) for macular oedema secondary to retinal vein occlusion: 12-month results of a prospective clinical trial

    Br J Ophthalmol

    (2009)
  • G.B. Jaissle et al.

    One-year results after intravitreal bevacizumab therapy for macular edema secondary to branch retinal vein occlusion

    Graefes Arch Clin Exp Ophthalmol

    (2009)
  • T. Sato et al.

    Simultaneous analyses of vitreous levels of 27 cytokines in eyes with retinopathy of prematurity

    Ophthalmology

    (2009)
  • T. Sato et al.

    Vitreous levels of erythropoietin and vascular endothelial growth factor in eyes with retinopathy of prematurity

    Ophthalmology

    (2009)
  • L. Kong et al.

    Intravitreous bevacizumab as anti-vascular endothelial growth factor therapy for retinopathy of prematurity: a morphologic study [letter]

    Arch Ophthalmol

    (2008)
  • S. Kusaka et al.

    Efficacy of intravitreal injection of bevacizumab for severe retinopathy of prematurity: a pilot study

    Br J Ophthalmol

    (2008)
  • E.J. Chung et al.

    Combination of laser photocoagulation and intravitreal bevacizumab (Avastin) for aggressive zone I retinopathy of prematurity

    Graefes Arch Clin Exp Ophthalmol

    (2007)
  • H. Quiroz-Mercado et al.

    Antiangiogenic therapy with intravitreal bevacizumab for retinopathy of prematurity

    Retina

    (2008)

    • Cited by (0)

    Manuscript no. 2009-1523.

    Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

    This study was partly supported by grants from the National Science Council, Taiwan (96-2314-B-182A-094).

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