This study will determine whether injections into the vitreous of an anti-vascular endothelial growth factor (VEGF) will reduce the incidence of blindness by suppressing the neovascular phase of retinopathy of prematurity (ROP) compared to a control group receiving conventional laser therapy. The purpose of this study is to determine the safety and efficacy of intravitreal bevacizumab in the treatment of ROP.

This phase 2 study will assess the anti-neovascularization activity of intravitreal bevacizumab, as determined by regression of neovascular vessels of retinopathy of prematurity (ROP), in neonates with acute stage 3 ROP in zone I or posterior zone II with plus disease. This study will enroll confirmed cases of vision threatening ROP (between ETROP and CRYO-ROP) which have definite plus disease. This will be done because of the controversy regarding determining plus disease and the increasing concern that many infants are being treated whose ROP would spontaneously regress. Bevacizumab will be administered intravitreally using 0.625 mg (0.025 ml) injections into each eye. There is no intent to give additional doses unless there is a recurrence of vision threatening stage 3 ROP with plus disease since the disease is self limited by completion of vascularization. Clinical response and any evidence of ocular toxicities will be documented both pre- and post-injection by RetCam retinal images and by fluorescein angiography when possible (structural documentation) and at 6 and 12 months of age by electroretinograms and by visual evoked potentials when possible (functional documentation). Any evidence of systemic toxicities will be documented by appropriate clinical and laboratory tests.

• Drug: Bevacizumab
• Procedure: Conventional Laser for ROP

• Experimental: Intravitreal Bevacizumab Therapy is the Experimental Arm of this Study
• Active Comparator: Conventional Laser to the Peripheral Retina is the Control Arm of this Study

• Mintz-Hittner HA, Kuffel RR Jr. Intravitreal injection of bevacizumab (avastin) for treatment of stage 3 retinopathy of prematurity in zone I or posterior zone II. Retina. 2008 Jun;28(6):831-8.
• Kong L, Mintz-Hittner HA, Penland RL, Kretzer FL, Chévez-Barrios P. Intravitreous bevacizumab as anti-vascular endothelial growth factor therapy for retinopathy of prematurity: a morphologic study. Arch Ophthalmol. 2008 Aug;126(8):1161-3. No abstract available.
• Mintz-Hittner HA. Correspondence. Retina. 2009 Mar 2; [Epub ahead of print] No abstract available.
• Mintz-Hittner HA, Prager TC. Reply. Retina. 2009 Mar 5; [Epub ahead of print] No abstract available.
• Mintz-Hittner HA, Best LM. Antivascular endothelial growth factor for retinopathy of prematurity. Curr Opin Pediatr. 2009 Apr;21(2):182-7.

Inclusion Criteria:

1. Infants who have been screened by the AAO, AAP, and the AAPOS guidelines (≤1500 grams at birth and ≤30 weeks gestation) who develop Stage 3 ROP in zone I or posterior zone II.
2. Informed Consent from a parent or guardian.

Exclusion Criteria:

1. Infants who have a congenital systemic anomaly or have a congenital ocular abnormality.
2. Infants who cannot be treated by conventional laser therapy because of problems with media clarity. Generally, blind external cryotherapy would be utilized as an initial therapy and the infant would be excluded from the study even if the media clear subsequently.
3. Informed Consent from a parent or guardian refused. This will mean that an infant automatically will receive laser therapy. Bevacizumab (Avastin®) treatment cannot be given outside of the Protocol. No data will be used from an infant without Informed Consent.