Pan-VEGF Blockade for the Treatment of Retinopathy of Prematurity
Status:
Terminated
Trial end date:
2009-07-01
Target enrollment:
Participant gender:
Summary
Retinopathy of Prematurity (ROP) is a leading cause of blindness in children in developed
countries around the world, and an increasing cause of blindness in developing countries.
The retina lines the inside of the eye. It functions as "film" within the camera which is the
eye. When an infant is born prematurely, the vascular network necessary to nourish the retina
has not fully developed. As a consequence, in some infants abnormal vessels proliferate
instead of the normal ones - a condition known as ROP. The abnormal vessels carry scar tissue
along with them, and may lead to retinal detachment and blindness if the eye is not treated.
The Multicenter Trial of Cryotherapy for Retinopathy of Prematurity (CRYO-ROP) Study
demonstrated that ablation of the peripheral avascular retina reduced the risk of poor
structural and visual outcome due to retinal distortion or detachment in ROP (1980's). The
ablated retina is not functional and is not amenable to regeneration.
Peripheral retinal ablation is not universally effective in fostering regression of ROP. This
is particularly true for an aggressive form of ROP (aggressive posterior ROP, or APROP) which
typically afflicts profoundly premature and infirm neonates. In this subset of infants,
progression of ROP to bilateral retinal detachment and blindness occurs despite timely and
complete peripheral retinal laser ablation.
Rationale The development of ROP is largely dependent on vascular endothelial growth factor
(VEGF). When an infant is born prematurely the relatively hyperoxic environment the baby is
introduced to shuts down the production of VEGF. Retinal maturation is delayed. Subsequently,
at a time when intraocular VEGF levels would normally be declining late in the third
trimester of pregnancy, abnormally high levels of VEGF are seen due to large areas of
avascular retina and associated tissue hypoxia.
The availability of FDA-approved drugs for anti-VEGF treatment renders it possible to treat
such eyes off-label. Available drugs include pegaptanib sodium (Macugen) for partial blockage
of VEGF-A, or drugs such as ranibizumab (Lucentis) and bevacizumab (Avastin), which cause
complete blockage of VEGF-A.
As VEGF is required in the developing retina for normal angiogenesis, and our goal is not to
penetrate tissue, but to block the excessive levels of VEGF trapped within the overlying
vitreous which is responsible for the abnormal vasculature in ROP.
For purposes of this study the investigators have chosen bevacizumab (Avastin), which will:
a) attain complete blockage (vs. Macugen) of intravitreal VEGF-A, and; b) which is limited in
its ability to penetrate tissues because it is a full antibody (vs. Lucentis, an antibody
fragment specifically designed for better tissue penetration), and is more likely to restore
VEGF homeostasis within the developing retina.