By J. Michael Jumper, MD
The concept of using vascular endothelial growth factor (VEGF) inhibition to treat retinopathy of prematurity (ROP) is attractive. Intravitreal injection of a VEGF inhibitor may halt the disease process before traction retinal detachment occurs. This therapy may make it possible to treat an eye with media opacity that could not be treated with laser photocoagulation of the avascular peripheral retina. Also, only one or a few VEGF inhibitor intravitreal injections may be required, as the proliferative phase of ROP tends to be self-limiting. However, there is little published data on this subject; what exists is only in the form of small case series.
The current article is a retrospective review of 22 eyes of 11 consecutive infants that were followed for between 18 and 85 weeks after a single intravitreal Avastin (bevacizumab) injection for high-risk, stage three ROP. The results are impressive, with complete regression of extraretinal fibrovascular tissue and plus disease seen in all cases.
Pupillary dilation and media clarity improved in cases with tunica vasculosa lentis and iris vessel engorgement. Most impressive was the photodocumentation of continued normal retinal vascularization beyond the ridge after treatment. This suggested that intravitreal VEGF inhibition may yield better retinal function and vision than laser photocoagulation.
Many questions remain unanswered regarding the use of an intravitreal VEGF inhibitor for ROP. Doses of bevacizumab used in the literature range from 50 to 60 percent of the dose most commonly used in adults for neovascular AMD, while the vitreous volume of a neonate is one-sixth that of an adult. The current study used 50 percent of the common neovascular AMD dose. The authors found no systemic side effects of VEGF inhibition, but side effects may have been difficult to differentiate from the myriad medical problems already present in the infants. Also, the technique used by the authors of injecting 1.5 mm posterior to the limbus, directed toward the optic nerve, is controversial. Other authors have suggested that pars plicata entry 0.5 mm posterior to the limbus into the vitreous cavity is safer in premature infants.
Further studies on intravitreal VEGF inhibitor injection for ROP should be prospective. Currently, there are at least two multicenter, randomized, prospective trials being conducted.
Financial Disclosures
Dr. Jumper receives grant support from Alcon Laboratories, Inc., Bausch & Lomb Surgical, Eyetech (OSI), Genentech, Inc., Novartis Pharmaceuticals Corp., Allergan, Inc., and Ista Pharmaceuticals. Dr. Jumper is also a consultant to and receives lecture fees from Genentech.