April 27, 2020Neonatology
Preterm babies are at high risk of abnormal blood vessel growth in the retina, the light-sensitive tissue in the back of the eye. These abnormal blood vessels are fragile and prone to leaking. If left untreated, vessel growth can lead to scarring and retinal detachment, the main cause of retinopathy of prematurity (ROP) related vision loss. ROP is one of the leading causes of blindness in children. Established ROP treatments include laser therapy and cryotherapy. Both interventions work by causing the abnormal blood vessels to stop growing before they can cause scarring and retinal detachment.
According to a study published on 23 April 2020 in JAMA Ophthalmology, babies born prematurely who require treatment to prevent blindness from ROP could be treated with a dose of Avastin (bevacizumab) that is a fraction of the dose commonly used for ROP currently. Avastin is one of several available drugs that inhibit abnormal blood vessel growth by suppressing the overproduction of a signal protein called vascular endothelial growth factor (VEGF). The FDA approved Avastin in 2004 as a cancer therapy. Since then, ophthalmologists have used it off-label to inhibit abnormal blood vessel growth in ROP, as well as in other ocular disorders. Results from a clinical trial published in 2011 confirmed the benefit of using Avastin over laser therapy for treating the most severe cases of ROP, which occur in a region of the retina known as posterior zone.
The current study performed by the Pediatric Eye Disease Investigator Group (PEDIG), hoped to pinpoint the lowest possible therapeutic dose of Avastin by testing progressively lower doses in 10-14 infants per dose. The authors did not want to start by testing an ineffective dose and risk a child going blind, so they started with 40% of the dose commonly used for ROP. When a dose was successful, they halved it and then tested that dose. Eventually they cut the dose in half seven times. According to the authors, results showed that 0.004 mg of Avastin, a dose that is just 0.6% of the dose used in the 2011 study of Avastin for ROP, may be the lower limit to be effective for most infants with ROP. The authors added that the findings have set the stage for a randomized controlled trial comparing long-term effects of low-dose Avastin with laser therapy for treating ROP. The current plan is to follow children over time to compare the long-term effects of each strategy on vision and organ development. Previous studies suggest that babies treated with Avastin versus laser may be less likely to become myopic and require glasses for nearsightedness as they grow older.
The current study involved 59 preterm infants with type 1 ROP, the most severe form. Each infant had one eye treated by a single injection containing 0.016 mg, 0.008 mg, 0.004 mg, or 0.002 mg of Avastin. If the other eye required treatment, it received twice the concentration (one dose level higher). By comparison, currently used doses of Avastin for ROP range from 0.25 mg to 0.625 mg. Treatment was considered a short-term success if ROP improved by day four after therapy, and if there was no recurrence or need for additional treatment within four weeks. Such success was achieved in all eyes treated with the 0.016 mg and 0.008 mg doses, and in 9 of 10 eyes receiving 0.004 mg, but only in 17 of 23 eyes receiving 0.002 mg, resulting in the conclusion that 0.004 mg may be the lowest effective dose.