According to results from the CARE-ROP study, Low doses of anti-VEGF therapy with ranibizumab are effective in infants with retinopathy of prematurity (ROP). The study findings were published in the JAMA Pediatrics
"The CARE-ROP results show that both ranibizumab doses (24% vs. 40% of the adult dose) were equally effective in treating ROP (94% vs. 93% success in per-protocol treated eyes),” Dr. Andreas Stahl from University of Freiburg said. “Systemic VEGF levels were not suppressed following ranibizumab treatment.”
Vascular endothelial growth factor (VEGF) is a main driver of ROP pathophysiology. The anti-VEGF bevacizumab halts progression of severe ROP but suppresses VEGF plasma levels for weeks, raising questions about potential adverse effects on organ development in infants.
Dr. Stahl and colleagues evaluated the efficacy and safety of two doses of intravitreal ranibizumab (0.12 mg and 0.20 mg) in a randomized, double-blind trial of 19 infants (38 eyes) with ROP. Sixteen infants completed the trial (three died of causes unrelated to treatment).
The proportion of infants without the need for rescue therapy through 24 weeks, the primary endpoint, was 88.9% (8/9) in the 0.12-mg group and 85.7% (6/7) in the 0.20-mg group. No infant with gestational age greater than 25 weeks required rescue therapy.
At the final visit, 12 of 20 eyes (60.0%) in the 0.12-mg group and 10 of 18 eyes (55.6%) in the 0.20-mg group had no ROP, and all remaining eyes had ROP stage 1 in the anterior zone II or III. Two eyes that required rescue therapy responded well and had fully resolved ROP at the final visit.
Two infants in each group (8 eyes total) had recurrences severe enough to warrant retreatment, and their outcomes at the end of the study were either no ROP or stage 1 ROP in anterior zone II or III. Physiologic vascularization appeared to proceed faster and to reach complete vascularization more frequently in eyes receiving lower doses of ranibizumab.
Ranibizumab treatment did not reduce mean VEGF levels in either group. “The follow-up study period of CARE-ROP is ongoing and comprises 1-, 2- and 5-year follow-up visits with standardized pediatric and ophthalmologic examinations,” he added.
Dr. Janice C. Law said, “great to see that the lower dose was able to regress plus disease and retinopathy immediately. (This) shows us that our current level of dosing (1/2 the concentration of adult wet, age-related macular degeneration dose) is still more than the premature infants needs to regress plus disease.”
“It is definitely a wonderful adjunct for severe cases of posterior disease or in patients who do not dilate well for laser due to increased vascular activity,” she said. “Standard of care is still laser ablation. In posterior disease, I recommend continued use of anti-VEGF, but not as monotherapy. Laser should always follow anti-VEGF treatment due to the high reactivation and recurrence rate.”