OSN Europe: Possible consequences on organogenesis, neurodevelopment still a concern with use of anti-VEGFs in ROP

There may be a rationale for using anti-VEGFs in cases of severe retinopathy of prematurity to prevent neovascularization, but concerns exist about the possible detrimental effects of VEGF suppression on the organogenesis and neurodevelopment of preterm infants.

A study published earlier this year in JAMA Ophthalmology showed that Avastin (bevacizumab, Genentech/Roche) remained in the systemic circulation for as long as 8 weeks after intravitreal injection and that VEGF expression was inhibited for that time. And the same authors showed in a 2-year retrospective study, unpublished but presented at the American Society of Retina Specialists meeting in Vienna, that patients treated with intravitreal bevacizumab and laser had a higher incidence of significant mental (P = .028) and psychomotor (P = .002) impairment at 24 months than patients treated with laser alone.

“Though further and larger studies are needed, our findings highlight the need for caution,” Wei-Chi Wu, MD, PhD, professor of ophthalmology at Chang Gung Memorial Hospital, Taoyuan, Taiwan, said.

In the same study, a group of patients treated with anti-VEGF alone did not show a significant difference in neurodevelopment compared with patients treated with laser alone.

According to Wu and co-authors, destruction of the blood-retinal barrier by laser photocoagulation may result in a higher level of anti-VEGF leakage in the systemic circulation.

“We also had a higher incidence of zone 1 ROP in this group, and it is likely that patients with zone 1 ROP have a less mature avascular retina, which may also cause more anti-VEGF leakage into the systemic circulation,” he said. “On the other hand, these babies had worse systemic conditions prior to treatment, a lower birthweight and probably more immature systemic organs, which may be another explanation for the worse outcomes.”

Currently, Wu and his group are conducting a further follow-up study of these patients, testing vision outcomes and neurodevelopment up to the age of 3 years to 5 years. This information will be important to assess the long-term safety of anti-VEGFs in the treatment of ROP, he said.

A lack of scientific data

Regarding the study presented by Wu, Antonio Capone Jr., MD, professor of biomedical sciences at Oakland University, USA, and professor at the European School for Advanced Studies in Ophthalmology, Lugano, Switzerland, said that “short of any randomized prospective multicenter study, this is the best sort of data we have at present.” He said he trusts Wu, formerly his fellow, to produce even more interesting follow-up data.

Click here to read the full cover story published in Ocular Surgery News Europe Edition, October 2015.