This article is more than 5 years old. Information may no longer be current.
Anti-VEGF shows promise in the treatment of ROP, but safety concerns remain
Compared to cryotherapy or laser, anti-VEGF treatment has the advantage of leaving an intact retina.
Click Here to Manage Email Alerts
Intravitreal ranibizumab may be effective in the treatment of stage 3 plus retinopathy of prematurity and might have a better safety profile compared with bevacizumab, according to a study.
ROP involves disorganized growth of retinal blood vessels, which may result in scarring and retinal detachment. Because VEGF is involved at all stages of the disease, the use of anti-VEGF as a treatment strategy has raised considerable interest in recent years.
“The early phase after premature birth is characterized by an increased oxygen level and consecutive inhibition of VEGF production. Vessel growth stops. In phase 2, the oxygen level decreases and VEGF production increases, leading to neovascularization. At that point, the eye may develop stage 3 ROP with plus disease, where upregulation of VEGF leads to severely abnormal new vessel growth. At this stage, treatment is mandatory,” Marcel Menke, MD, said at the Euretina meeting in Milan.
Cryotherapy and, more commonly, laser photocoagulation have been shown to be effective in reversing the abnormal growth of blood vessels, but they destroy the peripheral areas of the retina, leading to a certain amount of visual field defects.
The BEAT-ROP trial
Avastin (bevacizumab, Genentech/Roche) was suggested by the BEAT-ROP trial as an alternative way to treat stage 3 plus ROP by reducing VEGF expression. It was a prospective, controlled, multicenter study that included 150 children treated with either 0.0625 mg of intravitreal bevacizumab or laser photocoagulation. The primary outcome was recurrence of ROP in one or both eyes requiring treatment before 54 weeks.
“The recurrence of ROP was significantly lower with bevacizumab compared to laser, mostly in the cases where the disease was located in zone 1. Interestingly, recurrence also occurred significantly later in the cases treated with anti-VEGF compared to laser. A mean interval of 19 vs. 6 days was found in the two groups,” Menke said.
A positive aspect of anti-VEGF as a therapy is that it does not involve destruction of the peripheral retina, where normal vascularization can continue to grow, he said. However, due to the later-onset recurrence, patients must be followed carefully for a longer period.
Menke said that there were limitations to the BEAT-ROP study. The number of patients was too small to assess safety, and there were no visual acuity records or follow-up data beyond the 54 weeks of the study.
“In addition, laser results were worse in this study compared to common literature. Recurrence after laser was 26%, while the literature reports an incidence of 11% to 14%,” he said.
The better results of anti-VEGF therapy had a negative counterpart in the higher mortality rate, which was 6.6% compared to 2.2% in the laser group.
“This may be related to the fact that the dose of bevacizumab was relatively high taking into account the small ocular volume, retinal surface and body weight of the patients,” he said.
Using ranibizumab
With this in mind, and taking into account the findings of the CATT study, in which bevacizumab was shown to have more systemic side effects than Lucentis (ranibizumab, Genentech/Novartis) in age-related macular degeneration patients, Menke and colleagues used ranibizumab as an alternative treatment for ROP.
“Though off-label for pediatric use, ranibizumab is designed and approved for intravitreal injection and has a shorter half-life (3.2 days) than bevacizumab (5.6 days). We therefore expected a higher safety profile for ranibizumab in these cases,” he said.
Six eyes of four children were treated with 0.3 mg ranibizumab; all eyes had ROP 3 plus in zone 2. Gestational age ranged from 24 to 26 weeks, and birth weight was between 450 g and 745 g. Treatment was given between weeks 34 and 38. Intravitreal injection was performed with a 30-gauge needle through the conjunctiva, approximately 1.5 mm behind the nasal limbus.
After the treatment, four eyes showed normal, complete vascularization. Two eyes still showed ROP 1 in zone 2, but without plus. No additional treatment was necessary. Five months later, five eyes had complete vascularization, and one eye remained without vascularization in zone 3 but showed no recurrence of ROP.
“We had a few complications. In three eyes we had to perform an anterior chamber paracentesis to reduce IOP, and one eye had a completely collapsed anterior chamber after injection,” Menke said.
He said that the intravitreal injection frequently leads to an increase in IOP. Performing a paracentesis before the procedure might therefore be advisable. On the other hand, the softness of infants’ eyes may frequently and easily lead to anterior chamber collapse.
One of the infants developed nasopharyngitis 2 days after injection.
“This complication has been reported in 12% to 16% of AMD cases,” Menke said.
“It is clear that anti-VEGF injection therapy is beneficial in this aggressive stage of ROP and offers the great advantage of leaving an intact retina,” he said.
Ranibizumab is likely to have a better safety profile than bevacizumab. However, the overall safety of anti-VEGF therapy in premature children is still a matter of controversy, he said.
“We don’t know what the long-term effects are and what the consequences on visual development may be,” Menke said.
Studies are needed, but small numbers of patients are a typical limitation when it comes to implementing research in pediatric ophthalmology, he said.– by Michela Cimberle
- For more information:
- Marcel Menke, MD, can be reached at Department of Ophthalmology, Inselspital, University of Berne, Berne, Switzerland; email: marcel.menke@insel.ch.
Disclosure: Menke has no relevant financial disclosures.