Intravitreal bevacizumab: Improved vascular pattern after treatment in ROP

Take-home message: After intravitreal bevacizumab injection in eyes with treatment requiring-retinopathy of prematurity, there was growth and maturation of retinal vessels, although certain abnormalities remained.

By Lynda Charters; Reviewed by Andrée Henaine-Berra, MD

Mexico City-Anti-vascular endothelial growth factor (VEGF) therapy has been initiated recently for the treatment of retinopathy of prematurity (ROP).

However, no studies have described the retinal angiographic findings in patients treated with intravitreally administered bevacizumab (Avastin, Genentech), said Andrée Henaine-Berra, MD.

Previous studies dating back to 1971 and others performed more recently have described the angiographic characteristics in eyes with ROP, and the angiographic findings in eyes with this disease before and after they underwent laser treatment.

These studies showed that fluorescein angiography is safe and useful for studying the maturation of vessels in the premature retina, said Dr. Henaine-Berra, attending physician at the Retina Department, Hospital General “Dr. Manuel Gea González,” in Mexico City, Mexico.

Effects of bevacizumab

Dr. Henaine-Berra and colleagues studied 26 patients (47 eyes; 16 girls, 10 boys) in a prospective, nonrandomized case series from January 2008 to December 2012, recruited at Hospital “Dr. Luis Sánchez Bulnes,” Asociacion para Evitar la Ceguera en Mexico, Mexico City.

All patients had stage 3 threshold or pre-threshold ROP.

Investigators obtained fundus photographs and performed fluorescein angiography just before and 1 month after administration of intravitreal 0.75-mg bevacizumab injections. A wide-field digital pediatric imaging system (RetCam II, Clarity Medical Systems) was used.

When taking photographs and performing fluorescein angiography, the investigators administered 0.1 ml/kg of intravenous fluorescein.

A neonatologist evaluated all patients systemically during the procedure. No adverse events were observed. All patients were followed until retinal vascularization reached zone III.

The mean birth weight was 1,216 g (780 to 2,400 g), and the mean gestational age was 29.3 weeks (range, 26 to 32 weeks).

Pre-treatment findings in all eyes were vascular tortuosity, absence of foveal avascular zone, areas of capillary nonperfusion throughout the vascularized retina, and a demarcation line with leakage secondary to neovascularization, Dr. Henaine-Berra said.

In contrast, findings after treatment with intravitreal bevacizumab were decreased vascular tortuosity in 45 (95.74%) eyes, angiographic evidence of a foveal avascular zone in 25 (53.19%) eyes, and marked neovascular regression, which was followed by flattening of the demarcation line and vessel growth to the capillary-free zones in all eyes, she said.

In 33 (70.21%) eyes, investigators also observed formation of vascular loops, or shunts, in the areas of the retina in which there previously had been no vessels before treatment and perivascular leakage in 39 (82.97%) eyes.

In 14 (29.78%) eyes, capillary closure behind the demarcation line persisted as well as permanently dilated capillaries, referred to as popcorn lesions, in 10 (21.27%) eyes, according to Dr. Henaine-Berra.

Series of observations

Following treatment with intravitreal bevacizumab in these infants with ROP, investigators observed a series of events, the first of which was regression of neovascularization.

This was followed by flattening of the demarcation line and vessel growth to the capillary-free zones.

The vasculature continued to develop toward the peripheral retina in all patients, but did not reach the ora serrata in some of the infants, Dr. Henaine-Berra noted. Importantly, there was no reactivation of the neovascularization while the patients were followed.

Dr. Henaine-Berra offered two possible explanations for why vascularization toward the retinal periphery begins again following treatment, especially when VEGF is blocked.

• VEGF levels decrease sharply when treatment is administered, but then the levels subsequently begin to increase.

• Bevacizumab blocks only isoform A of VEGF, but the other isoforms may contribute to the continued vascularization.

Following treatment with bevacizumab, the vascular pattern improves in patients with ROP. Based on the study, investigators concluded that fluorescein angiography is a safe follow-up method for this patient population.

Despite an abnormal vascular pattern after patients with ROP have been treated with anti-VEGF therapy, small vessels develop, directional flow is established, and the vascular density is adjusted.

Dr. Henaine-Berra underscored the need for longer, prospective multicenter studies to confirm the safety profile of intravitreal bevacizumab in the treatment of ROP.

Andrée Henaine-Berra, MD

E: andreehenaine@gmail.com

This article was adapted from Dr. Henaine-Berra’s presentation during the 2014 meeting of the American Academy of Ophthalmology. Dr. Henaine-Berra has no financial interest in any aspect of this report.