Major Article
Retinal fluorescein angiographic changes following intravitreal anti-VEGF therapy

https://doi.org/10.1016/j.jaapos.2013.12.009Get rights and content

Purpose

To describe the retinal vascular morphology in eyes injected with intravitreal bevacizumab for treatment-requiring retinopathy of prematurity (ROP).

Methods

In this prospective, nonrandomized case series, fundus photographs and fluorescein angiography in patients diagnosed with stage 3 threshold or prethreshold ROP, were obtained immediately before and 1 month after injection of 0.03 cc (0.75 mg) of intravitreal bevacizumab using wide-field digital pediatric imaging system.

Results

A total of 47 eyes of 26 patients were included. Before treatment, fluorescein angiography showed vascular abnormalities, including capillary nonperfusion throughout and shunting in the vascularized retina, demarcation line, limited vessel development, new vessels leakage, avascular periphery and absence of foveal avascular zone. After intravitreal bevacizumab, fluorescein angiography showed involution of the neovascularization, flattening of the demarcation line and subsequent growth of vessels to the capillary-free zones. During the following weeks large areas devoid of microvessels were seen as well as vascular remodeling with uneven spacing of the retinal capillaries and vascular loops in the areas that were previously devoid of vessels. In some patients, retinal vessels in the far periphery never developed: patients with these findings did not subsequently develop pathological neovascularization.

Conclusions

In this study cohort, patients showed improvement of their abnormal vascular findings after intravitreal bevacizumab, however even when the vascular pattern remained abnormal, there was creation of small vessels, establishment of directional flow, maturation of retinal vessels, and adjustment of vascular density.

Section snippets

Subjects and Methods

The study protocol was reviewed and approved by the Ethics Committee and Institutional Review Board of the Association for the Prevention of Blindness in Mexico (Asociación para Evitar la Ceguera en México). Patients diagnosed with stage 3 threshold or prethreshold ROP as defined in the International Classification of ROP4 and the ETROP Study were recruited from January 2008 to December 2012.5 Informed parental consent was obtained prior to any study procedure.

Treatment was performed under

Results

Results are summarized in e-Supplement 1 (available at jaapos.org). A total of 47 eyes of 26 patients (16 males) were included. The mean gestational age was 29.3 weeks (range, 26-32 weeks). Mean birth weight was 1216.4 g (range, 780-2400 g).

At baseline, vascular tortuosity was observed in all eyes, as was absence of the foveal avascular zone (FAZ), capillary nonperfusion throughout the vascularized retina, and presence of a demarcation line with leakage secondary to neovascularization (

Discussion

Anti-VEGF therapy with bevacizumab has been applied in patients with treatment-requiring ROP to prevent vascular proliferation and promoting regression of the disease.6, 7, 8, 9 VEGF is essential for retinal blood vessel formation in the embryo and protects retinal vessels from hyperoxia-induced obliteration. However, although VEGF is required to sustain immature retinal vessels, the production of VEGF is suppressed under hyperoxia.3, 10 VEGF is also critical for the survival of

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