Large Study Finds Bilateral Anti-VEGF Injection on Same Day Appears Safe

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Acute intraocular inflammation was less common for ranibizumab than aflibercept.

Some of the more serious local adverse side effects reported after intravitreal injection of anti-VEGF agents include acute intraocular inflammation, endophthalmitis, and retinal detachment. In patients who need both eyes treated with an anti-vascular endothelial growth factor (VEGF) agent, some ophthalmologists inject one eye and wait a week before injecting the second to reduce the risk of such adverse side effects.

However, experts note that the potential benefits of this strategy require an additional office visit and increase the burden of treatment for ophthalmologists, patients, and payers. In addition, they question whether delaying the second injection for a week clearly poses a lower risk of adverse side effects than injecting both eyes on the same day does.

As a result, many ophthalmologists give same-day bilateral injections. For example, in a 2010 survey, 46% of U.S. retinal specialists reported that they give bilateral injections during a single visit.

To shed greater light on the safety of unilateral injections vs. bilateral same-day injections of anti-VEGF agents, an Iberian team retrospectively reviewed the records of 1,024 patients whose eyes were injected with aflibercept or ranibizumab by the same two surgeons at the University and Polytechnic Hospital La Fe in Valencia, Spain, between January, 2011, and March, 2016. Miguel Ruão, MD (pictured), Department of Ophthalmology, Centro Hospitalar Entre Douro e Vouga, Santa Maria da Feira, Portugal, was also a member the study team and lead author of the study report.

The investigators’ goal was to determine the number of cases of acute intraocular inflammation, endophthalmitis, or retinal detachment that occurred after these injections. The study included data from 8,127 injections; 6,560 were unilateral, and 1,612 were bilateral. Of the unilateral injections, 5,805 were ranibizumab, and 755 were aflibercept. Of the bilateral injections, 1,495 were ranibizumab, and 117 were aflibercept.

In most cases, the indication for injection was nAMD, for which 4,557 injections were used. Less common indications included diabetic retinopathy (1,725 injections), retinal vein occlusion (922), myopic choroidal neovascularization (520), and other (448).

In the study group as a whole, the investigators found 19 cases of acute intraocular inflammation. They also found one culture-proven case of endophthalmitis, which occurred in the unilateral injections group. Moreover, 18 of the 19 cases of acute intraocular inflammation also occurred in the unilateral injections group. And in the single case in which acute intraocular inflammation occurred after bilateral injection, it occurred in only one eye.

These results translate into a 0.233% rate of acute intraocular inflammation and a 0.012% rate of culture-proven endophthalmitis in the group as a whole. In the unilateral injections group, the rate of acute intraocular inflammation was 0.274%, and the rate of endophthalmitis was 0.015%. In contrast, in the same-day bilateral injections group, the rate of acute intraocular inflammation was 0.062%, and the rate of endophthalmitis was 0%.

The investigators also reported the rate of side effects by type of anti-VEGF agent used.

For acute intraocular inflammation, aflibercept resulted in six cases after 872 injections, and ranibizumab resulted in 13 cases after 7,300 injections.

However, although ranibizumab resulted in a lower rate of acute intraocular inflammation than aflibercept (0.178% vs. 0.688%, respectively), the only endophthalmitis case occurred in an otherwise healthy 83-year-old man with nAMD who received ranibizumab. A culture of a sample taken from this patient tested positive for Streptococcus pneumoniae.

In addition, retinal detachment occurred in five cases in the unilateral injections group, or at a rate of 0.076%. No cases of retinal detachment occurred in the bilateral same-day injections group.

“In our opinion, bilateral same-day injections are very well tolerated by patients, time-saving, and economically more favorable” relative to unilateral injections given in different eyes of the same patient on different days, the team concluded.

A report of the study, “Safety of bilateral same-day intravitreal injections of anti-vascular endothelial growth factor agents,” first appeared online in Clinical Ophthalmology in February.

Related Coverage:

Wet AMD: Aflibercept Best at Reducing Severe Increases in Pigment Epithelial Detachment Height

Ranibizumab Approved by FDA for Myopic Choroidal Neovascularization

Prophylactic Topical Antibiotics Did Not Decrease Rate of Endophthalmitis after Intravitreal Injection in Retrospective Study

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Peter A. Campochiaro, MD: RGX-314 for nAMD | Image Credit: Johns Hopkins Medicine
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