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Intravitreal aflibercept injections suppress aqueous VEGF levels
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Intravitreal aflibercept injections maintained aqueous VEGF concentrations under the lower limit of quantification in eyes with neovascular age-related macular degeneration, researchers found.
A prospective study included 27 eyes of 27 patients with active choroidal neovascularization secondary to AMD. Mean patient age was 77.5 years.
Patients initially received three 2-mg intravitreal aflibercept (Eylea, Regeneron) injections every 4 to 6 weeks. They received additional aflibercept injections on an as-needed basis when spectral-domain optical coherence tomography (SD-OCT) findings showed persistent or recurrent choroidal neovascularization. Mean total number of injections was 5.5.
The researchers used SD-OCT to assess anatomic outcomes. They also collected aqueous humor specimens before aflibercept injections to analyze VEGF-A concentrations. Visual acuity and fundus images were also evaluated.
Baseline aqueous humor VEGF concentrations were 90.6 pg/mL.
Results showed that in all patients, intravitreal aflibercept injections held aqueous VEGF concentrations under the lower limit of quantification, or less than 4 pg/mL.
Mean duration of VEGF suppression under the lower limit of quantification was at least 71 days.
VEGF concentration rebounded above the lower limit of quantification at 55 days in one patient and greater than 56 days in 20 patients; the degree of aqueous VEGF recovery after 56 days was uncertain in six patients, according to the researchers.
Disclosure: See the study for a full list of all authors’ relevant financial disclosures.
Perspective
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Andrew P. Schachat, MD
Fauser, Schwabecker and Muether report that, on average, VEGF concentrations in the aqueous were suppressed below the ability of their assay to detect for about 10 weeks after intravitreal aflibercept (Eylea, Regeneron) injections. I am not a lab scientist and cannot comment on whether they selected an appropriate assay technique, or if they do the assay correctly. Let us trust the authors and the reviewers and accept that they do; but anecdotally, I understand that measuring VEGF levels is not a simple task. Also, it seems to me that vitreous and retinal levels are what matter, so let us also accept that the aqueous levels speak to what is going on posteriorly. Their findings make sense based on what we see clinically, and for me, the proof is in the clinical pudding.
The VIEW trials studied aflibercept to treat neovascular age-related macular degeneration, and monthly treatment was compared with treatment every 2 months after three loading doses. Monthly outcomes paralleled the every-2-month strategy. One can see some “wobble” in the anatomic effects (see figure 4 in Heier’s paper), so maybe the activity is wearing off a little at 30 days, but treating at 60-day intervals does maintain control. Fauser and colleagues find that the mean duration of complete VEGF suppression was at least 71 days, which is 2 weeks longer than the recommended dosing interval. The data make sense and are reassuring.
Reference: Heier JS, et al. Intravitreal aflibercept (VEGF Trap-Eye) in wet age-related macular degeneration. Ophthalmology. 2012; doi: 10.1016/j.ophtha.2012.09.006.
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