• Written By: Daniel M. Miller, MD, PhD

    Recent case reports have documented sustained IOP elevation after intravitreal bevacizumab and ranibizumab. But detailed studies on this subject are few. This retrospective analysis of 215 eyes receiving injections with bevacizumab and/or ranibizumab examined a number of questions about a possible link.

    Overall, they found that 6 percent had sustained IOP elevation requiring medical or laser intervention. Of the eyes receiving only bevacizumab, 9.9 percent had sustained elevated IOP, compared with 3.1 percent in the ranibizumab group(p=0.049). The authors point out that the 3.1 percent prevalence for the ranibizumab subgroup is only slightly higher than the percentage that has been documented as the overall prevalence of sustained ocular hypertension after intravitreous injection of any substance (2.4 percent), excluding triamcinolone acetonide.

    A subgroup analysis comparing bevacizumab eyes at two independent retina centers showed one center had a 2.4 percent rate of sustained IOP elevation, which is comparable with the overall ranibizumab subgroup (3.1 percent), which suggests that the anti-VEGF protein itself might not be the cause of IOP elevation and raises the question of injection technique or other variables being responsible for the observed differences.

    The authors note that the two centers obtain their bevacizumab from different compounding pharmacies. The center with the higher prevalence of IOP spikes obtained repackaged bevacizmuab from an outside compounding pharmacy, while the center with fewer cases obtained bevacizumab in the original vial and repackaged the medication on site prior to injection. It is possible that transportation and storage of bevacizumb in plastic syringes could, over time, lead to aggregation of proteins and/or leaching of silicone from the syringe barrel and rubber stopper, both of which can then deposit in the trabecular meshwork leading to an increase in aqueous outflow facility.

    Though the glaucoma subgroup was small, this study found that patients with pre-existing glaucoma experienced higher rates of elevated IOP compared to those without glaucoma (33 percent vs 3.1 percent respectively). Interestingly, the total number of injections and the interval between them didn't appear causative.

    Prospective studies investigating this phenomenon are under way, as well as further in vitro testing of repackaged bevacizumab and commercial ranibizumab samples, to help elucidate some of the factors leading to the findings of this study.