Inflammatory Complications of Intravitreal Anti-VEGF Injections

Abstract

Intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) agents is a commonly used therapy for numerous retinal diseases. The most commonly used of these medications are bevacizumab, ranibizumab, aflibercept, and brolucizumab. However, intravitreal administration of these agents is also associated with several inflammatory and non-inflammatory adverse events. The three inflammatory adverse events are sterile intraocular inflammation, brolucizumab-associated retinal vasculitis, and post-injection endophthalmitis. This narrative review summarizes the current literature regarding these conditions, including their epidemiology, presentation, management, outcomes, and pathogenesis. The inflammatory adverse events also share a number of overlapping features, which can make them difficult to discern from one another in a clinical context. This review discusses certain distinguishing features of these conditions that may aid providers in discerning between them and establishing the correct diagnosis.

Low-Dose Recombinant Adeno-Associated Virus-Mediated Inhibition of Vascular Endothelial Growth Factor Can Treat Neovascular Pathologies Without Inducing Retinal Vasculitis

“…As for safety, we found that high titers of rAAV2.7m8 and rAAV2 expressing KH902 resulted in a vascular sheathing pathology that is associated with immune cell infiltration. A similar pathology has also been reported in patients receiving anti-VEGF treatment who experienced a worsening in vision 3,19,20 (NCT04418427). We show that this phenotype is associated with increased expression of intercellular adhesion molecule 1 (ICAM1) and vascular cell adhesion molecule 1 (VCAM1), two proteins that are essential for extravasation of immune cells by increasing vessel wall interaction with immune cells.…”

“…Inflammatory complications after intravitreal delivery of anti-VEGF drugs have been documented for all drugs currently in use 3 . Recent clinical findings reported the occurrence of ocular vasculitis with associated decrease in vision in some wet AMD patients who received an intravitreal injections of a novel anti-VEGF antibody that is smaller and presumably may diffuse better to the back of the eye 19,20 .…”

“…Inhibition of VEGF function has been shown to reduce neovascular pathologies and edemas in the eye. Consequently, different anti-VEGF therapies have been developed to treat neovascularization, in particular in AMD and diabetic retinopathy 3 . However, anti-VEGF drugs require repeat injections to maintain stable and long-term treatment efficacy.…”

“…However, anti-VEGF drugs require repeat injections to maintain stable and long-term treatment efficacy. Some patients require quite frequent injections, which increases the risk of side effects, such as intraocular hemorrhage and ocular hypertensions 3,4 . Additionally, the burden to patients that require such intense injection regimes is high.…”

New and Innovative Treatments for Neovascular Age-Related Macular Degeneration (nAMD)

“…Furthermore, there was an increased risk of developing retinal scarring and geographic atrophy in nAMD patients 2 to 5 years after initiating treatment [ 14 ]. Complications such as vitreous and subconjunctival hemorrhage, fluid accumulation under the fovea, increased intraocular pressure, endophthalmitis, and ocular inflammation have also been described [ 15 , 16 , 17 , 18 ].…”