Acute, Sustained, Intraocular Pressure increases following Anti-Vascular Endothelial Growth Factor Treatment for Retinal Conditions: A Review of Clinical Evidence and Guidelines

Vascular endothelial growth factor (VEGF) is a protein that is upregulated as a result of capillary dropout, hypoxia, and local inflammation secondary to increased intraluminal venous pressure from retinal vein compression and other forms of vascular occlusion such as branch retinal vein occlusion (BRVO) and choroidal retinal vein occlusion (CRVO).¹ VEGF is linked to the development of retinal diseases like age-related macular degeneration (AMD) and macular edema which are leading causes of vision loss.^2,3 AMD and macular edema have been the target of several therapeutic developments including non-pharmaceutical options such as, macular grid laser photocoagulation augmentation (MGLA), laser-induced chorioretinal anastomosis, and surgery (e.g., pars plana vitrectomy).¹ Pharmaceutical options are primarily corticosteroids and anti-VEGF agents. Steroids such as, triamcinolone and dexamethasone (DEX) function by decreasing inflammation and edema through the modulation of vascular permeability and inflammatory agents like VEGF.¹ Common anti-VEGF agents are aflibercept, bevacizumab, pegaptanib sodium, and ranibizumab. Aflibercept (115 kDa) is a soluble recombinant decoy receptor fusion protein, bevacizumab (149 kDa) is a recombinant full-length humanized monoclonal immunoglobulin G1 antibody, pegaptanib sodium is a selective antagonist, while ranibizumab (48 kDa) is a recombinant humanized immunoglobulin G1 kappa isotype antibody fragment.^1,3 In the Health Canada drug product database, aflibercept and ranibizumab are listed as antineovascularization agents, bevacizumab is listed as an antineoplastic, and pegaptanib sodium is listed as an anti-VEGF agent for AMD.⁴ Anti-VEGF agents are linked to a number of adverse effects such as, sustained elevated intraocular pressure (IOP), endophthalmitis, cataract progression, vitreous hemorrhage, retinal tears and detachments, pain, vitreous floaters, and inflammation.^2,3 Patients may also experience non-ocular effects like hypertension, nasopharyngitis, and headache.² Sustained elevated IOP may self-resolve or may need to be controlled by additional anti-VEGF agents, IOP-lowering topical or oral medication (e.g., carbonic anhydrase inhibitor), or surgery (e.g., trabeculectomy, laser trabeculoplasty, laser peripheral iridotomy, or filtration surgery).³ The aim of this report is to summarize the evidence regarding risk factors that lead to acute, sustained IOP increases that require surgery following anti-VEGF intravitreal injection treatment for retinal disease, and to review the relevant evidence-based guidelines.