Pharmacological principles of intravitreal drug therapy and their implications for clinical practice: a primer for the ophthalmologist

Intravitreal (IVT) anti-vascular endothelial growth factor (anti-VEGF) therapies are the standard of care for retinal diseases such as neovascular age-related macular degeneration (nAMD) and diabetic macular oedema (DMO). Despite the favourable efficacy and safety profiles of these therapies, decreasing the treatment burden is still an unmet need because frequent injections may be required over many years. The pharmacokinetic and pharmacodynamic properties of IVT therapies, such as ocular half-life and clearance, can affect the duration of VEGF suppression and thus influence clinical outcomes. Although some properties are inherent to the drug molecule (such as molecular weight, binding affinity and potency) and cannot be altered without changing the structure of the molecule, other factors (such as the dose of the drug) can be increased, which may prolong VEGF suppression time in the eye and, in turn, may lead to a more durable effect of the drug. In addition to pharmacokinetic and pharmacodynamic properties, individual patient factors such as age, surgical history and disease status can also affect the pharmacokinetics, pharmacodynamics and observed effectiveness of a drug. This article reviews the key pharmacological properties of IVT anti-VEGF treatments for nAMD and DMO often referred to in the literature, and aims to elucidate their meaning and clinical relevance for managing retinal diseases.