The ocular compartment presents distinct challenges for drug delivery. For the scope of this review, the authors focus on two specific diseases of the posterior segment of the eye including age related macular degeneration (AMD) and diabetic macular edema for which current successful treatments include protein-based molecules delivered into the eye via repeat intravitreal injection. Distinct from the neovascular form of AMD, a large unmet need remains in the advanced dry form of AMD. In consideration of the next wave of biotherapeutics for intraocular application, combination targeted agents are expected. Here the authors review technologies to engineer dual targeting into protein-based therapeutics for intravitreal delivery with an additional aim of minimizing systemic exposure after intraocular injection. In the summary the authors highlight two of these forms, DAPRin and Fab’2, as important to monitor closely as bispecifics for ocular therapy development.