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Introduction: Intravitreal anti-vascular endothelial growth factor (VEGF) injections for exudative age-related macular degeneration (eAMD) are effective and safe but require frequent injections and have nonresponding patients. Geographic atrophy/dry AMD (gaAMD) remains an unmet medical need. New therapies are needed to address this leading cause of blindness in the increasing aged population., Areas Covered: This paper reviews the pathogenesis of macular degeneration, current and failed therapeutics, therapies undergoing clinical trials and a rationale for why certain AMD therapies may succeed or fail., Expert Opinion: VEGF-inhibitors reduce both vascular leakage and neovascularization. Experimental therapies that only address neovascularization or leakage will unlikely supplant anti-VEGF therapies. The most promising future therapies for eAMD, are those that target, more potently inhibit and have a more sustained effect on the VEGF pathway such as KSI-301, RGX-314, CLS-AX, EYEP-1901, OTX-TKI. GaAMD is a phenotype of phagocytic retinal cell loss. Inhibiting phagocytic activity of retinal microglial/macrophages at the border of geographic atrophy and reducing complement derived activators of microglial/macrophage is the most promising strategy. Complement inhibitors (Pegcetacoplan and Avacincaptad pegol) will likely obtain FDA approval but will serve to pave the way for combined complement and direct phagocytic inhibitors such as AVD-104.

Introduction: Diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) are the two complications of diabetes that cause visual loss and blindness. Laser photo-coagulation in the past was used to prevent progression of disease to these advanced stages. Advances in pathophysiologic understanding of DME and PDR have ushered the development of effective targeted therapy that given intravitreally improves vision and prevents blindness. While effective, these therapies require frequent administration and are not universally effective., Areas Covered: This purpose of this paper is to review the current pathophysiologic understanding and treatments for DME and PDR as well as the novel treatments currently being developed. The treatments will be juxtaposed to the factor in the disease cascade being targeted. The potential role of these novel treatment in the clinical armamentarium are postulated., Expert Opinion: Mono-therapy, single category targeting is the current strategy being utilized clinically. However, diabetic retinopathy needs combination therapy. Therapies that will prove successful will address multiple factors involved in the pathogenesis of diabetic retinopathy.

Introduction: The clinical development of anti-VEGF therapies for the treatment of exudative age-related macular degeneration (wet AMD) has revolutionized ophthalmology. Indeed, it has provided clinicians and patients with treatments that lessen visual loss from in a disease that once was uniformly blinding. Although blindness is yet to be eradicated from AMD, repeated intraocular anti-VEGF injections are required to preserve a patient's vision. Therefore, further advances in this field are necessary., Areas Covered: This review provides an overview of the agents that are in mid-stage phase trials for both exudative (wet AMD) and nonexudative macular degeneration (dry AMD). For wet AMD, new agents intend to enhance efficacy, develop alternative delivery such as eye drops, investigate alternate targets and construct sustained release strategies. For advanced dry AMD, the goal is to develop a strategy to slow or stop progressive loss of retinal tissue seen in geographic atrophy, the hallmark of advanced dry AMD., Expert Opinion: It is important to develop better more sensitive biomarkers, validating different approvable clinical trial endpoints and stratifying patients on their genetic polymorphisms. These developments should help to progress the already rapidly developing field of macular degeneration therapy.