Diabetic Macular Edema: Current Understanding, Pharmacologic Treatment Options, and Developing Therapie

Abstract

Diabetic retinopathy and diabetic macular edema comprise a major source of visual disability throughout the developed world. The etiology and pathogenesis of macular edema is intricate and multifactorial, in which the hyperglycemic state in diabetes induces a microangiopathy. Through several inflammatory and vasogenic mediators, including vascular endothelial growth factor (VEGF) upregulation and inflammatory cytokines and chemokines, pathologic changes are induced in the vascular endothelium triggering breakdown of the blood retinal barrier, causing extravasation of fluid into the extracellular space and manifesting clinically as macular edema, resulting in visual loss. The advent of medications targeting the VEGF pathway has led to great clinical improvements compared with the previous standard of care of laser therapy alone, as shown in studies such as RISE, RIDE, VIVID, VISTA, and DRCR. However, analyses have shown that many patients have inadequate response or are nonresponders to anti-VEGF therapy, demonstrating the need for additional therapies to more comprehensively treat this disease. Although corticosteroid treatments and implants have demonstrated some efficacy in adjunctive and supplemental treatment, the need to more adequately treat macular edema remains. Our knowledge of diabetic macular edema continues to grow, leading to new currently available and emerging pharmacotherapies to further enhance our treatment and restore vision in those affected by diabetic macular edema. This review will discuss the pathogenesis of diabetic macular edema and the pharmacologic therapies available for its treatment, including anti-VEGF, steroids, and newer therapies still in development, such as angiopoietin antagonists, Tie2 agonists, kallikrein inhibitors, interleukin inhibitors, and others.

Reduction in Retinal Thickness Fluctuations After Treatment With Fluocinolone Acetonide Implant for DME: A Post-Hoc Analysis of the USER Study

“…2,3 A variety of DME treatment options are available, including laser photocoagulation, antivascular endothelial growth factor (VEGF), steroids, and surgical therapy, 4 with anti-VEGF being the first-line treatment option. 5,6 However, many patients have a suboptimal response or are nonresponders to anti-VEGF therapy, 7,8 with deteriorating clinical outcomes over time, often because of nonadherence to the therapeutic regimen. 9 Consequently, patients with persistent DME despite anti-VEGF therapy receive second-line corticosteroid injections into the vitreous humor to reduce the levels of inflammatory cytokines responsible for macular edema.…”

In vivo measurement of trabecular meshwork stiffness in a corticosteroid-induced ocular hypertensive mouse model

“…Due to their antiinflammatory, antiangiogenic, and antipermeability properties (1), corticosteroids are widely used in the eye clinic to treat a variety of disorders, such as macular edema, age-related macular degeneration, diabetic retinopathy, and uveitis (2–7), and, after cataract surgery, to reduce inflammation (8). Unfortunately, ocular hypertension [elevated intraocular pressure (IOP)] is the major adverse event following ocular corticosteroid treatment, occurring in a dose-dependent manner regardless of delivery route.…”

In Vitro and Ex Vivo Evaluation of Nepafenac-Based Cyclodextrin Microparticles for Treatment of Eye Inflammation

“…Treating inflammation at the posterior segment classically involves ophthalmic steroids as well as nonsteroidal anti-inflammatory drugs (NSAIDs) [8,9]. The repetitive use of traditional corticosteroids Treating inflammation at the posterior segment classically involves ophthalmic steroids as well as nonsteroidal anti-inflammatory drugs (NSAIDs) [8,9].…”

“…Treating inflammation at the posterior segment classically involves ophthalmic steroids as well as nonsteroidal anti-inflammatory drugs (NSAIDs) [8,9]. The repetitive use of traditional corticosteroids Treating inflammation at the posterior segment classically involves ophthalmic steroids as well as nonsteroidal anti-inflammatory drugs (NSAIDs) [8,9]. The repetitive use of traditional corticosteroids such as fluocinolone, dexamethasone, prednisolone, or fluorometholone can lead to undesirable side effects, such as high intraocular pressure, risk of infection, cataract formation, or macular edema [10].…”