Extended duration strategies for the pharmacologic treatment of diabetic retinopathy: current status and future prospects

ABSTRACT

Introduction: Intraocular pharmacotherapy (vascular endothelial growth factor [VEGF] inhibitors and corticosteroids) has become first-line therapy for diabetic retinopathy (DR). A series of intraocular injections is usually required before disease modulation decreases the treatment burden in some patients, but others with chronic diabetic macular edema may require intensive longer-term therapy.

Areas covered: Recent studies showing successful pharmacologic treatment of proliferative DR will probably lead to increased use of pharmacotherapy, thereby further emphasizing the need for longer duration drugs. Recently approved anti-VEGF drugs (aflibercept) and corticosteroids (dexamethasone and fluocinolone inserts) provide extended durations of action. Longer action anti-VEGF molecules, sustained release devices and pumps, and encapsulated cell technology, may further decrease treatment burden, though regulatory approval may not occur for at least 5 years. Oral medications (danazol and minocycline) and modified topical drugs (loteprednol) will require daily administration but may decrease the frequency of visits to physicians’ offices. Intravitreally administered drugs that target different biochemical pathways are being developed as monotherapy and combination therapy, and their effects on durability remains to be seen.

Expert opinion: The rich development pipeline promises to provide improved therapeutic options in addition to drugs and devices with longer duration of action.

KEYWORDS:

• Aflibercept
• bevacizumab
• corticosteroids
• diabetic macular edema
• ranibizumab
• sustained release devices
• vascular endothelial growth factor

Article highlights

• The current preferred treatment of center-involving diabetic macular edema usually includes monthly intravitreal injections of a vascular endothelial growth factor inhibitory drug for up to 6 months followed by frequent assessments with additional injections performed as-needed.

• Vascular endothelial growth factor inhibitory drugs currently in phase III trials (abicipar and RTH258) may be effective with q3month dosing.

• Anti-VEGF eluting reservoirs and encapsulated cell technology may ultimately eliminate the need for repeated intravitreal injections but they have only advanced to phase II AMD trials.

• Recently approved corticosteroid inserts (dexamethasone delivery system and fluocinolone acetonide) provide extended durations of action – 3 months to 3 years – but they are usually relegated to second line therapy.

• Orally administered drugs might decrease the need for frequent clinic visits but their efficacy has not been proven.

• Drugs that target other angiogenic and inflammatory pathways may ultimately prove to be effective for the treatment of DME but they may not provide extended durations of action.

This box summarizes key points contained in the article.

Declaration of interest

MW Stewart is on the Advisory Board for Allergan and Regeneron and has received Institutional Research Support from the both companies. MW Stewart is a consultant for Boehringer-Ingelheim and Momenta Pharmaceuticals. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the paper apart from those disclosed.