A review of therapies for diabetic macular oedema and rationale for combination therapy

Abstract

Diabetic macular oedema (DMO) is responsible for significant visual impairment in diabetic patients. The primary cause of DMO is fluid leakage resulting from increased vascular permeability through contributory anatomical and biochemical changes. These include endothelial cell (EC) death or dysfunction, pericyte loss or dysfunction, thickened basement membrane, loss or dysfunction of glial cells, and loss/change of EC Glycocalyx. The molecular changes include increased reactive oxygen species, pro-inflammatory changes: advanced glycation end products, intracellular adhesion molecule-1, Complement 5-9 deposition and cytokines, which result in increased paracellular permeability, tight junction disruption, and increased transcellular permeability. Laser photocoagulation has been the mainstay of treatment until recently when pharmacological treatments were introduced. The current treatments for DMO target reducing vascular leak in the macula once it has occurred, they do not attempt to treat the underlying pathology. These pharmacological treatments are aimed at antagonising vascular endothelial growth factor (VEGF) or non-VEGF inflammatory pathways, and include intravitreal injections of anti-VEGFs (ranibizumab, aflibercept or bevacizumab) or steroids (fluocinolone, dexamethasone or triamcinolone) as single therapies. The available evidence suggests that each individual treatment modality in DMO does not result in a completely dry macula in most cases. The ideal treatment for DMO should improve vision and improve morphological changes in the macular (eg, reduce macular oedema) for a significant duration, reduced adverse events, reduced treatment burden and costs, and be well tolerated by patients. This review evaluates the individual treatments available as monotherapies, and discusses the rationale and potential for combination therapy in DMO.

A specific phosphorylation regulates the protective role of αA-crystallin in diabetes

“…Treatment with anti-VEGF agents or corticosteroids benefit a subset of patients with advanced retinopathy, specifically macular edema (2), but more effective treatments are needed for the early stage of the disease. Over the past two decades, numerous studies have demonstrated the neurodegenerative element of DR (3)(4)(5), but the underlying mechanisms of neurodegeneration remain to be clearly established.…”

The Use of Intravitreal Anti-VEGF and Triamcinolone in the Treatment of Radiation Papillopathy

“…The effects of combining corticosteroids with anti-VEGF agents are thought to be both additive and complimentary. Corticosteroids block non-VEGF-dependent inflammatory pathways, including the arachidonic acid pathway [25]. In vivo studies have confirmed that in addition to their anti-inflammatory effects, corticosteroids also inhibit the secretion of angiogenic mediators from retinal microvascular pericytes [26].…”

Panretinal Photocoagulation vs. Panretinal Photocoagulation Plus Intravitreal Ranibizumab in High-Risk Proliferative Diabetic Retinopathy

“…Macular oedema is the leading cause of visual loss in diabetic retinopathy patients. 13 The intravitreal anti-VEGF injection can reduce macular interstitial fluid or oedema that, even when subclinical might cause retinal functional impairment. 14 In our study, no difference in average CSMT emerged between the groups throughout the 24-week follow-up period.…”