Insights in resistant diabetic macular oedema
Reviewed by Sofia Rokerya

This article gives a bird’s eye review of the different modalities for the treatment of diabetic macular oedema (DME). The debut of anti-VEGFs has brought a paradigm shift in DME management. This treatment has now become a major breakthrough in the management of centre-involving (CI)-DME, replacing laser photocoagulation. The main disadvantage of anti-VEGF monotherapy, however, remains the high frequency of injections per year and the risk of injection-associated adverse events which may incur huge economic and social burden on patients and healthcare systems. In addition, the clinical response to anti-VEGF therapy is variable, and persistent DME still remains a challenge due to its complex pathogenesis and involvement of different biochemical pathways. In these cases, switching between different anti-VEGF drugs is an option which takes advantage of the molecular differences and the pharmacological targets for each of these agents. Bevacizumab, ranibizumab and aflibercept each have different binding affinities for VEGF and different half-lives in the vitreous and these drugs have been switched around to achieve resolution in resistant cases. Corticosteroids serve as the second-line drug for DME treatment and as one of the main therapies in control of persistent DME. Intravitreal triamcinolone, fluocinolone insert and dexamethasone implant are available agents. However, their use is limited by the side-effects of cataract and glaucoma. Macular laser photocoagulation has been in use to treat DME since the ETDRS report was published in 1985. It may cause macular scars and central scotoma, choroidal neovascularisation and subretinal fibrosis. To prevent these from occurring, subthreshold lasers such as Micropulse, and the PASCAL system that enables delivery of calculated endpoint energy are now rife. Pars plana vitrectomy (PPV) with or without internal limiting membrane (ILM) peeling is currently recommended as a therapeutic option in cases of persistent DME associated with tractional changes in the vitreomacular interface. OCT biomarkers, including serous retinal detachment (SRD), disorganisation of the retinal inner layers (DRIL), cysts, hyperreflective dots (HRD), outer retinal layers (ORL) and outer nuclear layers (ONL) alterations, and central macular thickness (CMT) have been identified as prognostic and predictive factors in patients with DME as they are associated with different levels of inflammatory biomarkers in the eye that can be taken into consideration when selecting the therapeutic strategy. Future contenders in the therapeutic arena include Conbercept, Brocolizumab and Faricimab. Faricimab, is a novel dual action Ang-2/anti-VEGF antibody designed for intraocular use that inhibits two inflammatory pathways. Also on the horizon, one sees the port delivery system (PDS) with ranibizumab long-acting drug delivery system that enable the continuous delivery of a customised formulation of ranibizumab into the vitreous and the Rho-Kinase Inhibitors sustained-release intravitreal implant. However, the battle is far from won, and the quest for future treatment perspectives include an individualised management of DME, with the development of novel anti-VEGF agents with longer duration of action in the vitreous cavity, PDS for anti-VEGF, serum and aqueous humor measurement of inflammatory cytokines, evaluation of OCT biomarkers to guide therapy, agents targeting different biochemical pathways such as angiopoetin-2 and IL-6, and insight into neuroprotective agents for DME. Multicentre randomised clinical trials may provide evidence for these novel agents in future.

New insights in resistant diabetic macular edema.
Kuroiwa DAK, Malerbi FK, Regatieri CVS.
OPHTHALMOLOGICA
2021;244(6):485-94.