New treatments for diabetic macular edema

Abstract

This work comprehensively reviews the latest treatment options for diabetic macular edema (DME) used in its management and presents further work on the topic. Diabetic retinopathy is an important and increasingly prevalent cause of preventable blindness worldwide. To meet this increasing burden there has recently been a proliferation of pharmacological therapies being used in clinical practice. A variety of medical treatment options now exist for DME. These include non-steroidal anti-inflammatory drugs such as nepafenac, as well as intravitreal steroids like triamcinolone (kenalog). Long-term results up to 7 years after commencing treatment are presented for triamcinolone. Studies are reviewed on the use of dexamethasone (ozurdex) and fluocinolone (Retisert and Iluvien implants) including the FAME studies. A variety of anti-vascular endothelial growth factor (anti-VEGF) agents used in DME are considered in detail including ranibizumab (lucentis) and the RESTORE, RIDE, RISE and Diabetic Retinopathy Clinical Research Network (DRCR.net) studies. Bevacizumab (avastin) and pegaptinib (macugen) are also considered. The use of aflibercept (eylea) is reviewed including the significance of the DA VINCI, VISTA-DME, VIVID-DME and the DRCR.net studies which have recently suggested potentially greater efficacy when treating DME for aflibercept in patients with more severely reduced visual acuity at baseline. Evidence for the anti-VEGF agent bevasiranib is also considered. Studies of anti-tumour necrosis factor agents like infliximab are reviewed. So are studies of other agents targeting inflammation including minocycline, rapamycin (sirolimus) and protein kinase C inhibitors such as midostaurin and ruboxistaurin. The protein kinase C β inhibitor Diabetic Macular Edema Study is considered. Other agents which have been suggested for DME are discussed including cyclo-oxygenase-2 inhibitors like celecoxib, phospholipase A2 inhibitors, recombinant erythropoietin, and monoclonal anti-interleukin antibodies such as canakinumab. The management of DME in a variety of clinical scenarios is also discussed - in newly diagnosed DME, refractory DME including after macular laser, and postoperatively after intraocular surgery. Results of long-term intravitreal triamcinolone for DME administered up to seven years after commencing treatment are considered in the context of the niche roles available for such agents in modern management of DME. This is alongside more widely used treatments available to the practitioner such as anti-VEGF agents like aflibercept (Eylea) and ranibizumab (Lucentis) which at present are the mainstay of pharmacological treatment of DME.

Keywords: Diabetic macular edema, Diabetic macular oedema, Triamcinolone, Anti-vascular endothelial growth factor agents, Steroids, Non-steroidal anti-inflammatory drugs, Biologicals, Protein kinase C inhibitors

Core tip: Current evidence suggests the anti-vascular endothelial growth factor (anti-VEGF) agents aflibercept and ranibizumab are the most effective agents for most patients with diabetic macular edema. Aflibercept may be more effective when vision is very low. Other drugs retain niche roles including bevacizumab owing to lower costs, steroids like triamcinolone which can be effective many years later, dexamethasone and non-steroidal anti-inflammatory drugs like nepafenac. Also considered are anti-tumour necrosis factor agents like infliximab, anti-interleukins like canakinumab, anti-inflammatories including minocycline, rapamycin (sirolimus) and protein kinase C inhibitors midostaurin and ruboxistaurin. Fluocinolone implants, anti-VEGF agents bevasiranib and pegaptinib, cyclo-oxygenase-2 inhibitors like celecoxib, phospholipase A2 inhibitors and recombinant erythropoietin are discussed.