Diabetic retinopathy - Emerging treatments

Intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy (for proliferative retinopathy)

The standard treatment for proliferative diabetic retinopathy, panretinal photocoagulation (PRP), reduces the rate of severe visual loss by approximately 50%.[74][99][100][101] It is, however, associated with all peripheral visual field loss, impairment of night vision, and exacerbation of diabetic macular edema. A reduced risk of the development of proliferative retinopathy was noted in trials of ranibizumab for the treatment of macular edema.[91] A randomized trial was therefore carried out to compare intravitreal ranibizumab with PRP for the treatment of proliferative diabetic retinopathy.[122] In ranibizumab-treated patients, at 2 years, visual acuity was noninferior to PRP, peripheral visual field sensitivity was greater, and diabetic macular odema and vitrectomy were less common. However, at 5 years, loss to follow-up was approximately one third of the total cohort, excluding deaths. A study evaluating the efficacy of aflibercept in the treatment of proliferative diabetic retinopathy achieved good control of proliferative retinopathy with a median of 4 injections over the course of 1 year.[123]

Intravitreal anti-VEGF therapy for nonproliferative retinopathy before the development of center-involving diabetic macular edema

The DRCRnet Protocol W study compared sham injection with intravitreal aflibercept in the management of moderate-severe/severe nonproliferative retinopathy. Patients with center-involving diabetic macular edema were excluded from the study. The risks over 2 years of developing center-involving diabetic macular edema or proliferative diabetic retinopathy were 43% in the sham group, and 16% in the aflibercept-treated group. There was no difference in visual acuity between the two groups.[36] The PANORAMA study compared two different regimens of intravitreal aflibercept injection with sham for patients who had severe treatment-naive nonproliferative diabetic retinopathy with no diabetic macular edema and best-corrected visual acuity of 20/40 or better. The risks over 2 years of developing proliferative diabetic retinopathy or center-involving diabetic macular edema were 50% in the sham group and 16% to 19% in the aflibercept-treated group. No visual acuity difference was identified between groups.[124]

Brolucizumab

Brolucizumab, an anti-VEGF monoclonal antibody, is approved by the Food and Drug Administration (FDA) for the treatment of diabetic macular edema. When compared with aflibercept, brolucizumab was shown to have comparable efficacy and a longer duration of action in the treatment of neovascular age-related macular degeneration.[125] Ongoing phase 3 trials have demonstrated similar findings in the management of diabetic macular edema. There is, however, a 5% risk of intraocular inflammation, and approximately one quarter of such patients will develop visual loss.[126]

Aflibercept (high-dose regimen)

A high-dose regimen of intravitreal aflibercept, given every 8 to 12 weeks, has been approved in the US for diabetic retinopathy (extended to 16 weeks for diabetic macular edema). A phase 2/3 trial is ongoing.[127]

Ranibizumab (port delivery system)

The port delivery system with ranibizumab uses a surgically placed permanent refillable ocular implant to deliver a ranibizumab formulation over long periods. 24-weekly refills have been shown to be of comparable efficacy to monthly ranibizumab injections in the management of neovascular age-related macular degeneration.[128] It should be noted that 5% of patients suffered vitreous hemorrhage following implantation and endophthalmitis occurred in 1.6%, which compares unfavorably with standard intravitreal injection. The delivery system has potential for use in diabetic macular edema.