Table 1 Potential Therapeutics for Diabetic Retinopathy

Somatostatin

Neuroprotective, antiangiogenic. Downregulated in retinas of diabetics, associated with retinal neurodegeneration [54].

Recently completed multi-center phase II-III trial (EUROCONDOR) to assess the safety of topically administered somatostatin. (EudraCT Number: 2012–001200-38) Results have yet to be published.

Glucagon-like peptide (GLP-1)

Neuroprotective [55]

Intravitreal injections of exedin-4 (a GLP-1 analogue) prevent ERG abnormalities in rats with streptozotoin-induced diabetes [56]. Topical administration of GLP-1R agonists prevents retinal neurodegeneration in mice with diabetes [57].

2 large clinical trials of GLP-1 analogues in type 2 diabetics with high cardiovascular risk (LEADER and SUSTAIN-6) have shown neutral benefit [58] or even worsening of DR compared to placebo [59]. However, these studies were not designed to assess progression of DR.

Doxycycline

Anti-inflammatory and neuroprotective [60]

Low-dose oral doxycycline improves inner retinal function in DR compared to placebo [61].

Although statistical significance was achieved at multiple time points, it was a small, proof-of-concept trial.

Interleukin 1β (IL-1β)

Inflammatory cytokine

Systemic IL-1β inhibition has been shown to stabilize retinal neovascular changes in proliferative DR and reduce macular edema [62].

Open-label, small, prospective pilot study. Reduction in macular edema was not statistically significant.

Tumor necrosis factor α (TNF-α)

Inflammatory, induces vascular changes

Intravitreal injection of TNF-α inhibitor decreased capillary degeneration in diabetic rats [63].

Very small study in rats, with other primary endpoints.