Treatment of diabetic retinopathy: Recent advances and unresolved challenges

Table 1 The drugs under current development for the treatment of diabetic macular edema

Drug	Study design	Results
Danazol	23 eyes: 12-wk placebo-control	Significant decreases in CRT (-86% vs -29%) and macular volume (P = 0.05)
		Improvement in BCVA by 1 category (14% vs 47%)
Minocylcine	5 eyes: Minocycline 100 mg BID for 6 mo	Improved BCVA and CRT compared to historic
		controls
Loteprednol etabonate (topical)	20 eyes: Single masked, 2-dose, randomized trial	Phase II clinical trial (KPI-121-C-004) underway
Dexamethasone phosphate	Iontophoresis driven into the eye EGP-437	Positive results in 15 patients
PAN-90806	4 monotherapy arms in phase I/II trial	Maintenance therapy after single anti-VEGF injections
Diclofenac	57 eyes: Intravitreal diclofenac vs bevacizumab	Diclofenac achieved better improvement in BCVA compared to bevacizumab (Δ -0.08 LogMAR vsΔ +0.04 LogMAR, P = 0.033)
		Bevacizumab improved macular edema slightly
		better
Sirolimus	Phase I trial: Dose- escalating, subconjunctival of intravitreal injections	Subconjunctival: median increase in BCVA was +4.0 letters at 45 d
		Intravitreal: Median increase in BCVA was +4.0 letters at 90 d
Fasudil	Single intravitreal injections of fasudil with bevacizumab	At 4 wk ΔBCVA (0.84 ± 0.35 LogMAR to 0.49 ± 0.29 LogMAR; P = 0.003) and mean ΔCRT (448 ± 123 μm to 347 ± 76 μm; P = 0.001)
Luminate (ALG-001)	Phase IIb DME trial (targets integrin receptors)	Data expected third quarter of 2016
Plasma kallekrein inhibitor (KVD001)	Phase II trials: Monotherapy for resistant DME combined with anti-VEGF	Phase I trial demonstrated safety after intravitreal injections
REGN910 (Ang 2 Ab)	Phase I trial	Completed. Now planning phase II trials for nAMD and DME

Important drug characteristics and early phase trial results are documented. CRT: Central retina thickness; BCVA: Best corrected visual acuity; VEGF: Vascular endothelial growth factor; LogMAR: Logarithm of minimal angle of resolution; DME: Diabetic macular edema; Ang: Angiopoietin; Ab: Antibody; nAMD: Neovascular age-related macular degeneration; BID: Twice daily; EGP: Eyegate pharmaceuticals.