ABSTRACT
Introduction
Diabetic macular edema (DME) is a vision threatening accumulation of fluid within the macula. Current treatments involve the use of intravitreal anti-vascular endothelial growth factor (anti-VEGF), steroids, and laser to preserve vision.
Areas covered
This review covers phase III therapeutics including KSI-301, which targets VEGF-A, UBX1325 which promotes apoptosis of senescent vascular endothelial cells and topical dexamethasone drops. Phase I and phase II therapeutics are also discussed including APX3330, a reduction-oxidation factor (Ref-1) inhibitor, ASP8232 – a vascular adhesion protein-1 (VAP-1) inhibitor, OTT-166, an anti-integrin agent, EYE103, a Wnt agonist and AXT107 and AG-73305, which have both anti-integrin and anti-VEGF functions. Tyrosine kinase inhibitors such as EYP-1901 and AXPALI, and YD312, gene therapies such as 4D–150 and RGX-314.
Expert opinion
Current treatments for DME are limited greatly by the need for frequent dosing, treatment adherence, and invasive administration. Newer technologies that promote alternative routes of administration or increased longevity hold promise for the management of DME.
Article highlights
Diabetic macular edema (DME) is a leading cause of vision loss.
Current treatments for DME are effective for some, but not all, and have significant limitations including high treatment burden, invasiveness, and side effects.
Newer therapies are being studied that target various mechanisms of DME development.
Many therapeutics target the effects of vascular endothelial growth factor (VEGF)
Other therapies focus on other components of DME pathogenesis including vessel permeability, endothelial dysfunction, inflammation, and apoptosis.
Abbreviations
DME | = | diabetic macular edema |
VEGF | = | vascular endothelial growth factor |
VEGFR | = | vascular endothelial growth factor receptor |
PDGFR | = | platelet derived growth factor receptor |
BCVA | = | best corrected visual acuity |
CST | = | central subfield thickness |
DR | = | diabetic retinopathy |
NPDR | = | non-proliferative diabetic retinopathy |
PDR | = | proliferative diabetic retinopathy |
ETDRS | = | early treatment diabetic retinopathy study |
DRSS | = | diabetic retinopathy severity scale |
VAP-1 | = | vascular adhesion protein 1 |
FGFR | = | fibroblast growth factor receptor |
nAMD | = | neovascular age-related macular degeneration |
RPE | = | retinal pigmented epithelium |
SC | = | subcutaneous |
HDs | = | hydroxyl dendrimers |
Fab | = | fragment antigen binding region |
RNAi | = | ribonucleic acid interference |
FDA | = | U.S. Food and Drug Administration |
Declaration of interest
RP Singh reports personal fees from Apellis, Iveric Bio, Eyepoint, Regenxbio, Genentech, Bausch and Lomb, Zeiss, Alcon, and Regeneron, and research grants from Jannsen. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Reviewer disclosures
A reviewer on this manuscript has disclosed they have a drug that they invented in a Phase II DME study and are an executive and board member in this company called Aviceda Therapeutics. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.