The current standard of care is to treat DME primarily with intraocular anti-VEGF injections. The agents in this class that we use (ie, anti-VEGFA therapies), whether an antibody or a recombinant protein, will gradually be cleared from the eye, resulting in rising VEGF levels. Ultimately, this would result in the development of recurrent edema, so we have to repeat the injections at regular intervals. 

There are several areas of innovation that may affect our approach to the management of DME. One is the identification of targets in addition to VEGF, which was our first validated target. Angiopoietin 2 (Ang2) is an example of that. Ang2 is our second validated therapeutic target for DME, and faricimab acts by blocking both VEGF and Ang2.

Further, there are additional targets that are not yet clinically validated and are the subject of ongoing clinical trials, including additional VEGF family members such as VEGFC and VEGFD. One approach to targeting these VEGF subtypes is to use antibodies or recombinant proteins that block VEGFC and VEGFD, in addition to VEGFA. Another approach is to use receptor tyrosine kinase inhibitors (TKIs) that directly block VEGF receptors so that all of the VEGF family members that signal through these receptors would be inhibited. Axitinib is one such pan-VEGF receptor inhibitor. The problem with this candidate has been optimizing its delivery. Sustained-release delivery of axitinib via a hydrogel implant is being investigated in neovascular age-related macular degeneration, and a suprachoroidal injection of axitinib is also being tested.   

Another area of innovation in the management of DME and other retinal diseases is the pursuit of new ways to increase the durability of existing therapies. This may be through novel delivery systems or through the use of gene therapy. Gene therapy involves the injection of a viral vector and the subsequent expression of a protein that blocks VEGF. The hope is that the gene therapy will provide continuous VEGF suppression for years or maybe even for the patient’s lifetime. But researchers are also investigating the viability of port delivery systems in which an implantable reservoir slowly releases an anti-VEGF agent into the vitreous cavity so that the patient can receive continuous anti-VEGF therapy for a full 6 months. At that time, the reservoir would be refilled. 

The treatment of DME is fairly intensive for most patients. They may be receiving 8 to 10 injections during the first or second year of treatment. Less frequent injections may be possible after some time, but, in other cases, injections as often as every 4 or 5 weeks may be needed for years. 

Identifying ways in which we can have more durable treatments is important. What sometimes happens to patients is that "life gets in the way." They get sick or they have a family member who has a problem, so they are not able to come in for their treatments, they miss a treatment, and their disease reactivates.