Throughout the body, any source of cellular damage (e.g., inflammation, infection, smoking, or high blood sugar) can liberate reactive oxygen species and set in motion an oxidative stress chain reaction that ultimately leads to tissue damage and pathology.
In retinal diseases, including diabetic macular edema (DME), oxidative stress activates multiple downstream pathways: increased vascular permeability; angiogenesis; inflammation; and apoptosis and neurodegeneration. These pathways may all be activated simultaneously-or their involvement may vary, depending on the individual patient and the disease stage.
Ophthalmologists are fortunate to have effective medications that address some of these pathways. Anti-VEGF agents target vascular permeability and angiogenesis, while steroids can address inflammation. However, there are no currently available agents that address all four pathways at once, and none that are neuroprotective.
Moreover, current therapies are insufficient-about 50% of DME patients still have edema after 1 year of anti-VEGF treatment.1
Even with state-of-the art therapies, patients may have continued leakage and/or vision that does not improve as much as ophthalmologists would like. It is possible that in these under- or non-responding patients, the VEGF-mediated pathways are not the primary pathways of damage.
David S. Boyer, MD
P: 213/483-8810 or E: [email protected]
Dr. Boyer is co-founder of Retina Vitreous Associates Medical Group, with six offices in and around Los Angeles. He is a consultant and member of Allegro's Scientific Advisory Board and has stock options in the company. He also serves as a consultant to Allergan, Bayer, Genentech, Regeneron, and Roche.
1. Dugel PU, Layton A, Varma R. Diabetic macular edema diagnosis and treatment in the real world: An analysis of Medicare claims data (2008 to 2010). Ophthalmic Surg Lasers Imaging Retina 2016;47:258-267.
2. Kenney CM, Chwa M, Cáceres-del-Carpio J, et al. Effects of anti-VEGF and ALG-1001 on human retinal cells in vitro. Association for Research and Vision in Ophthalmology Annual Meeting, 2018.