MMP-9 Inhibition for Recalcitrant Wet AMD

Wet (or neovascular) form of age-related macular degeneration (wAMD) is the most common cause of blindness in the Western world. Currently, anti-vascular endothelial growth factor (VEGF) intravitreal injections (IVI) remain the standard-of-care treatment for wAMD. Previous studies show that about 90% of treated patients lose minimal visual function after 2 years of follow-up. There is still, a subset of 15% patients, incomplete responders, that do not improve and possibly worsen due to the persistence of sub-retinal fluid (with or without intra-retinal fluid) with chronic treatment. The investigators plan to evaluate the effect of oral doxycycline versus placebo on the anatomic and functional outcomes in persistent sub-retinal eye fluid in neovascular wet age-related macular degeneration. This subset are incomplete or non-responders to current anti-VEGF intravitreal therapy.

The investigators plan to conduct a double masked, randomized study to assess the effect of low dose, oral doxycycline 50 mg once a day versus placebo in patients with wet age-related macular degeneration who are incomplete responders to anti-VEGF extended treatment regimens. The study will be conducted over 9 months with every 3 month assessments; 6 months administration period of doxycycline versus placebo (double masked, randomized) and a 3 month follow up period. The participant visits will occur during clinic visits for standard-of-care intravitreal injections (IVI). Medical information will be acquired from the standard of care optical coherence tomography (OCT), visual acuity (VA), and IVI administered (number, frequency and type of drug). Blood plasma and aqueous fluid (anterior chamber tap) samples and study drug tolerability will be obtained at baseline, 6 months and 9 months. Plasma will be obtained to assay for inflammatory markers: MMP-9 levels and questionnaires will be obtained on 1) vision quality of life, and 2) study drug tolerance at Baseline, 6 months and 9 months.