Aqueous proteins help predict the response of patients with neovascular age-related macular degeneration to anti-VEGF therapy

Abstract

Age-related macular degeneration (AMD), Neovascular AMD (nvAMD), Nonneovascular AMD (nnvAMD), Vascular endothelial growth factor (VEGF), anti-VEGF therapy, choroidal neovascularization, treat-and-extend, pro re nata, proteomics, complement, complement factor 3 (C3), complement factor H (CFH), complement factor H-related (CHFR) proteins, apolipoprotein-B100 (ApoB100), drusen Cao et al.,2

ANGPTL4 influences the therapeutic response of patients with neovascular age-related macular degeneration by promoting choroidal neovascularization

“…Using a hybrid of TAE and PRN protocols, which we designated TEP/M, we recently reported that ~30% of patients with nvAMD can be safely weaned off anti-VEGF therapy within 1 year ( 8 ). However, ~20% of patients with nvAMD failed treatment extension, requiring intraocular injections with anti-VEGF therapy every 4 weeks.…”

“…However, ~20% of patients with nvAMD failed treatment extension, requiring intraocular injections with anti-VEGF therapy every 4 weeks. Most of these patients still had fluid, despite this aggressive treatment regimen ( 8 ). These results demonstrate that a subset of patients with nvAMD are less sensitive to currently available anti-VEGF therapies and implicate other vasoactive mediators in the promotion of CNV in these patients.…”

“… ( A – C ) Aqueous ANGPT2 ( A ), EPO ( B ), and ANGPTL4 ( C ) levels of patients during initial 3 monthly mandatory treatment phase of a treat-and-extend protocol for patients with increasing intervals between treatments at 12 months (from subset of TEP/M patients divided into groups based on the required treatment interval at the end of year 1 using the TEP/M protocol to wean patients from treatment; ref. 8 ). Patients extended to 12 weeks had treatment paused, and patients were considered “weaned” off treatment if treatment pause reached 30 weeks.…”

“…In this regard, we recently described a hybrid of the treat-and-extend (TAE) and pro re nata (PRN) protocols, which we designated TAE, pause, and monitor (TEP/M), in which patients initially undergo 3 consecutive monthly injections with anti-VEGF therapy, followed by a TAE protocol in which the interval for the next treatment is extended (by 2 weeks) for patients who demonstrate an absence of activity ( 8 ). Patients who remain quiescent 12 weeks from their prior treatment enter a “treatment pause” and are switched to PRN treatment; treatment is resumed based on a decline in vision or worsening on clinical exam and/or imaging studies.…”

“…Patients who remain quiescent 12 weeks from their prior treatment enter a “treatment pause” and are switched to PRN treatment; treatment is resumed based on a decline in vision or worsening on clinical exam and/or imaging studies. Using this approach, we reported that patients with nvAMD at the end of 1 year can be divided into 3 groups: (a) patients who require monthly treatment with anti-VEGF therapy (i.e., patients who fail treatment extension; ~20% of patients); (b) patients who require less-frequent but ongoing treatment with anti-VEGF therapy (~50% of patients); and (c) patients who can be successfully weaned off treatment with anti-VEGF therapy (~30% of patients) ( 8 ). Interestingly, neither the pre- nor posttreatment aqueous fluid levels of VEGF correlated with the need for more-frequent — or less-frequent — treatment with anti-VEGF therapy ( 8 ), suggesting that other vasoactive mediators may contribute to the response of patients with nvAMD to treatment.…”