[HTML][HTML] VEGF/VEGFR2 blockade does not cause retinal atrophy in AMD-relevant models

D Long, Y Kanan, J Shen, SF Hackett, Y Liu, Z Hafiz… - JCI insight, 2018 - ncbi.nlm.nih.gov
D Long, Y Kanan, J Shen, SF Hackett, Y Liu, Z Hafiz, M Khan, L Lu, PA Campochiaro
JCI insight, 2018ncbi.nlm.nih.gov
Intraocular injections of VEGF-neutralizing proteins provide tremendous benefits in patients
with choroidal neovascularization (NV) due to age-related macular degeneration (AMD), but
during treatment some patients develop retinal atrophy. Suggesting that VEGF is a survival
factor for retinal neurons, a clinical trial group attributed retinal atrophy to VEGF suppression
and cautioned against frequent anti-VEGF injections. This recommendation may contribute
to poor outcomes in clinical practice from insufficient treatment. Patients with type 3 …
Abstract
Intraocular injections of VEGF-neutralizing proteins provide tremendous benefits in patients with choroidal neovascularization (NV) due to age-related macular degeneration (AMD), but during treatment some patients develop retinal atrophy. Suggesting that VEGF is a survival factor for retinal neurons, a clinical trial group attributed retinal atrophy to VEGF suppression and cautioned against frequent anti-VEGF injections. This recommendation may contribute to poor outcomes in clinical practice from insufficient treatment. Patients with type 3 choroidal NV have particularly high risk of retinal atrophy, an unexplained observation. Herein we show in mouse models that VEGF signaling does not contribute to photoreceptor survival and functioning:(a) neutralization of VEGFR2 strongly suppresses choroidal NV without compromising photoreceptor function or survival;(b) VEGF does not slow loss of photoreceptor function or death in mice with inherited retinal degeneration, and there is no exacerbation by VEGF suppression; and (c) mice with type 3 choroidal NV develop retinal atrophy due to oxidative damage with no contribution from VEGF suppression. Intraocular injections of VEGF-neutralizing proteins, a highly effective treatment in patients with neovascular AMD, should not be withheld or reduced due to concern that they may contribute to long-term visual loss from retinal atrophy.
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