Abstract
Purpose: :
VEGF inhibitors like bevacizumab is the new paradigm to treat neovascular macular degeneration (AMD). However VEGF is essential for normal biologic functions such as blood pressure regulation. VEGF induces NO production and relaxation of vasomotor tone. Intravenous injection of bevacizumab induces arterial hypertension in patients with AMD. Intravitreal (ITV) injection of bevacizumab limits systemic exposure to the anti-VEGF but directly exposes the retina. Therefore, the effect of ITV bevacizumab on retinal circulation was studied.
Methods: :
16 patients with neovascular AMD treated with 3 ITV injections of bevacizumab at 5-7 weeks intervals have completed the study. Blood diameter and flow measurements were performed on a major retinal arteriole with the Canon Laser Blood Flowmeter at baseline, one week after the first injection, just prior to the second injection and 5 weeks after the third injection. Neuroretinal rim and peripapillary blood flow were measured using Scanning Laser Doppler Flowmetry (SLDF) at the first and the fourth visit to assess the effect of an eventual arteriolar blood flow decrease on tissue perfusion. Ocular perfusion pressure (OPP) was calculated for each visit.
Results: :
Arteriolar diameter decreased from 122,2 ± 13,7 to 117,8 ± 12,2 (p=0,008) during the first week. The decrease remained stable until 5 weeks after the third injection (p=0,003). Arterial blood flow decreased non-significantly from 10,9 ± 3,8 to 10,6 ± 2,6 during the first week to reach a mean value of 9,8 ± 2,6 (p=0,13) 5 weeks after the third injection. A significant decrease in SLDF tissue perfusion from 169,8 ± 90,8 to 150,0 ± 70,9 (p=0,05) was observed in the neuroretinal rim, but no significant change was observed in the peripapillary retina. No significant OPP change was detected during the study.
Conclusions: :
Arteriolar diameter decreased significantly after the first ITV injection of bevacizumab and remained stable until the end of the study suggesting a long term effect on vascular tone. However this change was modest and did not significantly affect the arteriolar blood flow. Decreased perfusion was observed in the neuroretinal rim but there was no significant change in perfusion of the peripapillary retina. To our knowledge, this is the first report on the effect of bevacizumab on retinal circulation. More studies should be performed to confirm these results especially concerning the neuroretinal rim, which seems to be more sensitive to increased vascular tone.
Keywords: age-related macular degeneration • vascular endothelial growth factor • blood supply