title: Ultrasound assessment of ocular vascular effects of repeated intravitreal injections of ranibizumab for wet age-related macular degeneration.
abstract: OBJECTIVE
  Determine the effect of repeated intravitreal injections of ranibizumab (0.5 mg; 0.05 ml) on retrobulbar blood flow velocities (BFVs) using ultrasound imaging quantification in twenty patients with exudative age-related macular degeneration treated for 6 months.
  
  
  METHODS
  Visual acuity (ETDRS), central macular thickness (OCT), peak-systolic, end-diastolic and mean-BFVs in central retinal (CRA), temporal posterior ciliary (TPCA) and ophthalmic (OA) arteries were measured before, 2 days, 3 weeks and 6 months after the first injection. Patients were examined monthly and received 1-5 additional injections depending on ophthalmologic examination results.
  
  
  RESULTS
  Six months after the first injection, a significant increase in visual acuity 50.9 ± 25.9 versus 44.4 ± 21.7 (p < 0.01) and decrease in mean central macular thickness 267 ± 74 versus 377 ± 115 μm (p < 0.001) were observed compared to baseline. Although mean-BFVs decreased by 16%±3% in CRA and 20%±5% in TPCA (p < 0.001) 2 days after the first injection, no significant change was seen thereafter. Mean-BFVs in OA decreased by 19%±5% at week 3 (p < 0.001). However, the smallest number of injections (two injections) was associated with the longest time interval between the last injection and month 6 (20 weeks) and with the best return to baseline levels for mean-BFVs in CRA, suggesting that ranibizumab had reversible effects on native retinal vascular supply after its discontinuation. Moreover, a significant correlation between the number of injections and percentage of changes in mean-BFVs in CRA was observed at month 6 (R = 0.74, p < 0.001) unlike TPCA or OA.
  
  
  CONCLUSIONS
  Ranibizumab could impair the native choroidal and retinal vascular networks, but its effect seems reversible after its discontinuation.
authors.affiliation: Sorbonne-Paris-Cité, AP-HP, Lariboisiere hospital, Department of Clinical-Physiology - Functional-Investigations, Paris-Diderot University, Paris, France; Sorbonne-Paris-Cité, INSERM, U965, Paris-Diderot University, Lariboisiere Hospital, Paris, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Bonnin
authors.forename: Jean-Antoine C
authors.initials: JA
authors.lastname: Pournaras
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Makowiecka
authors.forename: Valerie
authors.initials: V
authors.lastname: Krivosic
authors.forename: Antoni W
authors.initials: AW
authors.lastname: Kedra
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Le Gargasson
authors.forename: Alain
authors.initials: A
authors.lastname: Gaudric
authors.forename: Bernard I
authors.initials: BI
authors.lastname: Levy
authors.forename: Yves S
authors.initials: YS
authors.lastname: Cohen
authors.forename: Ramin
authors.initials: R
authors.lastname: Tadayoni
authors.forename: Pascale
authors.initials: P
authors.lastname: Massin
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D001783:Blood Flow Velocity; D001794:Blood Pressure; D019842:Ciliary Arteries / Q000502:physiology*; D005260:Female; D006801:Humans; D007429:Intraocular Pressure; D058449:Intravitreal Injections; D008297:Male; D009880:Ophthalmic Artery / Q000502:physiology*; D011446:Prospective Studies; D000069579:Ranibizumab; D012039:Regional Blood Flow; D012161:Retinal Artery / Q000502:physiology*; D019233:Retreatment; D018615:Ultrasonography, Doppler, Color; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D014792:Visual Acuity; D057135:Wet Macular Degeneration / Q000188:drug therapy* / Q000503:physiopathology*
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000069579:Ranibizumab
keywords: age-related macular degeneration; anti-angiogenic therapy; central retinal artery; ciliary artery; ophthalmic artery