Aqueous vascular endothelial growth factor and ranibizumab concentrations after monthly and bimonthly intravitreal injections of ranibizumab for age-related macular degeneration
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To evaluate vascular endothelial growth factor (VEGF) and ranibizumab concentrations in eyes with age-related macular degeneration (AMD) after monthly and bimonthly intravitreal ranibizumab (IVR) injections.
Aqueous humor samples were obtained from 26 eyes with AMD before and after IVR injections. Nine eyes received three monthly injections and 17 eyes received two bimonthly injections. The VEGF and ranibizumab concentrations were measured by enzyme-linked immunosorbent assay.
The aqueous VEGF concentrations in the monthly injection group decreased below the lowest detectable limit in eight of nine eyes 1 month after the first injection and seven of nine eyes 1 month after the second injection (P < 0.001, mean baseline value, 94.7 pg/ml); the aqueous VEGF concentrations in the bimonthly injection group decreased below the lowest detectable limit in two of 17 eyes 2 months after the first injection (P < 0.001, mean baseline value, 152.4 pg/ml). The mean aqueous ranibizumab concentrations with monthly injections were 71.2 ng/ml 1 month after the first injection, and 96.3 ng/ml 1 month after the second injection. The mean aqueous ranibizumab concentrations in the bimonthly injection group were 2.5 ng/ml in 15 of 17 eyes, and below the lowest detectable limit in two of 17 eyes 2 months after the first injection.
In this pilot study with limited follow-up, intravitreal injection of ranibizumab can suppress aqueous VEGF completely for 1 month in most cases. Its effect does not last for 2 months enough to suppress VEGF completely in most cases, although aqueous VEGF at 2 months after intravitreal injection of ranibizumab is less than that before injection in most cases.
KeywordsAge-related macular degeneration Aqueous humor Ranibizumab Bimonthly intravitreal injection Vascular endothelial growth factor
Supported in part by a grant from the Ministry of Education, Culture, Sports, Science and Technology of Japan (#24592668) and a grant from the Ministry of Health, Labour and Welfare.
The authors have no proprietary interest in any aspect of this study. The funding organizations had no role in the design or conduct of this study.
- 1.Aiello LP, Pierce EA, Foley ED, Takagi H, Chen H, Riddle L, Ferrara N, King GL, Smith LE (1995) Suppression of retinal neovascularization in vivo by inhibition of vascular endothelial growth factor (VEGF) using soluble VEGF-receptor chimeric proteins. Proc Natl Acad Sci U S A 92:10457–10461PubMedCentralPubMedCrossRefGoogle Scholar
- 2.Lopez PF, Sippy BD, Lambert HM, Thach AB, Hinton DR (1996) Transdifferentiated retinal pigment epithelial cells are immunoreactive for vascular endothelial growth factor in surgically excised age-related macular degeneration-related choroidal neovascular membranes. Invest Ophthalmol Vis Sci 37:855–868PubMedGoogle Scholar
- 6.Krzystolik MG, Afshari MA, Adamis AP, Gaudreault J, Gragoudas ES, Michaud NA, Li W, Connolly E, O’Neill CA, Miller JW (2002) Prevention of experimental choroidal neovascularization with intravitreal anti-vascular endothelial growth factor antibody fragment. Arch Ophthalmol 120:338–346PubMedCrossRefGoogle Scholar
- 22.Schmidt-Erfurth U, Eldem B, Guymer R, Korobelnik JF, Schlingemann RO, Axer-Siegel R, Wiedemann P, Simader C, Gekkieva M, Weichselberger A, EXCITE Study Group (2011) Efficacy and safety of monthly versus quarterly ranibizumab treatment in neovascular age-related macular degeneration: the EXCITE study. Ophthalmology 118:831–839PubMedCrossRefGoogle Scholar
- 23.Holash J, Davis S, Papadopoulos N, Croll SD, Ho L, Russell M, Boland P, Leidich R, Hylton D, Burova E, Ioffe E, Huang T, Radziejewski C, Bailey K, Fandl JP, Daly T, Wiegand SJ, Yancopoulos GD, Rudge JS (2002) VEGF-Trap: A VEGF blocker with potent antitumor effects. Proc Natl Acad Sci U S A 99:11393–11398PubMedCentralPubMedCrossRefGoogle Scholar
- 24.US Food and Drug Administration (2011) FDA labeling information — Eylea http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/125387lbl.pdf. Accessed Nov 2011
- 25.Heier JS, Brown DM, Chong V, Korobelnik JF, Kaiser PK, Nguyen QD, Kirchhof B, Ho A, Ogura Y, Yancopoulos GD, Stahl N, Vitti R, Berliner AJ, Soo Y, Anderesi M, Groetzbach G, Sommerauer B, Sandbrink R, Simader C, Schmidt-Erfurth U, VIEW 1 and VIEW 2 Study Groups (2012) Intravitreal aflibercept (VEGF Trap-Eye) in wet age-related macular degeneration. Ophthalmology 119:2537–2548PubMedCrossRefGoogle Scholar
- 31.Lucentis (ranibizumab injection). Highlights of prescribing information. Available at: http://www.gene.com/gene/products/information/pdf/lucentis-prescribing.pdf. Accessed April 15, 2011.
- 34.Heier JS, Boyer D, Nguyen QD, Marcus D, Roth DB, Yancopoulos G, Stahl N, Ingerman A, Vitti R, Berliner AJ, Yang K, Brown DM, CLEAR-IT 2 Investigators (2011) CLEAR-IT 2 Investigators. The 1-year results of CLEAR-IT 2, a phase 2 study of vascular endothelial growth trap-eye dosed as-needed after 12-week fixed dosing. Ophthalmology 118:1098–1106PubMedCrossRefGoogle Scholar