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P. W. Conrad, D. N. Zacks, M. W. Johnson; Intravitreal Bevacizumab in Neovascular Age-Related Macular Degeneration: Clinical Evidence for a Dosing Interval of Two Months or More. Invest. Ophthalmol. Vis. Sci. 2007;48(13):4533.
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In the treatment of neovascular AMD, intravitreal ranibizumab is typically injected monthly, but the optimal dosing paradigm for the off-label use of bevacizumab is unknown. The fact that bevacizumab is 3 times larger than ranibizumab suggests that a less frequent dosing interval may be possible with this agent. We hypothesized that the effects of a single intravitreal injection of bevacizumab would persist for 8 weeks in most eyes.
We retrospectively reviewed the medical records of 25 consecutive patients with neovascular AMD treated with intravitreal bevacizumab by one of the authors (MWJ) between November, 2005 and June, 2006. Patients presenting during this time period received two induction injections given two months apart. Patients were included in this study (n = 15) if follow up data, including Snellen visual acuity and OCT, were available from 4 and 8 week visits after the initial injection. Additionally, OCT images were graded qualitatively by a single reader masked to the identity of the patient, visit date, and mean central retinal thickness measurements.
Compared with the baseline value of 20/200, mean visual acuity improved after a single bevacizumab injection to 20/125 at 4 weeks (p = 0.0153) and 20/100 at 8 weeks (p = 0.0027). Mean central retinal thickness was 316 µm at baseline and decreased to 223 µm and 206 µm at 4 and 8 weeks post-injection, respectively (p = 0.0003 and 0.0005). By masked OCT grading, macular fluid (cystoid edema and/or subretinal fluid) was resolved in 10/15 (66.7%) patients at 4 weeks and 11/15 (73.3%) patients at 8 weeks following the single intravitreal bevacizumab injection. Masked comparison of the 4 and 8 week OCT images showed that 3/15 (20%) patients had continued reduction in residual macular fluid between these time points. The macular fluid was graded as worse at 8 weeks compared with 4 weeks in only 1 (6.7%) patient, and was unchanged in the remaining 11 (73.3%) patients.
Based on these data, we believe that bevacizumab can be dosed in most eyes at intervals of 8 weeks or longer. The observation that a subset of eyes shows continued improvement in macular fluid between 4 and 8 weeks after a single injection suggests that a pharmacologic effect persists in the eye for approximately two months.
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