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William R Freeman, Natalia Camacho, Cheryl A Arcinue, Yang Qin, Mark Espina, Mostafa Alam, Qisheng You; High-dose Aflibercept for Eyes with Wet Age-Related Macular Degeneration Resistant to Standard Therapy. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):1655.
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Aflibercept has been shown to be effective in treating newly diagnosed wet age-related macular degeneration (AMD) and may be helpful in those resistant to previous anti-VEGF therapy. However, we have found eyes with persistent fluid despite continuous standard-dose aflibercept. We performed a retrospective, observational study to determine outcomes in these eyes after using high-dose aflibercept.
We reviewed 45 eyes of patients with neovascular AMD who developed resistance to standard regimen of aflibercept (2 mg every 8 weeks) and were subsequently switched to every-4-weeks (q4w) therapy (phase I). Patients with persistent incomplete response were further escalated to 4mg of aflibercept (phase II). All patients underwent cSLO fluorescein angiography and spectral-domain OCT (SD-OCT) in addition to complete ocular exam and ETDRS vision testing.
Phase I included 31 non-vitrectomized eyes shifted to q4w aflibercept for resistance to standard regimen. We found a good anatomic response with statistically significant decrease in central retinal thickness (CRT) at 6 months compared to baseline (p<0.0001). The mean change in CRT was 89.6 ±SD 68.2 microns.<br /> Phase II included 13 non-vitrectomized eyes escalated to 4mg aflibercept for persistent incomplete response to 2mg q4w aflibercept. There was a statistically significant difference between baseline and 3-month follow-up (p=0.05), with mean decrease of 65.3 ±SD 80.7 microns.<br /> A third group of 19 eyes received 4mg aflibercept after being vitrectomized. This group also showed significant decrease in CRT from baseline to 6-month follow-up (p<0.0001), with mean change in CRT of -91.4 ±SD 79.2 microns.<br /> ETDRS visual acuity was not significantly different between baseline and follow-up in either group; (p=0.43), (p=0.26) and (p=0.78) respectively. <br /> There were no significant ocular adverse events (ocular inflammation, vitreous hemorrhage, retinal detachment, sustained increase in intraocular pressure) or systemic adverse events (myocardial infarction, stroke, death) observed with the use of intravitreal aflibercept injections in this series.
High-dose aflibercept appears to be safe and effective in terms of anatomic outcomes and in preventing further visual loss in eyes with advanced wet AMD, resistant to standard dose therapy. It might be considered earlier in order to achieve better functional results.
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