First Author: A.Needham UK
Co Author(s): C. Southern J. Lane T. Singh 0 0 0 0 0 0 0 0 0
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Anti-VEGF therapies that directly target the molecular pathology of wet AMD have revolutionised its treatment. Trial data show clinically significant improvements in vision and anatomy with both ranibizumab and aflibercept; however, adherence to the fixed regimens used in trials can be impractical and, clinically, PRN dosing is usually employed; thus the effectiveness of these agents in our particular unit was worthy of investigation. Our audit sought to: •Determine whether aflibercept PRN was effective in treatment naïve and recalcitrant patients •Compare injection frequency between PRN and the standard fixed regimen •Compare visual and anatomic outcomes with aflibercept and ranibizumab PRN.
An independent NHS macula clinic in the North West of England, where patients were free to choose any intraocular anti VEGF drug that was available. All patients provided consent to be included in this audit.
We retrospectively analysed data from a population of patients with neovascular AMD who had been treated with intravitreal aflibercept on a PRN schedule between 13-December-2012 and 25-February-2014 and had 6–12 months of follow up (with visits every 4–6 weeks). The PRN schedule had employed the following retreatment criteria: new macula haemorrhage; reduction of 4m logMAR VA by 5 or more letters, or; the presence of persistent macula oedema or acute redevelopment of macula oedema on any Heidelberg OCT scan (quantified by automated Heidelberg software computer assisted image analysis using macula volume and foveal thickness). Our analysis included two distinct groups of patients: (1)anti VEGF treatment naïve patients and, (2)treatment recalcitrant patients, i.e. those who had been switched from ranibizumab (and/or bevacizumab) to aflibercept owing to an inadequate response to treatment (insufficient reduction of macular oedema, rapid recurrence of disease activity and/or high injection frequency). We analysed visual acuity, macular volume and foveal thickness before and after the initiation of aflibercept treatment; only treatment naïve patients with at least 3 months of data post-treatment, and treatment recalcitrant patients with at least 12-months of data pretreatment and 3 months post treatment were included. Patients who switched back to ranibizumab/bevacizumab were excluded.
In total, 205 patients were included in our analysis: •42 treatment naïve patients •163 treatment recalcitrant patients. Patients ranged from 59–97 years of age (mean 81 years) and 38% were male. In treatment-recalcitrant patients, VA stabilised at approx. 55 letters following switch to aflibercept, after having decreased by a mean of 5 letters from 59 in the 12 months previously. Furthermore, reductions in mean macular volume and foveal thickness were greater following switch than before: macular volume 3.38 µM3 12 months before aflibercept, 3.32 µM on aflibercept initiation, and 3.07, 3.30, 3.08 and 3.94 µM3 at 3, 6, 9 and 12 month follow-up; foveal thickness 333.60 µM 12 months before aflibercept, 315.95 µM on aflibercept initiation, and 293.55, 322.82, 281.08 and 400.80 µM at 3, 6, 9 and 12 month follow-up. On average, patients received injections less frequently with aflibercept than with prior anti-VEGF agents. In treatment-naïve patients, mean VA improved by 2 letters to 65 within 3–6 months of aflibercept initiation and continued to improve over the following 6 months of treatment. Mean macular volume reduced over the 12 month follow up (from 3.25 to 3.00 µM3) while mean foveal thickness was variable. Patients received aflibercept injections infrequently.
This retrospective clinical audit showed that, in our clinic, aflibercept administered on a PRN dosing schedule for neovascular AMD could arrest the visual decline that was occurring with prior anti-VEGF therapies, and promote improvements in macular and foveal anatomy. Moreover, in treatment naïve patients, PRN dosing of aflibercept was able to improve VA and reduce macular volume within 6 months of initiation. In both treatment recalcitrant and treatment naïve patients, aflibercept injections were required less frequently than once every 2 months on average. Longer-term follow up will confirm whether a PRN dosing schedule of aflibercept continues to provide improvements in vision and anatomy after the first year. Data for 18 months of follow up will be available at end July 2014.