title: High-frequency aflibercept injections in persistent neovascular age-related macular degeneration.
abstract: OBJECTIVE
  To report the 1-year outcomes of every-4-weeks (Q4W) as-needed aflibercept treatment in resistant neovascular age-related macular degeneration (nAMD) patients who had been treated and failed prior bevacizumab or ranibizumab injections, and who also responded poorly to every-8-weeks (Q8W) aflibercept treatment.
  
  
  METHODS
  Forty-three eyes of 39 patients with persistent nAMD despite monthly bevacizumab and/or ranibizumab injections and who were switched to Q8W 2-mg aflibercept injections, but showed persistence of fluid were included. Patients were treated with as-needed Q4W aflibercept injections with monthly monitoring. Maximum retinal thickness (MRT), central macular thickness (CMT), maximum pigment epithelial detachment height (PED) and best-corrected visual acuity (BCVA) were assessed and compared to baseline when high-frequency aflibercept was initiated.
  
  
  RESULTS
  A mean of 8 (interquartile range, 4-11) Q4W injections were given during the follow-up. MRT and CMT significantly decreased at all follow-up visits (p < 0.05); however, there was no significant change in maximum PED height (p > 0.05) at any visit. Mean BCVA was 0.38 ± 0.28 (logMAR) (≈20/63, Snellen) at baseline, and 0.4 ± 0.34 (logMAR) (≈20/76, Snellen) at 1 year (p = 0.76). Seventy-two percent of eyes maintained a final BCVA of 20/63 or better. Twelve eyes (28 %) had some subretinal scar tissue formation and 5 eyes (11.6 %) had evidence of atrophy at 1 year.
  
  
  CONCLUSIONS
  A stepwise algorithm with Q4W as-needed aflibercept treatment led to anatomic improvement in previously treated eyes which failed other therapies, including aflibercept every 8 weeks. Lack of visual improvement may be due to a ceiling effect as our eyes generally had good visual acuity.
authors.affiliation: Department of Ophthalmology, Jacobs Retina Center at the Shiley Eye Institute, University of California San Diego, La Jolla, CA, USA.|Department of Ophthalmology, Istanbul Training and Research Hospital, Istanbul, Turkey.
authors.forename: Ilkay Kilic
authors.initials: IK
authors.lastname: Muftuoglu
authors.affiliation: Department of Ophthalmology, Jacobs Retina Center at the Shiley Eye Institute, University of California San Diego, La Jolla, CA, USA.|Sharp Rees-Stealy Medical Group Division of Ophthalmology, San Diego, CA, USA.
authors.forename: Frank F
authors.initials: FF
authors.lastname: Tsai
authors.affiliation: Department of Ophthalmology, Jacobs Retina Center at the Shiley Eye Institute, University of California San Diego, La Jolla, CA, USA.
authors.forename: Raouf
authors.initials: R
authors.lastname: Gaber
authors.affiliation: Department of Ophthalmology, Jacobs Retina Center at the Shiley Eye Institute, University of California San Diego, La Jolla, CA, USA.
authors.forename: Mostafa
authors.initials: M
authors.lastname: Alam
authors.affiliation: Department of Ophthalmology, Jacobs Retina Center at the Shiley Eye Institute, University of California San Diego, La Jolla, CA, USA.
authors.forename: Amit
authors.initials: A
authors.lastname: Meshi
authors.affiliation: Department of Ophthalmology, Jacobs Retina Center at the Shiley Eye Institute, University of California San Diego, La Jolla, CA, USA. freeman@eyecenter.ucsd.edu.|Jacobs Retina Center at the Shiley Eye Institute, University of California San Diego, 94093 Campus Point Drive, La Jolla, CA, 92037, USA. freeman@eyecenter.ucsd.edu.
authors.forename: William R
authors.initials: WR
authors.lastname: Freeman
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D058449:Intravitreal Injections; D008266:Macula Lutea / Q000473:pathology*; D008297:Male; D040262:Receptors, Vascular Endothelial Growth Factor / Q000008:administration & dosage*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage*; D055213:Retinal Pigment Epithelium / Q000473:pathology*; D012189:Retrospective Studies; D013997:Time Factors; D041623:Tomography, Optical Coherence; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D014792:Visual Acuity; D057135:Wet Macular Degeneration / Q000175:diagnosis / Q000188:drug therapy*
chemical_list: D011993:Recombinant Fusion Proteins; D042461:Vascular Endothelial Growth Factor A; C533178:aflibercept; D040262:Receptors, Vascular Endothelial Growth Factor
keywords: Aflibercept; As-needed treatment; Monthly aflibercept; Persistent AMD; Resistant wet AMD; Wet AMD