Long-term outcomes of switching to aflibercept for treatment-resistant neovascular age-related macular degeneration

Acta Ophthalmol. 2019 Aug;97(5):e706-e712. doi: 10.1111/aos.14046. Epub 2019 Feb 11.

Abstract

Purpose: To report 4-year outcomes following the switch to aflibercept in treatment-resistant neovascular age-related macular degeneration (nAMD).

Methods: In this prospective, open-label, non-controlled, clinical trial, 49 patients with treatment-resistant nAMD received 2 mg intravitreal aflibercept as three loading doses every 4 weeks, followed by injections every 8 weeks for the first 48 weeks, then an individualized regimen for a further 36 months, following previous treatment with ranibizumab and/or bevacizumab. Outcome measures included best-corrected visual acuity (BCVA), central retinal thickness (CRT), pigment epithelial detachment (PED) height and geographic atrophy (GA) surface area.

Results: Of the 49 patients who were initially recruited, data from 39 eyes of 39 patients were available at 48-month follow-up. Mean age was 76.7 ± 7.2 years. Over the 48 months, these eyes received a mean of 32.1 ± 5.6 injections. The mean BCVA improved significantly following 12 months of treatment (4.9 ± 9.0 ETDRS letters, p < 0.001); however, this was not maintained and was similar to baseline after 48 months (mean difference -0.4 ± 13.3 letters between baseline and 48 months, p < 0.001). The reduction in CRT from baseline was 170.3 ± 143.3 μm (p < 0.001) with absence of macular fluid in 56% of the 39 eyes at the end of month 48. PED height reduced by a mean 77.5 ± 20.0 μm, and geographic atrophy increased by a mean of 4.1 ± 3.4 mm2 (p < 0.01) over the 48 months.

Conclusion: Aflibercept is an effective alternative therapy for treatment-resistant nAMD. Good anatomical and stable functional responses are achievable with continued therapy. The lack of continued visual improvement may be representative of GA progression, reflecting the progression of late-stage nAMD in these patients.

Keywords: age-related macular degeneration; anti-VEGF; long-term; treatment resistance.

Publication types

  • Clinical Trial

MeSH terms

  • Aged
  • Angiogenesis Inhibitors / administration & dosage
  • Bevacizumab / administration & dosage
  • Drug Resistance*
  • Drug Substitution
  • Female
  • Fluorescein Angiography / methods*
  • Follow-Up Studies
  • Fundus Oculi
  • Humans
  • Intravitreal Injections
  • Macula Lutea / pathology*
  • Male
  • Prospective Studies
  • Ranibizumab / administration & dosage
  • Receptors, Vascular Endothelial Growth Factor / administration & dosage*
  • Receptors, Vascular Endothelial Growth Factor / antagonists & inhibitors
  • Recombinant Fusion Proteins / administration & dosage*
  • Time Factors
  • Tomography, Optical Coherence / methods*
  • Treatment Outcome
  • Wet Macular Degeneration / diagnosis
  • Wet Macular Degeneration / drug therapy*
  • Wet Macular Degeneration / physiopathology

Substances

  • Angiogenesis Inhibitors
  • Recombinant Fusion Proteins
  • aflibercept
  • Bevacizumab
  • Receptors, Vascular Endothelial Growth Factor
  • Ranibizumab

Grants and funding