Combination therapy for neovascular age-related macular degeneration refractory to anti-vascular endothelial growth factor agents

Ophthalmology. 2013 Oct;120(10):2029-34. doi: 10.1016/j.ophtha.2013.03.016. Epub 2013 May 25.


Objective: To examine the outcomes of combination anti-vascular endothelial growth factor (VEGF) and photodynamic therapy (PDT) for the treatment of neovascular age-related macular degeneration (AMD) refractory to anti-VEGF monotherapy.

Design: Retrospective, interventional case series.

Participants: Twenty-six eyes of 26 patients treated with anti-VEGF monotherapy for neovascular AMD with persistent subretinal or intraretinal fluid after at least 3 anti-VEGF injections in the 7 months before combination treatment.

Intervention: Combination anti-VEGF treatment and PDT.

Main outcome measures: Visual acuity at 1 or 2, 3, and 6 months and central retinal thickness at 1 or 2, 3, and 6 months. Secondary outcome measures were change in number of fluid-free visits and interval between treatments in the 7 months before and 6 months after combination therapy.

Results: Statistically significant improvements in logarithm of the minimum angle of resolution visual acuities were present at 1 month (P = 0.01) and 3 months (P = 0.01). Significant decreases in central subfield retinal thickness on optic coherence tomography (OCT) were seen at 1 month (P = 4×10(-5)), 3 months (P = 3×10(-4)), and 6 months (P = 4×10(-5)) as compared with precombination treatment OCT scans. The percentage of patient visits with no subretinal fluid increased from 0.5% to 41% after the initiation of combination therapy (P = 1×10(-5)). The interval between treatments increased from once every 1.6 months in the 7 months before combination treatment to once every 2.7 months in the 6 months after combination treatment (P = 0.002). No ocular complications attributable to PDT were seen.

Conclusions: Rescue therapy with the combination of anti-VEGF and PDT in eyes that have failed anti-VEGF monotherapy resulted in a mean improvement in vision, a decreased central subfield retinal thickness, and an increase in fluid-free intervals.

Financial disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Angiogenesis Inhibitors / therapeutic use*
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Bevacizumab
  • Choroidal Neovascularization / complications
  • Choroidal Neovascularization / physiopathology
  • Choroidal Neovascularization / therapy*
  • Combined Modality Therapy / methods
  • Female
  • Humans
  • Macular Degeneration / complications
  • Macular Degeneration / physiopathology
  • Macular Degeneration / therapy*
  • Male
  • Middle Aged
  • Photochemotherapy*
  • Photosensitizing Agents / administration & dosage
  • Porphyrins / administration & dosage
  • Ranibizumab
  • Retrospective Studies
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors*
  • Verteporfin
  • Visual Acuity / physiology


  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal, Humanized
  • Photosensitizing Agents
  • Porphyrins
  • Vascular Endothelial Growth Factor A
  • Verteporfin
  • Bevacizumab
  • Ranibizumab