Time course and morphology of vascular effects associated with photodynamic therapy

Ophthalmology. 2005 Dec;112(12):2061-9. doi: 10.1016/j.ophtha.2005.09.007.

Abstract

Purpose: To evaluate the time course and morphologic features of verteporfin therapy-induced vascular effects using 3-dimensional topographic angiography (TAG) in patients with choroidal neovascularization (CNV).

Design: Prospective observational case series.

Participants: Fifty-three eyes of 53 patients with neovascular age-related macular degeneration and Treatment of Age-Related Macular Degeneration with Photodynamic Therapy/Verteporfin in Photodynamic Therapy characteristics were treated with verteporfin therapy using standard parameters.

Methods: Treatment effects were evaluated before and at 5 hours, 1 day, 1 week, and 3 months after treatment by serial confocal fluorescein angiography (FA) and indocyanine green angiography (ICGA). The axial distribution of fluorescence at each x-position and y-position within a tomographic scan of 32 images over a depth of 4 mm was analyzed, and a 3-dimensional profile was generated. Changes at the level of the CNV lesion and the collateral choroid were documented over time with respect to vascular closure, leakage resulting from vascular barrier breakdown, and alteration of physiologic perfusion.

Main outcome measures: Three-dimensional imaging of exudation and nonperfusion.

Results: At baseline, 3-dimensional FA and ICGA imaging demonstrated a well-defined prominent CNV complex. At 5 hours after verteporfin therapy, 3-dimensional FA identified an extensive increase in hyperfluorescent prominence as well as lesion extension in most verteporfin-treated eyes (65%), resulting from increased permeability and leakage due to a vascular barrier breakdown in the collateral choroid. Massive exudation throughout the entire light-exposed area was still noted in most eyes 1 day after treatment. At 1 week, the exudative response, seen in 3-dimensional imaging, had diminished substantially. Simultaneously, documented best by 3-dimensional ICGA, TAG demonstrated perfusion defects within the adjacent choroid, which started as early as 1 day after verteporfin therapy and persisted during extended follow-up. Three-dimensional angiography identified the morphologic features of hyperfluorescence and hypofluorescence more realistically than conventional angiography.

Conclusions: Three-dimensional angiography demonstrates a characteristic sequence of changes in the vascular architecture of the CNV lesion and the collateral choroid after verteporfin therapy. Choroidal neovascularization occlusion is associated with immediate massive exudation and is followed by occlusive effects within the collateral choroid. Knowledge of the time course and mechanisms of phototoxic events should help to develop appropriate combination treatment strategies.

MeSH terms

  • Capillary Permeability
  • Choroid / blood supply*
  • Choroid / pathology*
  • Choroidal Neovascularization / drug therapy
  • Choroidal Neovascularization / etiology
  • Choroidal Neovascularization / pathology*
  • Coloring Agents
  • Fluorescein Angiography
  • Humans
  • Imaging, Three-Dimensional
  • Indocyanine Green
  • Macular Degeneration / complications
  • Macular Degeneration / drug therapy
  • Macular Degeneration / pathology*
  • Photochemotherapy*
  • Photosensitizing Agents / therapeutic use
  • Porphyrins / therapeutic use
  • Prospective Studies
  • Time Factors
  • Verteporfin
  • Visual Acuity

Substances

  • Coloring Agents
  • Photosensitizing Agents
  • Porphyrins
  • Verteporfin
  • Indocyanine Green