May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Targeted Photodynamic Therapy for Treatment of Choroidal Neovascularization in a Laser-Induced Rat Model
Author Affiliations & Notes
  • F. Lu
    Yale Univ School of Medicine, New Haven, Connecticut
    Ophthal & Visual Sci,
  • Z. Hu
    Yale Univ School of Medicine, New Haven, Connecticut
    Molecular Biophysics and Biochemistry,
  • A. Garan
    Yale Univ School of Medicine, New Haven, Connecticut
    Molecular Biophysics and Biochemistry,
  • R. Adelman
    Yale Univ School of Medicine, New Haven, Connecticut
    Ophthal & Visual Sci,
  • Footnotes
    Commercial Relationships  F. Lu, None; Z. Hu, None; A. Garan, None; R. Adelman, None.
  • Footnotes
    Support  Paterson Trust Grant Lions of Connecticut
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 3768. doi:
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      F. Lu, Z. Hu, A. Garan, R. Adelman; Targeted Photodynamic Therapy for Treatment of Choroidal Neovascularization in a Laser-Induced Rat Model. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3768.

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Abstract

Purpose: : To study the efficacy of Targeted Photodynamic Therapy (TPT) using verteporfin conjugated to factor-VII for the treatment of choroidal neovascularization (CNV) in a rat model. Factor-VII binds specifically to tissue factor, which is expressed on endothelial cells of the CNV but not of normal vessels.

Methods: : Multiple CNV lesions were induced by laser photocoagulation of the retina in Norway-Brown rats. After 4 weeks, 17 rats received verteporfin conjugated to factor-VII injected intravenously (i.v.). Randomly selected lesions were treated with 689nm laser (50 J/cm2) for 30 or 60 minutes after i.v. injection, while the other lesions in the same eyes were not treated as an internal control. Another 2 control rats were treated with non-targeted verteporfin (6.0 mg/m2). All the lesions were evaluated by fluorescein angiography on 1, 7 and 14 days after laser treatment to compare the efficacy of targeted and non-targeted photodynamic therapy (PDT). Histopathology was performed on day 14 on some of the rat eyes after PDT.

Results: : In the CNV lesions treated by non-targeted PDT, leakage stopped in 25% of the lesions on day 7, but started to leak again on day 14. In the CNV lesions treated by targeted PDT (0.5mg/m2, 30min ), 67% (24/36) of the lesions did not leak on day 7, and 64% (23/36) on day 14. In rats treated by targeted PDT at a higher dose (1.0mg/m2, 30min), 75% (40/53) and 77% (41/53) of the lesions did not leak on day 7 and day 14, respectively (p<0.05). Histopathological examination showed no toxicity of targeted PDT on the ocular tissues.

Conclusions: : Verteporfin was conjugated to factor-VII and injected i.v. for targeting to Tissue Factor on the CNV in a rat model of laser-induced CNV. Using targeted verteporfin for PDT showed higher efficacy and safety than non-targeted verteporfin in stopping CNV leakage. Optimal efficacy for targeted verteporfin was achieved with 1/6 of the dose required for standard PDT.

Keywords: age-related macular degeneration • choroid: neovascularization • photodynamic therapy 
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