Volume 71, Issue 3 , Pages 135-142, March 2008
Comparison of Multiple Reduced-dose and Standard Light Application in Photodynamic Therapy in an Animal Model of Choroidal Neovascularization
Article Outline
Background
Current photodynamic therapy (PDT) for choroidal neovascularization (CNV) uses a standard radiant exposure of 50 J/cm2 at an irradiance of 600 mW/cm2. However, low-intensity PDT with verteporfin for neovascular tissue has been shown to be more effective than regular high-intensity PDT in an animal model of healthy choroids and corneal neovascularization. Low-intensity PDT also supposedly induces less retinal damage. In this study, we compared the effect of reduced-dose and standard light application PDT in an animal model of CNV.
Methods
A laser injury model was used to induce CNV 3 weeks prior to PDT in brown Norway rats. The CNV lesions were then treated with verteporfin PDT with a dose of verteporfin 6.0 mg/m2 and 5 activating doses of light energy (43, 53, 63, 73 and 83 seconds). Closure of CNV was assessed by fundus fluorescein angiography (FAG). Histopathologic study was done after the last FAG.
Results
PDT with verteporfin significantly reduced the CNV area compared with control non-treated groups 1 week after PDT (p < 0.05). Only those lesions treated for 63 seconds or longer retained their significantly attenuating effect on CNV up to 3 weeks after PDT. There was no significant difference between the inhibition effects induced by reduced-intensity light application for 63 or 73 seconds compared to the standard radiant exposure (83 seconds). Histopathologic study showed that eyes treated with PDT showed significantly less extent and vascularity of CNV lesion than control lesions.
Conclusion
Reduced-intensity PDT with 63-second duration seemed to be as effective as standard dose for CNV suppression. Considering the possible retinal damage following standard PDT, the PDT dose might be adjusted to reduce side effects. Further preclinical study will provide more data on what constitutes appropriate dosimetry for effective and safe PDT in CNV.
Key Words: age-related macular degeneration , choroidal neovascularization , dose , photodynamic therapy
No full text is available. To read the body of this article, please view the PDF online.
References
- Evolving European guidance on the medical management of neovascular age related macular degeneration . Br J Ophthalmol . 2006;90:1188–1196
- . Photodynamic therapy for subfoveal choroidal neovascularization secondary to age-related macular degeneration . J Chin Med Assoc . 2005;68:419–424
- . Intravitreal bevacizumab (Avastin) for neovas-cular age-related macular degeneration . Ophthalmology . 2006;113:363–372
- Maximum tolerated dose of a humanized anti-vascular endothelial growth factor antibody fragment for treating neovascular age-related macular degeneration . Ophthalmology . 2005;112:1048–1053
- . Short-term safety and efficacy of intravitreal bevacizumab (Avastin) for neovascular age-related macular degeneration . Retina . 2006;26:495–511
- Suppression of retinal neovascularization in vivo by inhibition of vascular endothelial growth factor (VEGF) using soluble VEGF-receptor chimeric proteins . Proc Natl Acad Sci USA . 1995;93:10457–10461
- Inhibition of vascular endo-thelial growth factor prevents retinal ischemia-associated iris neovascularization . Arch Ophthalmol . 1996;114:66–71
- . Vascular endothelial growth factor acts as a survival factor for newly formed retinal vessels and has implications for retinopathy of prematurity . Nat Med . 1995;1:1024–1028
- . Clinicopath-ological correlation of primary and recurrent choroidal neovas-cularisation following surgical excision in age-related macular degeneration . Br J Ophthalmol . 1998;82:480–487
- . Pegaptanib for neovascular age-related macular degeneration . N Engl J Med . 2004;351:2805–2816
- . Verteporfin photodynamic therapy in the rat model of choroidal neovascularization: angiogenic and histologic characterization . Invest Ophthalmol Vis Sci . 2002;43:2384–2391
- . Severe pigment epithelial alterations in the treatment area following photodynamic therapy for classic choroidal neovascularization in young females . Am J Ophthalmol . 2004;138:803–808
- . Retinal pigment epithelium changes after photodynamic therapy for choroidal neovascular-ization in pathological myopia . Acta Ophthalmol Scand . 2007;85:50–54
- Verteporfin therapy of subfoveal minimally classic choroidal neovascularization in age-related macular degeneration: 2-year results of a randomized clinical trial . Arch Ophthalmol . 2005;123:448–457
- . Comparison of reduced and standard light application in photodynamic therapy of the eye in two rabbit models . Graefes Arch Clin Exp Ophthalmol . 2004;244:773–781
- . Calculation of a new Meeh constant and experimental determination of burn size . Burns . 1996;22:607–611
- . The mechanism of Photofrin photobleaching and its consequences for photody-namic dosimetry . Photochem Photobiol . 1997;65:135–144
- . Tumor destruction and kinetics of tumor cell death in two experimental mouse tumors following photo-dynamic therapy . Cancer Res . 1985;45:572–576
- . The effect of fluence rate on tumor and normal tissue responses to photodynamic therapy . Photochem Photobiol . 1998;67:462–466
- . Relationships of tumor hypoxia and response to photodynamic treatment in an experimental mouse tumor . Cancer Res . 1987;47:3110–3114
- . Photodynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfin—one-year results of 2 randomized clinical trials: TAP report 1 . Arch Ophthalmol . 1999;117:1329–1345
- Expression of VEGF and PEDF in choroidal neovascular membranes following verteporfin pho-todynamic therapy . Am J Ophthalmol . 2006;142:95–104
- . Intravitreal bevacizumab (Avastin) in minimally classic and occult choroidal neovascularization secondary to age-related macular degeneration . Graefes Arch Clin Exp Ophthalmol . 2007;245:68–73
- Suppression of choroidal neovascularization by intramuscular polymer-based gene delivery of vasostatin . Exp Eye Res . 2005;81:673–679
PII: S1726-4901(08)70005-4
doi:10.1016/S1726-4901(08)70005-4
© 2008 Elsevier. Published by Elsevier Inc. All rights reserved.
Volume 71, Issue 3 , Pages 135-142, March 2008
