Abstract
Purpose: :
To evaluate the potential of a new hydrosoluble photosensitizer (WST11) to induce a selective and stable occlusion of choroidal CNV in the rat eye.
Methods: :
Choroidal CNV was induced in Lewis rats by Bruch membrane disruption using Argon laser photocoagulation (350mW, 0.1 sec, 50µm) combined with injections of Freund's adjuvant to the foot pads of treated rats. Fourteen days after photocoagulation, fluorescein angiograms and flat–mounted choroids ascertained the presence of CNV around the laser impact. Different doses of WST11 (2.5mg/Kg, 5mg/Kg, 7.5mg/Kg) were tested. Illumination was performed with a 753 nm laser using intensities of 50J/cm2 or 100J/cm2. Distance to light illumination (DLI) of 1 and 5 min. were also evaluated. Fluorescein angiographies were performed immediately after treatment (acute), 2 and 8 days after WST11 PDT using the above different parameters. To assess the effects of WST11 PDT, flat–mounted retinas and choroids and semi–thin histology sections of the lesion site were performed at each treatment time point.
Results: :
Using WST11 2.5mg/Kg, DLI 1min and a laser intensity of 50 or 100J/cm2, no vessel occlusion was observed at any of the time points tested. On semi–thin sections, the RPE cells and photoreceptors of treated areas around the lesion did not show any structural damage. Treatment with WST11 5mg/Kg, DLI 1min and 100J/cm2 induced occlusion of the CNV in 100% of the cases on day 2. The vessel occlusion remained stable on day 8 in 16/18 treated eyes. In two eyes, the occlusion observed on day 2 was transient with reopening of the vascular channels by day 8. Histology of these eyes showed that no structural damage of RPE cells and photoreceptors occurred within the illuminated area. Using the same WST11 dose (5mg/kg) and laser intensity (100J/cm2) but increasing the DLI to 5 min resulted in transient vascular occlusion on day 2 with reopening of the occlusion by day 8. Flat–mounted retinas and choroids prepared from eyes receiving the occlusive parameters 5mg/kg WST11, DLI 1 min. and 100J/cm2 confirmed that a selective occlusion of the CNV took place with no occlusion of the overlying retinal vessels.
Conclusions: :
Using well defined parameters, WST11 induces an efficient, selective and stable occlusion of CNV around the photocoagulated lesion in this model. The lack of collateral damage to the RPE and retina using WST11 indicates the potential for PDT selective therapeutic effects of this drug.
Keywords: photodynamic therapy • neovascularization • age-related macular degeneration