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B.A. Jackson, K. Zhang, T. Lin, J. Burke, L. Wheeler; Verteporfin PDT in the Paramacular Region of Normal Monkeys. A Comparison of Bolus and Infusion Administration . Invest. Ophthalmol. Vis. Sci. 2003;44(13):3949.
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Purpose: To compare the retinal angiographic, structural and functional effects from Verteporfin PDT delivered as a bolus or a slow infusion at different dye-to-laser time intervals (DLI) in normal primates. Methods: Cynomolgus monkeys (2-3 kg) were anesthetized with ketamine (10 mg/kg) and a paralytic (30 ug/kg vercuronium bromide) and administered a clinical dose of verteporfin (6 mg/m2) as a bolus (n=2) or infused at 1 ml/min for 10 mins (n=2). Six 1.2 mm spots (689 nm, 50 J/cm2, 600 mW/cm2, 83 secs) were concentrically placed in the paramacular region equi-distant from the fovea sequentially at 1, 5, 10, 15, 20 and 30 min after the end of verteporfin adminstration. Fluorescein angiography (Zeiss 450 ff fundus camera), indocyanine green angiography (Heidelberg Retinal Angiograph) and optical coherence tomography (OCT, Zeiss Stratus III) for retinal vasculature, choroid and structural assessments, respectively, were obtained pre and post PDT at Days 1 and 3. An assessment of retinal function with Multifocal electroretinography (mfERG) was made at Day 34 to Day 55 post PDT with the VERIS Science recording system (v. 4.9, with fundus camera stimulator). The peak luminance of the stimulus was set at 400 cd/m2 and the mm' sequence was used for recording (duration - 2 min) in both PDT and normal eyes (aged-matched controls). Results: Verteporfin did not affect the retinal vasculature except at 1 min DLI with the bolus dose. This dose also produced structural changes; retinal thickness increased ~ 140 % at days 1 and 3. There was choroidal occlusion with the bolus dose at 1, 5, 10 and 15 mins DLI, and at 1, 5, and 10 mins DLI with the infusion dose. The mfERG scalar product values (1st order kernel) were reduced by 65% and 55% of mean normal responses at corresponding areas after bolus dosing at 1 and 5 min DLI, respectively. Overall reduction of the ERG scalar product was shown in both methods of administration (~17% infusion and 35.8% bolus). The scalar product values in the foveal region were decreased (22% infusion and 46% bolus). Conclusions: Bolus application of verteporfin causes more retinal damage than infusion. Paramacular PDT appears to decrease foveal function up to 46%.
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