Effects of Triamcinolone Dose and Timing on Photodynamic Therapy with Verteporfin in the Rabbit Chorioretina

Abstract

Abstract: : Purpose: Photodynamic therapy (PDT) with verteporfin (Visudyne®; Novartis AG) induces a transient inflammation in patients with choroidal neovascularization. This inflammation may trigger further angiogenesis and may play a role in the reappearance of vascular leakage a few months after treatment. Therefore, adjunctive anti-inflammatory therapies may potentially reduce the iatrogenic effects of PDT and prolong therapeutic benefit. In this study, intravitreal administration of triamcinolone acetonide (TA) was assessed for its potential to inhibit inflammation induced by PDT with verteporfin in a rabbit chorioretinal model. In particular, the effects of the timing of the intravitreal administration of TA relative to PDT and the dose of TA on PDT-induced inflammatory and vascular responses were evaluated. Methods: An acute inflammatory response was induced by PDT with 0.2 mg/kg verteporfin and 15 or 25 J/cm2 light applied 15 min after verteporfin injection at a fluence rate of 600 mW/cm2 on a 5 mm spot in normal rabbit fundi. TA (1 or 4 mg) or saline was administered intravitreally two days prior or immediately after PDT. The rabbits were monitored for 2 days after PDT. The inflammatory and vascular responses to PDT in the chorioretina were evaluated by indirect ophthalmoscopy, fundus photography, fluorescein angiography, and by immunostaining chorioretinal tissues for leukocytes (CD45) and tissue activation (MHC class II). Results: Compared to the saline group, eyes treated with TA after PDT using 15 J/cm2, but not 25 J/cm2, exhibited less retinal edema. TA significantly suppressed CD45 and MHC II expression evoked by both PDT regimens by up to 70% when compared to the saline group, without appreciably impacting on choriocapillaris closure. There was no statistically significant difference between both dosing times, although stronger anti-inflammatory effects were achieved when TA was administered shortly after PDT. Both of the TA doses caused similar anti-inflammatory responses. Conclusions: This study supports the use of intravitreal TA as a post-therapy adjunct to PDT with verteporfin. Lack of TA dose response in the rabbit model supports the evaluation of a low TA dose, which may reduce the incidence of cataracts and increased intraocular pressure associated with the intravitreal administration of 4 mg TA in human.

Keywords: photodynamic therapy • inflammation • corticosteroids