The effects of intravitreal triamcinolone acetonide (TA) on collateral damage induced by verteporfin PDT in normal rabbits and cynomolgus monkeys

Abstract

Abstract: : Purpose: To determine the effect of intravitreal TA on structural and functional changes induce by verteporfin PDT in the normal fundi of rabbits and monkeys. Methods: Dutch–belted rabbits (2–3 kg) were injected with 100 ul of 40 mg/kg TA via intravitreal route at 1 hour or 8 days before PDT. The PDT procedure consisted of an infusion of 10 mls of verteporfin 0.2 mg/kg (3 mg/m²) @ 1 ml/min for 10 mins. Two PDT spots of 1.5 mm were made at 20 and 25 mins post–dye with a 689 nm laser at 600 mW/cm², 50 J/cm², 83 secs. Follow–ups were made at Days 1, 2 and 3 with color funduscopy, FAs and OCT. Cynomolgus monkeys (2–4 kg) received a 50 ul intravitreal injection of 40 mg/kg TA 3 days prior to PDT or 1 hour after PDT. The same verteporfin infusion protocol described above was used with a 0.5 mg/kg (6 mg/m²) dye dose, a 15 min dye:laser time, and a single 4 mm spot in the central macula. Follow–up procedures for monkeys included mfERG, OCT, FA, ICGA and color funduscopy @ baseline, Days 1, 3, 7, 14 and 28. Results: Verteporfin PDT caused transient accumulation of intra– and sub–retinal fluid in both species. In rabbits, 1 hour TA pre–treatment exacerbated the retinal edema, however, the 8–day pre–treatment protocol resulted in less retinal edema than control eyes, eg. @ Day 1 in the 20 min lesion, retinal thickness increases in the TA group = 124 ± 7% (n=2); control = 143 ± 13% (n=2). In monkeys, TA reduced PDT–induced retinal thickness increases in both treatment protocols at the Day 3 follow–up. Three–day pretreatment protocol: TA = –23 ± 13 % (n=2); control = 174 ± 109 % (n=2); 1–hour post–treatment protocol: TA = –11 ± 5 % (n=2); control = 76 ± 17 % (n=2). TA did not affect choroidal hypo–perfusion or retinal neurosensory dysfunction caused by PDT in the treatment zone. Conclusions:TA reduced intra–and sub–retinal accumulation of fluid produced by verteporfin PDT in rabbits and monkeys which is consistent with its well–known anti–permeability effect.

Keywords: photodynamic therapy • age–related macular degeneration