Pharmocological Effects of Intravitreal Fluocinolone Acetonide in RCS Rats With Chronic Subretinal Prothesis Implants

Abstract

Abstract: : Purpose: To examine the pharmacological effects of chronic intravitreal Fluocinolone Acetonide (FA) in RCS rats with subretinal polyimide implants (SI). Methods:Intravitreal drug delivery devices (IDDI) were inserted into RCS rats that received SI’s. Among 20 RCS rats aged 5.5 weeks, 5 received SI alone, 5 received SI and inactive IDDI and 10 received SI and FA–loaded IDDI. Active IDDI’s contained 75µg of FA, released at 3µg/day. Two weeks postoperatively, cell–count analysis of outer (ONL) and inner nuclear (INL) was performed using 40x H&E–stained photomicrographs for each of six regions, anterior, posterior, superior, inferior and overlying the temporally–placed subretinal impant and nasal to the disc. OCT and fundus photographs were obtained at weeks one and two. Results: OCT and fundus photographs showed no retinal detachments. Diffuse posterior subcapsular cataracts and corneal epitheliopathy developed in all animals that received an IDDI. This was more severe in the active IDDI group. Average ONL thickness among all regions for active IDDI+SI was 5.8 cells (sd: 0.97), inactive IDDI+SI 2.9 (sd:0.94) and SI only 2.9 (sd:1.2). Mean ONL thickness was statistically greater for the active IDDI+SI group as compared to inactive IDDI+SI (p=0.001) and SI only groups (p=0.01). Mean INL thickness among all regions for active IDDI+SI was 5.1 cells (sd: 0.47), inactive IDDI+SI 5.3 (sd:1.1) and SI only 5.0 (sd:0.39). No significant differences in INL thickness were measured for these three groups. Mean ONL thickness for unoperated fellow eyes was 2.2 (sd:0.55). This was not statistically different from the ONL thickness of the SI alone group. Conclusions: SI–implanted RCS rats that received intravitreal FA, demonstrated greater numbers of cells in the ONL as compared to animals that received inactive IDDI’s or SI’s alone. SI’s alone did not increase ONL or INL cell counts relative to unoperated fellow eye controls.

Keywords: retina • drug toxicity/drug effects • neuroprotection