Abstract
Purpose: :
To investigate the effect of intraocular injections of new dyes for intraocular surgery on the retina, the retinal pigment epithelium (RPE) and the choroid in an in vivo rat model.
Methods: :
Adult male Brown Norway rats were injected intravitreally with four dyes: LGSF; E68; BPB; CB dissolved in BSS at a concentration of 0.5% and 0.02% with BSS serving as control. Additional animals were treated with a single injection of 0.5%, 0.02, 0.002, and 0.0002% ICG or E68 0.002% into one eye. Adverse effects on the anterior and posterior segment were evaluated by slit lamp and ophthalmoscopy. Retinal toxicity was assessed by histology and retinal ganglion cell (RGC) quantification seven days after intravitreal administration of the respective dyes.
Results: :
Animals injected with either E68 0,5%, ICG 0,5%, and CB 0,5% showed a discrete staining of both cornea and lens. After injections of lower concentrations of the before mentioned or the other dyes, no staining of the anterior segment was observed. Histologic sections of the posterior segment following treatment with E68 revealed a consistent dose–dependent reaction. Injections with 0.02% ICG lead to focal degenerative changes of the outer retina in three out of seven eyes. Lower concentrations of ICG (0.002% and 0.0002%) showed no morphological changes. Treatment with CB showed heterogeneous morphological alterations. Eyes treated with BPB (0.5% and 0.02%), LGSF (0.5% and 0.02%), or BSS revealed normal morphology of the whole retina. Injections with E68 0.5% and ICG at all tested concentrations induced a significant loss of RGC if compared controls, most dramatically after E68 0.5% which diminished the number of RGC to 1263 ± 195 cells/mm2 (mean ± SEM, p<0.0001). Injections with lower concentrations of E68 or other dyes did not lead to statistically significant retinal ganglion cell loss.
Conclusions: :
Two of the tested 4 new dyes do not produce a significantly detectable toxic effect on the retina in an in–vivo rat model. However, the other two dyes and the commonly used ICG show changes in either histology and RGC numbers 7 days after intraocular injections. Further studies seem to be mandatory to ensure the safety characteristics of the new dyes in other models and/or pre–clinical studies before the clinical use of any of the dyes.
Keywords: drug toxicity/drug effects • retina • vitreoretinal surgery