Retinal Toxicity of Intravitreal Abatacept in Rabbit Eyes

Abstract

Purpose: : Abatacept is the first selective T-cell co-stimulation modulator approved for clinical use systemically in patients with refractory rheumatoid arthritis. Local inhibition of T-cell co-stimulation has previously been shown to inhibit experimental uveitis. The objective of our study was to assess the retinal toxicity of intravitreous abatacept in rabbit eyes.

Methods: : Six Dutch-belted rabbits received intravitreal injections of 5mg abatacept (.1cc) unilaterally. Fellow eyes were injected with balanced salt solution (0.1cc) and served as controls. Simultaneous, dark-adapted flash electroretinograms (ERG) were recorded 2 weeks following injection. Light microscopy was performed on both eyes of three animals, two weeks after injection.

Results: : Mean dark-adapted saturated a-wave amplitude was 159µV +/- 21 (SEM) in abatecept-injected and 143µV +/- 10 in control eyes (p=0.39, paired Student’s t-test). Mean light-adapted saturated a-wave amplitude was 130µV +/- 13 in the experimental and 119µV +/- 8 in the control eyes (p=.39, paired Student’s t-test). Mean saturated maximal b-wave amplitude measured 308µV +/- 26 in abatacept-injected eyes and 274µV +/- 21 in control eyes (p=0.26, paired Student’s t-test). Light microscopy disclosed unremarkable retinal layers, retinal pigment epithelium and choriocapillaris in treatment and control eyes.

Conclusions: : The present study showed no demonstrable electroretinographic or histologic evidence of toxicity 2 weeks following injection of 5mg of abatacept into rabbit eyes.

Keywords: drug toxicity/drug effects • electroretinography: non-clinical • uveitis-clinical/animal model