Immunosuppression by a subconjunctival implant releasing dexamethasone in a rabbit model of penetrating keratoplasty.

Abstract

To evaluate the efficacy of a subconjunctival dexamethasone-releasing implant in preventing rejection of penetrating keratoplasty (PK) in an animal model. Twenty-two rabbits underwent allogenic PK. After randomisation, they received either a 700 µg dexamethasone implant under the conjunctiva at the end of surgery (n=10), one dexamethasone 1 mg/mL eye-drop thrice daily (n=6) or a placebo thrice daily (n=6). The suture was left in place. Animals were observed weekly by slit-lamp and optical coherence tomography with quantification of transparency, neovascularisation and central corneal thickness (CCT). At 5-6 weeks, they were euthanised for histology. The residual dexamethasone concentration in ocular tissues was measured with an ultra-performance liquid chromatography-tandem mass spectrometer. Placebo group: early neovascularisation was systematic, penetrating the graft by 270-360° at 5-6 weeks. Rejection occurred in 50% of cases. Eye-drop and implant groups: similar course without rejection at 6 weeks and normal CCT. Neovascularisation was observed in 5/6 rabbits in the eye-drop group and in 6/8 in the implant group, with two cases of new vessels penetrating the graft from week 3. Neovascularisation scores did not differ significantly between the two treatments and were significantly lower than for the placebo. Histology was in agreement in all cases. Implants disappeared after 3-5 weeks. No local side effect was observed. Tissue concentrations were all higher at day 8 (n=2) in the implant group than in the eye drop group and lower at 6 weeks (n=8). In this PK model characterised by a high rejection rate, a subconjunctival dexamethasone implant was for 6 weeks as effective as the topical form in preventing allograft rejection.