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Immunosuppression by a subconjunctival implant releasing dexamethasone in a rabbit model of penetrating keratoplasty
  1. Emmanuel Crouzet1,
  2. Thibaud Garcin1,
  3. Anne-Sophie Gauthier1,
  4. Zhiguo He1,
  5. Chantal Perrache1,
  6. Xavier Delavenne2,
  7. Thierry Basset2,
  8. Michel Peoc’h1,3,
  9. Philippe Gain1,4,
  10. Gilles Thuret1,4,5
  1. 1Corneal Graft Biology, Engineering and Imaging Laboratory (BiiGC), EA2521, SFR143, Universite Jean Monnet, Saint-Etienne, France
  2. 2Pharmacology and Toxicology Laboratory, University Hospital, Saint-Etienne, France
  3. 3Anatomy and Cytopathology Department, University Hospital, Saint-Etienne, France
  4. 4Ophthalmology Department, University Hospital, Saint-Etienne, France
  5. 5Institut Universitaire de France, Paris, France
  1. Correspondence to Professor Gilles Thuret, Corneal Graft Biology, Engineering and Imaging Laboratory (BiiGC), EA2521, SFR143, University Jean Monnet, Saint-Etienne, France; gilles.thuret{at}univ-st-etienne.fr

Abstract

Aims To evaluate the efficacy of a subconjunctival dexamethasone-releasing implant in preventing rejection of penetrating keratoplasty (PK) in an animal model.

Methods 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.

Results 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).

Conclusions 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.

  • immunosuppression
  • penetrating keratoplasty
  • rejection
  • dexamethasone
  • subconjunctival implant
  • rabbit

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Footnotes

  • Contributors Design of the study: MP, TB, PG and GT; obtained funding: GT and PG; acquisition, analysis or interpretation of data: EC, TG, A-SG, ZH, CP, XD, TB and PG; drafting of the work: PG and GT; revising the work: EC, TG, A-SG, ZH, XD, TB, MP and PG; approval of the final version: all authors; and agreement for all aspects of the work: all authors.

  • Funding This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests Consultant for Laboratoires Thea and for Quantel Medical.

  • Ethics approval The experimental protocol was validated and approved by the ethics committee of the Saint-Etienne University animal facility (protocol CU14N03).

  • Provenance and peer review Not commissioned; externally peer reviewed.

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