A Glp Study To Assess Safety Of An Excimer Laser-Shaped, Electron Beam-Sterilized Allogenic Corneal Inlay (Allotex Sample) In New Zealand White Rabbits

The aim of this GLP study is to evaluate the safety of excimer laser-shaped, e-beam radiation-sterilized allograft corneal inlay implantation (Allotex) in New Zealand White Rabbits (NZWR).

Twenty NZWR (10 males and 10 females) were used for this study. These animals were divided into four groups. Group 1 received Allotex OD and trephined and cryogenically cut Fresh Human Tissue (FHT) OS. Group 2 received Allotex OD and FHT OS or Sham OS. Group 3 received Allotex OD and Hallo OS (e-beam sterilized human stromal tissue then trephined and cryogenically cut). Group 4 received Allotex OD or Sham OD and Halo OS.

Groups 1 and 3 were euthanized on Day 7, 30, or 93. Group 2 and 4 were euthanized on Day 182. Daily cage-side observations of rabbits were examined. Clinical ophthalmic examinations (slit-lamp biomicroscopy and indirect ophthalmoscopy) were performed on both eyes of all animals at baseline and on days 2, 3, 4, and before study termination. Ocular findings were scored according to the modified McDonald-Shadduck Scoring System. Following euthanasia, sections of corneal tissue were taken from three levels of the human corneal tissue implant site. The tissue was stained with haematoxylin and eosin and examined pathologically.

Corneal implantation of Allotex and control FHT and Hallo in NZWR was well tolerated through Day 180±5. Inflammatory biomicroscopic findings associated with the implantation procedure was presented in all the groups. These inflammatory reactions severity appeared to be less with the Allotex treatment group when compared to the control treatment groups. Early pathological findings in all groups were limited to procedural findings related to corneal inflammation/healing processes, such as corneal epithelial regeneration, increased stromal cell density, mononuclear/mixed cell infiltrates, neovascularization, edema, and necrosis of the corneal flap.

These procedural findings were generally histomorphologically similar or slightly less severe in Allotex samples compared to control eyes. At 90±3 days, there was ongoing improvement in procedural inflammatory and/or healing findings in all groups. At 180±5 days, there was almost complete resolution of procedural healing findings in all groups. Increased stromal cell density was observed in only one eye implanted with fresh human tissue.

Allotex, Control Halo and FHT were well tolerated by NZWRs. Inflammation after implantation was seen in all groups, but was less severe in the Allotex group.