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J. Kohn, I. J. Khan, C. Iovine, P. Velagaleti, E. Anglade, B. Gilger; Ocular Biocompatibility, Toxicity, and Distribution From Erodible Polycarbonate Polymer Episcleral Implants (LX212) in Rabbits. Invest. Ophthalmol. Vis. Sci. 2010;51(13):5326.
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© ARVO (1962-2015); The Authors (2016-present)
To evaluate ocular biocompatibility, erodability, toxicity and distribution of voclosporin (VCS) from polycarbonate polymer implants placed episclerally in New Zealand White rabbits.
Two polymers (AX2 [tyrosine-based polycarbonate] and AX6 [blend containing tyrosine-based polycarbonate]; ~2 x 15 x 0.5 mm; ~15 mg/implant wt; ~15% [~2 mg] VCS/implant) were evaluated. Twenty four female rabbits were randomly assigned to four groups (6/group) that had either one (left [OS]) or 3 (right [OD]) implants (AX2 or AX6) placed into the episcleral space in each eye. Toxicokinetics (whole blood) were evaluated before implantation, weekly for 8 wks, then every 2 wks for up to 30 wks. Comprehensive ophthalmic examinations and ERGs were performed prior to implantation, at 7 days, and just prior to euthanasia. Animals were euthanized at selected time points with implants and tissues from 1 eye/animal processed for drug analysis while the other eye was removed, fixed, and processed for histopathology.
Ophthalmic exam revealed mild conjunctival inflammation at the incision sites at 7 days which resolved by 4 wks. There was no implant loss or evidence of intraocular inflammation at any time after surgery. ERGs showed decreased mean b-wave amplitude at 4 wks in rabbits which received either one (OS) or three (OD) AX2 implants, however, no significant ERG differences were noted at later time periods or in AX6 implants. Histopathologically, mild mononuclear cell infiltrate and fibrosis was observed surrounding the implants. VCS blood concentrations were detected at <4 ng/mL for up to 20 wks. High drug levels were detected in various ocular tissues (including posterior segment of the eye) up to 30 wks. Less than 10% drug remained in implants at wk 22. Implants appeared progressively smaller with time with only small residual implants noted at 30 wks.
Single or triple LX212 episcleral implants in rabbits released VCS for 30 wks (last time point measured), were estimated to be resorbed by 40 wks and demonstrated excellent biocompatibility without ocular toxicity.
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