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Veterinary ophthalmology2001; 3(2-3); 105-110; doi: 10.1046/j.1463-5224.2000.00117.x

Long-term effect on the equine eye of an intravitreal device used for sustained release of cyclosporine A.

Abstract: OBJECTIVE: To determine the long-term toxicity of an intravitreal device releasing continuous cyclosporinee A (CsA) in normal eyes of horses by evaluating clinical signs, electroretinography, and histopathology. Animals Studied Ten adult horses with normal ophthalmic examinations were used in this study Procedure(s) Four horses had one eye implanted with a CsA device, and six horses had the right eye implanted with a CsA-containing device (10 eyes with CsA in total) and the left eye (six eyes in total) with the device without drug (control). The implants were placed in the vitreous of the eyes through a sclerotomy 1 cm posterior to the limbus in the dorso-temporal quadrant of the eye. Scotopic electroretinograms were performed prior to implantation and at 1 week, and at 1, 3, 6, 9, and 12 months postimplantation. Two of the unilaterally implanted horses were euthanized at 1 weeks postimplantation, and two at 6 weeks postimplantation. Two of the bilaterally implanted horses were euthanized at 6 months, two at 9 months, and two at 12 months postimplantation. At euthanasia, the eyes were removed, aqueous and vitreous humor aspirated, and tissues fixed in 10% buffered formalin and processed for histopathology. CsA concentrations were measured by high pressure liquid chromatography in the aqueous and vitreous humors, and in peripheral blood. RESULTS: The devices were tolerated well in 14 of 16 eyes. There was minimal postoperative inflammation in most eyes, with a normal appearance within 7 days. In two eyes implanted with the CsA device, severe inflammation resulted in phthisis bulbi by 28 days. One of these eyes exhibited suspected bacterial endophthalmitis, and one had a sterile endophthalmitis and cataract presumably from trauma to the lens during implantation. In the other 14 eyes, no change was observed in the scotopic electroretinograms (ERG) from preoperative results, and no significant differences between the right (CsA) and left (control device) eyes were observed. CsA levels in the aqueous and vitreous humor, and peripheral blood were below the detection limit of the HPLC. Histologic findings revealed only a mild lymphoplasmacytic cellular infiltrate in the ciliary body and pars plana near the implantation site. CONCLUSIONS: The CsA devices were well tolerated with no long-term complications from the implants themselves. However, complications may occur from inadvertent implantation trauma or contamination during surgery. The long-term safety of the device may make it useful for delivery of CsA in the control of equine recurrent uveitis.
Publication Date: 2001-06-09 PubMed ID: 11397291DOI: 10.1046/j.1463-5224.2000.00117.xGoogle Scholar: Lookup
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  • Journal Article

Summary

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The study investigates the long-term effects of intravitreous cyclosporinee A (CsA) implantation in horses, specifically looking at potential toxicity. The procedure generally had no significant complications, but some instances of inflammation were recorded.

Study Methodology

  • The researchers carefully selected ten adult horses with normal ophthalmic features to minimize possible external factors that could affect the study’s results.
  • The procedure involved implanting a CsA device in one eye for four horses, while six horses had the right eye implanted with a CsA-containing device and the left eye with a device without the drug (serving as a control).
  • The locations for implant were the vitreous of the eye through a sclerotomy, a purposeful cut or puncture, a centimeter posterior to the limbus in the dorso-temporal quadrant.
  • The researchers performed Scotopic electroretinograms (ERGs) – tests to measure the effect of the implant on eye function – before the procedure and at regular intervals (1 week, 1 month, 3 months, 6 months, 9 months, and 12 months) after surgery.
  • Depending on which interval they were at, some horses were euthanized to allow for a thorough examination of the eye structures and devices.

Findings

  • Most of the implants (14 out of 16 eyes) were well-received by the horses’ bodies with little to no inflammation recorded after the procedure. In these cases, the eyes regained their normal appearance within a week.
  • In two instances, severe inflammation occurred resulting in phthisis bulbi – a shrinking or atrophy of the eyeball – by 28 days. One of these instances was suspected to be bacterial endophthalmitis – an eye infection – and the other resulted from trauma to the lens during implantation.
  • Regarding the ERGs, no significant changes were observed in the results from before the procedure, indicating that eye function remained stable.
  • The CsA levels in the eye fluids and peripheral blood were found to be below the detection limit, suggesting limited if any systemic absorption of the drug.
  • Most histologic findings showed only very minor cellular infiltrate, further supporting the low inflammation response to the implant.

Conclusions

  • The CsA devices were generally well tolerated, with no long-term complications arising directly from the implants themselves.
  • The only notable complications were due to inadvertent surgical trauma or contamination during the procedure, highlighting the importance of surgical carefulness when implanting these devices.
  • Overall, the study suggests that the implantation of CsA devices could be a safe, long-term solution for the treatment of equine recurrent uveitis, a common eye disease in horses.

Cite This Article

APA
Gilger BC, Malok E, Stewart T, Ashton P, Smith T, Jaffe GJ, Allen JB. (2001). Long-term effect on the equine eye of an intravitreal device used for sustained release of cyclosporine A. Vet Ophthalmol, 3(2-3), 105-110. https://doi.org/10.1046/j.1463-5224.2000.00117.x

Publication

ISSN: 1463-5224
NlmUniqueID: 100887377
Country: England
Language: English
Volume: 3
Issue: 2-3
Pages: 105-110

Researcher Affiliations

Gilger, B.C.
  • Comparative Ophthalmology Research Laboratories, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USA; Veterinary Equine Research Center, North Carolina State University, Southern Pines, NC 28387, USA; Control Delivery Systems, Inc, Watertown, MA 02172, USA; Duke University Eye Center, Durham, NC, USA.
Malok, E.
    Stewart, T.
      Ashton, P.
        Smith, T.
          Jaffe, G.J.
            Allen, J.B.

              Citations

              This article has been cited 6 times.
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