April 2010
Volume 51, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2010
Retinal Toxicity of Cyclosporine Intravitreally Delivered by a Biodegradable Implant in Rabbits
Author Affiliations & Notes
  • F. P. Almeida
    Ophthalmology, Medical School University of São Paulo, Ribeirão Preto, Brazil
  • J. A. S. Ribeiro
    Ophthalmology, Medical School University of São Paulo, Ribeirão Preto, Brazil
  • R. C. Siqueira
    Ophthalmology, Medical School University of São Paulo, Ribeirão Preto, Brazil
  • A. Silva-Cunha
    Pharmacology, University of Minas Gerais, Belo Horizonte, Brazil
  • J. B. Saliba
    Pharmacology, University of Minas Gerais, Belo Horizonte, Brazil
  • R. Jorge
    Ophthalmology, Medical School University of São Paulo, Ribeirão Preto, Brazil
  • A. Messias
    Ophthalmology, Medical School University of São Paulo, Ribeirão Preto, Brazil
  • Footnotes
    Commercial Relationships  F.P. Almeida, None; J.A.S. Ribeiro, None; R.C. Siqueira, None; A. Silva-Cunha, None; J.B. Saliba, None; R. Jorge, None; A. Messias, None.
  • Footnotes
    Support  FAPESP - Grant (AM) 2007/59078-8
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 5584. doi:
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    • Get Citation

      F. P. Almeida, J. A. S. Ribeiro, R. C. Siqueira, A. Silva-Cunha, J. B. Saliba, R. Jorge, A. Messias; Retinal Toxicity of Cyclosporine Intravitreally Delivered by a Biodegradable Implant in Rabbits. Invest. Ophthalmol. Vis. Sci. 2010;51(13):5584.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract
 
Purpose:
 

To investigate the toxic effects of an intravitreal poly-lactic-co-glycolic acid (PLGA) biodegradable cyclosporine A (CsA) implant on retinal function in rabbits.

 
Methods:
 

Rabbits have been assigned to receive either an intravitreal implant of PLGA biodegradable system with 350 µg of CsA (n=4), or without the compound as control group (PLGA; n=4). Intensity-response relationship of dark-adapted electroretinography (ERG) responses was evaluated at baseline and 8 weeks after the procedure, by applying 13 increasing luminance white flash (4ms - 0.00003 to 100 cd.s/m²). A hyperbolic model was used to derivate the b-wave saturating amplitude (Vmax) and the luminance for reaching 50% of Vmax (k). Subsequently, light-adapted ERG was recorded after 10 min of light adaptation. In addition, slit lamp examination and intraocular pressure (IOP) measurements were performed weekly.

 
Results:
 

No effects were observed in respect to a-wave amplitude or Vmax in group PLGA (P>0.05). In contrast, in CsA, although no changes were observed on a-wave: mean ± SE: 164.3 ± 14.9 µV at baseline and 170.3 ± 20.3 µV 8 weeks after implant (P>0.05), a significant reduction on Vmax was observed, Vmax: 182.6 ± 9.9 µV at baseline and 100.0 ± 14.5 µV 8 weeks after implant (P<0.05). Consequently, eyes in CsA group showed negative ERG responses 8 weeks after treatment with b/a ratio reducing from 2.0 ± 0.1 at baseline to 1.1 ± 0.1 8 weeks after implant (P<0.05). No sign of inflammation was noticed on slit lamp examinations and IOP maintained stable during the study period.  

 
Conclusions:
 

The PLGA biodegradable system alone causes no ERG changes, while our data suggest that implants with CsA causes impairment on rod postreceptoral pathway function after 8 weeks follow-up. Further studies are necessary to determine structural changes, and the toxicity profile of CsA for this implant.

 
Keywords: electroretinography: non-clinical • retina • drug toxicity/drug effects 
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