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Br J Ophthalmol 2004;88:1201-1205 doi:10.1136/bjo.2003.039917
  • Laboratory science - Scientific reports

An intravitreal biodegradable sustained release naproxen and 5-fluorouracil system for the treatment of experimental post-traumatic proliferative vitreoretinopathy

  1. J A Cardillo1,2,*,
  2. M E Farah2,
  3. J Mitre2,
  4. P H Morales2,
  5. R A Costa1,
  6. L A S Melo2,
  7. B Kuppermann3,
  8. R Jorge1,
  9. P Ashton4
  1. 1Department of Ophthalmology, Hospital de Olhos de Araraquara, Araraquara, São Paulo, Brazil
  2. 2Department of Ophthalmology, Paulista School of Medicine, UNIFESP-EPM, Sao Paulo, Brazil
  3. 3Department of Ophthalmology, University of California Irvine, Irvine, California, USA
  4. 4Department of Ophthalmology, Tufts New England Medical Center, Boston, Massachusetts, USA
  1. Correspondence to: Dr J A Cardillo Hospital de Olhos de Araraquara, Rua Henrique Dall’Acqua 45, Araraquara-SP, Brazil 14802-530; jacardillohorizon.com.br
  • Accepted 1 February 2004

Abstract

Background/aims: To determine the potential of an intravitreal sustained release naproxen and 5-fluorouracil (NA/5-FU) codrug for the treatment of experimental proliferative vitreoretinopathy (PVR) in a model for trauma associated tractional retinal detachment (TRD).

Methods: Sustained release pellets were prepared by covalently linking naproxen to 5-fluorouracil. Drug release was tested in vitro and toxic effects were evaluated by electroretinography and light microscopy. Traumatic PVR was induced in pigmented rabbits by performing a scleral laceration, followed by repair and intravitreal injection of 0.4 ml of autologous blood. Thirty six eyes were treated with a sustained release implant containing 1.5 mg NA/5-FU as a codrug and 36 control eyes were submitted to surgery alone. Eyes were evaluated for TRD by serial indirect ophthalmoscope examination at different time points followed by postmortem fundus evaluation of the enucleated eye

Results: The NA/5-FU pellets were found to provide linear release of 5-FU and naproxen over the 30 day duration of the in vitro release test. Both the severity of PVR grade and the percentage of eyes with moderate or worse tractional detachment were significantly lower in eyes treated with the codrug pellet. There were no drug related toxic effects evident on histopathological or electroretinograph examination of eyes containing the NA/5-FU pellet.

Conclusions: The results suggest that this NA/5-FU codrug device effectively inhibits the progression of PVR in a rabbit trauma model that closely resembles PVR in humans. Additional studies to add knowledge to these initial findings and to clarify the potential of the codrug device for the treatment of human PVR are warranted.

Footnotes

  • ↵The authors have no financial interest in any of the products mentioned in this paper.

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