An intravitreal sustained-release triamcinolone and 5-fluorouracil codrug in the treatment of experimental proliferative vitreoretinopathy.
OBJECTIVE
To determine the efficacy and pharmacokinetics of an intravitreal sustained-release triamcinolone acetonide and 5-fluorouracil (TA/5-FU) codrug in the treatment of experimental proliferative vitreoretinopathy (PVR).


METHODS
The therapeutic efficacy of the TA/5-FU codrug was determined in a rabbit model that simulates human PVR. Intravitreal levels of triamcinolone and 5-fluorouracil were measured at different time points and drug release in vitro was tested. Toxic effects were evaluatedby electroretinograpy, clinical examination, and light microscopy.


RESULTS
Both the severity of PVR grade and the percentage of eyes with moderate or worse tractional detachment were significantly less in eyes treated with the codrug. The therapeutic effect of the intravitreal codrug was paralleled by sustained intravitreal levels of triamcinolone and 5-fluorouracil. There were no drug-related toxic effects evident on clinical or histopathologic examination of eyes containing the TA/5-FU codrug.


CONCLUSIONS
The intravitreal sustained-release TA/5-FU codrug effectively inhibits the progression of PVR in a rabbit model that closely resembles PVR in humans. The TA/5-FU codrug may simultaneously target different components of the wound-healing response.
Yang
C S
CS
Department of Ophthalmology, Duke University, Durham, NC 27710, USA.
Khawly
J A
JA
Hainsworth
D P
DP
Chen
S N
SN
Ashton
P
P
Guo
H
H
Jaffe
G J
GJ
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003692:Delayed-Action Preparations; D004195:Disease Models, Animal; D004343:Drug Implants; D004359:Drug Therapy, Combination; D004596:Electroretinography; D005472:Fluorouracil / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000493:pharmacokinetics; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D007267:Injections; D011817:Rabbits; D016896:Treatment Outcome; D014221:Triamcinolone / Q000008:administration & dosage* / Q000493:pharmacokinetics; D018630:Vitreoretinopathy, Proliferative / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D014822:Vitreous Body / Q000378:metabolism
D003692:Delayed-Action Preparations; D004343:Drug Implants; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D014221:Triamcinolone; D005472:Fluorouracil