Intravitreal sustained release corticosteroid-5-fluoruracil conjugate in the treatment of experimental proliferative vitreoretinopathy.
OBJECTIVE
Proliferative vitreoretinopathy (PVR) remains the most common cause of failed retinal detachment (RD) surgery. The authors compared the effectiveness of two intraocular sustained-release codrugs in suppressing PVR in a rabbit model a surgically implantable pellet releasing 5-fluorouracil (FU) and dexamethasone (DX) for 1 week and an injectable intravitreal sustained-release suspension releasing 5-FU and triamcinolone acetonide for 1 month.


METHODS
Sustained-release devices and suspensions were prepared to deliver equimolar quantities of corticosteroid and 5-FU. In group 1, devices were implanted surgically into the vitreous of the right eye of 10 New Zealand White rabbits. Ten control rabbits received surgical implantation of the suture only. In group 2, drug suspension was injected into the vitreous of the right eye of 10 New Zealand White rabbits. Ten control rabbits received injection of the vehicle only. One day later, each rabbit was injected intravitreally with 250,000 homologous rabbit dermal fibroblasts. Severity of PVR was graded clinically by two masked observers on days 3, 7, 10, 14, 21, and 28.


RESULTS
In group 1, clinical severity of PVR was less in the experimental group than in the control group at all time points, this was only statistically significant on day 10 (P = 0.04). Six eyes developed moderate to severe tractional RD or bullous RD in the control group by day 10 compared with none in the experimental group (P = 0.01). In group 2, the median clinical grading of eyes in the experimental group was significantly less than that in the control group at all time points through day 21 (P < or = 0.01).


CONCLUSIONS
Both the intravitreal sustained-release dexamethasone-5-FU device and the triamcinolone-5-FU suspension effectively inhibit the progression of PVR in a rabbit model. Simultaneous delivery of 5-FU and corticosteroid may target different components of the wound-healing process in this disease.
Berger
A S
AS
Department of Ophthalmology, Duke University, Durham, North Carolina, USA.
Cheng
C K
CK
Pearson
P A
PA
Ashton
P
P
Crooks
P A
PA
Cynkowski
T
T
Cynkowska
G
G
Jaffe
G J
GJ
D000818:Animals; D000963:Antimetabolites / Q000008:administration & dosage*; D003692:Delayed-Action Preparations; D003907:Dexamethasone / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004338:Drug Combinations; D016503:Drug Delivery Systems; D004343:Drug Implants; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage*; D005938:Glucocorticoids / Q000008:administration & dosage*; D008297:Male; D011817:Rabbits; D012163:Retinal Detachment / Q000209:etiology; D014221:Triamcinolone / Q000008:administration & dosage*; D018630:Vitreoretinopathy, Proliferative / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D014822:Vitreous Body
D000963:Antimetabolites; D003692:Delayed-Action Preparations; D004338:Drug Combinations; D004343:Drug Implants; D005938:Glucocorticoids; D014221:Triamcinolone; D003907:Dexamethasone; D005472:Fluorouracil