Suppression of Experimental Proliferative Vitreoretinopathy by Sustained Intraocular Delivery of 5-FU

Overview

Journal Int Ophthalmol

Specialty Ophthalmology

Date 1995 Jan 1

PMID 8537196

Citations 11

Authors

H Borhani

G A Peyman

M H Rahimy

H Thompson

Affiliations

Soon will be listed here.

Abstract

Treatment of proliferative vitreoretinopathy (PVR) requires a multidimensional approach. Recent studies have focused on pharmacologic techniques to inhibit intraocular cell proliferation by applying antimetabolite drugs. Side effects associated with these drugs and difficulties in achieving effective concentration inside the eye make drug delivery an important and difficult part of this approach. We have developed a sustained-release bioerodible device with modifiable release properties for intraocular drug delivery. In this study, we evaluated the efficacy of the device with two different concentrations of 5-fluorouracil (5-FU) in an experimental model of PVR in rabbit eyes. Both devices showed significant (P < 0.05) efficacy in prevention of PVR. Devices containing 20% 5-FU (total of 1 mg) were 100% effective in prevention of tractional retinal detachment. No significant complications, other than mild vitreous hemorrhage in a few cases, were associated with this method. Because pharmacologic therapy is used as an augmenting method to surgical therapy, these devices can be easily implanted inside the eye through a sclerotomy at the completion of surgery without any discomfort to patients. Slow release of drug by this method reduces the incidence of toxicity and increases the efficacy by providing a constant concentration of drug during the active period of the disease.

Citing Articles

Polymeric Implants for the Treatment of Intraocular Eye Diseases: Trends in Biodegradable and Non-Biodegradable Materials.

Garcia-Estrada P, Garcia-Bon M, Lopez-Naranjo E, Basaldua-Perez D, Santos A, Navarro-Partida J Pharmaceutics. 2021; 13(5).

PMID: 34065798 PMC: 8151640. DOI: 10.3390/pharmaceutics13050701.

Endogenous or Exogenous Retinal Pigment Epithelial Cells: A Comparison of Two Experimental Animal Models of Proliferative Vitreoretinopathy.

Wong C, Busoy J, Cheung N, Barathi V, Storm G, Wong T Transl Vis Sci Technol. 2020; 9(9):46.

PMID: 32934896 PMC: 7463202. DOI: 10.1167/tvst.9.9.46.

Inflammatory mediators of proliferative vitreoretinopathy: hypothesis and review.

Dai Y, Dai C, Sun T Int Ophthalmol. 2020; 40(6):1587-1601.

PMID: 32103371 PMC: 7242233. DOI: 10.1007/s10792-020-01325-4.

Intra-vitreal αB crystallin fused to elastin-like polypeptide provides neuroprotection in a mouse model of age-related macular degeneration.

Sreekumar P, Li Z, Wang W, Spee C, Hinton D, Kannan R J Control Release. 2018; 283:94-104.

PMID: 29778783 PMC: 6368441. DOI: 10.1016/j.jconrel.2018.05.014.

Modulated release from implantable ocular silicone oil tamponade drug reservoirs.

Cauldbeck H, Hellaye M, McDonald T, Long M, Williams R, Rannard S J Polym Sci A Polym Chem. 2018; 56(8):938-946.

PMID: 29610546 PMC: 5873246. DOI: 10.1002/pola.28973.

References

Chen E, Steinhorst U, Samsa G, Saloupis P, Hatchell D . The effect of combined daunorubicin and triamcinolone acetonide treatment on a refined experimental model of proliferative vitreoretinopathy. Invest Ophthalmol Vis Sci. 1992; 33(7):2160-4. View

Blumenkranz M, Hernandez E, Ophir A, Norton E . 5-fluorouracil: new applications in complicated retinal detachment for an established antimetabolite. Ophthalmology. 1984; 91(2):122-30. DOI: 10.1016/s0161-6420(84)34318-4. View

Wong V, Kitada S, Choo P, Lee D . Inhibition of rabbit ocular fibroblast proliferation by 5-fluorouracil and cytosine arabinoside. J Ocul Pharmacol. 1991; 7(1):27-39. DOI: 10.1089/jop.1991.7.27. View

HEIDELBERGER C, ANSFIELD F . EXPERIMENTAL AND CLINICAL USE OF FLUORINATED PYRIMIDINES IN CANCER CHEMOTHERAPY. Cancer Res. 1963; 23:1226-43. View

Blumenkranz M, Ophir A, CLAFLIN A, Hajek A . Fluorouracil for the treatment of massive periretinal proliferation. Am J Ophthalmol. 1982; 94(4):458-67. DOI: 10.1016/0002-9394(82)90239-2. View

Wiedemann P, Sorgente N, Bekhor C, Patterson R, Tran T, Ryan S . Daunomycin in the treatment of experimental proliferative vitreoretinopathy. Effective doses in vitro and in vivo. Invest Ophthalmol Vis Sci. 1985; 26(5):719-25. View

Mayerson P, Hall M, Clark V, Abrams T . An improved method for isolation and culture of rat retinal pigment epithelial cells. Invest Ophthalmol Vis Sci. 1985; 26(11):1599-609. View

Fastenberg D, Diddie K, Sorgente N, Ryan S . A comparison of different cellular inocula in an experimental model of massive periretinal proliferation. Am J Ophthalmol. 1982; 93(5):559-64. DOI: 10.1016/s0002-9394(14)77369-6. View

Araiz J, Refojo M, Arroyo M, Leong F, Albert D, TOLENTINO F . Antiproliferative effect of retinoic acid in intravitreous silicone oil in an animal model of proliferative vitreoretinopathy. Invest Ophthalmol Vis Sci. 1993; 34(3):522-30. View

10.

Lee D, Hersh P, Kersten D, Melamed S . Complications of subconjunctival 5-fluorouracil following glaucoma filtering surgery. Ophthalmic Surg. 1987; 18(3):187-90. View

11.

Koutsandrea C, Miceli M, Peyman G, Farahat H, Niesman M . Ciprofloxacin and dexamethasone inhibit the proliferation of human retinal pigment epithelial cells in culture. Curr Eye Res. 1991; 10(3):249-58. DOI: 10.3109/02713689109003447. View

12.

Barza M, Stuart M, Szoka Jr F . Effect of size and lipid composition on the pharmacokinetics of intravitreal liposomes. Invest Ophthalmol Vis Sci. 1987; 28(5):893-900. View

13.

Stern W, Heath T, Lewis G, GuErin C, Erickson P, Lopez N . Clearance and localization of intravitreal liposomes in the aphakic vitrectomized eye. Invest Ophthalmol Vis Sci. 1987; 28(5):907-11. View

14.

Assil K, Hartzer M, Weinreb R, Nehorayan M, Ward T, Blumenkranz M . Liposome suppression of proliferative vitreoretinopathy. Rabbit model using antimetabolite encapsulated liposomes. Invest Ophthalmol Vis Sci. 1991; 32(11):2891-7. View

15.

Stern W, GuErin C, Erickson P, Lewis G, Anderson D, Fisher S . Ocular toxicity of fluorouracil after vitrectomy. Am J Ophthalmol. 1983; 96(1):43-51. DOI: 10.1016/0002-9394(83)90453-1. View

16.

Tano Y, Sugita G, Abrams G, MACHEMER R . Inhibition of intraocular proliferations with intravitreal corticosteroids. Am J Ophthalmol. 1980; 89(1):131-6. DOI: 10.1016/0002-9394(80)90239-1. View

17.

Sanborn G, Anand R, Torti R, Nightingale S, Cal S, Yates B . Sustained-release ganciclovir therapy for treatment of cytomegalovirus retinitis. Use of an intravitreal device. Arch Ophthalmol. 1992; 110(2):188-95. DOI: 10.1001/archopht.1992.01080140044023. View

18.

Liu K, Peyman G, She S, Niesman M, Khoobehi B . Reduced toxicity of intravitreally injected liposome-encapsulated cytarabine. Ophthalmic Surg. 1989; 20(5):358-61. View

19.

Barrada A, Peyman G, Greenberg D, Stelmack T, Fiscella R . Toxicity of antineoplastic drugs in vitrectomy infusion fluids. Ophthalmic Surg. 1983; 14(10):845-7. View

20.

Stern W, Lewis G, Erickson P, GuErin C, Anderson D, Fisher S . Fluorouracil therapy for proliferative vitreoretinopathy after vitrectomy. Am J Ophthalmol. 1983; 96(1):33-42. DOI: 10.1016/0002-9394(83)90452-x. View