Proliferative vitreoretinopathy

Esser, P, Tervooren, D, Heimann, K, Kociok, N, Bartz-Schmidt, KU, Walter, P, and Weller, M, 1998. Intravitreal daunomycin induces multidrug resistance in proliferative vitreoretinopathy. Invest Ophthalmol Vis Sci 39, 164-170. 

S. Chang, E. Ozmert, N.J. Zimmerman, Intraoperative perfluorocarbon liquids in the management of proliferative vitreoretinopathy, Am. J. Ophthalmol. 106 (1988) 668-674. 

J.S. Rinkoff, E. de Juan Jr, B.W. Me Cuen, Silicone oil of retinal detachment with advanced proliferative vitreoretinopathy following failed vitrectomy for proliferative diabetic retinopathy. Am. J. Ophthalmol. 101 (1986) 181-186. 

H.C. Sell, B.W. Me Cuen, M.B. Landers, R. Machemer, Long-term results of successful vitrectomy with silicone oil for advanced proliferative vitreoretinopathy. Am. J. Ophthalmol. 103 (1987) 24-28. 

Silicon study group. Vitrectomy with silicone oil or sulfur hexafluoride gas in eyes with severe proliferative vitreoretinopathy Results of a randomized clinical trial. Silicone study report 1, Arch. Ophthalmol. 110 (1992) 770-779. 

Proliferative diabetic vitreoretinopathy (PDR) is characterised by the growth of blood vessels into the vitreous and neovascularisation of the retina. These neovascularisations lead to vitreous haemorrhage, creating additional fibrous epiretinal proliferations. 

B. Kirchhof, N. Sorgente, Pathogenesis of proliferative vitreoretinopathy. Modulation of retinal pigment epithelial cell functions by vitreous and macrophages. Dev. Ophthalmol. 16 (1989) 1-53. 

Disorders of the posterior segment of the eye are particularly difficult to treat. The efficient clearance mechanisms at the front of the eye reduce the concentrations of drug able to diffuse to the back of the eye. Futhermore, many of these disorders are chronic conditions, requiring continuous therapy. The diseases of the back of the eye include Cytomeaglovirus retinits (CMVR), Proliferative vitreoretinopathy (PVR), diabetic retinopathy, age-rated macular degeneration, endophthalmitis and retinitis pigmentosa. 

As mentioned above, intravitreal injection of drugs should be used in many cases to achieve therapeutic intravitreal drug levels. This is especially true for cases of viral retinitis, such as cytomegalovirus (CMV) retinitis and acute retinal necrosis (ARN) which require intravitreal injection of antivirals, or for the treatment of bacterial and fungal endophthalmitis or proliferative vitreoretinopathy [305]. It still remains a controversial issue whether liposomes can reach the retina after intravitreal injections and which vesicle physicochemical characteristics should be preferred for such formulations. 

Corticosteroids administered intravitreally bypass the blood-ocular barrier to achieve therapeutic levels in the eye while minimizing systemic side effects. Initial studies of intravitreal corticosteroids combined dexamethasone and gentamicin in the treatment of inflammation associated with experimentally reduced endophthalmitis.As of late, interest has shifted to triamcinolone acetonide because of the longer half-life in the vitreous and its use in treatment of proliferative vitreoretinopathies. 

McGUlem GS, Dacheux RF (1998) Migration of retinal microglia in experimental proliferative vitreoretinopathy. Exp Eye Res 67 371-375. 

Valeria Canto Soler M, Gallo JE, Dodds RA, Suburo AM (2002) A mouse model of proliferative vitreoretinopathy induced by dis-pase. Exp Eye Res 75 491-504. 

Weller M, Esser P, Heimann K, Wiedemann P (1991) Retinal microglia A new cell in idiopathic proliferative vitreoretinopathy Exp Eye Res 53 275-281. 

Chang S, Ozmert E, Zimmerman NJ. Intraoperative perfluorocarbon hquids in the management of proliferative vitreoretinopathy. Am J Ophthalmol 1988 106(6) 668-74. 

A heavier-than-water fluorinated silicone oil was used in the treatment of 30 selected cases of complicated retinal detachment due to proliferative vitreoretinopathy (n = 19), proliferative diabetic retinopathy with traction detachment (n = 2), giant retinal tears (n = 5), ruptured globe with retinal detachment (n = 2), massive choroidal effusion with retinal detachment (n = 1), and acute retinal necrosis with retinal detachment (n = 1) (13). Initial retinal reattachment was achieved in all cases. Complications included redetachment (n = l), cataract (n = 6), raised intraocular pressure (n = 4), hypotony (n = 4), keratopathy (n = 3), uveitis sjme-chia formation (n = 3), phthisis (n = 2), choroidal hemorrhage (n — 1), and vitreous hemorrhage n = 1). 

Proliferative vitreoretinopathy (PVR) is characterized by the proliferation of cells, thought to be mainly retinal pigment epithelial cells, macrophages, and fibroblasts... 

Sunalp M, Wiedemann P, Sorgente N. Effects of cytotoxic drugs on proliferative vitreoretinopathy in the rabbit cell injection. Curr Eye Res 1984 3 619-623. 

Moritera T, Ogura Y, Yoshimura N, et al. Biodegradable microspheres containing adriamycin in the treatment of proliferative vitreoretinopathy. Invest Ophthalmol Vis Sci 1992 33 3125-3130. 

Wiedemann P, Lemmen K, Schmiedl R, Heimann K. Intraocular daunorubicin for the treatment and prophylaxis of traumatic proliferative vitreoretinopathy. Am J Ophthalmol 1987 104 10-14. 

Joondeph BC, Peyman GA, Khoobehi B, Yue BY. Liposome-encapsulated 5-fluorouracil in the treatment of proliferative vitreoretinopathy. Ophthalmic Surg 1988 19 252-256. 

Rubsamen PE, Davis PA, Hernandez E, et al. Prevention of experimental proliferative vitreoretinopathy with a biodegradable intravitreal implant for the sustained release of fluorouracil. Arch Ophthalmol 1994 112 407-413. 

Yang CS, Khawley JA, Hainsworth DP, et al. An intravitreal sustained release triamcinolone 5-FU codrug in the treatment of experimental proliferative vitreoretinopathy. Arch Ophthalmol 1998 116 69-77. 

The use of intravitreal corticosteroids was first popularized by Machemer in 1979 (33) in an effort to halt cellular proliferation after retinal detachment surgery, and Graham (34), McCuen (35), Tano (36), and others have studied its use in both animal models and humans. In contrast to other corticosteroids with short half-lives following intravitreal injection, triamcinolone acetonide is an effective and well-tolerated (35,37) agent for intravitreal injection in conditions such as uveitis (38,39), macular edema secondary to ocular trauma or retinal vascular disease (40), proliferative diabetic retinopathy (41), intraocular proliferation such as proliferative vitreoretinopathy (42), and choroidal neovascularization from AMD (43,44). 

Jonas JB, Hayler JK, Panda-Jonas S. Intravitreal injection of crystalline cortisone as adjunctive treatment of proliferative vitreoretinopathy. Br J Ophthalmol 2000 84(9) 1064-1067. 

Figure 9 Effect of scleral plug containing adriamycin on experimental proliferative vitreo-retinopathy. The plugs significantly reduced the incidence of traction retinal detachment (P — 0.002). Abbreviation PVR, prolitrative vitreoretinopathy. Source From Ref. 16.

Zhou T, Lewis H, Foster RE, Schwendeman SP. Development of a multiple-drug delivery implant for intraocular management of proliferative vitreoretinopathy. J Control Release 1998 55 281-295. 

Hashizoe M, Ogura Y, Takanashi T, Kunou N, Honda Y, Ikada Y. Implantable biodegradable polymeric device in the treatment of experimental proliferative vitreoretinopathy. Curr Eye Res 1995 14 473-477. 

As described below, microdialysis probes have been used to deliver therapeutic concentrations of drugs that may be useful to treat a variety of retinal diseases (50 52). Drugs that target macular edema, syphilis, CMV retinitis, proliferative vitreoretinopathy and retinal degenerative diseases have been tested. However, treatment for other conditions with this approach, particularly intraocular malignancy, could be envisioned. 

Drug Delivery for Proliferative Vitreoretinopathy Prevention and Treatment... 

---