Experimental Model Of Proliferative Vitreoretinopathy Research Articles

Combined Pharmacologic Therapy in a Rabbit Model of Proliferative Vitreoretinopathy (PVR)

Purpose: This study was designed to evaluate the efficacy of a combined treatment, previously used to prevent fibrosis after glaucoma surgery, to inhibit an experimental model of proliferative vitreoretinopathy (PVR). Methods: Two groups of albino rabbits were used. In the control group (group 1, n = 14), experimental PVR was induced using vitrectomy, retinotomies, cryotherapy and intraocular injection of platelet-rich plasma. In the experimental group (group 2, n = 15), after PVR was induced, the following treatment was administered for 4 weeks: systemic methylprednisolone, sodium diclofenac and colchicine combined with topical atropine 1%, adrenaline 10% and dexamethasone phosphate 0.1%. Follow- up consisted of fundus examination for 4 weeks. Results were classified according to Fastenberg’s classification. Only retinal detachments were considered to compare the two groups. Nonparametric test was used. Results: Retinal detachments were observed in 85.7% of group 1 and 33.3% of group 2 at the end of the follow-up (p < 0.01). No major systemic complications were observed. Conclusions: Combined therapy seems to be useful for treating experimental PVR.

Inflammation Measurement and Immunocharacterization of Cell Proliferation in an Experimental Model of Proliferative Vitreoretinopathy

An experimental model of proliferative vitreoretinopathy was developed in the rabbit eye by injecting a solution of human platelet-rich plasma. In this model we evaluated the progression with time of intraocular inflammation and the rate and origin of cell proliferation. A sterile solution adjusted to 10⁷ platelets was injected into the right eye of a total of 46 pigmented and 14 albino rabbits. Animals were sequentially sacrificed at days 7, 14, 21 and 1 month after injection. Clinical evaluation of vitreoretinal proliferation, using a classification in six grades, and of anterior segment inflammation assessed by a Laser Flare Meter, were done for 1 month after injection, before histopathological analysis. Eighty percent of eyes developed tractional retinal detachment in 1 month. Histopathology showed intense cell migration and proliferation in the area of the ciliary body, as early as the seventh day, then further increasing rapidly. Infiltrates were composed of cytokeratin- and vimentin-expressing cells. Abnormal expression of vimentin was also found in ciliary and retinal epithelia and in Müller cells. Inflammation measured by the Laser Flare Meter was maximal at day 11 and then reached a plateau at significantly higher levels than controls. Albino rabbits showed significantly lower grades of proliferation, as compared to pigmented rabbits. This study thus clarified some characteristics of exper- imental vitreoretinal proliferations that proved similar to those in human diseases, such as the involvement of ciliary body and retinal pigment epithelium, the existence of inflammatory reactions preceding cell proliferation and strong changes in intermediate filaments. This may provide a simple and valuable model for antiproliferative assays and shed some light on the pathogenesis of intraocular proliferative disorders.

Porcine model of proliferative vitreoretinopathy with platelets

PURPOSE. To develop an experimental model of proliferative vitreoretinopathy (PVR) in the pig, and determine the efficacy of platelet-derived growth factor (PDGF) compared with different platelet plasma concentrates in its development. METHODS. Animals were divided into four groups of 12 pigs each. Groups 1, 2, and 3 underwent four 3-mm-long retinotomies, a partial mechanical vitrectomy, and six transconjunctival retinal cryoapplications and were injected intravitreally with, respectively, 0.2 ml of platelet rich plasma, 0.2 ml of a solution containing 200 ng of porcine PDGF, and 0.2 ml of platelet concentrated plasma. Group 4 received only an intra-vitreal injection of 0.2 ml of porcine PDGF. RESULTS. In Group 1, retinal detachments (RDs) developed in six eyes (50%) (two eyes, total RDs; four, extensive RDs). In Group 2, focal RDs developed in six eyes (50%). In Group 3, 11 eyes (92%) developed Rds (six eyes, total RDs; three, extensive RDs, two, focal RDs). Group 4, did not develop lesions. Statistically significant differences were found between Group 3 and the other groups. Group 2 RDs were associated with the presence of vitreoretinal membranes but there were no signs of PVR. In Groups 1 and 3, signs of anterior PVR, posterior PVR, and retinal holes with rolled edges were observed. CONCLUSIONS. We have developed a model of PVR in the pig, the retina of which more closely resembles that of humans. Platelet plasma more effectively contributed to the development of an experimental model of porcine PVR than 200 ng of PDGF. The efficacy depends on the platelet concentration of the plasma. These results suggest that other growth factors and plasma components may interact synergistically with PDGF in the pathogenesis of PVR.

Therapeutic effect of periocular corticosteroids in experimental proliferative vitreoretinopathy.

To test the therapeutic effect of periocular corticosteroid injection on outcome, vitreous cellular infiltrate, and vitreous soluble growth-stimulating activity in an experimental model of tractional retinal detachment resulting from proliferative vitreoretinopathy. An experimental model of proliferative vitreoretinopathy was induced in rabbits, which then were selected randomly to receive either periocular methylprednisolone acetate injection treatment or a placebo injection (control). Animals were examined and monitored to determine the degree of retinal detachment and proliferative vitreoretinopathy at weekly intervals for 4 weeks. Vitreous specimens were obtained each week and analyzed for cell number by flow cytometry and for soluble growth-stimulating activity using a bioassay. Eighty-six percent (12 of 14) of the rabbits receiving periocular steroid injection had retinas that remained attached, whereas only 13 percent (2 of 15) of control animals had retinas that remained attached. Periocular steroid injections were associated with a significant decrease in the vitreous soluble proliferation stimulating activity at all times during experimental proliferative vitreoretinopathy. Vitreous cellular infiltration also was reduced significantly in steroid-treated animals compared with that of control animals. Finally, the magnitude of the soluble growth-stimulating activity at day 7, before onset of proliferative vitreoretinopathy, was highly predictive of outcome 3 weeks later. Periocular steroids decreased the incidence of complicated retinal detachment caused by proliferative vitreoretinopathy in this rabbit model. Decreased vitreous cellular infiltrate and soluble proliferation stimulating activity within the vitreous microenvironment also was observed to be associated with successful outcome.

2128 Experimental model of proliferative vitreoretinopathy and inhibition by liposome-encapsulated 5-fluorouridine

2128 Experimental model of proliferative vitreoretinopathy and inhibition by liposome-encapsulated 5-fluorouridine

Experimental model of proliferative vitreoretinopathy and inhibition by liposome-encapsulated 5-fluorouridine

Experimental model of proliferative vitreoretinopathy and inhibition by liposome-encapsulated 5-fluorouridine

Suppression of experimental proliferative vitreoretinopathy by sustained intraocular delivery of 5-FU

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.

Corticosteroids and daunomycin in the prevention of experimental proliferative vitreoretinopathy induced by macrophages.

An experimental model of proliferative vitreoretinopathy (PVR) induced by macrophages simulates a special form of wound healing process in the eye and mimics the development of PVR from its initial stage. We used this model for the evaluation of drug efficacy in the prevention of PVR. One mg triamcinolone acetonide (TA), 10 micrograms daunomycin-liposome (DL), 5 micrograms free daunomycin (FD) and 0.1 ml saline or empty liposomes (as controls) were injected into the vitreous in four groups of animals (30 or 40 rabbit eyes each) after macrophage injection. Retinal detachment developed in 77.5% of the control eyes on day 28, compared to 13.3% of the TA-treated eyes (P < 0.01), to 33.3% of the eyes treated with DL (P < 0.01), and 50% of the FD-treated eyes (P < 0.05). TA cleared up from the vitreous within 35-63 days (average 45.5 days). The half-time of FD clearance was 145.5 min. Although DL declined rapidly during the first 2 days, there was an average of 0.64 microgram/ml daunomycin in the vitreous on day 14. Transmission electron microscopy showed that FD at a dosage of over 5 micrograms or DL over 20 micrograms was toxic to the retina and that up to 4 mg TA was nontoxic. These results suggest that steroids such as TA, given at the inflammatory stage, can effectively and safely prevent the development of PVR, and that encapsulation in liposomes of cytotoxic agents such as daunomycin can enhance drug efficacy and reduce toxicity. The time course of initiation and development of PVR is important in the selection of particular drugs.

Intravitreal and subretinal proliferation induced by platelet-rich plasma injection in rabbits.

We developed an experimental model of proliferative vitreoretinopathy (PVR) in albino rabbits by combining some factors suspected of causing the disease. Sixty nine eyes divided into six groups served as controls (Groups C 1-6). Forty nine eyes were divided into four experimental groups (Groups E 1-4). Group E1 (n = 12) was injected with 0.15 ml of platelet-rich plasma. In addition, Groups E2 (n = 12) and E3 (n = 12) underwent cryotherapy or vitrectomy. Group E4 (n = 13) underwent both procedures. Seven of the 13 Group 4 experimental eyes developed total retinal detachment and giant holes. None of the other groups developed more than two total retinal detachments or giant holes (P < 0.05). Light and electron microscopy showed intravitreal or preretinal proliferation composed of fibroblast-like cells. Retroretinal membranes appeared only in Group E4 eyes, composed of elongated cells with oval nuclei and abundant organelles in the cytoplasm. We believe these lesions mimic human PVR more closely than other models previously developed.

Daunorubicin treatment in a refined experimental model of proliferative vitreoretinopathy

A condition similar to proliferative vitreoretinopathy (PVR) in man can be produced by injecting 25,000 homologous dermal fibroblasts into rabbit eyes following gas compression of the vitreous. Daunorubicin (15 nmol) was effective in preventing retinal detachment in this model when injected simultaneously with the fibroblasts or in two doses (10 nmol followed by 5 nmol 4 h later) on the 3rd day after fibroblast injection. A single dose of 15 nmol on the 3rd day was not effective in preventing retinal detachment. These results suggest that daunorubicin may be clinically useful in preventing PVR when given by injection both at the time of vitrectomy as well as later, when protein exudation and pigment clumps in the vitreous cavity herald the onset of PVR.

Experimental model of proliferative vitreoretinopathy (PVR) in the vitrectomised eye: effect of silicone oil.

Silicone oil alone or as an adjunct to vitrectomy is widely used for the treatment of retinal detachment complicated by proliferative vitreoretinopathy (PVR). It appears to reduce the tendency for recurrent traction detachment, but the mechanism of this action is obscure. We have studied the effects of silicone oil in an experimental animal model. Twenty five thousand homologous fibroblasts were injected into the aphakic vitrectomised rabbit eye, and traction detachment of the vascularised retina (medullary rays) regularly resulted. Intraocular silicone oil did not influence the development of this experimental detachment.