tretinoin and Retinal-Detachment

Proliferative vitreoretinopathy (PVR) is a complex process. It causes contractile fibrocellular membranes that may prevent retinal reattachment. PVR therefore remains one of the most severe complications of rhegmatogenous retinal detachment (RD), with an incidence of 5-11%, and is among the most frequent causes of surgical failure (50-75%). Its severity derives from the complexity of the surgery required to treat patients and from its uncertain anatomic and functional prognosis. The first step in preventing PVR is to identify patients at risk by means of clinical and/or biological factors such as the characteristics of retinal tears (large size, number) and detachment (preexisting PVR, extent), and the use of cryotherapy. Surgeons must therefore adapt their surgical approach to the risk of PVR. The study of animal models and the natural history of the condition in humans demonstrate the importance of early antiproliferative treatment in the early stage of the disease. Combining 5-fluoro-uracil and heparin in the vitrectomy infusion lowers the rate of postoperative PVR onset in patients with PVR risk factors. The evaluation of new molecules and new dosages will lead to a decisive step in the fight against PVR.

Topics: Antibiotics, Antineoplastic; Colchicine; Daunorubicin; Fibrinolytic Agents; Fluorouracil; Glucocorticoids; Heparin; Humans; Immunosuppressive Agents; Intravitreal Injections; Keratolytic Agents; Retinal Detachment; Tretinoin; Tubulin Modulators; Vitreoretinopathy, Proliferative

Topics: Arsenic Trioxide; Blindness; Humans; Leukemia, Promyelocytic, Acute; Male; Middle Aged; Retinal Detachment; Tretinoin

To investigate the relationship between the level of retinoic acid (RA) in the subretinal fluid (SRF) and the extent of the vitreoretinopathy in 56 patients with rhegmatogenous retinal detachment, we studied the levels of RA in both SRF and serum using high liquid chromatography and also examined those levels in part of patients who took oral vitamin A 150,000 U.d-1. The results were that the level of RA in the SRF increased with the grade of the proliferative vitreoretinopathy (PVR); the levels of RA in both SRF and serum were significantly higher in the cases with vitamin A than those without. We conclude that retinoic acid metabolism between retinal pigment epithelial cells and neural epithelia was unbalanced after retinal detachment. Oral vitamin A is helpful to inhibit the genesis and development of the proliferative vitreoretinopathy.

Topics: Adolescent; Adult; Aged; Female; Humans; Male; Middle Aged; Random Allocation; Retina; Retinal Detachment; Tretinoin; Vitamin A; Vitreoretinopathy, Proliferative

The purpose of this study was to evaluate the effect of 13-cis-Retinoic Acid (RA) in Silicone-Fluorosilicone Copolymer Oil (SiFO) in a rabbit model of proliferative vitreoretinopathy (PVR). Rabbits underwent gas-compression vitrectomy. During gas-SiFO exchange, group 1 was injected with 1 ml (10 microg ml-1) 13-cis-RA in SiFO, group 2 with 1.5 ml (9 microg 1.5 ml-1) all-trans-RA in SiFO, group 3 with 1 ml SiFO alone, and group 4 with balanced salt solution (BSS). Groups 1-4 were also injected with 0.1 ml suspension of fibroblasts (75,000 0.1 ml-1) and 0.05 ml platelet rich plasma (70,000 0.1 ml-1), and were observed for 4 weeks. Group 5 was injected with SiFO alone, group 6 with 1 ml (10 microg ml-1) 13-cis-RA in SiFO, group 7 with 1.5 ml (9 microg 1.5 ml-1) all-trans-RA in SiFO, and group 8 with BSS. After 4 weeks, groups 5-7 underwent SiFO-BSS exchange. ERG and histopathology were performed to test for retinal toxicity in groups 5-8. The incidence of traction retinal detachment at 4 weeks was: group 1, 42.9%; group 2, 36.4%; group 3, 87.5%; and group 4, 88.9%. A significant difference in the incidence of PVR was noted between treated eyes (groups 1 and 2) and control eyes (groups 3 and 4) at 2, 3, and 4 weeks (P<0.05). No significant difference in the incidence of PVR was found between groups 1 and 2 during the same observation periods. ERG and histopathological studies showed no differences between the treated and the control fellow eyes (group 5-7) after 4 weeks. 13-cis-RA in SiFO (10 microg ml-1) is as effective as all-trans-RA in SiFO (9 microg 1.5 ml-1) in controlling the incidence of PVR when used for short term retinal tamponade and does not appear to be associated with retinal toxicity.

Topics: Animals; Electroretinography; Intraocular Pressure; Isotretinoin; Polymers; Rabbits; Retina; Retinal Detachment; Silicones; Tretinoin; Vitreoretinopathy, Proliferative

The authors evaluated the effect of retinoic acid (RA) in silicone oil (SiO) and in silicone-fluorosilicone (SiFO) copolymer oil in a new rabbit model of proliferative vitreoretinopathy (PVR).. To create the PVR model, three groups of rabbits were administered vitreous injections of approximately 100,000 homologous fibroblasts, 75,000 platelet-rich plasma (PRP), and fibroblasts + PRP, respectively. These rabbits were followed up ophthalmoscopically and histopathologically for as long as 2 months. Five additional groups of rabbits underwent gas-compression vitrectomy in one eye. Four days later, group 1 was administered intravitreous RA in SiFO (9 micrograms/ml) with approximately 150,000 fibroblasts and 70,000 PRP. Group 3 was administered the same amount of fibroblasts and PRP as group 1 with RA in SiO (9 micrograms/ml). Groups 2, 4, and 5 were administered the same amount of fibroblasts and PRP as groups 1 and 3 with 1 ml of SiFO, SiO, or balanced salt solution only, respectively. To evaluate RA toxicity, RA was injected in SiO (15 and 20 micrograms/ml) and RA in SiFO (10 micrograms/ml).. All eyes that were administered fibroblasts or PRP developed vitreous membranes, but those with PRP alone did not develop proliferative changes or retinal detachment; fibroblasts alone produced proliferative changes and retinal detachment after 2 to 3 weeks; fibroblasts + PRP produced similar changes within 3 days of injection. Retinoic acid (15 micrograms/ml) in SiO and RA (10 micrograms/ml) in SiFO was well tolerated. Retinal atrophic changes were found in eyes with 20 micrograms/ml RA in SiO. The retinal detachment rate was lower (P < 0.05) in the eyes that were administered fibroblasts + PRP and RA than in the controls. Significant differences were found in the degrees of PVR among the groups.. RA could be useful in PVR treated with SiO or for eyes treated intraoperatively with heavier-than-water SiFO when it is used as a short-term retinal tamponade.

Topics: Animals; Blood Platelets; Disease Models, Animal; Drug Carriers; Fibroblasts; Injections; Rabbits; Random Allocation; Retina; Retinal Detachment; Silicone Oils; Tretinoin; Vitreoretinopathy, Proliferative; Vitreous Body

The aims were to obtain a controlled intravitreous release of retinoic acid (RA) by injecting drug loaded microspheres of biodegradable polymers and to study the potential use of this RA delivery system in a rabbit model of proliferative vitreoretinopathy (PVR).. The release of RA in vitro from 15 mg of 50-50 poly(DL-lactide-co-glycolide) (PLGA) in 1 ml of water at room temperature was measured with a spectrophotometer. In a rabbit model of PVR, 11 eyes were injected with 5 mg of microspheres containing 22 micrograms of RA/mg of PLGA, and seven control eyes were injected with microspheres of the same polymer that did not contain RA. In a third group, six rabbits were injected with 5 mg (n = 3) and 10 mg (n = 3) of microspheres containing RA.. The initial concentration of RA was 20.8 micrograms/mg of PLGA. The release curve showed a fairly constant daily release of 7 micrograms/d for about 30 days. At 40 days, the release rate decreased to about 6 micrograms/d. After 40 days, 82.8% of the RA was released. Four of 11 treated rabbits (36%) and 7/7 (100%) controls showed tractional retinal detachment (TRD) (P < 0.01) after 2 months. Histopathologically, a mild, localized, foreign body reaction was observed.. The authors obtained a sustained release of RA from PLGA microspheres in vitro for 40 days. A single injection of RA-loaded microspheres in suspension in BSS was effective in reducing the incidence of TRD after 2 months in a rabbit model of PVR.

Topics: Animals; Biocompatible Materials; Biodegradation, Environmental; Delayed-Action Preparations; Disease Models, Animal; Drug Carriers; Eye Diseases; Female; Lactic Acid; Male; Microspheres; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Polymers; Rabbits; Retinal Detachment; Retinal Diseases; Tretinoin; Vitreous Body

To evaluate, in vitro, the solubility and stability of all-trans RA in silicone oil (SiO) and, in vivo, the stability and the antiproliferative effect of all-trans RA in SiO on an experimental model of PVR.. The solubility and stability of RA in SiO, in vitro and in vivo, were evaluated by HPLC. Rabbits underwent unilateral gas-compression vitrectomy and gas-SiO exchange. Rabbits received 10 micrograms (n = 17), 5 micrograms (n = 11), and 2 micrograms (n = 9) of all-trans RA in SiO, and SiO only (n = 12). All rabbits received an intravitreous injection of 150,000 fibroblasts.. RA is stable in SiO in vitro, but some isomerization from all-trans to 13-cis was observed under light exposure. In vivo, after 1 week, trace amounts of RA in SiO were observed in the controls and in the experimental animals, suggesting a steady state between the release of RA from the SiO and from the retina to the SiO. The rate of fractional retinal detachment was significantly lower in the animals that received 10 and 5 micrograms of RA than in the controls (P < 0.05). No statistical differences were found between the eyes treated with 10 and 5 micrograms of RA. Eyes that received 2 micrograms of RA showed no difference from the control group.. The in vivo data suggest that retinoic acid might be useful as an antiproliferative agent in human eyes.

Topics: Animals; Cell Division; Cells, Cultured; Chromatography, High Pressure Liquid; Disease Models, Animal; Drug Stability; Eye Diseases; Female; Fibroblasts; Male; Rabbits; Retinal Detachment; Retinal Diseases; Silicone Oils; Solubility; Tretinoin; Vitreous Body