isotretinoin and Vitreoretinopathy--Proliferative

Proliferative vitreoretinopathy (PVR) remains the most significant obstacle to successful retinal reattachment surgery. Preclinical studies continue to add insights into the complex molecular events leading to PVR development, helping to identify new targets for potential prophylactic or therapeutic agents. This article reviews the recent evidence supporting surgical and medical treatments for PVR.. PUBMED was used for literature search. Clinical studies regarding surgical management of PVR from January 1, 2000 to August 1, 2014 were included. Clinical studies regarding medical management of PVR from January 1, 2000 to August 1, 2014 were included if the design of study was a randomized controlled trial.. Many recent studies have evaluated surgical and medical strategies for the treatment and prevention of PVR. Newer vitreoretinal surgery technology (23- and 25-gauge vitrectomy) and tamponade agents (heavy silicone oils) have been studied. Medical therapies evaluated include antiinflammatory agents, low molecular weight heparin, 5-fluorouracil, 13-cis-retinoic acid, and daunorubicin, amongst others.. Surgical management with pars plana vitrectomy, with or without scleral buckle or inferior retinectomy, remains an effective treatment for PVR-related detachments. Consensus regarding a preferred surgical strategy remains controversial. Many medical therapies have been studied but fail to demonstrate a statistically significant benefit in clinical trials. Further studies to clarify the efficacy of available and novel treatment options are warranted.

Topics: Anti-Inflammatory Agents; Endotamponade; Fluorouracil; Heparin, Low-Molecular-Weight; Humans; Immunosuppressive Agents; Isotretinoin; Scleral Buckling; Vitrectomy; Vitreoretinopathy, Proliferative

Proliferative vitreoretinopathy (PVR) is a vision-threatening disease and a common complication of surgery to correct rhegmatogenous retinal detachment (RRD). Several models of the pathogenesis of this disease have been described with some of these models focusing on the role of inflammatory cells and other models focusing on the role of growth factors and cytokines in the vitreous which come into contact with intraretinal and retinal pigment epithelial cells. New experiments have shed light on the pathogenesis of PVR and offer promising avenues for clinical intervention before PVR develops. One such target is the indirect pathway of activation of platelet-derived growth factor receptor alpha (PDGRα), which plays an important role in PVR. Clinical trials assessing the efficacy of 5-fluorouracil (5-FU) and low-molecular-weight heparin (LMWH), daunorubicin, and 13-cis-retinoic acid, among other therapies, have yielded mixed results. Here we review inflammatory and other mechanisms involved in the pathogenesis of PVR, we highlight important clinical trials, and we discuss how findings at the bench have the potential to be translated to the bedside.

Topics: Animals; Clinical Trials as Topic; Daunorubicin; Fluorouracil; Heparin, Low-Molecular-Weight; Humans; Inflammation; Isotretinoin; Receptor, Platelet-Derived Growth Factor alpha; Vitreoretinopathy, Proliferative

To determine whether postoperative oral 13-cis-retinoic acid (RA) treatment could improve the outcome of vitreoretinal surgery with silicone oil for the management of proliferative vitreoretinopathy (PVR).. Prospective controlled randomized interventional case series.. This study included 35 eyes of 35 patients with primary rhegmatogenous retinal detachment and PVR. All patients underwent surgical repair by similar procedures. The RA group consisted of 16 patients who received 10 mg oral RA twice daily for eight weeks postoperatively. The control group included 19 patients without taking RA. The outcome measure included the rate of retinal attachment, macular pucker formation, ambulatory vision, and RA-related side effects.. At last follow-up (at least one year postoperatively), 15 of 16 eyes (93.8%) in the RA group and 12 of 19 eyes (63.2%) in the control group maintained retinal attachment (P = .047). The rate of macular pucker formation was significantly lower in the RA group (18.8% vs 78.9% in the control group; P = .001). A higher rate of ambulatory vision was achieved in the RA group as compared to the control group (56.3% vs 10.5%; P = .009).. Postoperative administration with oral moderate dosage of RA for eight weeks appears to maintain retinal attachment, decrease the macular pucker, and improve vision after surgical repair for eyes with PVR.

Topics: Administration, Oral; Female; Follow-Up Studies; Humans; Isotretinoin; Laser Coagulation; Lens Implantation, Intraocular; Male; Middle Aged; Postoperative Complications; Prospective Studies; Recurrence; Retinal Detachment; Scleral Buckling; Silicone Oils; Treatment Outcome; Visual Acuity; Vitrectomy; Vitreoretinopathy, Proliferative

To examine the effect of low-dose, oral isotretinoin in lowering the risk of proliferative vitreoretinopathy (PVR) following rhegmatogenous retinal detachment (RRD) repair.. Prospective, open label, dual-cohort study with pathology-matched historical controls. The prospective experimental arms included two cohorts, composed of 51 eyes with recurrent PVR-related RRD and 58 eyes with primary RRD associated with high-risk features for developing PVR. Eyes in the experimental arms received 20 mg of isotretinoin by mouth once daily for 12 weeks starting the day after surgical repair. The primary outcome measure was single surgery anatomical success rate at 3 months following the study surgery.. The single surgery anatomic success rate was 78.4% versus 70.0% (p=0.358) in eyes with recurrent PVR-related retinal detachment exposed to isotretinoin versus historical controls, respectively. In eyes with RRD at high risk for developing PVR, the single surgery success rate was 84.5% versus 61.1% (p=0.005) for eyes exposed to isotretinoin versus historical controls, respectively. For eyes enrolled in the experimental arms, the most common isotretinoin-related side effects were dry skin/mucus membranes in 106 patients (97.2%), abnormal sleep/dreams in 4 patients (3.7%) and fatigue in 3 patients (2.8%).. The management and prevention of PVR is challenging and complex. At the dose and duration given in this study, oral istotretinoin may reduce the risk of PVR-associated recurrent retinal detachment in eyes with primary RRD at high risk of developing PVR.

Topics: Administration, Oral; Adult; Aged; Female; Humans; Isotretinoin; Male; Middle Aged; Multivariate Analysis; Pilot Projects; Prospective Studies; Retinal Detachment; 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

To determine if postoperative oral 13-cis-retinoic acid alters the rate of recurrent retinal detachment in eyes undergoing surgery for proliferative vitreoretinopathy (PVR).. Twenty eyes of 20 adult patients with a detachment due to PVR were identified after retrospective review of the patient records of a single vitreoretinal surgeon (EdJ) over an 18-month period (January 1992-August 1993). All 20 eyes underwent surgical repair using similar techniques. Ten patients received 40 mg oral 13-cis-retinoic acid twice daily for 4 weeks postoperatively (study group). The remaining ten patients did not (control group). The main outcome measure was retinal attachment or detachment.. No statistically significant differences in preoperative patient characteristics or surgical procedure were present between the groups. Nine of ten eyes in the study group remained attached during a mean follow-up of 8.3 months, whereas four of ten eyes in the control group remained attached (P = 0.061) during a mean follow-up of 9.6 months. The rate of macular pucker was similar between the groups. The one eye in the study group that redetached did not have PVR. Of the six eyes in the control group that detached, four had 6 or more clock hours of PVR. The final visual acuity was better than 20/400 in six study eyes and four control eyes.. Despite the small sample size and retrospective nature, the postoperative administration of oral 13-cis-retinoic acid appears to decrease proliferative vitreoretinopathy and increase the rate of retinal attachment after surgical repair. A prospective, randomized, controlled clinical trial is warranted.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Female; Follow-Up Studies; Humans; Isotretinoin; Male; Middle Aged; Prognosis; Recurrence; Retinal Detachment; Retrospective Studies; Visual Acuity; Vitreoretinopathy, Proliferative