Oral colchicine for prevention of proliferative vitreoretinopathy: a randomized clinical trial.

Abstract

Proliferative vitreoretinopathy (PVR), as the most common cause of retinal detachment (RD) surgery failure, is characterized by proliferation of cellular elements including glial, retinal pigment epithelial and inflammatory cells. Recently, it has been suggested that presence of neural progenitor cells (NPC) in the ciliary marginal zone may also be one of the causes of PVR (Johnsen et al. 2012). Prevention of PVR seems to be central to achieve long-term satisfactory anatomical and functional results after RD surgery. An animal study showed that oral colchicine, which inhibits microtubule polymerization by binding to tubulin and inhibits cell proliferation, significantly reduces RD due to PVR (Lemor et al. 1986b). The present double-masked, controlled clinical trial was conducted to evaluate the effects of oral colchicine on the prevention of PVR in eyes undergoing scleral buckling (SB). In this study, 184 eyes of 184 patients with rhegmatogenous RD undergoing SB were randomly assigned to oral colchicine 1 mg twice daily versus placebo starting from the day after SB for 7 weeks. The patients were followed for 6 months. Of 184 patients, 161 (76 eyes in the colchicine group and 85 eyes in the placebo group) completed the 6-month follow-up. Colchicine was discontinued in nine patients (9.8%) due to gastrointestinal side-effects. Retinal redetachment due to PVR grade C occurred in nine eyes (11.8%) in the colchicine group and 13 eyes (15.3%) in the placebo group (p = 0.39). Best-corrected visual acuity improved significantly in both groups with no statistically significant difference between the two groups in this regard (p = 0.41). Macular pucker was noted in 3 (3.5%) and 1 (1.3%) eyes in the colchicine and placebo groups, respectively (p = 0.62). Logistic regression analysis showed that intravitreal gas injection was significantly associated with higher risk of retinal redetachment (odds ratio = 3.7; 95% CI, 1.1–12.5; p = 0.03). Results of this study demonstrated that oral colchicine 1 mg twice daily for 50 days had no significant effect on the prevention of retinal redetachment due to PVR. In an in vitro study, Lemor et al. (1986a) showed that colchicine is a potent inhibitor of RPE, astrocyte and fibroblast proliferation and migration. Their experimental study also demonstrated that oral administration of colchicine significantly reduced the incidence and severity of tractional RD associated with fibrocellular proliferation, without histologic signs of retinal toxicity (Lemor et al. 1986b). However, in a study on human subjects, Berman and Gombos reported no beneficial effects of oral colchicine in eyes with PVR secondary to PDR, sickle retinopathy, trauma and venous occlusive diseases (Berman & Gombos 1989). The present RCT also did not reveal any significant effect of oral colchicine on the prevention of PVR after SB. This could be attributed to the complexity of the PVR process, which may imply the need for simultaneous addressing of multiple pathways in the PVR cascade. In a study by Johnsen et al. (2012), it was demonstrated that in human eyes with PVR, proliferation of both non-glial and glial cells costaining NPC-associated markers was evident around the ora serrata region. These cells may not react well to colchicine and other antiproliferative agents. Our study showed that intravitreal gas injection within 1 week after SB surgery increases the risk of retinal redetachment due to PVR. Intravitreal injection of an expanding gas bubble in a non-vitrectomized eye may result in marked increase in flare and RPE cells in the vitreous cavity. In addition, the ruptured cortical vitreous may play a role as a scaffold for the epiretinal membranes (Griffiths & Richardson 1990). This may explain the increased risk of PVR after intravitreal gas injection in our study.