Low molecular weight heparin for the treatment of retinal vein occlusion: a systematic review and meta-analysis of randomized trials

Abstract

Retinal vein occlusion is a frequent cause of visual loss for which few effective therapies are available. Anticoagulation with low molecular weight heparin might be of value in its treatment. We conducted a systematic review and meta analysis of randomized trials evaluating the effect of low molecular weight heparin in patients with retinal vein occlusion. Data sources included MEDLINE, EMBASE, HealthSTAR, the Cochrane Library, Lilacs, the Investigative Ophthalmology and Visual Science database and gray literature. Main outcome was the mean difference between the visual acuity measured at baseline and at six months expressed in the logMAR scale. Secondary outcome was a composite of any adverse ocular outcome including: worsening of visual acuity, visual fields or fluorescein angiography, or development of iris neovascularization, any neovascularization or neovascular glaucoma. Subgroup analyses for branch versus central retinal vein occlusion were conducted. We identified 1,084 references of which 3 studies comparing low molecular weight heparin with aspirin (229 evaluable patients) were included. Overall, the pooled mean visual acuity difference was -0.23 logMAR (95% CI -0.38, -0.09; P=0.002) in favor of low molecular weight heparin. Low molecular weight heparin was associated with a 78% risk reduction for developing any adverse ocular outcome (pooled RR 0.22; 95% CI 0.10, 0.46; P<0.001). In subgroup analyses benefits seemed lower in branch retinal vein occlusion. No increased vitreous hemorrhages were observed. In patients with retinal vein occlusion treatment with low molecular weight heparin seems to be associated with improvement in the visual acuity and less adverse ocular outcomes. These benefits might differ in patients with central as opposed to branch retinal vein occlusion. Further studies are required to confirm these findings and clarify its benefits in specific subgroups of patients before definitive recommendations can be made.

Figure 1.

Flow diagram of the systematic review. IOVS Investigative Ophthalmology and Visual Science; ASH American Society of Hematology; ISTH International Society on Thrombosis and Haemostasis; ARVO Association for Research in Vision and Ophthalmology; RCT Randomized controlled trial.

Figure 2.

Forest plot of the mean difference in visual acuity expressed in the logarithm of the minimum angle of resolution (logMAR) scale in studies comparing low molecular weight heparin versus aspirin for the treatment of recent-onset retinal vein occlusion. LMWH low molecular weight heparin; SD standard deviation; IV inverse variance; CI confidence interval

Figure 3.

Forest plots showing the odds ratios and risk ratios for the occurrence of any adverse ocular outcome (see text for definition) in studies comparing low molecular weight heparin versus aspirin for the treatment of recent-onset retinal vein occlusion. LMWH low molecular weight heparin; CI confidence interval; CRVO central retinal vein occlusion; BRVO branch retinal vein occlusion.