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. IntroductionRetinal vein occlusion (RVO) is a common and important cause of visual loss. In population-based studies its prevalence has been reported to be around 0.6% and up to 4.6% in patients 80 years old or older with a 10-15 year cumulative incidence ranging between 1.6 and 1.8%.1-4 Studies evaluating predictors of RVO have consistently shown an association with risk factors for atherosclerosis such as hypertension, dyslipidemia, and diabetes 4,5 as well as ocular comorbidities such as glaucoma; 5,6 conversely, it has been suggested that the presence of RVO in patients under 70 years of age might be associated with increased cardiovascular mortality.7 In contrast, the association between RVO and thrombophilic risk factors for venous thrombosis, such as factor V Leiden, prothrombin G20210A, and deficiencies of antithrombin, protein C and protein S seems to be weak at best. The exceptions are hyperhomocysteinemia and the presence of antiphospholipid antibodies which are associated with an odds ratio (OR) for developing RVO of 8.9 and 3.9, respectively. 8 Long-term...

Retinal vein occlusions: a review for the internist

“…Although present evidence is weak and based on data from three small trials [45][46][47], it is the first time that we have some evidence in this field. A recent meta-analysis confirms these data [50].Thus, we suggest for our RVO patients, if diagnosed within 15 days from clinical manifestations, LMWHs at anticoagulant doses for 10-15 days followed by half dose for a total of 90 days, according to Ageno et al's protocol [45]. A careful safety assessment is necessary during treatment.…”

Trombofilia y factores de riesgo vascular en la obstrucción venosa retiniana

“…Squizzato et al 11 , en un metaanálisis que analizó 384 pacientes (234 con trombosis de vena central de la retina y 150 con afectación de rama), sugirieron que la terapia antitrombótica, en particular las HBPM, pudieran ser los fár-macos más eficaces en la fase aguda de la OVR, en relación al pronóstico visual. También Lazo-Langner et al 26 sugieren la superioridad de las HBPM frente a la aspirina. En nuestra opinión, dado que los pacientes con OVR constituyen un grupo heterogéneo desde el punto de vista etiológico (ya que en la mayoría de los casos predomina la arterioesclerosis y en un menor porcentaje la trombofilia), y también son diferentes respecto al tiempo de evolución de la trombosis, es difícil establecer un tratamiento único para todos ellos.…”

Hyper-Homocysteinemia and other Inherited Thrombophilic Factors Inducing Retinal Vein Occlusion. The Employment of Novel Orals Anti-Coagulants is Possible?

“…Current guidelines recommend an initial treatment with Low Molecular Weight Heparins (LMWHs) [35]. These are useful for their additional properties, such as anti-angiogenic effect [36], anti-inflammatory and immunomodulatory properties [37][38][39]. Practically, if diagnosed within 15 days, LWMH must be administered for two first weeks.…”