Anti-vascular endothelial growth factor for macular oedema secondary to branch retinal vein occlusion
ABSTRACT Branch retinal vein occlusion (BRVO) is one of the most common occurring retinal vascular abnormalities. The pathogenesis of BRVO is thought to involve both retinal vein compression and damage to the vessel wall, possibly leading to thrombus formation at sites where retinal arterioles cross retinal veins. The most common cause of visual loss in patients with BRVO is macular oedema (MO). Grid or focal laser photocoagulation has been shown to reduce the risk of visual loss and improve visual acuity (VA) in up to two thirds of individuals with MO secondary to BRVO, however, limitations to this treatment exist and newer modalities have suggested equal or improved efficacy. Recently, antiangiogenic therapy with anti-vascular endothelial growth factor (anti-VEGF) has been used successfully to treat MO resulting from a variety of causes. As elevated intraocular levels of VEGF have been demonstrated in patients with retinal vein occlusions there is a strong basis for the hypothesis that anti-VEGF agents may be beneficial in the treatment of vascular leakage and MO.
To investigate the efficacy and safety of intravitreal anti-VEGF agents for preserving or improving vision in the treatment of MO secondary to BRVO.
We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 7), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to August 2012), EMBASE (January 1980 to August 2012), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to August 2012, the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 7 August 2012 and the clinical trials registers on 10 September 2012.
We included randomised controlled trials (RCTs) and quasi-RCTS of at least six months duration where anti-VEGF treatment was compared with another treatment, no treatment, or placebo. We excluded trials where combination treatments (anti-VEGF plus other treatments) were used and trials that investigated the dose and duration of treatment without a comparison group (other treatment/no treatment/sham).
Two review authors independently extracted the data. The primary outcome was the proportion of participants with an improvement from baseline in best-corrected visual acuity (BCVA) of greater than or equal to 15 letters (3 lines) on the Early Treatment in Diabetic Retinopathy Study (ETDRS) Chart at six months and at 12 months of follow-up. The secondary outcomes we report are the proportion of participants who lost greater than or equal to 15 ETDRS letters (3 lines) and the mean VA change at six months and any additional follow-up intervals as well as the change in central retinal thickness on optical coherence tomography (OCT) from baseline and final reported follow-up, the number and type of complications, the number of additional interventions administered and any adverse outcomes. Where available, the cost benefit and quality of life data reported in the primary studies is presented.
We found one RCT and one quasi-RCT that met the inclusion criteria after independent and duplicate review of the search results. The studies used different anti-VEGF agents and different study groups which were not directly comparable.One multi-centre RCT (BRAVO) conducted in the USA randomised 397 individuals and compared monthly intravitreal ranibizumab (0.3 mg and 0.5 mg) injections with sham injection. The study only included individuals with non-ischaemic BRVO. Although repeated injections of ranibizumab appeared to have a favourable effect on the primary outcome, approximately 50% of the ranibizumab 0.3 mg group and 45% of the ranibizumab 0.5 mg group received rescue laser treatment which may have an important effect on the primary outcome. In addition, during the six-month observation period 93.5% of individuals in the sham group received intravitreal ranibizumab (0.5 mg). This cross-over design limits the ability to compare the long-term impact of ranibizumab versus a pure control group.The second trial was a small study (n = 30) from Italy with limitations in study design that reported a benefit of as-required intravitreal bevacizumab (1.25 mg) over laser photocoagulation in MO secondary to BRVO. We present the evidence from these trials and other interventional case series.
The available RCT evidence suggests that repeated treatment of non-ischaemic MO secondary to BRVO with the anti-VEGF agent ranibizumab may improve clinical and visual outcomes at six and 12 months. However, the frequency of re-treatment has not yet been determined and the impact of prior or combined treatment with laser photocoagulation on the primary outcome is unclear. Results from ongoing studies should assess not only treatment efficacy but also, the number of injections needed for maintenance and long-term safety and the effect of any prior treatment.
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ABSTRACT: The pathogenetic role of vascular endothelial growth factor (VEGF) in long-term retinal and kidney complications of diabetes has been demonstrated. Conversely, little is known in diabetic neuropathy. We examined the modulation of VEGF pathway at mRNA and protein level on dorsal root ganglion (DRG) neurons and Schwann cells (SC) induced by hyperglycaemia. Moreover, we studied the effects of VEGF neutralization on hyperglycemic DRG neurons and streptozotocin-induced diabetic neuropathy. Our findings demonstrated that DRG neurons were not affected by the direct exposition to hyperglycaemia, whereas showed an impairment of neurite outgrowth ability when exposed to the medium of SC cultured in hyperglycaemia. This was mediated by an altered regulation of VEGF and FLT-1 receptors. Hyperglycaemia increased VEGF and FLT-1 mRNA without changing their intracellular protein levels in DRG neurons, decreased intracellular and secreted protein levels without changing mRNA level in SC, while reduced the expression of the soluble receptor sFLT-1 both in DRG neurons and SC. Bevacizumab, a molecule that inhibits VEGF activity preventing the interaction with its receptors, restored neurite outgrowth and normalized FLT-1 mRNA and protein levels in co-cultures. In diabetic rats, it both prevented and restored nerve conduction velocity and nociceptive thresholds. We demonstrated that hyperglycaemia early affected neurite outgrowth through the impairment of SC-derived VEGF/FLT-1 signaling and that the neutralization of SC-secreted VEGF was protective both in vitro and in vivo models of diabetic neuropathy.PLoS ONE 09/2014; 9(9):e108403. DOI:10.1371/journal.pone.0108403 · 3.53 Impact Factor
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ABSTRACT: To evaluate the anatomic and functional effect of microincision vitrectomy surgery (MIVS) with internal limiting membrane (ILM) peeling for macular edema secondary to branch retinal vein occlusion (BRVO). The medical records of 101 eyes of 101 patients who had undergone MIVS with ILM peeling for macular edema secondary to BRVO were studied. Patients were classified into ischemic and non-ischemic BRVO based on angiograph. The best-corrected visual acuity (BCVA) and central foveal thickness (CFT), determined by spectral domain optical coherence tomography, were evaluated at baseline and at 1, 3, 6, and 12 months postoperatively. Preoperative mean logarithm of the minimum angle of resolution (logMAR) BCVA ± standard deviation (SD) was 0.52±0.43 and mean CFT ± SD was 489.4±224.9 μm. Postoperative mean BCVA ± SD values were 0.41±0.35, 0.35±0.41, 0.29±0.36, and 0.25±0.41, and mean CFT values were 370.1±148.9, 327.5±157.5, 310.9±154.9, and 274.4±135.3 μm at 1, 3, 6, 12 months, respectively. The mean BCVA was significantly improved at 3, 6, and 12 months postoperatively (all P<0.05), and the mean CFT was significantly decreased at all postoperative follow-up time points (all P<0.05). At the 12-month postoperative evaluation, BCVA had improved by 0.2 logMAR units in 50 eyes (60.0%) with ischemic BRVO and in nine eyes (50.0%) with non-ischemic BRVO. Six eyes (6.0%) experienced recurrence or persistence of macular edema at 12 months postoperatively. MIVS with ILM peeling for macular edema secondary to BRVO is effective in improving visual acuity and foveal morphology with low recurrence of macular edema.Clinical ophthalmology (Auckland, N.Z.) 01/2015; 9:439-44. DOI:10.2147/OPTH.S75659
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ABSTRACT: Abstract The treatment of neovascular age-related macular degeneration (AMD) and other pathologic ocular conditions that overexpress the vascular endothelial growth factor (VEGF) has been revolutionized in the last decade by the introduction of intravitreal agents that target the VEGF pathway. Since treatment trials are designed primarily to assess the prevention of vision loss caused by ocular conditions, they are inadequate for detecting rare, but potentially serious, systemic side effects. The aim of this article is to present what the ophthalmologist needs to know about systemic complications from anti-VEGF therapy and review the likelihood that these side effects occur in the context of small, but often-repeated, intravitreal doses of these potent biological medications. Preferred practice patterns need to be developed that weigh the ability of these medications to mitigate potentially blinding conditions, while at the same time minimizing the risk of adverse outcomes in specific patient populations that possess multiple and often interrelated medical comorbidities.Seminars in Ophthalmology 11/2014; 29(5-6):263-75. DOI:10.3109/08820538.2014.959195 · 1.20 Impact Factor