Role of Ranibizumab in macular edema due to branch retinal vein occlusion

INTRODUCTION: Retinal vein occlusion (RVO) is the second most common cause of retinal vascular disease after diabetic retinopathy. Previous studies have reported the prevalence of RVO In the population-based Blue Mountains Eye Study (Australia), the prevalence of retinal vein occlusion was 1.6%. In the Framingham Eye Study (USA), of the 2,631 persons who underwent a screening examination, 4 of the 156 eyes found to have retinopathy had a retinal vein occlusion. The Beaver Dam Study (USA) reported a prevalence of 0.6% in patients older than 43 years. The incidence of RVO is estimated 180 000 eyes per year in United States, and branch retinal vein occlusion is the more common of the two presentations, accounting for approximately 80% of RVO. Macular edema is one of the leading cause of vision loss in patients with either central or branch retinal vein occlusions (CRVO or BRVO). This edema is found to be due to hypoxia-induced up regulation of vascular endothelial growth factor(VEGF) that loosens endothelial tight junctions leading to increase in vascular permeability and deposition of exudative material. There have been various attempts to reduce macular edema such as macular grid photocoagulation, intravitreal injections of triamcinolone acetonide or bevacizumab , but the definitive treatment modality is yet to emerge. AIM OF THE STUDY: Primary Objectives To study the efficacy of ranibizumab 0.5 mg in management of macular edema due to BRVO in terms of mean change from baseline in best corrected visual acuity(BCVA) over a 6 month treatment period. Secondary Objectives To study the efficacy of ranibizumab 0.5 mg in reducing intraretinal thickness changes on Optical Coherence Tomography (OCT) in eyes with macular edema due to BRVO . To compare the results obtained with ranibizumab therapy with those obtained with other modalities of treatment such as Laser photocoagulation and intavitreal Bevacizumab . To study ocular and systemic safety of intravitreal ranibizumab in eyes with macular edema due to BRVO. MATERIALS AND METHODS: Study Design: It is an investigative , open-label, randomized prospective interventional study done to collect the long-term efficacy and safety data in Indian patients with visual impairment due to macular edema secondary to branch retinal vein occlusion. Inclusion Criteria: • Patients with macular edema due to BRVO (confirmed by fundus photography, fluorescein angiography, OCT) • Male and female aged from 35 years and above • Baseline best-corrected visual acuity (BCVA) in the study eye Study Eye < 6/12 using Snellen chart • Central macular thickness on OCT >250 microns • Patients willing to provide signed, written informed consent Exclusion Criteria: • Additional eye disease that could compromise VA • Ocular inflammation • Intraocular surgery ≤1 month before presentation • Uncontrolled glaucoma • Prior treatments with laser photocoagulation or other intervention for macular edema due to BRVO • Pregnancy Treatment Groups: Ranibizumab group - Ranibizumab(single dose) + Laser. Bevacizumab group - Bevacizumab ( single dose) + Laser. Laser group – Laser only. Study Duration: 6 months. Methodology: All eligible patients were randomized to one of the three treatment group. Patients were followed until 6 months. Primary end point in this study was to assess the efficacy of ranibizumab 0.5 mg , by evaluating mean change from baseline in bestcorrected visual acuity (BCVA). Secondary endpoints in this study included the evaluation of tolerability and safety of ranibizumab 0.5 mg , and the Best corrected Visual acuity on snellens chart, intraretinal thickness changes in Optical Coherence Tomography (OCT) and Intraocular safety of intravitreal injection of Ranibizumab in comparison to intravitreal Bevacizumab and laser. RESULTS: This investigative, open-label, prospective randomized interventional study was performed at the retina clinic of a tertiary eye care facility in southern India over a period of 12 months ( 1st June 2009 to 31st May 2010). Thirty patients (30 eyes), comprising 12 males and 18 females (age range 38 to 74 years), who presented with macular edema due to BRVO during the study period, who satisfied the inclusion criteria and who provided consent for participation, were included in the study. DISCUSSION: Branch retinal vein occlusion (BRVO) is the second most common cause of retinal pathology after diabetic retinopathy. In most patients, macular edema is the predominant cause of visual loss although severe non-perfusion of perifoveal capillaries is an additional source of reduced vision. Elevated intra ocular levels of VEGF have been demonstrated in eyes with BRVO and this has been linked to vascular leakage, Thus there is a strong rationale for using VEGF antagonists in eyes with macular edema following BRVO. CONCLUSION: Branch retinal vein occlusion (BRVO) is the one of the most common cause of retinal pathology after diabetic retinopathy. In most patients, macular edema is the predominant cause of visual loss although severe non-perfusion of perifoveal capillaries is an additional source of reduced vision. Elevated intra-ocular levels of VEGF have been demonstrated in eyes with BRVO and this has been linked to vascular leakage. Thus, there is a strong rationale for using VEGF antagonists such as ranibizumab and bevacizumab in eyes with macular edema following BRVO. Although the effect of anti VEGF agents is very rapid and dramatic, the effect is short-lived and repeated injections are required which, in turn, increases the cost of treatment. If the permanent effects of laser (i.e. permanent stoppage of vascular leakage as compared to the temporary effects of intravitral injections) can be combined with the rapid (but temporary) effect of intravitreal injections of anti-VEGF agents, then it not only reduces the number of intravitreal injections but also reduces the financial burden of treatment, which is very important in developing countries like India. In conclusion, both ranibizumab and bevacizumab treatment in macular edema due to BRVO result in gain in visual acuity and reduction in intraretinal thickness which occurs rapidly. However, these anti-VEGF agents should always be combined with a more permanent treatment such as laser photocoagulation, which would yield much better results than any single mode of treatment alone. SUMMARY: Ranibizumab is a recently-described molecule that exhibits an antagonistic action on vascular endothelial growth factor (VEGF). Therefore, it is potentially useful in the management of macular edema that follows branch retinal vein occlusion (BRVO). The aim of the study described in this dissertation was to demonstrate the efficacy of ranibizumab (0.5 mg, intravitreal injection) over a six-month treatment period in eyes with macular edema due to BRVO. Primary measures of efficacy demonstrated during the study period were a) an improvement in mean best corrected visual acuity (BCVA) and b) a reduction in mean central foveal thickness (CFT) , as assessed by optical coherence tomography (OCT).