Anti‐vascular endothelial growth factor for macular edema secondary to central retinal vein occlusion
Abstract
Background
Central retinal vein occlusion (CRVO) is a common retinal vascular disorder in which macular edema (ME) may develop, with a consequent reduction in visual acuity. The visual prognosis in CRVO‐ME is poor in a substantial proportion of patients, especially those with the ischemic subtype, and until recently there has been no treatment of proven benefit. Macular grid laser treatment is ineffective, and whilst a few recent randomized controlled trials (RCTs) suggest short‐term gains in visual acuity with intravitreal steroids for patients with non‐ischemic CRVO‐ME, there is no established treatment for ischemic CRVO‐ME. Anti‐vascular endothelial growth factor (anti‐VEGF) agents have been used to treat ME resulting from a variety of causes and may represent a treatment option for CRVO‐ME.
Objectives
To investigate the effectiveness and safety of intravitreal anti‐VEGF agents in the treatment of CRVO‐ME.
Search methods
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2010, Issue 8), MEDLINE (January 1950 to August 2010), EMBASE (January 1980 to August 2010), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to August 2010), Cumulative Index to Nursing and Allied Health Literature (CINAHL) (January 1937 to August 2010), OpenSIGLE (January 1950 to August 2010), the metaRegister of Controlled Trials (mRCT) (www.controlled‐trials.com) and ClinicalTrials.gov (www.clinicaltrials.gov). There were no language or date restrictions in the search for trials. The electronic databases were last searched on 10 August 2010.
Selection criteria
We considered RCTs that compared intravitreal anti‐VEGF agents of any dose or duration to sham injection or no treatment. We focused on studies that included individuals of any age or gender with unilateral or bilateral disease and a minimum of six months follow up. Secondarily, we considered non‐randomized studies with the same criteria, but did not conduct a separate electronic search for these.
Data collection and analysis
Two review authors independently assessed trial quality and extracted data.
Main results
We found two RCTs that met the inclusion criteria after independent and duplicate review of the search results. These RCTs utilized different anti‐VEGF agents which cannot be assumed to be directly comparable. We, therefore, performed no meta‐analysis. Evidence from these trials and from other non‐randomized case series is summarized in this review.
Authors' conclusions
Ranibizumab and pegaptanib sodium have shown promise in the short‐term treatment of non‐ischemic CRVO‐ME. However, effectiveness and safety data from larger RCTs with follow up beyond six months are not yet available. There are no RCT data on anti‐VEGF agents in ischemic CRVO‐ME. The use of anti‐VEGF agents to treat this condition therefore remains experimental.
Plain language summary
Anti‐vascular endothelial growth factor for macular edema secondary to central vein occlusion
Central retinal vein occlusion (CRVO) is thought to affect between one and four people per thousand at any one time, and is associated with increasing age, high blood pressure, diabetes, glaucoma and various disorders of the blood. It frequently causes sudden painless vision loss in one eye, although sometimes the vision loss may be minimal. If the vein blockage leads to inadequate oxygen delivery to the sensitive retinal tissue, the CRVO is considered to be of the 'non‐perfused' or 'ischemic' subtype. More commonly, blood flow and oxygen delivery are restored following the vein blockage and the CRVO is considered to be of the 'perfused' or 'non‐ischemic' subtype, which has a better visual outcome. Various other complications may develop over hours, days, weeks or months. These include macular edema (ME), in which fluid collects within the retina and causes reduction in vision. Until recently there has been no evidence‐based treatment for this condition and many potential treatments, including laser, have been found to be ineffective. Recent studies suggest that an injection or implant of steroids in the eye may be of at least short‐term benefit to patients with the perfused subtype of the condition. However, steroids are associated with significant side effects and there is currently no evidence that the benefit is sustained, or that patients with the non‐perfused subtype of CRVO benefit from this treatment. Anti‐vascular endothelial growth factor (anti‐VEGF) agents have been used successfully to treat patients with other retinal vascular disorders, including several conditions associated with ME. Whilst anti‐VEGF treatment appears to be associated with improved vision in a proportion of patients with perfused CRVO‐ME, there are currently no well‐designed studies with a sufficient follow‐up time in the literature to allow a conclusion about their medium and long‐term effectiveness and safety to be drawn. The outcomes of several trials with follow up exceeding one year are keenly awaited, and the use of anti‐VEGF agents for CRVO‐ME remains experimental.
