April 11, 2015
In patients with branch retinal brain occlusions (BRVOs) and central retinal vein occlusions (CRVOs), the second-most-common retinal disorders, decreased blood flow through the retinal vasculature results in tissue ischemia, upregulates vascular endothelial growth factor (VEGF), breaks down the blood-retinal barrier and causes vision loss, primarily because of macular edema.
"Impressive results from the pivotal phase III registration trials led to the approval of ranibizumab and aflibercept for the treatment of macular edema due to CRVO and ranibizumab for BRVO," says Michael W. Stewart, M.D., with the Department of Ophthalmology at Mayo Clinic's campus in Jacksonville, Florida.
"Compared with ranibizumab and aflibercept, however, bevacizumab is generally more available, is less expensive and produces comparable gains in vision — but level I evidence for the use of bevacizumab in the treatment of retinal vein occlusions is not available," he says.
Dr. Stewart's team conducted a six-month pilot study that explored the effects of combined anti-VEGF (bevacizumab) and corticosteroid (dexamethasone implant) therapy on eyes with macular edema due to BRVO and CRVO, and compared them with bevacizumab monotherapy. Results appeared in Clinical Ophthalmology in 2014.
"Our intent was to determine if intravitreal bevacizumab combined with the dexamethasone intravitreal implant 0.7 mg improves visual acuity and macular thickness more than does bevacizumab monotherapy in eyes with macular edema due to branch and central retinal vein occlusions," says Dr. Stewart.
Thirty subjects were enrolled in the study. Eligible patients had macular edema of less than one year's duration due to BRVO or CRVO, with central subfield thickness (CST) > 250 μm. Best corrected visual acuity scores at baseline were > 24 and < 80 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, or > 20/230 and < 20/25 Snellen equivalents.
Subjects were randomly assigned to one of two study groups:
- The monotherapy group (15 eyes) received intravitreal bevacizumab 1.25 mg at baseline followed by a sham dexamethasone implant injection at the time of randomization one week later. Additional bevacizumab injections were given at monthly intervals when the CST measured > 250 μm.
- The combination therapy group (15 eyes) received intravitreal bevacizumab 1.25 mg at baseline followed by an intravitreal dexamethasone implant 0.7 mg (DEX) injection at the time of randomization one week later. Bevacizumab injections were repeated monthly when the CST measured > 250 μm.
Re-injections of DEX or sham DEX (in the monotherapy group) were performed at month four or month five (one week after the repeat bevacizumab injection) if the CST measured > 250 μm.
At each visit, best corrected ETDRS visual acuities were measured and slit-lamp examinations, intraocular pressure measurements, fundus examinations and time-domain optical coherence tomography were performed. Fluorescein angiography was performed at baseline and at month six.
Secondary end points met
The team identified the study's primary end point as visual acuity in the combination group compared with visual acuity in the bevacizumab group at six months. Secondary end points included mean changes in CST, proportions of eyes with CST < 250 μm and number of bevacizumab injections required by each group.
At six months, several secondary end points were met. Patients receiving combined therapy:
- Required fewer bevacizumab re-injections than did those receiving monotherapy (two versus three; P = 0.02)
- Experienced greater mean reductions in CST from randomization (- 56 μm versus + 45 μm; P = 0.01)
- Were more likely to have resolved all edema (CST < 250 μm) (7/11 versus 2/14; P = 0.02)
The primary end point was not met. Mean visual acuity changes from baseline were similar in the two groups (P = 0.75).
"This pilot trial suggests that, compared with bevacizumab monotherapy, combining bevacizumab with the dexamethasone implant leads to more rapid improvements in vision and CST in patients with macular edema due to RVOs, while requiring fewer bevacizumab injections," says Dr. Stewart.
"For patients who are already pseudophakic and who are not steroid responders," he says, "adding DEX to a regimen of bevacizumab injections is unlikely to significantly increase the risk of complications, and for those patients who are unable to visit physicians' offices monthly, less frequent treatments with combination therapy may be a palatable alternative to the more frequently administered bevacizumab monotherapy."
For more information
Maturi RK, et al. A 6-month, subject-masked, randomized controlled study to assess efficacy of dexamethasone as an adjunct to bevacizumab compared with bevacizumab alone in the treatment of patients with macular edema due to central or branch retinal vein occlusion. Clinical Ophthalmology. 2014;8:1057.