In a small retrospective study, eyes receiving intravitreal bevacizumab (Avastin, Genentech) within 3 months of a central retinal vein occlusion showed rapid improvement in anatomic abnormalities and subsequent improvement in vision. The benefits were maintained with repeated injections after a mean follow-up of 1 year.
Dr. Spaide reported on outcomes of six eyes of five patients who were treated with bevacizumab 1.25 mg/0.05 ml within 90 days of the CRVO and followed for a minimum of 6 months (mean, 12 months).
Comprehensive ophthalmologic examinations showed that the treatment quickly reversed macular edema (ME) as well as other anatomic features of CRVO, including retinal hemorrhages, venous tortuosity, venous dilation, and optic nerve head swelling. Visual acuity (VA) improved as well.
"This study is very small, retrospective, and has limitations of its design. However, the benefits observed are encouraging, and similar results have been reported in a prospective study of patients treated with intravitreal ranibizumab [Lucentis, Genentech]," said Dr. Spaide, a vitreoretinal specialist in private practice in New York.
"These findings suggest that further study is warranted to determine the possible efficacy of early anti-vascular endothelial growth factor [VEGF] treatment in the management of CRVO and also to explain the possible disease mechanisms, as it is difficult to explain amelioration of nearly every aspect associated by the condition if it were caused by occlusion alone," he said.
The five patients had a mean age of about 70 years, and four were taking a medication with some anticoagulant activity at the time they developed their CRVO. No patient had other ocular conditions that would have limited their vision.
Patients were seen monthly after receiving bevacizumab, and the anti-VEGF treatment was repeated based on the following criteria: decrease in VA in association with any hemorrhage, increase in retinal hemorrhages, presence of residual or recurrent ME demonstrated by optical coherence tomography (OCT) or fluorescein angiography. The number of administered injections ranged from four to 10 (mean, 5.8).
The assessment of responses to the anti-VEGF treatment included best-corrected VA, ME determined by OCT-measured macular thickness, grading of optic nerve head swelling, and calculation of the tau index as a metric of blood vessel tortuosity and an equivalent venous diameter for venous dilation.
In all patients, the tau index, equivalent venous diameter, central macular thickness, and optic disc edema score had improved significantly from baseline by the 1-month examination, and all of these measures remained relatively stable thereafter. Mean baseline VA was about 20/400 and was unchanged at 1 month. It began to improve at 2 months, however, and was significantly improved from baseline at last follow-up (mean, 20/53).
Discussing the possible mechanisms for the benefits observed, Dr. Spaide noted that the idea that ME is the cause for CRVO-associated vision loss has provided the rationale for investigating prior therapeutic interventions, including grid laser photocoagulation and intravitreal triamcinolone. Although those modalities have been shown to be effective for reducing CRVO-related ME, vision does not change after the laser treatment and improves only transiently after triamcinolone injection, he said.
In contrast, previous experience with early intravitreal bevacizumab in eyes with CRVO showed that it was associated with rapid anatomic improvements and subsequent gains in VA, he added.
"We know that CRVO causes damage to the retina, and it would seem logical that the amount of damage could increase over time," Dr. Spaide said. "Therefore, we postulated that perhaps treating CRVO early could obviate some of the permanent destruction to allow for a better visual prognosis."