The August 2011 issue of the British Journal of Ophthalmology contains an article that caught my attention. In the article, entitled Sustained elevation of intraocular pressure after intravitreal injections of anti-VEGF agents (Translation: Sustained high pressure within the eye after injection with Avastin or Lucentis), the authors investigated several critical issues surrounding the longer-term safety of Lucentis and Avastin, injectable drugs used to treat macular degeneration.
Some Background
In May, preliminary results from the Comparison of Age-Related Macular Degeneration (AMD) Treatments Trials (CATT), which tested the effectiveness of Avastin (bevacizumab) versus Lucentis (ranibizumab) in a head-to-head clinical trial, were published online in the New England Journal of Medicine.
Initial reports indicated that Avastin, a drug approved to treat some cancers and commonly used “off-label” to treat age-related macular degeneration (AMD), was as effective as the Food and Drug Administration (FDA)-approved Lucentis for the treatment of AMD.
Blood Vessel Growth and Anti-VEGF Drugs
Angiogenesis is a term that describes the growth of new blood vessels and plays a critical role in the normal development of body organs and tissue. Sometimes, however, excessive and abnormal blood vessel development can occur in diseases such as cancer (tumor growth) and AMD (retinal and macular bleeding).
Substances that stop the growth of these excessive blood vessels are called anti-angiogenic (anti=against; angio=vessel; genic=development), and anti-neovascular (anti=against; neo=new; vascular=blood vessels).
The focus of current anti-angiogenic drug treatments for wet AMD is to reduce the level of a particular protein (vascular endothelial growth factor, or VEGF) that stimulates abnormal blood vessel growth in the retina and macula; thus, these drugs are classified as anti-VEGF treatments. At present, Lucentis and Avastin are administered by injection directly into the eye after the surface has been numbed.
About the Research
The authors asked several important research questions:
- What is the frequency of sustained elevated intra-ocular pressure (IOP) [i.e., fluid pressure inside the eye] after anti-VEGF injections?
- What is the frequency of sustained elevated IOP in patients receiving Lucentis versus Avastin?
- Is glaucoma a risk factor for sustained elevated IOP in these eyes?
- The authors also highlighted a possible association between the risk of elevated IOP and the handling, storage, and preparation of Avastin.
The Research Results
The OSN Super Site provides a concise summary of the research results:
Some patients who received intravitreal [i.e., into the eye] anti-VEGF injections showed sustained elevated IOP. The study included 215 eyes that received injections of Avastin and/or Lucentis for wet age-related macular degeneration.
The researchers evaluated frequency of injections, number of injections, and changes in IOP. Also, data were analyzed independently for patients with and without pre-existing glaucoma.
Sustained elevated IOP occurred in 10 eyes (9.9%) in patients treated with Avastin only and three eyes (3.1%) in patients treated with Lucentis only. The difference was statistically significant.
Higher rates of elevated IOP were reported in patients with pre-existing glaucoma (33%) compared with those without (3.1%). This difference was also statistically significant.
Another analysis of the eyes that received Avastin at two different centers found that one center had an elevated IOP rate of 15.3% while the other had a rate of 2.4%. This may imply that the anti-VEGF protein itself might not be the cause of IOP elevation and raised the question of other potential variables.
‘[The study] highlights a possible association between the risk of elevated IOP and the source of Avastin injected, another area that should be further investigated to ensure proper standards for handling, storage and preparation of [Avastin and other] protein-based therapeutic agents,’ the authors said.
What Does This Mean?
There are two important points to consider:
- First, this study is a retrospective one, which has limitations. A retrospective study collects data from past records and does not follow up with patients in the present. A prospective study, on the other hand, studies and measures a group of individuals over time and follows up with study patients in the future. The authors state that additional prospective studies are are needed to verify the results and better understand these findings.
- Second, it’s helpful to know how Avastin is handled, stored, and prepared in order to understand the authors’ recommendation for additional investigation. Avastin, unlike Lucentis, does not come prepared in single-dose ready-made vials for eye injections because the FDA has not yet approved it for that purpose. Pharmacies, therefore, must compound (i.e., remix or prepare a single dose of) Avastin for eye injections from packaging that is intended for intravenous use. This has raised concerns about Avastin sanitation and sterility issues.
VisionAware will provide updates on all aspects of this important research as they become available.