Age-Related Macular Degeneration: Lucentis Raises Stroke Risk Interview with:
Takashi Ueta, M.D., Ph.D.
Assistant Professor, Department of Ophthalmology
Graduate School and Faculty of Medicine
The University of Tokyo

Medical Research: What is the background for this study? What are the main findings?

Dr. Ueta: In 2009 we had reported an initial systematic review and meta-analysis which include pivotal RCTs but the number of the included studies were only 3 (MARINA, ANCHOR, FOCUS). During the following several years, more trials comparing different dosages and frequencies of ranibizumab treatment were conducted, which made us to update our meta-analysis.

Based on our updated meta-analysis, increase in several systemic vascular adverse events was observed: 86% increase in odds ratio (OR) for the risk of cerebrovascular accident (CVA) when 0,5 mg ranibizumab used. 89% increase in OR for the risk of CVA when monthly ranibizumab of any dosage is used. 57% increase in OR for the risk of non-ocular hemorrhage when ranibizumab of any dosage with any frequency is used.

Medical Research: What should clinicians and patients take away from your report?

Dr. Ueta: Many ophthalmologists have not realized the possible increase in the systemic vascular risks by ranibizumab for age-related macular degeneration. I assume this is largely because the frequency of CVA and other systemic vascular adverse event is low (usually up to several % of AMD patients per year). However, our meta-analysis by including data for more than 6500 patients showed significant increase in the risk of CVA and non-ocular hemorrhage by ranibizumab.

Anti-VEGF therapy including ranibizumab is critically important for the treatment of ocular disorders. However, we need to care about systemic risk when it is used.

To schedule dose and frequency of ranibiuzmab with paying attention to the risk profile of age-related macular degeneration patients could reduce the likelihood of systemic vascular adverse events. For example, recent history of CVA and uncontrolled hypertension are the top risk factors for CVA.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Ueta: In our meta-analysis we focused on ranibizumab because it has been evaluated through the largest number of RCTs and patients. I speculate that other anti-VEGF drugs including bevacizumab and aflibercept could have similar effects on systemic vasculature. However, current evidence through RCTs has not been sufficient for the evaluation of these drugs in comparison to ranibizumab.


Systemic Vascular Safety of Ranibizumab for Age-Related Macular Degeneration

Ueta T1, Noda Y2, Toyama T2, Yamaguchi T3, Amano S2.
Ophthalmology. 2014 Jul 12. pii: S0161-6420(14)00486-2. doi: 10.1016/j.ophtha.2014.05.022.