THE FREQUENCY OF INJECTIONS FOR MACULAR DEGENERATION: The art, the science, the rationale


This month, we have a guest post on the blog from Dr. Marc Peden.

As many of our snowbirds who see multiple retinal specialists will tell you, various doctors often have very different injection protocols, making this topic very confusing for many patients. Currently, most retinal physicians adhere to one of three treatment methods:

  • Continued interval therapy or ‘monthly’ -injection given every 4 weeks (Avastin and Lucentis) or 8 weeks (Eylea)
  • ‘Treat and extend’ -monthly injections until clinically stable per physician, then increasing intervals between injections
  • ‘PRN’ or as needed- injections given monthly until deemed clinically stable by physican and then retreat if patient becomes symptomatic or demonstrates new activity of disease.

So why the different methods?

In 2006, the results of ANCHOR and MARINA (2 large trials looking at effectiveness of Lucentis dosed monthly for AMD) knocked our socks off by providing visual improvements and stability never before seen. Since then, other trials have followed looking at ways to obtain equal outcomes with fewer injections, indeed, the utopia for all retinal physicians and their patients. Studies repeatedly show that manufacturer recommended monthly therapy results in the best visual outcomes yet at the price of more frequent injections. In fact, patients from the original trials who were switched from monthly injections to as needed after 2 years, lost half of their visual gains in the subsequent year, conferring that the best way to maintain vision is to prevent the disease from progressing.

More recently the National Eye Institute sponsored randomized trial called the Comparison Of Age-related Macular Degeneration Treatments Trial (CATT) compared efficacy of Avastin (bevacizumab) to Lucentis (ranibizumab) dosed monthly or as needed. At two years, this study showed that when compared head to head, PRN treatment was inferior to monthly and resulted in poorer visual outcomes.

While treat and extend seems like a reasonable compromise between the two treatment regimens, unfortunately, no large clinical trials have been performed to compare the outcomes of this technique against monthly therapy. By virtue of the fact that this technique extends the interval outside the 4 week therapeutic window of the drug, patients are left unprotected with an increasing risk of recurrence and irrecoverable vision loss, and in fact, we have seen patients develop bleeding when extended from 4 to 6 weeks. So while we will sometimes extend patients beyond monthly therapy if they have remained stable for several months, it is important that they understand and accept the potential risks. For the most part, however, we advocate adhering to manufacturer recommended dosing intervals as multiple trials have confirmed the best visual outcomes with this technique.