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Emerging technologies hold promise for treatment of retinal disease
In the fifth report from the OSN Section Editor Summit, Retina/Vitreous Section Member Judy E. Kim, MD, discusses various cutting-edge issues in her subspecialty.
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It is difficult to talk about a single most “hot topic” in the retina field because there is so much happening. In this article, I will focus on a few controversial subjects as well as some topics that are indicative of the direction we are heading in the near future.
Medical therapeutic options
Treatment of AMD is, without a doubt, one of the most important topics in retina currently. In the realm of anti-VEGF therapies, we have a family feud: the inexpensive brother Avastin (bevacizumab, Genentech) vs. the younger, expensive brother Lucentis (ranibizumab, Genentech). Father Genentech is looking on, either with glee or chagrin, we can’t be sure.
This dramatic scenario raises a lot of questions about how we manage AMD. We still don’t know which of these two drugs is better or safer. Avastin has a longer half-life, and it may have a theoretical increased systemic risk compared with Lucentis. As for Lucentis, Genentech issued a letter warning that the 0.5-mg dose has a higher stroke incidence compared with the 0.3-mg dose.
 Judy E. Kim |
Although the labeling for Lucentis calls for monthly dosing based on the clinical trial design, the optimal dosing frequency is still unknown. In practice, doctors may not be doing monthly dosing for 2 years, as it was in the clinical trials. We are still trying to figure out the best way to treat our patients with the least number of injections.
Therefore, we still have a number of questions to answer: Which drug is better? How to determine the best dosing interval? When can we stop treatment? When do we switch to a different drug? We have these questions because we still do not know how to define treatment failure in the setting of anti-VEGF treatments. Furthermore, we are dealing with a disease that can recur with cessation of treatment.
There is also the possibility that, once we have gained anatomic and visual success with Lucentis or Avastin, Macugen (pegabtanib sodium, OSI/Pfizer) could play a role as a maintenance therapy. The LEVEL study is currently trying to answer that question. Macugen injections given every 6 weeks have been shown to be safe over 2 to 3 years. However, we do not know whether initial visual improvement gained with Lucentis or Avastin can be maintained on Macugen alone.
Combination therapies may allow us to give fewer injections and still achieve a good visual outcome. But which combination therapy should we use? Even among anti-VEGF therapies, there is currently Lucentis, Avastin and Macugen, and in the future, the VEGF Trap from Regeneron, small interfering RNAs and other therapies in the pipeline.
There is also the possibility of combination therapy with photodynamic therapy (PDT) with Visudyne (verteporfin, Novartis/QLT). We can use it the way it was approved to be used, but there is concern about toxicity with multiple PDT treatments. Therefore, some retina specialists advocate using PDT with reduced fluence.
There are entirely new classes of compounds for AMD in the pipeline, such as pigment epithelial derived factor. The questions for these are, again, what therapy and what combination should we use? Also, will the combination treatment result in comparable visual improvement as Lucentis monotherapy?
In addition to different agents, various drug delivery methods may exist. For example, dexamethasone can be given via the sub-Tenon’s route, intravitreally or even via a sustained release route. Sustained drug delivery of other compounds may play an increasingly important role in the future.
I think eventually we will get an AMD cocktail of sorts; we just don’t know which combination will make the most effective and desirable “recipe” yet.
Surgical issues
Just like anterior segment surgeons, we have moved toward small-incision surgery to allow sutureless pars plana vitrectomy. Sutureless vitrectomy affords patient comfort, quicker visual recovery and potentially shorter surgical time. Most retina surgeons are currently using 20-gauge systems with 1-mm sclerotomy incisions that need to be sutured, but many are switching to 25-gauge sutureless systems with 0.5-mm incisions.
Yet surgeons who initially used 25-gauge instruments felt that the instruments were not stiff enough and that the port size was too small, causing vitrectomies to take longer. Now, 23-gauge instruments are available, and perhaps they will be a happy compromise with the benefits of the 20-gauge and 25-gauge instruments.
Finally, a sutureless 20-gauge system is also being tested. This may be the most economical method, because not as many new instruments need to be purchased, yet it maintains the benefits of the sutureless system. I believe sutureless vitrectomy is here to stay.
Retinal imaging
The Stratus OCT (Carl Zeiss Meditec) has allowed us to see a lot of pathology we could not see before and has revolutionized how we take care of our patients. However, it still has limitations. It gives only six-line scans; therefore, if a retinal pathology happens to exist between these line scans, we will miss it.
Now there is a new technology called spectral-domain, or Fourier-domain, OCT. It scans the retina in a particular area of the macula entirely. It works fast and even allows us to see three-dimensional images, not just two-dimensional line scan images as in time-domain OCT.
A number of different companies are competing for a place in the market. For example, at the American Academy of Ophthalmology meeting last year, eight to ten companies were working on it.
All this competition will make the product better and possibly even cheaper. So should we all sell off our Status OCT and get spectral-domain OCT? I think it is still too early to do that. It is unclear which system and software will be the most user-friendly and what type of data will be most helpful in a clinical setting.
However, these new imaging technologies will allow for better detection of retinal pathologies. For example, we may be able to quantitate drusen size and volume, measure blood flow through retinal and choroidal vessels and better elucidate the origin and extent of choroidal neovascular membranes, macular edema and other retinal disease.
These improving technologies may be able to detect diseases or drug efficacy earlier, so that we don’t have to wait 2 to 5 years to see which AMD drugs are effective.
For more information:
- Judy E. Kim, MD, can be reached at the Medical College of Wisconsin, 925 N. 87th St., Milwaukee, WI 53226; 414-456-7875; fax: 414-456-6300; e-mail: judykim@mcw.edu. Dr. Kim has no direct financial interest in the products mentioned in this article, nor is she a paid consultant for any companies mentioned.