AMD Update 13: Retinal Procedures on the Rise

A new study, just published in the October issue of Archives of Ophthalmology and reported by Ophthalmology Web, MedPage Today, and Medscape Medical News,  shows that among those in the Medicare population (age 65 plus), treatments for retinal conditions nearly doubled between 1997 and 2007 – and this trend is expected to continue with the aging of the population and seniors living longer.

Since more than 50% of all permanent blindness in older Americans is the result of two different retinal diseases: age-related macular degeneration and diabetic retinopathy. Advancing age raises the risk for both conditions. As the number of US residents older than 65 years continues to grow -- the figure is predicted to double by 2040 -- the incidence of both diseases will likely escalate. To prepare for that prospect, the researchers analyzed Medicare fee-for-service claims filed during the 10-year period 1997 - 2007.

The new report, "Use of retinal procedures in Medicare beneficiaries from 1997 to 2007", by Pradeep Y. Ramulu, M.D., M.H.S., Ph.D., of the Wilmer Eye Institute, Johns Hopkins University, Baltimore, and colleagues, states:  "Retinal disease is highly prevalent among older individuals, and both age-related macular degeneration (AMD) and diabetic retinopathy account for more than half the irreversible blindness in older Americans. The prevalence of both macular degeneration and diabetic retinopathy increases with age, and the number of Americans affected by these conditions is expected to increase substantially as the number of Americans older than 65 years doubles from 2010 to 2040." The authors continued, as background information to the article, "The last decade has seen substantial changes in the treatment options available for many retinal diseases, particularly in the treatment of neovascular AMD," a form of the disease involving abnormal blood vessel growth in the eye.

Procedure volumes changed most markedly for treatments directed toward neovascular AMD. New treatments for this condition include intravitreal therapy-injections of drugs administered directly into the eye-of antibodies that block the formation of new blood vessels. (Both Avastin and Lucentis.) Between 1997 and 2001, fewer than 5,000 such injections were performed each year. However, rates more than doubled each year through 2006, increasing between 2001 (when 4,215 of these procedures were performed) and 2007 (when injections totaled 812,413). “These treatments now represent a major component of the treatment of retinal disease”, the researchers observed.

Aside from the VEGF inhibitors, other pharmacologic agents used for intraocular injections have included steroids for macular edema and pegaptanib (Macugen) for macular degeneration.

Prior to the introduction of pharmacologic agents, including Avastin in 2005  and Lucentis in 2006, the sole treatment option to have demonstrated benefit for choroidal neovascularization was thermal laser treatment. Thermal laser treatments also fell by 83% between 1997 and 2007, from a high of 56,966 to 13,821. Then in 2000, photodynamic therapy became available.

Photodynamic therapy peaked in 2004 with 133,565 procedures and then decreased 83 percent to 22,675 procedures in 2007. Laser treatment of choroidal lesions (potentially cancerous eye tumors) and neovascular AMD also decreased 83 percent, from a peak of 82,089 in 1999 to 13,821 in 2007.

Vitrectomy-surgical removal of the gel inside the eye, used to treat retinal detachments – increased 72 percent, from 11,212 in 1997 to 19,923 in 2007. Scleral buckling, a treatment for the same condition involving placing a silicon buckle around the eye, can be performed with or without vitrectomy. Scleral buckling alone became less common during the study period (a 69 percent decrease, from 8,691 to 2,660).

The increasing use of retinal procedures means that greater attention should be paid to the financial implications, the authors observed. The annual price tag for ranibizumab (Lucentis) is about $24,000 for a single patient, and investigations are needed to determine if lower-cost options (Avastin) could provide equivalent improvements in vision and quality of life. For instance, a study currently underway – the CATT Study,  is comparing the less costly Avastin with Lucentis in a double-blinded four-arm study. (Initial results of this study are expected to be released early next year.)

"Observing use patterns adds value, because it demonstrates how disease is treated and can be used to identify possible discrepancies between the best evidence-based treatments for a condition (as defined by clinical trials and meta-analyses from the literature) and current practice patterns," the authors concluded. "In this report, we observed that intravitreal injections of pharmacologic agents have gained widespread acceptance for the treatment of neovascular AMD and that vitrectomy is being increasingly applied to a wide range of retinal conditions."

The researchers stated several limitations to their study: the focus on only Medicare claims prohibited the discovery of trends in those younger than 65 years and prevents generalization of findings to those with private insurance, and in addition, possible systematic errors in coding may have biased results.

The National Institutes of Health supported the study.

References:

Arch Ophthalmol. 2010;128:1335-1340

Ophthalmology Web

MedPage Today

Medscape Medical News

Menu 17: Updates for June – September 2010

June through September turned out to be busier than anticipated. A number of new technologies emerged that I decided to write about. Included in these were a new sustained release drug delivery system, Iluvien; the use of lasers to treat eye floaters – in both the U.S. and in Europe; the idea of using femtosecond lasers to postpone the need for cataract surgery; a primer on the use of stem cells in ophthalmology; and a new device, the AdaptDx, for the early detection and progression of dry AMD.

In addition, I added two writeups in my Avastin vs Lucentis series; wrote about a new hand-held laser-based device to detect cancerous vs non-malignant tumors in breast cancer; and a clinical update on the Ellex 2RT technique for treating AMD.

All in all, a busy three months.

Here are the details:

Avastin/Lucentis Updates:

Avastin/Lucentis Update 40: Lucentis is Approved for Treating Macular Edema in Retinal Vein Occlusion

According to an announcement from Genentech, Lucentis has been approved by the FDA for treating macular edema following retinal vein occlusion (RVO), this following a six-month priority review by the FDA.

Avastin/Lucentis Update 41: The Story Behind the Invention of Avastin and Lucentis

In helping a university student obtain some research for a paper she was preparing for a journalism class, I inadvertently was able to obtain the rights to publish an exciting story that Wendy Bedale had written about the story behind the story of the invention of Avastin and Lucentis. Her story, based on her experience with her aunt undergoing treatment for AMD has hit a nerve with my readers. I hope you enjoy it as much.

Ellex 2RT Update:

Ellex 2RT Updated Clinical Results: ARVO 2010

Here is a report on the first results of some key pilot studies undertaken in Australia and reported at the May 2010 ARVO Meeting in Ft. Lauderdale, FL.

And, Some New Technologies:

A New Laser-based Diagnostic to Detect Malignant Breast Cancer Tumors

The story of the Beckman Laser Institute hand-held laser-based diagnostic that can detect between cancerous and benign breast tumors.

Iluvien and the Future of Ophthalmic Drug Delivery Systems

I received a press release from Alimera about its Iluvien sustained release drug delivery system that could administer its payload for up to three years in the retina to treat macula edema and decided I wanted to learn more about this system and the others that may be out there. This incentive led me to obtain the details about Iluvien and the other sustained release drug delivery systems either on the market, or on the verge of becoming available. This report was the result.

Using Lasers to Treat Vitreous Floaters: Laser Vitreolysis

About twenty years ago I saw an ad from Dr. Scott Geller advertising the use of his YAG laser to treat eye floaters. I called and interviewed the good doctor, but did not write up his story at the time. Then in June, I saw another item about the use of lasers to treat floaters and decided the time was right to find out more about the technique and write up this phenomenon.

I managed to locate the three doctors (including, still, Dr. Geller) who were specializing in this technique and interviewed them for this story. Once it got published on the web, it quickly became one of the best read of the over 160 postings on my Journal.

Using Lasers to Treat Vitreous Floaters: Laser Vitreolysis – Part 2

Dr. Scott Geller was the first ophthalmologist in the United States to use a laser to treat eye floaters. He was trained by Dr. Franz Fankhauser of Switzerland, probably the first ophthalmologist to use his YAG laser in doing work in the vitreous.

When I asked Dr. Geller how he got started using his laser to treat floaters, he told me that he would like to think about it and write about his experience. Here, in his own words, (The Origin of Clinical Laser Vitreolysis) are his recollections.

Using Lasers to Treat Vitreous Floaters: Laser Vitreolysis in the UK and Europe

Upon seeing the popularity of my writeup about the three U.S. doctors specializing in using lasers to treat eye floaters, I decided to followup that story with one about the doctors I was able to find in Europe and the UK that also did this. I identified six doctors across the pond and was able to get five of them to agree to be interviewed similarly as their U.S. compatriots. Once published, this story has also received very strong response.

Femtosecond Laser Cataract Removal: The Second Revolution? And, What is Laser Photolysis?

I read an article that described some of the many new applications for the femtosecond laser including cataract removal and laser photolysis. I had not heard  this term before and after looking into it, decided that the idea of photobleaching the human lens to clarify it and postpone the need for cataract surgery for between 3-7 years deserved to be told to my audience.

A Primer on the Use of Stem Cells in Ophthalmology

I had came across an interesting news release from International Stem Cell Corporation (ISCO) announcing that it had formed a new business unit, Cytovis, to focus on stem cell programs in ophthalmology, including CytoCor for the cornea and CytoRet for the retina.

That got me thinking about how little I knew about what was going on in stem cell research in ophthalmology, despite having written about two developments in the field, the London Project to Cure Blindness and the University of California Irvine (UCI) program to develop an artificial retina based on stem cell research.

I decided to become better informed by taking a closer look at what was happening in this field, and presenting that story. This in-depth report is the result.

Stem Cells in Ophthalmology -- An Update: AstraZeneca Joins the Fray

A few days after completing and publishing the story about the use of stem cells in ophthalmology, the announcement of AstraZeneca getting involved in the ophthalmic stem cell industry required an update. I wrote a brief about the news, and then revised my original report to include the information. So, you can read about AstraZeneca here, as well as in the original report above.

Selective Laser Trabeculoplasty (SLT) Technology for Treating Open-Angle Glaucoma to be Featured on the Discovery Channel

I received a press release from Lumenis, that it’s SLT technology was going to be featured on the Discovery Channel’s Health Heroes program during the September 24-27, 2010 period. It got me thinking about how I have always been a believer that SLT is a superior first option for treating open-angle glaucoma, and this announcement gave me the opportunity to reiterate this once again.

The announcement also gave me the opportunity to provide the links to my previous writings on the subject of treating glaucoma.

And, finally:

Apeliotus Vision Science’s AdaptDx Device for Early Detection of Dry AMD – A First Report

I follow The Massachusetts Eye and Ear Infirmary on Twitter, and late in August, I noticed a message looking for candidates to participate in a trial using the Apeliotus AdaptDx to detect the early stages of dry AMD. This was the first I had heard about either this company or the device, and my natural curiosity compelled me to look further into both. This report is the result of my curiosity.

Avastin/Lucentis Update 42: One-Year Results of Controlled Comparison Study Published

Last October, I came across the six-month results of one of the first blinded, double-masked comparison studies run between Avastin and Lucentis, sort of a mini-CATT Study. This study was done by researchers at the Boston University School of Medicine in cooperation with the VA Boston, and was published in the American Journal of Ophthalmology. I published their news release describing the study and the six-month results as Avastin/Lucentis Update 29.

This weekend, the same group announced the one-year results of this study, this time published in Eye, a peer-reviewed publication of The Royal College of Ophthalmologists in the UK.

This study, although done with a minuscule sample size compared to the CATT Study (twenty two patients enrolled, compared with 1200 in the CATT Study), is probably an indicator of what to expect when the results of the CATT Study are released, some time early next year.

For that reason, here is what Dr. Subramanian and her colleagues reported:

Researchers find no difference in drugs for macular degeneration

Researchers from Boston University School of Medicine (BUSM) and the VA Boston Healthcare System have conducted a study that failed to show a difference in efficacy between Bevacizumab (Avastin) and Ranibizumab (Lucentis) for the treatment of age-related macular degeneration (AMD). The study, which appears currently on-line in Eye, is believed to be the first study to describe one-year outcomes of a prospective, double-masked, randomized clinical trial directly comparing bevacizumab to ranibizuamab. Last October, these same researchers published early, six month outcomes of the same study, which also failed to show a difference in efficacy between these two drugs for treating AMD.

AMD is the leading cause of blindness over the age of 50 in developed Western countries. It presents in two forms, exudative (wet) or nonexudative (dry). Wet AMD is often more visually devastating with a higher risk of blindness. The gold standard of treatment for wet AMD is ranibizumab (Lucentis, Genentech Inc.), which was FDA approved as an eye injection in 2006. Bevacizumab (Avastin, Genentech Inc.) was FDA approved for the treatment of colorectal cancer in 2004, but has also been used worldwide in an off-label fashion as an eye injection for the treatment of wet AMD. Lucenitis costs approximately $2000.00 per injection, while Avastin costs approximately $50.00 per injection. While both drugs have shown independently to be effective in treating wet AMD, it was uncertain if both drugs were equally efficacious or if either one was better.

In this study, patients were enrolled in a 2:1 ratio to receive either the Avastin or Lucentis. Patients were given eye injections of Avastin or Lucentis every month for the first three months, followed by monthly examination and testing. They received further injections on an as needed basis for one year.

Fifteen patients received Avastin and seven patients received Lucentis. There was no significant difference in visual acuity and anatomic outcomes between the two groups. Both groups had an average improvement in vision of 1.5 lines on the vision testing chart, and only one patient (who was in the Lucentis group) lost a significant amount of vision (three lines or more). In addition, patients in the Avastin group underwent an average of eight injections over one year, while patients in the Lucentis group underwent an average of four injections.

"With the exception that total injections given to subjects over one year were significantly different between the two treatment arms, visual and anatomic outcomes at one year failed to show a significant difference between both groups," said lead author and Principal Investigator Manju Subramanian, MD, an assistant professor in Ophthalmology at BUSM. According to the authors, further studies with larger sample sizes are warranted.

###

This study is the result of work supported with resources and the use of facilities at the Veterans Affairs Boston Healthcare System, Jamaica Plain, Mass., USA. The VA Boston funded the cost of medications for this study.


Abstracted from the paper published in Eye:

Bevacizumab vs ranibizumab for age-related macular degeneration: 1-year outcomes of a prospective, double-masked randomised clinical trial
M L Subramanian, G Abedi, S Ness, E Ahmed, M Fenberg, M K Daly, A Houranieh and E B Feinberg

Purpose

To report 1-year visual and anatomic outcomes of a prospective, double-masked randomised clinical trial comparing bevacizumab with ranibizumab for the treatment of age-related macular degeneration (AMD).

Methods

Patients who met inclusion criteria were randomised 2:1 to bevacizumab or ranibizumab. All subjects and investigators (except for the pharmacist responsible for study assignments) were masked to treatment arms. Visual acuity was taken on an Early Treatment Diabetic Retinopathy Study chart. Patients were given either bevacizumab or ranibizumab every month for the first 3 months, followed by an optical coherence tomography-guided, variable-dosing treatment schedule. Main outcomes measured included visual acuity, foveal thickness, and total number of injections over the 1-year treatment period.

Results

In total, 15 patients received bevacizumab and 7 patients received ranibizumab. The average pre-operative visual acuity was 34.9 letters in the bevacizumab group, and 32.7 letters in the ranibizumab group. At 1-year follow-up, mean vision was 42.5 letters in the bevacizumab group, and 39.0 letters in the ranibizumab group. Two-tailed t-test failed to showed statistical significance between the two groups (P=0.5). Patients in the bevacizumab group underwent an average of eight injections, whereas patients in the ranibizumab group underwent a mean of four injections (P=0.001).

Conclusion

The 1-year outcomes of a prospective, double-masked, randomised clinical trial comparing bevacizumab with ranibizumab failed to show a difference in visual and anatomic outcomes between the two treatments for choroidal neovascularisation in AMD. Total injections given over the treatment period were significantly different between the two groups. Further studies with larger sample sizes are warranted.

Some of the accompanying graphics are presented below:

Table 1. Patient Demographics Distribution

Table 3 Summary of Visual Acuities and Anatomic Outcomes

Figure 1 Visual Acuities

Figure 2 Central Macular Thickness

Editors Comments:

It is interesting to note that although no difference was found in visual outcomes between Avastin and Lucentis, fewer injections of Lucentis were required to maintain the visual outcomes. The authors tried to explain this as follows:

“Patients in the bevacizumab (Avastin) group underwent statistically significant more  injections than those in the ranibizumab (Lucentis) group (p=0.001). The reason for this is unclear and difficult to interpret. As a larger molecule with a longer half-life, one would intuitively expect patients receiving bevacizumab to undergo fewer injections. One possible reason for this may be a tachyphylactic response.”  (A rapidly decreasing response to multiple doses of a drug.)

“Results from the Pan-American Collaborative Retina Study found, when comparing 2 doses of bevacizumab (1.25mg vs 2.5mg) that patients receiving the higher dose underwent more injections (Arevalo JF, Sanchez JG, Wu L, et al. Comparison of 2 doses of primary intravitreal bevacizumab for subfoveal CNV in AMD at 24 months: Results from the Pan-American Collaborative Retina Study Group. Association for Research in Vision and Ophthalmology, May 3, 2010).”

“An alternative possibility is that patients in the ranibizumab group had a more  robust and immediate response during the first 3 months than those in the bevacizumab group, (see Figure 2), and as OCT findings were the primary guide for re-treatment, the early and more dramatic change in foveal thickness in this treatment arm may have contributed to fewer injections over time.”

It will be interesting to see how this small study correlates to the larger study(s) as the CATT Study and other comparative studies – undertaken in several countries around the world –  are released over the next year or so.