A recent study, published in Graefe’s Archive for Clinical and Experimental Ophthalmology, has attempted to “identify factors and problems influencing treatment adherence in patients undergoing anti-VEGF therapy for neovascular age-related macular degeneration under real-life conditions.” Graefe’s Archive is an international journal that presents original clinical reports and experimental studies by ophthalmologists and vision research scientists in order to provide rapid dissemination of experimental clinical information.
The study, entitled Adherence to ranibizumab [i.e., Lucentis] treatment for neovascular age-related macular degeneration in real life, was authored by Katharina M. Droege, Philipp S. Muether, Manuel M. Hermann, Albert Caramoy, Ulrike Viebahn, Bernd Kirchhof, and Sascha Fauser, all of whom are affiliated with the Center of Ophthalmology, Department of Vitreo-Retinal Surgery, University of Cologne, Germany.
More about the Research
From the article introduction:
Age-related macular degeneration (AMD) is a major cause of visual impairment in developed countries. For neovascular AMD, studies have demonstrated the efficacy of ranibizumab [i.e., Lucentis] therapy … and have shown significant improvements in visual acuity, macular thickness, and quality of life. Trials have shown that it is necessary to either inject monthly or to follow a pro re nata [meaning “as needed”] (PRN) regimen with monthly controls and injections for recurrent or persistent activity.
Monthly visits in both regimens impose a considerable burden for the patient. No information is available on the motivation and problems for the patient following this treatment. It is also not clear whether patients would prefer a fixed dosing or a PRN regimen. In this study we analyzed factors influencing therapy adherence in real life.
About Age-Related Macular Degeneration (AMD)
In wet macular degeneration, the choroid (a part of the eye containing blood vessels that nourish the retina) begins to sprout abnormal vessels that develop into a cluster under the macula (called choroidal neovascularization).
The macula is the part of the retina that provides the clearest central vision. Because these new blood vessels are abnormal, they tend to break, bleed, and leak fluid under the macula, causing it to lift up and pull away from its base. This damages the fragile photoreceptor cells, which sense and receive light, resulting in a rapid and severe loss of central vision.
Angiogenesis is a term used to describe the growth of new blood vessels and plays a crucial 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, these drugs are administered by injection directly into the eye after the surface has been numbed.
Avastin is an anti-VEGF drug that is FDA-approved since 2004 for intravenous use in colorectal cancer. It is currently used on an “off-label” basis (i.e., via eye injection) to treat wet AMD.
Lucentis was developed specifically for injection in the eye to block blood vessel growth in AMD. In 2005, clinical trials established Lucentis as highly effective for the treatment of wet AMD. The FDA approved Lucentis in 2006..
The Study Results and Conclusions
The authors summarized the study results as follows:
Results: Forty-two men and 53 women were included. After a mean follow-up time of 675 days, adherence was 81.1 %. The mean number of follow-up visits was 19, the mean number of [eye] injections was ten. Seven patients withdrew from treatment due to subjective dissatisfaction with benefit. Other reasons for loss to follow-up were death in one case, serious general disease in three patients, and treatment options closer to home in five cases.… 62.1 % of patients were afraid of a negative examination result, whereas 19.0 % were afraid of [eye] injections. A major problem was travel to and from the hospital (46.3 %), with 61.5 % of patients requiring escort.
Conclusion: Despite necessary monthly visits, patients showed a high adherence to therapy. The major problem was travel to and from the hospital. From the patients’ point of view, anxiety of a negative examination result was more pronounced than fear of intraocular injections, which would be an argument for continuous injections rather than for a PRN regimen.
A Word about the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT)
Year Two results from the Comparison of Age-Related Macular Degeneration (AMD) Treatments Trials (CATT) that evaluated the effectiveness of Avastin versus Lucentis in a head-to-head clinical trial have been published. CATT is a multi-center clinical trial, funded by the National Eye Institute (NEI), a part of the National Institutes of Health.
The CATT study tested both monthly dosing in Lucentis trials, and dosing pro re nata [meaning “as needed”] (PRN) in Avastin trials.
From an NEI press release summarizing the CATT study results:
At two years, Avastin and Lucentis … improve vision when administered monthly or on an as-needed basis, although greater improvements in vision were seen with monthly administration.
“Both drugs were highly effective regardless of the approach to dosing. There was slightly less vision gain with as-needed treatment. Patients seeking the small extra advantage of monthly treatment need to be mindful of the additional burden, risks, and costs of monthly injections. Since as-needed dosing required 10 fewer eye injections over the course of two years and yielded similar visual results, many patients may choose this option,” said Daniel F. Martin, M.D., study chair for CATT.
VisionAware will continue to provide updates for ongoing macular degeneration research as they become available.