Late Breaking News
Clinical Briefs August 2010
- Categorized in: August 2010
Implantable Telescope Approved for AMD FDA approved the Implantable Miniature Telescope (IMT) to improve vision in some patients with end-stage age-related macular degeneration (AMD) last month. Surgically implanted in one eye, the IMT is a small telescope that replaces the natural lens and provides an image that has been magnified more than two times.
The IMT is available in two models: one that provides 2.2 times magnification and another providing 2.7 times magnification. The IMT is designed to magnify and project images onto a healthy portion of the retina and is intended for implantation in only one eye; the non-implanted eye is used for peripheral vision.
The IMT is for use in patients ages 75 years and older with stable severe to profound vision impairment (when vision impairment has not changed over time) caused by blind spots (bilateral central scotoma) associated with end-stage AMD. These patients also have evidence of a visually significant cataract.
Patients agree to undergo training with an external telescope prior to implantation to determine whether adequate improvement in vision with the external telescope can be obtained and to verify if the patient has adequate peripheral vision in the eye that would not be implanted. Patients also agree to participate in a post-operative visual training program.
In a 219-patient, multi-center clinical study of the IMT, 90% of patients achieved at least a 2-line gain in either their distance or best-corrected visual acuity, and 75% of patients improved their level of vision from severe or profound impairment to moderate impairment.
Because the IMT is a large device, implantation can lead to extensive loss of corneal endothelial cells (ECD), the layer of cells essential for maintaining the clarity of the cornea, and chronic endothelial cell loss. The chronic rate of endothelial cell loss is about 5% per year. Significant losses in ECD may lead to corneal edema, corneal decompensation, and the need for corneal transplant. In the study, 10 eyes had unresolved corneal edema, with five resulting in corneal transplants. The calculated five-year risk for unresolved corneal edema, corneal decompensation, and corneal transplant are 9.2%, 6.8%, and 4.1%, respectively.
To ensure that the risks of IMT implantation are sufficiently and consistently communicated to patients, the FDA and the manufacturer created detailed labeling, including an Acceptance of Risk and Informed Decision Agreement, which patients must complete prior to IMT implantation. The agreement provides a guide for patients and their physicians to discuss the risks associated with IMT implantation. Patients should be given adequate time to review all of the information regarding the IMT.
As a condition of FDA approval, the manufacturer, VisionCare Ophthalmic Technologies Inc of Saratoga, CA, must conduct two post-approval studies. In one study, VisionCare must continue follow-up on the subjects from its long-term follow-up cohort for an additional two years. Another study of 770 newly enrolled subjects will include an evaluation of the endothelial cell density and related adverse events for five years after implantation.
Testosterone Trial Stopped Due to CV Events
A clinical trial of testosterone treatment in older men has found a higher rate of adverse cardiovascular events, such as heart attacks and elevated blood pressure, in a group of older men receiving testosterone gel compared to those receiving placebo. Due to these events, the treatment phase of the trial was stopped. The trial stoppage was reported June 30 online in The New England Journal of Medicine. The study was supported by a grant to Shalender Bhasin, MD, at Boston Medical Center from the National Institute on Aging.
Decreased muscle strength may contribute to difficulties in mobility, such as in walking or climbing stairs, which can limit older persons’ independence. Testosterone treatment has been shown to improve muscle strength in some older men, but it is not yet known whether it would reduce mobility limitations in older men with low testosterone levels. The TOM (Testosterone in Older Men) Trial was designed to address this question. The treatment phase of the trial was stopped on December 31, 2009, following a review by the study’s safety monitoring board, which found that 23 of the 106 men in the trial who had received testosterone experienced adverse cardiovascular-related events during the study, compared to five of the 103 men who received placebo.
The cardiovascular-related events included heart attack, heart rhythm disturbances and elevated blood pressure, and one death from a suspected heart attack. The safety board weighed the severity of the adverse events in relation to the potential benefits and recommended that participants stop taking study medications and that enrollment be stopped.
The men who experienced cardiovascular events were treated by their personal physicians for their specific conditions. No new participants will be enrolled in the study. The study team will continue to monitor the health of all participants for at least another year after stopping testosterone use to further evaluate effects of the treatment.
The study authors noted that physicians and patients, especially older men, should consider this study’s findings on adverse effects along with other information on the risks and benefits of testosterone therapy. They also noted that further research is needed to clarify the safety issues raised by this trial. They cautioned that the ability to draw broader conclusions about the safety of testosterone therapy based on these findings is constrained by several factors, including this study’s small size and the fact that the study’s population was older and had higher rates of chronic diseases and mobility limitation than individuals in most other studies.
In addition, the trial’s eligibility criteria excluded men with severely low testosterone levels, limiting the ability to make inferences about safety in this population. The authors noted that the testosterone doses and serum levels in this trial may be higher than those usually used in clinical practice and in some previous clinical trials.
NIH Announces Grants to Foster Partnership Between US and India
The National Institute of Biomedical Imaging and Bioengineering announced the availability of supplemental funding for eligible NIBIB-supported research grants to facilitate collaborative work among researchers in the US and India. The grants will be used to develop low-cost diagnostic and therapeutic medical technologies that can be used in underserved communities worldwide. Applicants are encouraged to submit proposals for any collaborative technology development or device that would be appropriate in a low-resource setting, such as low-cost imaging devices or point-ofcare screening tests.
The supplemental funding is an initiative between NIBIB and the Department of Biotechnology of the Ministry of Science and Technology in India. In October 2007, NIBIB and DBT entered into a bilateral agreement to develop low-cost healthcare technologies aimed at the medically underserved. In 2008, NIBIB and DBT held a joint workshop on Low-Cost Diagnostic and Therapeutic Medical Technologies. Approximately 60 scientists, engineers, and clinicians from the US and India identified leading areas of opportunity for improvements in healthcare for individuals with chronic conditions in low resource settings. As a result of this workshop, NIBIB and DBT are initiating jointly funded initiatives that capitalize on the expertise and resources of the two nations.
Researchers Discover How Folate Promotes Spinal Cord Healing
The vitamin folate appears to promote healing in damaged rat spinal cord tissue by triggering a change in DNA, according to a laboratory study funded by NIH. The researchers showed that the healing effects of the vitamin increased with the dosage, until regrowth of the damaged tissue reached a maximum level. After this threshold was reached, regrowth declined progressively with increasing doses until it reached the level seen in the absence of the vitamin.
Specifically, folate stimulated a process known as DNA methylation, a natural biochemical process in which chemical compounds known as methyl groups are attached to DNA. The study results suggest that a greater understanding of the chemical sequences associated with folate metabolism and DNA methylation may lead to new techniques to promote healing of damaged spinal cords and other nervous system injuries.
Because of folate’s role in fetal spinal cord development, the researchers sought to determine if the vitamin could promote healing in damaged adult nervous system tissue. In a previous study, the researchers showed that folate could enhance the regrowth of axons, or nerve fibers, in rats with spinal cord injuries.
In the current study, they measured folate’s effects at various doses. They found that as the dose increased, so did the amount of axon regrowth. Beyond the peak dose of 80 micrograms per kilogram of body weight, the effect decreased but without causing toxicity or nerve damage.
To understand how folate helps repair damaged axons, the researchers undertook additional observations. They found that injured nerve tissue began producing surface receptors for folate. Folate fits into the receptors, like a key fits into a lock, and then is absorbed into the nerve cell. After folate was absorbed into injured nervous system tissue, the nerve cells began producing enzymes that attach methyl groups to DNA. Chemically blocking folate from binding to the nerve cells, or blocking the methylation enzymes, hindered the nerve healing process. The researchers also tested the methylation of spinal cord DNA at various doses of folate and found that, like the regrowth of axons, DNA methylation peaked at a dose of 80 micrograms folate per kilogram of body weight.
Standardized Form Leads To Better End-Of-Life Care
A program in which individuals used a standardized form signed by a physician to communicate their end-of-life care preferences on issues such as levels of medical intervention and tube feeding lead to significantly better adherence to treatment preferences than more traditional methods of communication, according to a new study.
The study, supported by the National Institute of Nursing Research, appeared in the July issue of the Journal of the American Geriatrics Society. It was the first to directly compare this program (Physician Orders for Life-Sustaining Treatment or POLST) to traditional practices such as do-not-resuscitate orders (DNR).
POLST is designed for individuals with progressive chronic illness or frailty and is a standardized form on which patient preferences are listed as physician orders for cardiopulmonary resuscitation; medical interventions such as comfort measures (non-life-sustaining measures to relieve pain and suffering), limited intervention or full treatment; use of antibiotics; and tube feeding.
Using 60-day chart data from more than 1,700 living and deceased long-stay nursing facility residents, the study analyzed the levels of treatment received by residents with or without POLST forms or traditional medical orders. The study found that residents who used a POLST form to indicate their preference for comfort care were 59% less likely to receive life-sustaining medical interventions that were not requested, when compared to residents with DNR orders, suggesting that POLST promotes closer adherence to documented treatment preferences than DNR orders.