The American Academy of Ophthalmology will team with the Food and Drug Administration on a program to help ophthalmologists reduce Toxic Anterior Segment Syndrome, a rare, but potentially sight-stealing complication of cataract surgery. As a part of the FDA’s Proactive TASS Program, the AAO will help to create a physician registry to track TASS occurrences. The registry, which is currently in a pilot stage, will assist the FDA in determining the cause of the condition in order to prevent future outbreaks.
Currently, the identification of TASS outbreaks is dependent on surgeons and surgical centers keeping detailed records of all products and equipment used during cataract surgery. However, this can be cumbersome and underreporting is suspected. The new online reporting mechanism will be housed with the AAO-sponsored registry for Physician Quality Reporting System, a system that ophthalmologists use regularly, making reporting more convenient.
The AAO will serve as a consultant in the program, helping to determine the data to be collected and to recruit cataract surgeons to participate. The academy also will be involved in the analysis of the data collected at the end of the pilot to determine if changes are needed prior to the creation of a permanent registry.
The academy’s efforts are part of a broader FDA program that is one of the first proactive surveillance programs to monitor the multiple medical devices used in cataract surgery and to aid in early identification of a national TASS outbreak. The FDA will use the pilot to develop the permanent registry that can be used by regulatory agencies as well as clinicians. The registry will provide a better understanding of factors present in the development of adverse events and outbreaks in patients who have received intraocular lenses.
Nanoparticles May Work to Deliver Drugs
Hitching a ride into the retina on nano-particles called dendrimers offers a new way to treat age-related macular degeneration and retinitis pigmentosa, say investigators at the Mayo Clinic, Wayne State University and Johns Hopkins. Their study shows that steroids attached to the dendrimers target the damage-causing cells associated with neuroinflammation, leaving the rest of the eye unaffected and preserving vision. The findings appear in the journal Biomaterials.
Dry AMD and RP are caused by neuroinflammation, which progressively damages the retina and can lead to blindness. “There is no cure for these diseases,” says Mayo Clinic ophthalmologist Raymond Iezzi, MD, a lead author of the study. “An effective treatment could offer hope to hundreds of millions of patients worldwide.”
Dr. Iezzi and fellow principal author Rangaramanujam Kannan, PhD, an ophthalmology professor at the Wilmer Eye Institute of Johns Hopkins, developed an intracellular, sustained-release drug delivery system. The research, conducted in part at Wayne State University’s Kresge Eye Institute with collaboration from Wayne State’s College of Engineering and Ligon Research Center of Vision, tested the dendrimer delivery system in rats that develop neuroinflammation.
The target was microglial cells, inflammatory cells in charge of cleaning up dead and dying material in the eye, Dr. Iezzi says. When activated as “trash collectors,” the cells cause damage via neuroinflammation. The microglial cells gobble up the dendrimers, and the drug then shuts down the cells’ activity.
“Surprisingly, the activated micro-glia in the degenerating retina appeared to eat the dendrimer selectively, and retain them for at least a month. The drug is released from the dendrimer in a sustained fashion inside these cells, offering targeted neuroprotection to the retina,” Dr. Kannan says.
The treatment reduced neuroinflammation in the rat model and protected vision by preventing injury to photoreceptors in the retina. Though the steroid offers only temporary protection, the treatment as a whole provides sustained relief from neuroinflammation.
Seizure Drug Could Retard Tumors’ Spread
A drug commonly used to treat seizures appears to make eye tumors less likely to grow if they spread to other parts of the body, according to researchers at Washington University School of Medicine in St. Louis. Their findings are available online in the journal Clinical Cancer Research.
Uveal melanoma can be very aggressive and metastasize from the eye to other organs, especially the liver. “Melanoma in general, and uveal melanoma in particular, is notoriously difficult to treat once it has metastasized and grown in a distant organ,” says principal investigator J. William Harbour, MD. “We previously identified an aggressive class 2 molecular type of uveal melanoma that, in most cases, already has metastasized by the time the eye cancer is diagnosed, even though imaging the body can’t detect it yet. This microscopic amount of cancer can remain dormant in the liver and elsewhere for several years before it begins to grow and becomes lethal.”
Once this happens, the prospects for survival are poor, according to Dr. Harbour, the Paul A. Cibis Distinguished Professor of Ophthalmology and Visual Sciences and professor of cell biology and of molecular oncology.
Dr. Harbour’s new study shows that drugs known as histone deacetylase (HDAC) inhibitors alter the conformation of the DNA of the aggressive form of uveal melanoma, which changes the way key genes are expressed, rendering the tumor cells less aggressive.
“We looked at uveal melanoma cells in the laboratory and in an animal model, and we found that HDAC inhibitors can block the growth and proliferation of tumor cells,” he says. “HDAC inhibitors appear to reverse the aggressive molecular signature that we had identified several years ago as a marker for metastatic death. When we look at aggressive melanoma cells under the microscope after treatment with HDAC inhibitors, they look more like normal cells and less like tumor cells.”
Because HDAC inhibitors already are on the market, Dr. Harbour says he thinks it may be possible to quickly begin testing the drugs in patients with aggressive forms of uveal melanoma.
Clinical trials of HDAC inhibitors could begin in the next six to 12 months. Already, other researchers have applied for funding to begin testing an HDAC inhibitor called SAHA (suberoylanilide hydroxic acid) in patients with metastatic uveal melanoma.
“I think this is a reasonable place to start in the challenging effort to improve survival in patients with metastatic uveal melanoma,” Dr. Harbour says. “I suspect that the best role for HDAC inhibitors will be to slow or prevent the growth of tumor cells that have spread out of the eye but cannot yet be detected. This might lengthen the time between the original eye treatment and the appearance of detectable cancer in the liver and elsewhere.”
Like the chicken pox virus that lives for years in nerve cells without affecting health, Dr. Harbour says treatment with HDAC inhibitors may allow patients with aggressive melanomas to live for many years without any detectable spread of their disease.
Dr. Harbour and his colleagues previously developed a screening test to predict whether the cancer would be likely to spread to the liver and other parts of the body. The test is helpful because although less than 4 percent of patients with uveal melanoma have detectable metastatic disease, up to half will eventually die of metastasis even after successful treatment of the tumor with radiation, surgery, or, in the worst cases, removal of the eye.
Tumors that tend to remain contained within the eye are called class 1 uveal melanomas. With a needle biopsy, doctors can quickly determine whether a tumor is likely to be a class 1 cancer or whether it carries a molecular signature that identifies it as a high-risk, class 2 melanoma. Dr. Harbour’s team developed a test to identify the class 2 molecular signature, and that test is now being used around the world to detect the aggressive form of uveal melanoma.
CMS Rule Would Make Payments Transparent
The Centers for Medicare & Medicaid Services has proposed a rule that will increase public awareness of financial relationships between drug and device manufacturers and certain health-care providers. This is one of many steps under the Affordable Care Act designed to increase transparency in the health-care system, which can lead to better care at lower costs, the agency says.
The proposed rule would require manufacturers of drugs, devices, biologicals and medical supplies covered by Medicare, Medicaid or the Children’s Health Insurance Program to report to CMS payments or other transfers of value they make to physicians and teaching hospitals. The proposed rule would also require manufacturers and group purchasing organizations to disclose to CMS physician ownership or investment interests.
This increased transparency is intended to help reduce the potential for conflicts of interest that physicians or teaching hospitals might face as a result of their relationships with manufacturers.
Drug and biologic manufacturers, medical device or supply manufacturers and GPOs would be affected by the new reporting requirements. These organizations, as well as the physicians and teaching hospitals, would have an opportunity to review and correct information prior to its publication.
The ACA provides that violators of the reporting requirements will be subject to civil monetary penalties (CMPs), capped at $150,000 annually for failing to report, and $1 million for knowingly failing to report.
CMS is proposing that data collection will not begin on Jan. 1, 2012 and that manufacturers and GPOs do not need to begin data collection until final regulations are issued. Depending on the timing of the final rule, CMS is proposing that manufacturers and GPOs will be required to submit a partial year on March 31, 2013. Once the data has been submitted, CMS will aggregate manufacturer submissions at the individual physician and teaching hospital level, provide them with a 45-day period to confidentially review and, if necessary, correct the data, and make the data publicly available by Sept. 30, 2013.
CMS will accept comments on the proposed rule until Feb. 17, 2012, and will respond to them in a final rule to be published in 2012.