“Cataract surgery rates are rising in all age groups between 50 and 90, but the greatest increase is in the 70- and 80-year-olds. And part of that is that our older population, or the aging baby boomers, are working longer, they want to be more active, they have more demands on their vision,” says senior author Jay Erie, MD, a Mayo Clinic ophthalmologist. “That’s why they’re looking for surgery sooner — so that they can remain independent, remain active, continue to work.”
Despite the common nature of cataracts, the United States has little current population-based data on cataract surgery, information that can help estimate demand. For the Mayo study, researchers mined the National Institutes of Health-funded Rochester Epidemiology Project to identify cataract surgeries in Olmsted County, Minn., from 2005 to 2011. The project, a partnership of Mayo Clinic, Olmsted Medical Center and other health providers, makes the county one of few places worldwide where researchers can examine medical data on virtually everyone to see how often conditions strike and whether treatments succeed. The research found:
• Cataract surgery has increased steadily, peaking in 2011 at a rate of 1,100 per 100,000 people.
• Sixty percent of people receiving cataract surgery on one eye returned within three months to have it performed on the second eye, a significant increase over the number in a previous Mayo study, which covered 1998 to 2004.
• The mean annual rate of cataract surgery for women was significantly higher than for men.
• There were significant increases in cataract surgery over the past 32 years among people in all age groups, except those 90 and older.
The trend raises questions about treatment costs and the resources needed to meet demand, Dr. Erie says. Medicare, for example, typically covers cataract surgery for its patients; in general, cataract surgery on a Medicare patient costs roughly $3,000 per eye.
“Ophthalmology and ophthalmol-ogists and patients and payers are beginning to look at ways they can weigh the visual benefits to the individual patient against the cost to society as a whole, and how we can maximize the outcome and minimize the cost to society.” Dr. Erie says.
New Test Could Diagnose RP
A new Duke University study says it can link what is in a patient’s urine to gene mutations that cause retinitis pigmentosa. The findings appear online in the Journal of Lipid Research.
“My collaborators, Rong Wen, MD, PhD, and Byron Lam, MD, at the Bascom Palmer Eye Institute in Florida first sought my expertise in mass spectrometry to analyze cells cultured from a family in which three out of the four siblings suffer from RP,” said Ziqiang Guan, PhD, an associate research professor of biochemistry in the Duke University Medical School and a contributing author of the study.
Dr. Guan’s collaborators had previously sequenced the genome of this family and found that the children with RP carry two copies of a mutation at the dehydrodolichol diphosphate synthase (DHDDS) gene, which makes the enzyme that synthesizes organic compounds called dolichols. In humans, dolichol-19, containing 19 isoprene units, is the most abundant species.
The DHDDS mutation, which was found in 2011, is the latest addition to more than 60 gene mutations that have been implicated in RP. This mutation appears to be prevalent in RP patients of Ashkenazi Jewish origin, and one in 322 Ashkenazi carries one copy of the mutation.
“I knew from my previous experience in analyzing urine samples from liver disease patients that I can readily detect dolichols by liquid chromatography and mass spectrometry,” Dr. Guan said. Using these techniques, he analyzed urine and blood samples from the six family members and found that instead of dolichol-19, the profiles from the three siblings with RP showed dolichol-18 as the dominant species. The parents, each of whom carries one copy of the mutated DHDDS gene, showed intermediate levels of dolichol-19 and higher levels of dolichol-18 than their healthy child. Dr. Guan believes dolichol profiling could effectively distinguish RP caused by DHDDS mutation from that caused by other mutations.
Dr. Guan and his collaborators hope to develop the dolichol profiling method as a first-line diagnostic test to identify RP patients with abnormal dolichol metabolism. They think this mass spectrometry-based detection method will help physicians provide more personalized care to RP patients, especially to young children whose retinal degeneration has not fully developed.
“Since the urine samples gave us more distinct profiles than the blood samples, we think that urine is a better clinical material for dolichol profiling,” he said. Urine collection is also easier than a blood draw and the samples can be conveniently stored with a preservative. The team is now pursuing a patent for this new diagnostic test for the DHDDS mutation.
There are currently no treatments for RP, but Dr. Guan hopes his research will shed light on potential drug design strategies for treating RP caused by DHDDS mutation. “We are now researching ways to manipulate the dolichol synthesis pathway in RP patients with the DHDDS mutation so that the mutated enzyme can still produce enough dolichol-19, which we believe may be important for the rapid renewal of retinal tissue in a healthy individual,” he says.
Topical AMD Treatment Shows Promise
Researchers from Tufts University School of Medicine and the Sackler School of Graduate Biomedical Sciences have identified a possible topical treatment for AMD in a study of mice that shows promise for clinical use. The findings, published in PLoS ONE, are the first to report successful topical use of a compound capable of inhibiting symptoms associated with both dry AMD and wet AMD and could represent a breakthrough for treatment of these conditions.
The team of researchers from Tufts, led by Rajendra Kumar-Singh, PhD, reported in their proof-of-concept study that topical application of a compound called PPADS (pyridoxalphosphate-6-azophenyl-2’,4’-disulfonic acid) inhibits damage to ocular tissue that impacts the individual’s ability to see color and fine detail, as well as reducing neovascularization related to advanced AMD.
According to the National Eye Institute, more than 7 million people in the United States are at substantial risk of developing AMD. Only the wet form of AMD can be treated, with injections every four to 12 weeks that can be uncomfortable, risky and burdensome to patients. The development of a topical eye-drop treatment that works in both dry and wet AMD could increase treatment adherence and reduce patient discomfort by reducing or removing the need for direct injections.
“An ideal therapy would be one that can be self-administered daily by patients. Further studies are needed to determine safety, dosage, and other factors before advancement of this therapy towards clinical trials, but our study suggests that there’s significant promise for the development of self-administered topical treatments for age-related macular degeneration in humans,” said Dr. Kumar-Singh, an associate professor of ophthalmology at Tufts University School of Medicine.
To test the effectiveness of a topical application of PPADS, the team of researchers induced the tissue damage and blood vessel growth characteristics of AMD in anesthetized mice. The topical treatment was then administered every 24 hours for three consecutive days. The researchers then examined the eye tissues one week later to assess for progression of the damage and blood vessel growth.
“Our study found that topical application of the PPADS compound works on two fronts” said first author Kerstin Birke, PhD, a postdoctoral scholar at Tufts. “First, it stops the damage to eyes caused by pores formed in the membrane, which leads to cell death within the eye, by stopping an immune system process known as complement, which is responsible for dry AMD. Second, it prevents the formation of the blood vessels that can leak and damage the eye, a process associated with wet AMD.” REVIEW