NSAIDs Reduce CME in High-Risk Patients
A history of retinal vein occlusion multiplies a cataract patient’s risk for postoperative cystoid macular edema (CME) more than 30-fold, but the means for eliminating this added risk might already be sitting on pharmacy shelves, Massachusetts researchers concluded.
Their study of CME risks used data from 1,659 consecutive cataract surgeries performed from July 2001 through April 2006 by ophthalmology residents at the Massachusetts Eye and Ear Infirmary. The overall rate of clinically significant CME after the 1,659 surgeries was 2.35 percent (39 cases).
A multivariate regression analysis showed that, in nondiabetic patients, a history of retinal vein occlusion raised the odds ratio for CME to 31.75 (P < 0.001; 95 percent confidence interval 5.85–172.29).
The researchers analyzed the data with and without diabetic patients included because of the potential difficulty of differentiating cystoid macular edema and diabetic clinically significant macular edema. When diabetic patients were included, retinal vein occlusion was still significantly related to CME (OR 47.12; P < 0.001; 95 percent CI 9.40–236.11).
“Retinal vein occlusions are known to cause chronic macular edema, but to our knowledge there have been no reports that a history of RVO without macular edema can increase the risk for developing [cystoid macular edema] after uneventful cataract surgery,” the authors write.1
In the nondiabetic sample, the researchers also found statistical evidence for two already-known predictive factors for pseudophakic CME: epiretinal membranes (OR 4.93; P = 0.03; 95 percent CI, 1.20–20.30) and prosta-glandin use (OR 12.45; P = 0.04; 95 percent CI, 1.14–136.15).
But it was when accounting for the medication that their department protocol requires for diabetics and for patients with intraoperative complications, such as posterior capsular rupture, that the statistics uncovered a possible way to eliminate the extra risk: topical nonsteroidal anti-inflammatory drugs (NSAIDs).
The data showed that diabetics and patients with capsular rupture or vitreous loss, given NSAIDs in addition to steroids for a mean of three postop months, developed CME at a rate similar to pseudophakes with no risk factors.
When they did develop CME, it lasted half as long as when treated solely with steroids (82.6 ± 56.9 days, vs. 176.0 ± 106.5 days). Untreated, CME took 249.0 ± 2.8 days to resolve.
“This finding may support the use of prophylactic NSAIDs for the first three postoperative months to protect against the development of CME,” the authors write.
1 Henderson, B. A. et al. J Cataract Refract Surg
Ophthalmology World News
River Blindness Worm Becoming Drug Resistant
There was great excitement in the public health community in 1995 when a high-powered international partnership announced that it would send teams swooping into remote areas of Africa and eradicate onchocerciasis (“river blindness”) in a matter of 12 years.
A dozen years and 400 million doses of ivermectin later, the Onchocerca volvulus worm appears to have been stronger than this coalition of public health experts, African governments, a big pharmaceutical company, private charities, the World Health Organization and a former U.S. President (Jimmy Carter).
The estimated number of infected people has nearly doubled since the eradication program began (to 37 million from 20 million in 1995), according to WHO. Instead of speaking of eradication, the program’s publications now talk of its efforts to “reduce onchocerciasis as a public health and socioeconomic problem.”
Last summer, there was more bad news. A team of parasitologists reported that the only available drug treatment, ivermectin (Mectizan), appears to be causing selection for genetic changes that, in other nematode parasites, have been markers of ivermectin-resistance.1
The researchers tested adult worms taken from infected people prior to any drug treatments and then after three years of ivermectin at two different dosage levels. Half of the patients were treated annually, which was the standard in the late 1980s and early 1990s, and the other patients received medication every three months.
In recent years, more frequent dosing was adopted in some areas on the premise that it would accelerate the disease’s elimination from endemic areas. (In 2002, a WHO study used computer simulations to show that, depending on parasite levels in the infected, it would take as many as 40 years of annual treatments to eradicate the disease in an area.2)
However, more intense and more frequent medication schedules yielded the greatest number of changes in genes associated with drug resistance, the researchers reported in a new open-access journal of the Public Library of Science, PLoS Neglected Tropical Diseases.
The senior author of the study, Roger Prichard, PhD, noted that ivermectin normally kills the parasite’s microfilarial (larval) stage, leaving the adult worms alive in the host but with impaired reproductive ability. However, the genetic changes were in the mature worms.
“The drug kills the existing microfilariae and stops the adult parasites from producing new microfilariae for many months,” said Dr. Prichard, who is a professor at the McGill University Institute of Parasitology in Montreal. “The first of these effects still seems to be working satisfactorily. However, the effect on stopping parasite reproduction seems to be impaired where the resistance is appearing.”
The concerns about resistance raised by this and other recent research studies prompted WHO and the World Bank (which administers the treatment program’s funding) to convene a meeting of experts last fall, to discuss how to address the possible drug resistance in the river blindness parasite, Dr. Prichard said.
“Until now, there has been very little, if any, monitoring for drug resistance in onchocerciasis. I believe that this will now change. It must,” he said. “Some of the research questions can be addressed relatively quickly—ivermectin resistance is widespread in parasites of farm animals and there is much research on that related problem. Other needed research will take longer but needs to be started immediately and given some priority.”
1 Bourguinat, C. et al. PLoS Negl Trop Dis
2 Winnen, M. et al. Bulletin of the World Health Organization
Retisert: Pressure on IOP
It makes intuitive sense that, if an implanted device releases tiny amounts of a corticosteroid continuously inside the eye for two and a half years, the “steroid responders” among implant recipients might experience a chronic rise in intraocular pressure.
But a recent study seems remarkable nonetheless. Researchers pooled clinical trial data that contain figures about the incidence and magnitude of high IOP during clinical trials of an intraocular steroid implant (Retisert). IOP reached 10 mmHg or more above the preoperative level in 71 percent of 584 eyes. It rose 30 mmHg or more in 55.1 percent of the eyes; 40 mmHg or more in 24.7 percent; and 50 mmHg or more in 6.2 percent. Pressures took a mean of about 13 months to reach their peak before pressure-lowering treatment was begun.1
IOP-lowering medication was prescribed for 437 eyes (74.8 percent). However, by the end of three years, 36.6 percent of the total eyes required pressure-lowering surgery, mostly trabeculectomies. Thirteen patients had their implants removed surgically to control IOP, but the drop was sufficient to avoid trabeculectomy in only five eyes.
By comparison, the authors write, intravitreal injections of triamcinolone acetonide have been reported in several studies to raise IOP in 36.3 percent to 48.6 percent of injected eyes, depending on the definition used for elevated IOP.
They also suggest that the apparently higher incidence and magnitude of IOP elevation in the Retisert eyes, compared with intravitreal triamcinolone, might be misleading. “The higher incidence of elevated IOP with the [fluocinolone acetonide] intravitreal implant may be related to constant exposure to corticosteroid throughout the implant’s 30-month lifespan,” they write. “Given the delayed IOP elevation that required therapy in the current study, it is likely that the reported incidence of elevated IOP after [intravitreal triamcinolone] would be considerably higher with repeated . . . injections over a similar study period.”
1 Goldstein, D. A. Arch Ophthalmol
OCT May Spot, Monitor MS
Optical coherence tomography, the technology developed for ophthalmologists, is gaining a fan base among neurologists who want a better way to diagnose and monitor the course of multiple sclerosis.
Following up on an idea in Ophthalmology in February 2006,1 a multi-institutional team of researchers used OCT to measure the thickness of the retinal nerve fiber layer in 40 patients with MS and 15 healthy controls, then compared the results to brain size measured with MRI.2
Brain atrophy shown by an MRI scan is generally accepted as the best available surrogate marker for axons demyelinating and dying in MS. However, it is expensive; variables such as inflammation can make the brain look better or worse than the patient’s clinical symptoms would suggest; and brain atrophy occurs too late in the disease course for MRI to help physicians diagnose MS early, when the available therapies have their greatest potential effect.
After accounting for age differences between groups, the researchers found a positive correlation coefficient (0.46; P = 0.003) between a thinner retinal nerve fiber layer and decreasing brain size on MRI. The correlation was stronger for the relapsing remitting type of MS (0.69; P = 0.001).
The senior author of the study, Peter A. Calabresi, MD, associate professor of neurology at Johns Hopkins and director of the Multiple Sclerosis Center there, said the results suggest that OCT might be the simple, relatively inexpensive and clinically relevant marker of MS occurrence and progression that the field needs.
“This is a measure of nerve damage, and a pure measure of unequivocal nerve injury will predict disability better in these patients,” Dr. Calabresi said. “OCT also is an easy office-based tool usable by many different types of physicians.”
1 Fisher, J. B. et al. Ophthalmology
2 Gordon-Lipkin, E. et al. Neurology