Repeated exposure of the eye to ophthalmic antibiotics appears to be associated with the emergence of resistant strains of microbes among patients undergoing intraocular injection therapy for neovascular retinal disease, according to a report in the September issue of Archives of Ophthalmology.

Treatment for neovascular age-related macular degeneration increasingly involves monthly ocular injections of medication, and this treatment is also being studied for eye problems related to diabetes and retina vein occlusions. Ophthalmologists routinely prescribe ophthalmic antibiotics after every injection to prevent endophthalmitis. “Repeated exposure of ocular flora, however, may select for resistant bacterial strains and cultivate ‘superbugs’ with multiple-drug resistance that may considerably affect the treatment of ocular infections,” write the authors.

Stephen J. Kim, MD, and Hassanain S. Toma, MD, from the Vanderbilt University School of Medicine, Nashville, Tenn., conducted a randomized, controlled, longitudinal study of 48 eyes of 24 patients who, in one eye each, received intraocular injection. At baseline and after every injection, researchers obtained cultures of the conjunctiva for both treated and control eyes. Patients were randomized to one of four antibiotics and after each injection used only the antibiotic they were assigned. The researchers tested the bacterial samples for susceptibility to 16 antibiotics and analyzed the bacterial DNA. Injections were administered every four weeks for at least four consecutive months, and patients were followed for one year.

Repeated exposure to fluoroquinolone antibiotics was associated with coagulase-negative staphylococci that demonstrated significantly increased rates of resistance to both older- and newer-generation fluoroquinolones. Repeated exposure to azithromycin was associated with CNS that demonstrated significantly increased resistance to macrolides and decreased resistance to both older- and newer-generation fluoroquinolones. Specimens of CNS from treated eyes demonstrated significant increases in multiple-drug resistance; for example, 81.8 percent of CNS specimens appeared resistant to at least three antibiotics, and 67.5 percent appeared resistant to at least five antibiotics.

The researchers suggest that their results demonstrate rapid development of resistance from CNS to certain antibiotics, and that this resistance is maintained when the antibiotic is periodically readministered. “This finding has considerable implications because conjunctival flora are presumed to be the predominant source of postinjection endophthalmitis,” they write, adding that research suggests one strain of CNS is associated with greater intraocular inflammation than are strains more susceptible to antibiotics. “Our findings,” the authors conclude, “indicate the need for more judicious use of ophthalmic antibiotics after intraocular injection to reduce the potential emergence and spread of antimicrobial resistance.”

Vitamin D, Nutrients May Reduce AMD
Eating a diet high in vitamin D, as well as the nutrients betaine and methionine, might help reduce the risk of macular degeneration, according to new research led by Johanna M. Seddon, MD, ScM, director of the Epidemiology and Genetics Service, New England Eye Center, and professor of ophthalmology, Tufts University School of Medicine.

The team’s study of identical twins from the U.S. World War II Twin Registry also found that the more a person smoked, the higher their risk of developing macular degeneration. The study, published in Ophthalmology on July 1, is the first to look at a large number of identical twin pairs in which one twin had early age-related macular degeneration and the other had late-stage AMD. AMD is highly heritable, with genetic factors determining up to 71 percent of the disease’s severity, as determined by a previous study of this twin registry by the same research team. By examining identical twins with the same genes but whose disease was at different stages, researchers were able to identify environmental and behavioral factors that may contribute to severity of the disease. “We wanted to know why, if they have the same genes, do they have different stages of the disease?’’ said Dr. Seddon.

The study used a survey of personal dietary and health habits to determine variations. Twins whose AMD was at the early stages tended to consume more vitamin D from dietary sources such as fish or milk than their brothers. Vitamin D may reduce the risk of macular degeneration because it has anti-inflammatory properties. It may also block the formation of new blood vessels that can grow under the macula, leaking blood and causing vision loss in the more severe stages of the disease. Similarly, Dr. Seddon’s research team also found that higher intakes of betaine and methionine were linked to a slower progression of the disease. These nutrients have also been linked to epigenetic mechanisms, a change in DNA, not attributable to a change in the actual DNA sequence. This is the first time these nutrients have been linked to AMD. Betaine is found in fish, grains and spinach, while methionine is found in poultry, fish and dairy foods.

The study also found that among the pairs of twins, the twin who was the heavier smoker tended to have the more severe case of AMD. These results indicate that both genetic susceptibility and environmental factors are important, that epigenetic factors may also be involved, and further underscores the importance of modifiable behaviors, especially avoiding smoking and eating a healthy diet, to help prevent or delay the progression of macular degeneration.

“Eat a healthy diet with lots of fruits and vegetables, and that can make a difference, even if you have a genetic susceptibility to macular degeneration,’’ said Dr. Seddon, “and of course don’t smoke.’

UM Surveys Providers on Older Drivers
Drivers over age 65 are the fastest-growing segment of the driving population, and their eye-care providers are playing an increasingly important role in assessing their ability to drive safely.

Kellogg Eye Center researcher David C. Musch, PhD, MPH, recently led a multidisciplinary University of Michigan study team who surveyed how 500 vision-care providers in Michigan assess the driving capabilities of their senior patients.
Dr. Musch and his team found that the majority of eye-care providers feel it’s their responsibility to ask senior patients about driving, and most do it routinely. They test visual acuity and peripheral vision but often fail to ask about other factors—such as medical conditions or medications—that might affect the ability to drive. Inquiries about glare, driving at night and reading signs were very common (87 percent), but questions about challenging driving situations—merging or backing up—or the patient’s driving record were very infrequent (8 percent).

Many eye-care providers (81 percent) stress that certain resources—driving assessment guidelines, clinical screening instruments and a patient self-evaluation tool—would help them in assessing the driving capabilities of their senior patients, and help to address higher accident rates for older drivers.

“We’ve identified a need and a desire on the part of vision-care professionals to help,” says Dr. Musch, who cites research indicating that when seniors lose the ability to drive, there are consequences. These individuals have higher rates of depression and social isolation, more limited access to health care services, and are more likely to need long-term care. “Our goal is to intervene and work with our patients in modifying their driving habits. This will allow them to drive appropriately and maintain their independence,” he says.

While most eye-care providers feel confident in their ability to determine whether vision is adequate for safe driving, few consider themselves the most-qualified professional to identify unsafe drivers. Only a small number of eye-care providers (8 percent) communicate driving concerns with the patient’s primary-care physician or refer patients to driving rehabilitation specialists or driving school. And, when asked about reporting unsafe drivers, some common concerns were negative impact on the doctor-patient relationship, liability issues, doctor-patient confidentiality and patients’ quality of life.

Still, eye-care providers are among the most important professionals in seniors’ health care, and they need to be on the lookout for seniors who may need special attention, says Dr. Musch. Identifying and providing effective resources to eye-care providers to aid them in evaluating and assisting patients is the next step in the process, he says.

Drug Offers New MOA in IOP Lowering
Acucela Inc. and Otsuka Pharmaceutical Co. have initiated a Phase I/II clinical trial for OPA-6566, an adenosine A2a receptor agonist being developed as an ophthalmic solution to reduce intraocular pressure in open-angle glaucoma or ocular hypertension patients. OPA-6566 was discovered by Otsuka.

The compound offers a new mechanism of action not seen in conventional glaucoma medications, and has demonstrated the ability to lower intraocular pressure by stimulating aqueous humor outflow via trabecular meshwork by activation of the adenosine A2a receptor. 

The trial will be conducted at clinical sites in the United States in patients with open-angle glaucoma or ocular hypertension and will test for safety, tolerability and the IOP-lowering effects of OPA-6566. The trial is designed as a first-in-human, randomized, multicenter, investigator-masked, placebo- and active-controlled, dose-escalation study with 28 days of treatment in patients with open-angle glaucoma or ocular hypertension.

Estimates projected that in 2010 there would be 60.5 million people with OAG and angle closure glaucoma, and that number was expected to increase to 79.6 million by 2020. Bilateral blindness was expected to be present in approximately 4.5 million people with OAG and 3.9 million people with ACG in 2010, and was expected to rise to 5.9 and 5.3 million people in 2020, respectively.

Results Due in Phase II Dry-Eye Study
RegeneRx Biopharmaceuticals announced that treatment and follow-up have been completed on 69 patients in its Phase II clinical trial with RGN-259 for the treatment of dry-eye syndrome, five more than the number of evaluable patients contemplated in the trial’s protocol. After all study data completes the quality-control process and data lock, it will then undergo statistical analyses. The trial is on schedule for top-line results to be reported in late October.

This double-masked, placebo-controlled clinical trial will evaluate the safety and efficacy of RGN-259, the Company’s proprietary preservative-free eye drops, in patients with dry-eye syndrome. Patients received RGN-259 or placebo twice daily for 30 days. Signs and symptoms of dry eye, such as the degree of ocular surface damage, ocular itching, burning and grittiness, among others, were graded periodically during and following the treatment period.

In two animal models RGN-259 reduced ocular surface defects associated with dry-eye syndrome compared with both positive and negative controls. In one experiment RGN-259 performed better than Restasis, the only drug currently approved to treat dry-eye syndrome, in reducing such damage. In several comparisons to controls, the clinical improvements with RGN-259 were statistically significant. This data was presented at the 2011 ARVO meeting.