Two research studies have shown that a strong topical NSAID may play a role in the treatment of choroidal neovascularization secondary to age-related macular degeneration.

One study evaluated adjuvant bromfenac 0.09% ophthalmic solution (Xibrom, Ista Pharmaceuticals) with ranibizumab (Lucentis) treatment of CNV secondary to AMD for the possible modulation of the duration of treatment. Calvin A. Grant, MD, of Advanced Retinal Institute Inc., Palos Heights, Ill., and colleagues found that the use of Xibrom reduced the number of Lucentis injections needed to control the disease by a factor of 2.83.

"Xibrom and Lucentis patients showed better visual acuity outcomes than Lucentis alone. The use of Xibrom increased the number of patients responding to Lucentis," says Dr. Grant.

The retrospective analysis compared patients using Xibrom adjunctively with ranibizumab injections for neovascular membrane secondary to AMD to patients on Lucentis alone. At baseline, the two patient populations were equivalent in terms of disease as evidenced by the mean baseline OCT measurements. "Over a six-month period, compared to Lucentis alone, a greater percentage of patients on Xibrom showed gains in visual acuity," says Dr. Grant.

In addition, 71 percent of patients treated with Lucentis and Xibrom gained one or more lines of vision on the EDTRS scale compared to 19 percent on Lucentis alone. And 32 percent of patients on combination therapy gained three or more lines of vision in six months compared to none with Lucentis alone. Dr. Grant says this correlated with a greater reduction in macular thickness for the Xibrom adjunctive group. The logMAR visual acuity changes showed a statistically significant difference, with patients on Xibrom and Lucentis gaining an average of 1.6 lines of vision (0.12 logMAR) versus less than one line for Lucentis alone (0.06 logMAR). These patients gained this with fewer mean injections of Lucentis: 1.6 injections in six months versus 4.5 in the Lucentis-only group.

"The data strongly suggest a beneficial adjunctive role for Xibrom in the management of wet AMD and, indeed possibly to other retinal indications where anti-VEGF therapy is indicated," he says. "A well-controlled prospective trial should be performed to confirm these data."

Dr. Grant notes that while this study was conducted on humans as a part of their normal treatment of AMD, animal research is important as well. "There are models of dry and wet ARMD that I think would do well with this line of research. It is important in that it may reduce the number of injections that are needed of anti-VEGF agents both Avastin and Lucentis," he says.

"Presently there is a multicenter prospective clinical trial that is being designed which I plan on being a part of," he says. "Collectively, we have to look at ways to decrease the burden and risk we subject our patients to. There is very little downside and a significant upside in treating every patient in this manner while we await the prospective data."

In another study, Tetsuo Kida, of Senju Pharmaceutical Co. in Kobe, Japan, and colleagues reported that topical bromfenac 0.1% ophthalmic solution significantly inhibited laser-induced CNV in 19 female mice. "It is well known that the inflammatory process is involved in the pathogenesis of ARMD," says Dr. Kida. "As shown in our result, a strong topical NSAID potently suppressed experimental CNV in mice in comparison with a single treatment of VEGF-neutralizing protein, and this result as monotherapy with bromfenac is likely to lead to innovation of the treatment of ARMD."

In this model, the researchers evaluated the inhibitory effect of topically applied bromfenac sodium 0.1% ophthalmic solution (Bronuck, Senju Pharmaceutical) which is the same formulation as bromfenac 0.09% ophthalmic solution in mice with CNV induced by laser photocoagulation, and compared the effect of bromfenac 0.1% with VEGF-neutralizing protein, recombinant murine VEGF receptor 1/Fc chimeric protein.

"Measurement of the CNV area demonstrated that treatment with topical bromfenac 0.1% for two weeks resulted in significantly smaller CNV lesions than that with saline. Bromfenac 0.1% and murine VEGFR-1/Fc inhibited CNV at the rate of 71 percent and 51 percent, respectively," he explains.

"These animal and human studies provide AMD patients with a lot of merits such as a low-cost treatment (because Lucentis is so expensive), improvement of patient's and doctor's compliance and reduction of risk of intraocular complications (because bromfenac applies topically), and so on," says Dr. Kida. He adds that he plans to continue research in this area to elucidate a mechanism of action for the results.


New Imaging Device May Detect Diabetes

Two scientists at the University of Michigan Kellogg Eye Center have invented a device that captures images of the eye to detect metabolic stress and tissue damage that occur before the first symptoms of disease are evident.

For people with diabetes—diagnosed or not—the new device could offer potentially significant advantages over blood glucose testing, the "gold standard" for diabetes detection.

The device takes a specialized photograph of the eye and is non-invasive, taking about five minutes to test both eyes.

In the July Archives of Ophthalmology, Victor M. Elner, MD, PhD, and Howard R. Petty, PhD, report on the potential of the new instrument to screen for diabetes and determine its severity. If further testing confirms the results to date, the new instrument may be useful for screening people who are at risk of diabetes but haven't been diagnosed.

"Our objective in performing this study was to determine whether we could detect abnormal metabolism in the retina of patients who might otherwise remain undiagnosed based on clinical examination alone," says Dr. Elner, a professor in the Department of Ophthalmology and Visual Sciences at U-M Medical School.

Metabolic stress, and therefore disease, can be detected by measuring the intensity of cellular fluorescence in retinal tissue. In a previous study, Drs. Petty and Elner reported that high levels of flavoprotein autofluorescence act as a reliable indicator of eye disease.

In their new study, the researchers measured the FA levels of 21 individuals who had diabetes and compared the results to age-matched healthy controls. They found that FA activity was significantly higher for those with diabetes, regardless of severity, compared to those who did not have the disease. The results were not affected by disease severity or duration and were elevated for diabetics in each age group: 30 to 39 years, 40 to 49 years, and 50 to 59 years.

Given the increasing prevalence of diabetes, the FA device holds the potential to help address a leading and growing public-health concern. Some 24 million Americans have diabetes and an additional 57 million individuals have abnormal blood sugar levels that qualify as pre-diabetes, according to the latest report from the Centers for Disease Control and Prevention. In addition, 4.1 million people over the age of 40 suffer from diabetic retinopathy.

Twelve individuals in the study were known to have diabetic retinopathy. The individuals with diabetic retinopathy in at least one eye had significantly greater FA activity than people with diabetes who do not have any visible eye disease.

"The abnormal readings indicated that it may be possible to use this method to monitor the severity of the disease," says Dr. Elner.

Hyperglycemia is known to induce cell death in diabetic tissue soon after the onset of disease but before symptoms can be detected clinically. "Increased FA activity is the earliest indicator that cell death has occurred and tissue is beginning to break down," says Dr. Petty, professor of ophthalmology and visual sciences, and professor of microbiology and immunology at the U-M Medical School. "FA serves as a 'spectral-biomarker' for metabolism gone awry, and we can use the results to detect and monitor disease."

Elevated FA does not always mean that an individual has diabetes. "Because of the prevalence of diabetes in our population, individuals with abnormally high FA would be prompted to undergo glucose-tolerance testing," says Dr. Elner. "If the findings were negative for diabetes, we would look for other causes of ocular tissue dysfunction."


DSAEK May Offer a Better Alternative for Children

Descemet's stripping automated endothelial keratoplasty may offer improved vision while overcoming the technical difficulty and low success rate of traditional penetrating keratoplasty in children, say reports in the current issue of the Journal of AAPOS (American Association for Pediatric Ophthalmology and Strabismus).

The issue includes two case reports on the successful use of DSAEK in children with corneal disease. If the results are borne out by further research, DSAEK could provide an alternative to traditional corneal transplantation—a notoriously difficult procedure in children, failing more often than it succeeds.

Bennie H. Jeng, MD, and colleagues at the Cleveland Clinic Cole Eye Institute performed DSAEK in a 21-month-old boy, while Mark M. Fernandez, MD, and colleagues  at Duke University Eye Center report the results of DSAEK in a 9-year-old boy. Both children had irreversible damage to the corneal endothelium after complications of cataract surgery.

In adults, DSAEK is gaining favor as an alternative to PK for several reasons. One key advantage is much more rapid recovery of vision—within six to 12 weeks after DSAEK, compared to six to 12 months with PK. Shorter recovery time is especially important in young children with developing vision, who are at risk of further, potentially severe amblyopia. Both children in the case reports had good results, showing improved vision within a few months after DSAEK. Being less invasive, DSAEK also has a lower risk of certain complications compared to PK. Postoperative management is simplified because no sutures are placed in the cornea.

Many questions remain, however. Since most children who need corneal transplants have other abnormalities as well, DSAEK may be an option in only about 20 percent of cases. The need to have the patient lie flat for 24 hours after surgery poses challenges in young children, and concerns about potential complications and long-term results must be addressed. Other treatment options are emerging as well, including the use of a keratoprosthesis.