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June 2006

News in Review
A Look at Today's Ideas and Trends
By Linda Roach, Contributing Writer
Edited by Brian A. Francis, MD

• Postop Infection Reduced Significantly
• Gene Therapy Gives Sight
• New SLO Is in the Works to Detect Problems Earlier
• Making the Adjustment to Accommodating IOLs

Postop Infection Reduced Significantly

For the first time, ophthalmologists can cite a large, prospective, placebo-controlled clinical study that found a clear difference between two approaches to preventing endophthalmitis with antibiotics— but the European study’s support for intracameral cefuroxime over levofloxacin won’t necessarily settle the issue in the United States.

“This confirmation that a potentially blinding complication of postoperative intraocular infection can be reduced fivefold should convince surgeons to adopt the use of intracameral cefuroxime as a standard part of the procedure of modern phacoemulsification cataract surgery,” said study chairman Peter Barry, MD, of the Royal Victoria Eye & Ear Hospital and St. Vincent’s University Hospital, both in Dublin, Ireland.

Based on retrospective studies, Sweden is the only country where up until now ophthalmologists have endorsed the intracameral administration of cefuroxime, a second-generation cephalosporin, after cataract surgery.

But in the United States, clinical practice and recent research have concentrated on finding the best topical antibiotic for the job, bypassing levofloxacin in favor of the fourth-generation fluoroquinolones gatifloxacin (Zymar) and moxifloxacin (Vigamox). (The Academy’s Preferred Practice Pattern guidelines for adult cataract make no recommendation about antibiotic prophylaxis, leaving the decision to the individual physician. See the PPP at

David F. Chang, MD, clinical professor of ophthalmology at the University of California, San Francisco, and a member of the Academy’s cataract PPP panel, called the European study’s results “a major and important development.” He continued, “The many surgeons already routinely administering intracameral antibiotics for their cataract patients can now feel that this principle has been validated. Direct intracameral injection of a precise amount of drug certainly makes more sense than placing antibiotic in the infusion bottle.

“However, it is important to realize that the ‘control arm’ was topical levofloxacin started either 18 hours postoperatively or immediately before surgery, and the en-dophthalmitis rate in these patients was surprisingly high,” Dr. Chang noted. “The study does not tell us how intracameral cefuroxime would have compared with the most common prophylactic practice in the United States —preoperative dosing for one to three days with topical fourth-generation fluoroquinolones—and whether it is therefore necessary in this context.”

Dr. Barry persuaded the European Society of Cataract and Refractive Surgeons to sponsor a 35,000-patient study beginning in September 2003. All patients received preoperative povidone-iodine, and all were treated with topical levofloxacin starting 18 hours postoperatively. The prophylaxis regimes tested were:

  • Two 1-drop doses of topical levofloxacin 0.5 percent beginning one hour before surgery.
  • The same levofloxacin dosing as directly above combined with 1 milligram intracameral cefuroxime, at the conclusion of surgery.
  • Intracameral cefuroxime alone.
  • No preoperative topical levofloxacin or intracameral cefuroxime.

By last December, 16,000 patients in eight European Union countries were part of the study, and 13,698 had completed follow-up. But an interim data analysis showed the endophthalmitis rates differed so much that recruitment was halted and the data were unmasked.

They showed 23 infections in 6,862 patients who did not receive cefuroxime (3.35 cases per 1,000), compared to five in the 6,836 patients treated with the drug (0.73 cases per 1,000). The researchers also were surprised to detect no statistical difference between endophthalmitis rates with or without preoperative levofloxacin.

ESCRS plans to use the results to revise its guidelines on preventing postoperative endophthalmitis. In November, the Academy is scheduled to release an update of its PPP for adult cataract, which will discuss this issue.

Deborah S. Jacobs, MD, assistant clinical professor of ophthalmology at Harvard University and chair of the Academy’s cornea/anterior segment subspecialty panel of the Ophthalmic Technology Assessment Committee, said objective evidence in this area hasn’t been available before this.

“Practice patterns in the U.S. have changed, despite the lack of good evidence, and certainly the pharmaceutical industry has an interest in the adaptation of certain patterns,” Dr. Jacobs said. “As the ESCRS experience is appreciated and reviewed further, it will no doubt generate further evaluation of intracameral antibiotics. As more literature emerges on intracameral antibiotic prophylaxis against endophthalmitis, an assessment might well be undertaken.”

Dr. Chang said, “Attention should next be focused on determining the most appropriate antibiotic for intracameral prophylaxis, and on the development of commercially available preparations that would reduce some of the risks inherent in ‘homemade’ off-label formulations.”

Research Report

Gene Therapy Gives Sight

Michigan scientists who recently made blind mice “see” accomplished this feat with the most time-tested tool of all—nature itself—instead of with the microelectronics of an artificial retina or the surgical approach of transplanting stem cells.

Using an adeno-associated viral vector, the team at Wayne State University in Detroit delivered a gene for a photosensitive molecule used by green algae, channelrhodopsin-2 (ChR2), into the retinal ganglion cells (RGCs) of a photoreceptor-deficient mouse strain. (ChR2 responds to the same chromophore as rods in vertebrates do, 11-cis retinal.)

This converted these cells of the inner retina from their normal role as secondary mediators of information gathered by rods and cones into direct receptors for signals sent to the visual cortex. The RGCs retained their ChR2-based photosensitivity for more than a year, the researchers say.1

The approach was exciting because of the work itself and because it points to possible therapies—albeit distant ones—for degenerative retinal diseases in humans.

“The investigators have made a paradigm shift in the field . . .,” says a commentary published with the study.2 “This publication is clearly a significant first step into this new field of re-engineering retinal interneurons as genetically modified ‘prosthetic’ cells.”

But questions remain. RGCs contain melanopsin receptors, the mechanism by which light hitting the retina tells the brain to stop releasing the sleepiness hormone melatonin, thus regulating sleep and wake cycling. This process is known to be active even in the congenitally blind. Zhuo-Hua Pan, PhD, associate professor of anatomy and cell biology at Wayne State University and a coauthor of the study, said the group has not yet investigated whether conferring another type of photosensitivity on the RGCs interferes with melanopsin and the animals’ circadian rhythms.

1 Bi, A. et al. Neuron 2006;50(1):23–33.
2 Flannery, J. and K. Greenberg. Neuron 2006;50(1):1–3.

Technology Update

New SLO Is in the Works to Detect Problems Earlier

The excitement about the imaging capabilities of the confocal scanning laser ophthalmoscope (SLO) has hardly waned, yet already an improvement that could give retinal specialists even more information is around the corner.

This modified version of an SLO, of which there are only two prototype devices so far, contains an added detector that can track natural fluorescence emitted over time by retinal molecules, counting it at the level of single photons, said Elizabeth Gaillard, PhD, associate professor of chemistry, biochemistry and biological sciences at Northern Illinois University.

The reason for this added level of complexity? To be able to detect molecular changes from retinal degeneration long before any obvious physical signs appear.

“In a disease like age-related macular degeneration, damage occurs on the cellular level first, and only later is there gross anatomical change,” Dr. Gaillard said. “Our goal is to detect changes earlier in the disease process than currently is possible.”

She is part of a group that includes research scientists James P. Dillon, PhD, at Columbia University in New York, and Dietrich Schweitzer, PhD, at the University of Jena in Germany, where the prototypes were built.

The modified SLO would detect endogenous fluorescence from various marker molecules in the retina, timing how long the fluorescence lasts after laser illumination, Dr. Gaillard said. There would be no need for dyes, Dr. Gaillard noted. “Most tissue, as it ages, becomes more fluorescent and we’re monitoring that native fluorescence.

“The way we do measurements, we’re able to see very subtle changes in retinal physiology in real time,” Dr. Gaillard said. “One of the fluorescent molecules we’re looking at is directly related to cellular respiration—so any changes from normal would indicate that the cells weren’t healthy.”

But the group will need to develop baseline data on the time-based fluorescence profiles of molecules found in healthy and diseased retinas, and about the small shifts that occur, for instance, when a molecule becomes oxidized.

“It should give ophthalmologists a tool for making much earlier diagnoses of retinal disorders,” she said. “The earlier you intervene, the better the outcome for patients.”

Patient Care

Making the Adjustment to Accommodating IOLs

Call it a case of impatient patients. These are the pseudophakes who opt for the accommodating Crystalens IOL (Eyeonics). Even though they were told that optimal near vision takes three to six months to achieve, they often show up a month after surgery worried that something is wrong, said Paul S. Koch, MD, in private practice in Warwick, R.I.

This spring at the meeting of the American Society of Cataract and Refractive Surgery, Dr. Koch reported on his 12-week program to reduce the need for hand-holding: a daily dose of word search puzzles.

Each of the six collections he designed gives the patient, in effect, a two-week exercise prescription for stimulating pseudophakic accommodation and strengthening the ciliary muscle, he said.

The type size in the puzzles starts at 24 points and decreases with each successive collection, down to 9 points at the end.

Eyeonics was so pleased by the idea that they took it over from Dr. Koch and posted the puzzles for downloading on their Web site.1 There are no studies showing the puzzles make a measurable difference in visual outcome. Instead, the payoff comes in happy patients who have an easier way to heed their doctor’s orders, Dr. Koch said.

“They don’t whine as much,” Dr. Koch told an amused audience. “Instead they look forward to completing each book because it means they’re getting better.”