Watch for Patients With MRSA or MRSE
It is no longer just health care workers whom ophthalmologists should view as at risk for postoperative infection by antibiotic-resistant bacteria, according to a study of cataract surgery patients at 10 sites across the United States.
Approximately half of the 399 patients in the study had preoperative lid or conjunctival presence of methicillinresistant forms of Staphylococcus epidermidis (MRSE) or S. aureus (MRSA).1 These are the most common pathogens causing endophthalmitis (S. epidermidis) after phacoemulsification and bacterial keratitis (S. aureus) after refractive surgery.
The researchers found that more than 90 percent of their methicillin-resistant bacterial isolates came from patients who were not health care workers—the group that previously was implicated as the major source of antibiotic-resistant bugs in health care settings.
The findings also confirmed a 2007 report of three cases of communityacquired MRSA keratitis after LASIK.2
The results underline the need for ophthalmologists to take extra steps to prevent endogenous MRSE or MRSA from causing postoperative infections, said Eric D. Donnenfeld, MD, clinical professor of ophthalmology at New York University, and a co author of the study.
“The situation is very similar to HIV. We cannot assume a patient is not at risk. Antibiotic resistance is so high right now that you should just presume that every patient you see has MRSE or MRSA among their endogenous eyelid and conjunctival flora,” Dr. Donnenfeld said.
The researchers swabbed the subjects’ eyelids and conjunctiva prior to surgery to identify the bacteria present and test them in vitro for susceptibility to oxacillin, a drug in the same family as methicillin. (Methicillin is no longer commercially available, but its name survives in the MRSE/MRSA designations.)
More than 75 percent of the bacterial isolates were either S. epidermidis or S. aureus. About half of the S. epidermidis isolates and a quarter of S. aureus isolates were resistant to oxacillin, the researchers found.
In 2005, about 14 percent of the MRSA infections occurred in people who had no traceable exposure according to the CDC. However, local and regional variations have been reported. Between January 1996 and December 2004 at Miami’s Bascom Palmer Eye Institute, MRSE accounted for 52 of 86 (60 percent) cases of endophthalmitis secondary to S. epidermidis.3
Dr. Donnenfeld said he also has seen an increase in MRSE or MRSA cases referred to his practice’s eye surgery center.
“The high rate of oxacillin (methicillin)-resistant Staphylococcus species on the ocular surface of cataract surgery patients in the present study underscores the need to use an antibiotic in the perioperative period with a favorable profile against gram-positive species, including MRSA and MRSE,” the study’s authors write.
Although fourth-generation fluoroquinolones all have similar efficacies in clinical testing, Dr. Donnenfeld said he prefers to use a drop preserved with benzalkonium chloride. There appears to be a synergistic antimicrobial effect in the eye when both the drug and BAK are present.4
Dr. Donnenfeld said that at the eye surgery center where he is medical director the anti-MRSE/MRSA protocols include:
- Minimizing infection risk by treating even mild blepharitis before refractive surgery. He recommends a week of hot compresses, eyelid cleansing (SteriLid) and azithromycin 1 percent (Aza- Site) drops applied to the ocular surface and also rubbed into the lid margins, twice daily.
- Beginning a fourth-generation fluoroquinolone on the day of LASIK rather than at the time of surgery. He continues the antibiotic for five days postoperatively.
- Dosing with the antibiotic for three days before cataract surgery and 10 days after.
- Using intracameral vancomycin during cataract surgeries.
1 Olson, R. et al. Poster #004, National Surveillance: Methicillin Resistance of Staphylococcus
Species Among Non-Healthcare Workers Undergoing Cataract Surgery. Presented at the Joint Meeting of the American Academy of Ophthalmology, Sunday, Nov. 9, 2008, Atlanta.
To view the poster, go to www.aao.org/2009, scroll to “Meeting Archive,” then find “Scientific
2 Solomon, R. et al. Am J Ophthalmol 2007;143(4):629–634.
3 Miller, D. M. et al. Ophthalmic Surg Lasers Imaging 2007;38(6): 446–451.
4 Moshirfar, M. et al. Ophthalmology 2007;114(4):686–691. Dr. Donnenfeld is a consultant to Allergan, which funded the research.
Consider Phaco for Some Glaucoma Patients
How do you normally treat glaucoma patients? Drops? Laser or scalpel surgery? According to Richard L. Lindstrom, MD, cataract extraction may be the appropriate procedure for most patients with combined cataract and glaucoma.
“In my opinion, rather than just thinking of cataract surgery as a way to restore acuity, we should think of it as a way to bring intraocular pressure into a safer range,” he said. “I don’t believe this approach compromises the treatment of glaucoma—it actually enhances treatment.” Dr. Lindstrom is in private practice at Minnesota Eye Consultants in Minneapolis.
Retrospective data from a study by Dr. Lindstrom and colleagues1 of more than 700 patients have convinced Dr. Lindstrom that cataract extraction lowers IOP more than previously realized, that the pressure reduction is directly proportional to the preoperative IOP, and that it should be considered as an alternative to combined cataract/glaucoma filtration surgery. This approach would spare patients the more difficult recovery associated with filtration surgery, yet allow it later if necessary, he noted.
Dr. Lindstrom said he factors in elevated IOP and glaucoma as an indication for cataract surgery—recommending surgery earlier than if cataract were the only diagnosis—especially if medical management is failing.
As evidence, he cites retrospective analysis of IOP levels after phacoemulsification and intraocular lens placement in 712 normotensive, ocular hypertensive and glaucoma eyes. All procedures were performed at Minnesota Eye Consultants or Schulze Eye Surgery in Savannah, Ga. Patients were seen one to 10 years after surgery (mean: 4.5 years).
Patients in each of the three groups were further categorized into five subgroups based on their IOP at the time of surgery, ranging from a high of 31 mmHg to a low of 5 mmHg. Stratifying the patients revealed that IOP pressure reductions were directly proportional to preoperative IOP in all three patient groups, Dr. Lindstrom said. The researchers found that:
- The higher the IOP at surgery, the greater the IOP reduction after surgery.
- Age did not affect the magnitude of the IOP reduction.
- 74 percent of eyes with an IOP 20 mmHg converted to normotensive eyes (IOP 19mmHg) after surgery for the 10 years of the study.
- 77 percent of these eyes diagnosed with glaucoma had IOP 19mmHg after surgery for the 10 years of the study.
- Pressure reductions achieved at one year were sustained for 10 years in all patient groups.
Dr. Lindstrom hypothesizes that age-related lens changes are a major cause of ocular hypertension, and eventually of glaucoma. Lens removal thus improves ocular outflow and reduces IOP. In advanced glaucoma, phaco/IOL surgery alone might be insufficient, and these patients with severe glaucoma damage or very high pressures may still do best with a combined procedure, he added.
“But I just want ophthalmologists to appreciate the impact cataract surgery has on IOP, and to take advantage of that when it’s in the patient’s best interests,” he said.
1 Cataract surgery in the glaucoma patient. Presented at the Joint Meeting of the American Academy of Ophthalmology Monday, Nov. 10, 2008, Atlanta.
Keep an Eye on Anti-VEGF Patients
New research reveals that reducing the levels of vascular endothelial growth factor (VEGF) in adult mice causes the death of photoreceptors and Müller glia in the retina, as well as loss in visual function, according to one study.1 Despite the popularity and dramatic outcomes associated with anti-VEGF drugs for wet age-related macular degeneration, the authors say their results indicate the need for more caution in the use of these medications.
“Although adult mice eyes are different from those of humans, the study may indicate that we need to be conservative when using anti-VEGF drugs,” said lead author Patricia D’Amore, PhD, senior scientist and professor of ophthalmology and pathology at the Schepens Eye Research Institute.
In the study, the scientists mimicked the action of anti-VEGF drugs by giving adult mice a soluble VEGF receptor known as sFlt1. The systemic administration of sFlt1 had no effect on blood vessels of the inner retina, but the scientists did note a significant increase in the number of dying cells of the inner and outer nuclear layers, including amacrine cells, Müller cells and photoreceptors. Using electroretinograms, the team then measured visual function in the mice and found a significant reduction in both alpha- and beta-wave amplitude, which is indicative of considerable loss of photoreceptor function.
In parallel tissue culture studies, the scientists found that suppressing VEGF in Müller cells led to their death, indicating that Müller cells both make VEGF and use it for survival. They also showed that VEGF acts as a protectant for photoreceptor cells. In fact, the research indicates that both photoreceptors and Müller cells express VEGFR2, the major VEGF signaling receptor, and Müller cells express VEGF.
“Our data show that there is normal endogenous VEGF in a mouse eye, and we also showed for the first time that there is a primary signaling VEGF receptor, VEGFR2, on adult photoreceptor cells,” Dr. D’Amore said.
What does all this mean for clinical practice? Dr. D’Amore said that ophthalmologists should proceed with prudence when using anti-VEGF therapy for wet macular degeneration and note any problems in visual function in patients receiving these drugs. She adds that anecdotal reports have noted thinning of the retina with anti-VEGF medications. “In the future, treating wet macular degeneration may best be done by titrating anti-VEGF medications, or combining them with other treatments,” she said.
Susan B. Bressler, MD, professor of ophthalmology at the Wilmer Eye Institute, said, “With any new drug, physicians have a responsibility to be alert for adverse effects—particularly those that were identified as potential adverse effects when the drug was tested in human trials. And there is always a possibility, though small, that additional adverse events may surface that were not recognized to be significant during human trials—and these may only come to light by close postmarketing surveillance.”
1 Saint-Geniez, M. et al. PLoS ONE
Autologous Plasmin Enzyme vs. Diabetic Macular Edema
A technique recently developed and tested in Valencia, Spain, offers diabetic patients with macular edema who have been unresponsive to photocoagulation and other intravitreal treatments a new option. “A 0.2 milliliter intravitreal injection of autologous plasmin enzyme effectively reduces macular thickening in more than 20 diabetic macular edema patients treated during our clinical trial . . . improving visual acuity in at least the short-to-medium term,” according to Patricia Udaondo, MD, lead investigator of this clinical study at Hospital Universitario de Valencia’s retina unit.1
The Valencia team used optical coherence tomography to evaluate the efficacy of intravitreal plasmin injections for their patients, all of whom had bilateral DME, allowing doctors in the clinical trial to treat one eye with plasmin, while the other eye acted as a control. The initial study showed that baseline central macular thickness of an average 541 µm decreased significantly. It was an average of 241 µm at one month and 244 µm at four months. The control group showed no significant changes. Visual acuity in the treated group went from 0.618 logMAR to 0.43 logMAR.
Over the past 14 months, the team has treated more than 45 patients with DME. Of that group, approximately 40 percent needed a second injection three-to-four months later.
“Whether or not the intravitreal plasmin injection is sufficient treatment for a permanent cure remains to be seen,” said Dr. Udaondo. “It may be that some patients will need two injections a year. We will know more once we’ve completed further studies to assess the technique’s long-term efficacy. What we do know, however, is that the injection is easy to prepare, simple enough to be done in a doctor’s office, and has proven extremely safe, with no complications noted from the medication itself. And this treatment doesn’t contraindicate the posterior use of other treatments.”
—Nancy Bronstein ___________________________
1 Intravitreal plasmin without associated vitrectomy as a treatment for refractory diabetic mac ular edema. Presented at the Joint Meeting of the American Academy of Ophthalmology, Sunday, Nov. 9, 2008, Atlanta.
In the Lab
Mouse Studies Show Hope for Diabetes, Sjögren’s
Researchers at the Medical College of Georgia were surprised to discover that an antioxidant found in green tea may prevent or delay the onset of type 1 diabetes. They also found that the antioxidant—polyphenol epigallocatechin-3-gallate (EGCG)—reduced the severity and delayed the onset of salivary gland damage associated with Sjögren’s syndrome.
Sjögren’s syndrome is characterized by inflammatory cell infiltration of the lacrimal and salivary glands. This profusion results in a loss of secretory function, thus causing ocular and oral health problems. There is no known cure for Sjögren’s syndrome, and treatment primarily involves the alleviation of symptoms by using artificial lubricants that act as saliva or tear substitutes.
Using a mouse model of Sjögren’s syndrome, researchers studied the effects of EGCG to determine whether it protects against autoimmune-induced pathological changes in the salivary glands. Mice were given either water or purified EGCG dissolved in water. The results indicated that EGCG consumption at 0.2 percent resulted in a moderate level of serum total autoantibodies, and fewer mice developing insulin-dependent diabetes.1 Lymphocytic infiltration also was reduced during the disease-advancing stage, apoptotic activity was inhibited and the expression of cell nuclear proliferation markers PCNA and Ki-67 was suppressed in the salivary glands.
“Although the researchers looked at the lymphocytes in the salivary glands, these are very similar to the glands that make tears. It would be interesting for ophthalmology researchers to collaborate with this group to investigate the effects on the eye,” said Penny A. Asbell, MD, professor of ophthalmology at Mount Sinai School of Medicine and director of the cornea service and refractive surgery center. “These are very provocative findings and whether or not they are going to correlate with human disease is difficult to determine. We hear a lot about nutritional supplements and do not have the data, even in an animal model, to support whether they are efficacious or not.”
1 Gillespie, K. et al. Life Sciences
EyeNet thanks Susan B. Bressler, MD, Steven I. Rosenfeld, MD, and William Trattler, MD, for their help with this issue’s News in Review.