Today’s news from the 2010 ICOI meeting brought to you by EyeWorld magazine
Sessions continued Saturday at the 5th International Conference on Ocular Infections in Palm Beach, Florida. Among the hot topics discussed were endophthalmitis, fluorquinolone efficacy, blepharitis, and drug delivery systems.
Vitrector size may play role in endophthalmitis
The rates of endophthalmitis are significantly higher after 25-gauge vitrectomy than found in the general literature after cataract surgery (1 in 100 cases post-vitrectomy vs. 1 in 1000 in the U.S. and 1 in 2000 in Sweden after cataract surgery), said J.F. Arevalo, M.D. “There is a higher risk of endophthalmitis after PPV, and this has stayed consistent through the years,” he said.
Dr. Arevalo discussed results from the Endophthalmitis Post-Vitrectomy Multicenter Study, which analyzed the number of cases that occurred with a 25-gauge and 20-gauge needles over the course of 2 years (Jan. 2005-Dec. 2006). With the 25-gauge, the incidence was 0.69% (12 of 1,738 pars plana vitrectomy) compared with 0.03% (3 of 9,421) when the surgery was performed with 20-gauge. With the 25-gauge, 10 were treated with subconjunctival cefazolin, and the endophthalmitis resolved. In the 25-gauge cases, coagulase-negative Staph was responsible for 6 cases (50%), in the 20-gauge coagulase-negative Staph was responsible for 33% (one eye).
Post-endophthalmitis treatment, 67% of the patients in the initial 25-gauge group had a visual acuity of 20/400, compared with 100% of those in the 20-gauge group.
In the two years since that study, a secondary one comparing 25-gauge to 23- and 20-gauge found rates of endophthalmitis remained about the same in the 20-gauge and 23-gauge groups, but “declined fourfold in the 25-gauge group,” Dr. Arevalo said. Although no definitive answer was given, it could be that the more experience a surgeon becomes with 25-gauge, the lower the risk.
Blepharitis can be severe, speaker says
Blepharitis—both anterior and posterior—is a common disease and can be “severe,” said David Hwang, M.D., professor of ophthalmology and co-director of the cornea service, University of California, San Francisco. Dr. Hwang spoke here at an industry-sponsored breakfast. Blepharitis is also common when other ocular morbidities are present—when there are objective signs of blepharitis upon presentation, 59% also had cataract and 93% also had age-related macular degeneration, Dr. Hwang said, citing two published studies.
“Blepharitis can cause persistent symptoms,” he said. Left untreated, the anatomic changes that can affect ocular health “can lead to end-stage pathologies,” he said.
Contact lens wear can alter the tear-epithelial interface. Lastly, he said blepharitis may be a risk factor in patients undergoing LASIK: it may be associated with diffuse lamellar keratitis or marginal infiltrates, and may increase tear instability and postoperative infection, he said.
Efficacy of newer kind of fluoroquinolone
Compared to ciprofloxacin, gatifloxacin, and levofloxacin, besifloxacin had improved in vitro potency against S. aureus and S. epidermidis ocular isolates resistant to another ophthalmic fluoroquinolones, according to a poster presentation here. Lynne S. Gearinger and colleagues at Bausch & Lomb (Rochester, N.Y.) conducted microbroth dilution MIC testing on 29 ciprofloxacin-resistant Staphylococcus aureus isolates and 22 ciprofloxacin-resistant Staphylococcus epidermidis isolates. Resistance to ciprofloxacin was previously determined. MIC-90 values against all isolates, including methicillin resistant and susceptible strains were 4/4 for besifloxacin, 256/64 for ciprofloxacin, 32/32 for gatifloxacin, 256/256 for levofloxacin, and 32/32 for moxiflocaxin.
Besifloxacin (Bausch & Lomb, Rochester, N.Y.) has improved efficacy against many of the bacteria that cause ocular infections, in particular Pseudomonas, said John Sheppard, M.D., MMSc., during an industry-sponsored breakfast.
Besifloxacin, delivered in the DuraSite (Insite Pharmaceuticals, Alameda, Calif.) vehicle, has shown a “log order or more of resistance when compared to the typical fluoroquinolones we use today,” Dr. Sheppard continued. As part of a multicenter study, he noted the AUC of besifloxacin is “better in QD, BID, and QID dosing,” he said.
The MICs were better against the most common bacteria when compared to moxifloxacin or gatifloxacin, as well as in comparison to the macrolide azithromycin. “In a rabbit ocular penetration study, besifloxacin was 10 times more concentrated than moxifloxacin and eight times more concentrated than gatifloxacin,” he said. The “fluorochloroquinolones may be the future of antibacterial drugs for ocular use,” he said.
New delivery systems include silicone, nanoparticles
Sustained delivery technologies that deliver customizable amounts of drugs to the eye can include silicone wafers and nanoparticles. “We need something better than eye drops to deliver ocular medications,” said Eugene de Juan, Jr., M.D., at University of California San Francisco. “Very few of the medications we deliver topically are retained. Think of it like this: eye drops are like trying to get oil into the engine of a car by pouring it on the hood.” Because of how the tear film rapidly clears medications delivered in drop form, “only about 1/1000th of the medicine in a drop gets to the target,” Dr. de Juan said.
He suggested punctal plugs may be a viable delivery vehicle in the future, as long as the punctal plugs remain in the eye. “Overall, we will see a prolonged and effective sustained release of glaucoma and other ocular medicines delivered through the tear film,” he said.
In the retina arena, William Freeman, M.D., professor of ophthalmology at University of California, San Diego and director, Jacobs Retina Center, told attendees about work on silicone wafers that can be sewn into the sclera to deliver anti-vascular endothelial growth factor drugs over a longer period of time. “A nanoporous delivery vehicle system can be customized for different drugs; pore size and pore density is controlled electrochemically,” he said. Current models indicate using this technology will allow a sustained release of Avastin (bevacizumab, Genentech) over the course of 120 days, he said.
Richard M. Awdeh, M.D., assistant professor of ophthalmology at Bascom Palmer Eye Institute, Miami, said the use of nanoparticles holds great promise in ophthalmology. “They have multiple materials and shapes, can be metallic or inorganic, can have rods, spheres or cages, and can be up to hundreds of nanometers in size,” he said. The likely ocular targets will be between 2 and 90 nanometers, he said. There are several regulatory issues that will have to be addressed before the technology can be thoroughly studied, he said. Among them: there is currently no nanotherapeutic approved by the Food and Drug Administration, although there is now a NanoTechnology Interest Group (NTIG) that has been formed to address bioequivalence issue, as well as safety, efficacy and pharmatoxicity questions.
Contact lens-associated microbial keratitis
Speakers during this session concurred any soft contact lens—with the notable exception of daily disposable group—increases the risk of microbial keratitis, especially in young males who smoke. The rates of ulcerative keratitis is about 20 per 10,000 in extended wear soft contact lens wearers, which decreases to 4 per 10,000 in daily wear soft contact lens wearers, said Oliver Schein, M.D., professor of ophthalmology at Wilmer Eye Institute, Baltimore. Over the past 25 years, “the risk factors have been quite consistent,” he said, “with contact lens hygiene and environment remaining the leading cause.”
Wearing contact lenses overnight increases the risk of microbial keratitis fivefold, he said. “There have been no severe cases reported in those wearing daily disposable lenses,” Dr. Schein said.
The pathogenesis of microbial keratitis in contact lens wearers has four factors: biofilm, corneal exposure to microbes, increase susceptibility to keratitis, and virulence factors, said John Dart, M.D., Moorfields Eye, London. “Why do extended wear silicone hydrogel users develop it more?” he asked. “They seem to have an increased susceptibility to infection.”
Whereas once hypoxia was thought to be a major contributor, that theory has been disproved, with the realization that stagnation of the tear film under soft contact lenses, reducing the organism clearance, he said. “Daily disposable lenses decrease the risk of severe microbial keratitis, but they don’t change the risk of mild microbial keratitis,” Dr. Dart said.
Donald S.C. Tan, FRCOphth, director of the Singapore Eye Research Institute, said that while the Asian region comprises 60% of the world’s population, very few articles on the epidemiology of infectious/ulcerative keratitis have been published from the region. He said contact lens wear accounts for 54.5% of microbial keratitis in Japan, 44.3% in Taiwan, 34% in Singapore, 26% in Hong Kong, 25.7% in Malaysia, 18.6% in Thailand, yet only 0.56% in Southern India. “Without a doubt, Pseudomonas is the leading bacteria,” he said, accounting for 86% of the infections in Hong Kong, and 79% in Singapore.
In the Chicago area, “about 33% of all microbial keratitis occurs in contact lens wearers,” said Elmer Y. Tu, M.D., director or cornea/external disease at University of Illinois Eye and Ear Infirmary. In general, there remains seasonality and geographic influences on the outbreaks of keratitis—with increases generally seen in the warmer months, he said. Environmentally, domestic hard water supplies can also play a role, he added.
In Japan, poor contact lens hygiene and wearing time compliance has been the leading causes of microbial keratitis, said Yoshikazu Shimomura, department of ophthalmology, Kinki University School of Medicine, Osaka. In an outbreak in his country, 233 cases spread across 224 major ophthalmology clinics over the course of 1 year were identified, he said. Mean age was 28 (range: 9-90 years old) and 129 were male. “There were only nine cases in hard contact lens use,” he said. “It makes them safer than other types of contact lens use.
© 2010 ASCRS
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