Each year, world-renowned eye care scientists share their research at the Association for Research in Vision and Ophthalmology annual conference. Valuable information gleaned from the many studies at this year’s meeting (held May 5-9 in Seattle) can aid clinicians in developing best-practice guidelines while raising important questions that will direct future research efforts.

It’s always difficult sifting through hundreds of abstracts to identify the most useful ones that can translate into immediate clinical practice. This year’s highlights include risk factors related to lens wear, how to prevent infection stemming from lens and storage case contamination, disinfection efficacy and treatment options when disaster strikes.

As no single study is likely to provide the definitive answer to a research question, the findings below should be viewed with a perspective that acknowledges our full body of literature. Nevertheless, this year’s crop of abstracts provides many thought-provoking new ideas that will help us move forward.

New Information on Risk Factors and Prevention
Inherent in any lens wear is a full range of risks that hopefully can be minimized by addressing identifiable factors responsible for getting an infection.

How might we best minimize these inherent risks? Several abstracts address these topics. Important to any discussion or investigation of infection are geographic differences in pathogens encountered, risks to travelers, lens storage case contamination and antimicrobial efficacy of disinfecting solutions.

Risk Factors for Contact Lens-related Microbial Keratitis in Singapore (Abstract ID: 509/B0146)
Elevated risk of microbial keratitis was associated with showering while wearing lenses (a three-fold higher risk), while washing and drying hands prior to handling lenses lowered the risk eight-fold. Chinese ethnicity also lowered risk seven-fold in this study, possibly due to socioeconomic factors. Behavioral and innate factors should be investigated further.

Traveler’s Contact Lens Associated Keratitis (TCLAK): Establishing Preventive and Treatment Guidelines to Close a Gap in Ophthalmic Care (Poster: 511/B0148)
Though the incidence of lens-associated keratitis is low, an increasing number of new cases are identified in travelers due to greater lens use, long duration of wear and travel outside the US. There appears to be higher morbidity risk due to decreased access to ophthalmic care abroad.     

The lack of specific recommendations regarding precautions to take while traveling internationally is an obvious patient education gap that requires attention. The authors designed guidelines that include strict adherence to proper hygiene and care, seeking immediate attention if the eye gets red, irritated or experiences vision loss, and advises patients to not overwear lenses while traveling.

Quorum-sensing Molecules in the Preferential Selection of Pseudomonas aeruginosa From Contaminated Contact Lens Cases (Abstract ID: 513/B0150)
“Quorum-sensing” proteins/genes were studied to document and correlate their role in the selection of Pseudomonas aeruginosa as a preferential corneal pathogen from contaminated contact lens cases, according to Bascom Palmer researchers. In 76.9% of studied lens cases, Pseudomonas emerged as the corneal pathogen of all matched control/cornea cultures. No proteins recovered correlated with Acanthamoeba species, Klebsiella oxytoca or Mycobacterium chelonae.

The researchers concluded that the production and expression of quorum-sensing genes and signaling molecules in contact lens case ecosytems may allow for the preferential selection of P. aeruginosa as a corneal pathogen. Understanding this mechanism in more detail may lead to the development of new solutions to reduce or neutralize this advantage.

An Examination of the Effects of Evaporation on Antimicrobial Efficacy of Contact Lens Care Solutions (Abstract ID: 5480/A0179)
Partial evaporation of multipurpose solutions (MPS) by failing to cap solutions properly may result in loss of antimicrobial efficacy of the solution, leading to contact lens-related infections. In this study from Abbott Medical Optics, evaporation was induced in four MPS products, which were then challenged with P. aeruginosa, Serratia marcescens, S. aureus, Candida albicans and Fusarium solani. Test solutions were compared at four hours to the non-evaporated solutions.

This study demonstrated that with partial evaporation up to 4x (simulating the action of not capping a lens case properly), MPS solutions can lose significant disinfection ability. More pronounced loss was shown in solutions that failed to meet criteria when non-evaporated. Only one MPS tested (an investigational solution) showed full efficacy of disinfection when evaporated at the 4x level.

New FDA guidelines could involve evaporation testing and any loss of efficacy, to attempt to reflect real-world conditions.

The Evaluation of the Biocidal Efficacy of Multipurpose Solutions Against Mixed Cultures of Pseudomonas aeruginosa With a Variety of Individual Organisms (Abstract ID: 521/B0158)
This study by investigators at Bausch + Lomb investigated biocidal activity to better simulate polymicrobial contamination of contact lens cases. The organisms used were not the standard five organisms, but rather six separate mixtures of organisms that included P. aeruginosa and one of the following: Candida albicans, Candida tropicalis, Fusarium solani, Fusarium oxysporum, Aspsergillus brasiliensis and Aspergillus fumigatus. Ten percent organic soil was added for an additional challenge. The mixed inoculum was then used to challenge the MPS. Four- and six-hour time points were evaluated. Results were recorded using log reductions.

Results varied according to the MPS used. Fungi were recovered more than P. aeruginosa. Recovery for the four-hour time point ranged from 0.2 log reduction to >4.6 (no microbial recovery observed). The six-hour time point ranged from 0.0 log reduction to >4.6 log reductions.

This study demonstrated that MPS have a broad range of in vitro antimicrobial activity against P. aeruginosa and fungal mixtures. These results could demonstrate actual use conditions because environmental contaminants are frequently mixtures of organisms.

Antimicrobial Activity of Mela-mine or Cathelicidin Bound Contact Lenses (Abstract ID: 507/B0144)    
The development of an antimicrobial contact lens would have the ability to reduce the rate of contact lens-related adverse events. This study, conducted by Allergan, Brien Holden Vision Institute and Bausch + Lomb, evaluated two cationic peptides coated on contact lenses for their activity against P. aeruginosa and S. aureus. Minimal inhibitory concentration of two peptides, melamine (a synthetic peptide) and cathelicidin (LL37), were measured against strains of P. aeruginosa and S. aureus.

Increasing concentrations of peptides were bound covalently to contact lenses. Cell death of the bacteria was used to measure the antimicrobial activity compared to the control lenses with no melamine or LL37. Covalently bound LL37 was not active against S. aureus; melamine on contact lenses had activity against both bacterial types. This suggests differing mechanisms of action against gram-negative or gram-positive bacteria by these two cationic peptides.

Risk Factors for Microbial Bioburden During Daily Wear of Silicone Hydrogel Contact Lenses (Abstract ID: 5479/A0178)
This study from Case Western Reserve University, University Hospitals Eye Institute-Case Medical Center and Alcon Labs assessed risk factors associated with substantial microbial bioburden of lids, cases and silicone hydrogel lenses with daily wear.

A total of 218 patients were fit with lotrafilcon A lenses, randomized to use either a preserved MPS or a peroxide care system, and followed for one year. Lenses, lids, cases and transport saline were cultured at selected visits.

Univariate analysis showed that current or past smokers, clerical occupations and solution type were associated with greater risk of microbial bioburden on lenses, cases or both. Gender, age, healthcare occupations, solution type and other demographic factors were associated with lid bioburden or saline contamination. Mulitivariate analysis also showed clerical occupations at significantly greater risk of microbial contamination on lenses and cases.

Solution type was associated with microbial bioburden in cases, but not lids, lenses or transport saline. Hydrogren peroxide solution was associated with increased lens case bioburden, but not with bioburden of lids, lenses and transport saline. Case contamination was not a risk factor for corneal inflammatory events in this study.

Selenium Covalently Incorporated into the Polymer of Contact Lens Material Inhibits Bacterial Biofilm Formation (Abstract ID: 497/B0134)
Silver has been used as an antimicrobial agent in contact lens cases, but has drawbacks (allergy risk, variable antimicrobial effect, cost, reliance on the agent leaching out of the case). Selenium is a good alternative to silver: it does not have to leach out of the case to be active because it kills by catalytic formation of superoxide radicals, and is much less expensive.

This study investigated the ability of selenium covalently incorporated into the polypropylene polymer of injection-molded contact lens case material to inhibit biofilm formation by different bacteria. Polypropylene containing selenium showed over 7 logs (complete) inhibition against S. aureus, S. maltophilia and P. aeruginosa, and was fully active after soaking in PBS for the equivalent of eight weeks.

Updates on Pathogens in Lens-related Infections

Surveillance has identified antibiotic resistance of ocular pathogens. These “bugs” have relevance to lens wearers due to different vectors of exposure. It’s important to identify emerging resistance patterns that vary greatly depending on where you practice.

Believe it or not, we’re still talking about Acanthamoeba keratitis. Protozoan infection rates have not dropped as expected. We must remain vigilant in looking for ways to minimize even the rare, nonbacterial infections experienced by lens wearers. Microbiologic profiles in younger lens wearers are valuable and shared below.

Antibiotic Resistance Surveillance of Ocular Pathogens—Four Years of ARMOR Study Results (Abstract ID: 2904/B0273)
The ARMOR surveillance study reported Year-4 data on 456 isolates of Streptococcus aureus, coagulase-negative staphlococci (CoNS), P. aeruginosa and H. influenzae from 25 sites that were subjected to susceptibility testing. Drug resistance among H. influenzae isolates was not observed.

Non-susceptibility rates were similar to those of the previous three years. Overall resistance rates did not show substantial changes over the four-year study. A number of isolates showed resistance to commonly used ophthalmic antibiotics. Among MRSA and MRCoNS isolates, multidrug resistance was especially prevalent.

Specific findings include:

  • P. aeruginosa isolates were nonsusceptible for ciprofloxacin (9.1%), imipenem (11.4%), tobramycin (4.5%) and polymycin B (4.5%).
  • S. pneumoniae isolates were nonsusceptible to imipenem (13.1%), penicillin (4.9%), chloramphenicol (3.3%) and azithromycin (41.0%).
  • S. aureus and CoNS isolates were nonsusceptible to oxacillin/methicillin (37.3-41.9%), ciprofloxacin (33.8-36.6%), clindamycin (18.3-31.3%), azithromycin (58.8-60.1%) and other antibiotics.
  • More than 33% of S. aureus and CoNS isolates were resistant to three or more antibiotics.
  • Methicillin-resistant isolates of S. aureus (MRSA) and CoNS (MRCoNS) were predominantly drug resistant (>73%).

Risk Factors of Severe Acanthamoeba Keratitis (Abstract ID: 5435/A0134)
Japanese researchers studied risk factors for severe Acanthamoeba keratitis by comparing severe cases to mild ones (i.e., those with a good prognosis) in a nine-case series.

A history of topical steroid use was found in four eyes in the severe group and three in the mild group. Mean number of corneal scrapings was 13.8 in the severe group and 5.6 in the mild group. Kerato-precipitates were present in all eyes in the severe group. Also in the severe group, S. aureus was found in one case by palpebral conjunctiva culture, which was resistant to topical antibiotics.

They concluded that the use of corticosteroids and the presence of kerato-precipitates are possible risk factors for severe Acanthamoeba keratitis. Attention is also required in patients with comorbidities such as diabetes mellitus and bacterial co-infection.

Clinical and Microbiological Profile of Infectious Keratitis in Children (Poster Board: #B0100)
In this retrospective study of pediatric patients with infectious keratitis in Mexico City, 78% of patients showed predisposing factors. Ocular trauma, including contact lens wear, was the most common (25%). Factors responsible for visual impairment may be delay in eye care, visual axis involvement, inadequate adherence to treatment and low positivity of cultures.

Pseudomonas aeruginosa isolates were resistant to ceftazidime, the first-line drug in gram-negative keratitis. Susceptibility to gentamycin was observed. Staphylococcus sp. showed multiple antibiotic resistance in a majority of cases.

Infectious Keratitis in Mexico—10-Year Experience in Corneal Scrapes (Poster Board: #B0091)
Another retrospective study conducted in Mexico City reported the distribution, microbiologic trends and antibiotic sensitivity patterns of infectious keratitis cases from January 2002 to December 2011. In all, 1,638 corneal scrapings were taken. A pathogen was recovered in 616 samples (38%). Bacterial keratitis accounted for 544 of the positive cultures (88%).

Results showed a non-significant increase in recovered gram-positive and gram-negative micro-organisms over time. An increase in resistance to methicillin in almost half the MSRA and MRCNS islolates was observed. In the last five years of the study, ceftazidime-resistant P. aeuroginosa increased to nearly 90%.

Vancomycin-resistant micro-organisms accounted for 9.9% of all gram-positive isolates while 13.3% of all bacterial isolates were resistant to quinolones. For now, the authors conclude that this justifies quinolones as monotherapy broad-spectrum treatment for bacterial keratitis.

The Proctor Experience With Acanthamoeba Keratitis From 1996-2012 (Poster: #B0105)
This retrospective study described the presentation, management and outcomes of Acanthamoeba keratitis (AK) patients in the Bay area before and after an AK epidemic beginning in 2004-2005.

Forty-one patients (42 eyes) demonstrated culture-proven AK. From 1996-2004, there were zero to three AK cases. From 2005-2011, there were three to six cases. This trend is significant (p=0.003). The number of microbiology-positive AK cases has increased since 2005 and has not remitted.

The duration of symptoms in 1996-2004 is not statistically different from 2005-2012. Visual acuity at presentation was not significantly different from pre-2005 and 2005 to present.

The number of culture-proven AK cases has not decreased to pre-epidemic levels in the Bay Area. Before and after 2005, a median time of four weeks of symptoms prior to diagnosis was endured, and patients presented with visual acuity morbidity. Even with increased awareness, diagnosing AK does not appear to be happening any earlier in its course.

Advances in Treatment
New therapies are always exciting to share with readers. This year’s abstracts look at preclinical evaluations of several new therapies for corneal infections including rare, nonbacterial keratitis. Ongoing research should help identify new strategies in treating these morbid corneal conditions.

Clinical Outcomes and Prognostic Factors Associated With Acanthamoeba Keratitis Treated With Pentamidine Isethionate (Poster Board: #B0103)
This retrospective Japanese study described the clinical characteristics, time of presentation, treatment, outcomes and prognostic factors on a series of 24 patients and 26 eyes with Acanthamoeba keratitis (AK) treated with pentamidine isethionate.

A review of all patients was performed, including age, gender, time to diagnosis, use of corticosteroid before diagnosis, combination of bacterial of fungal infections, diagnostic method, initial visual acuity, duration of pentamidine isethionate treatment, side effects and final visual acuity. Treatment failure was defined as AK recurrence or needing a therapeutic deep anterior lamellar keratoplasty.

The onset of symptoms was greatest in September. AK was diagnosed either by typical clinical presentation or by culture. Forty-two percent of eyes were diagnosed previously with herpetic keratitis; 58% were treated with corticosteroid eye drops. Five eyes had combined bacterial or fungal infections. Twenty-two eyes were contact lens wearers. Hospital time averaged 26.9±21.7 days. Visual acuity improved from 1.41logMAR±1.00logMAR to 0.19logMAR±0.34logMAR. Soft contact lens wearers tended to have a higher risk of infection and failure is likely to be associated with stromal involvement.

Predictors of Outcome in Fungal Keratitis Using Data From the Mycotic Ulcer Treatment Trial (Abstract ID: 2900/B0269)
The purpose of this study was to determine baseline factors predictive of outcome in fungal keratitis among the Mycotic Ulcer Treatment Trial (MUTT I) Group.

MUTT I was a multicenter, randomized, double-masked, NEI-funded clinical trial that compared outcomes in 323 patients with fungal keratitis receiving 5% topical natamycin or 1% topical voriconazole.

Significant predictors of worse three-month visual acuity were worse baseline acuity, larger epithelial defect size at presentation and randomization to voriconazole instead of natamycin in the trial. For three-month infiltrate/scar size, significant predictors include larger infiltrate and epithelial defect size, worse presenting visual acuity and use of topical antifungals prior to trial enrollment. Predictors of corneal perforation were worse presentation visual acuity, older age and randomization to voriconazole instead of natamycin. The predictors of longer time to epithelialize were epitithelial defect size and presentation ulcer depth.

Study findings suggest that it is difficult to change the course of an ulcer even with proper treatment—ulcer severity at presentation is highly predictive of worse outcomes—but a better understanding of predictive factors may help guide future treatment decisions and management.

Clinically relevant information is not always apparent in high-level research abstracts, but ARVO posters and papers are teeming with valuable information that can be applied to clinical practice. Knowing how to reduce risk and prevent morbidity in lens wearers is extremely useful information.

Knowing how to identify in a timely fashion and better treat rare, devastating infections in lens wear is crucial. ARVO has helped us do so year after year.

I hope that you have found this year’s review helpful. For more information and all the abstracts, please visit www.arvo.org/abstracts.