This year, research pertaining to the cornea focuses on infection control, contact lens care and dry eye management. The following findings aim to demonstrate effective treatment methods, infection prevention techniques, and a further understanding of genetic disease.
Infection Management
Many studies this year focused on the management of ocular infections, through combination therapy for severe corneal infections or topical treatment for chronic blepharitis. Its important to maximize effective kill rates when treating severe corneal infections in order to reduce morbidity. Although toxicity is increased with multiple agent therapy, the eventual outcome is often improved. Refractory blepharitis and blepharoconjunctivitis continue to plague a great number of patients. Topical and oral drugs that help control inflammatory responses are now a major part of any successful treatment plan.
A small case series examined the efficacy of sutureless amniotic membrane transplant in patients with severe bacterial keratitis and persistent epithelial defect and ulcer.5948/A554 Researchers at the
Using combination therapy may increase the efficacy of the treatment regimen, say researchers from the Bascom Palmer Eye Institute, in Miami.2668/D900 Using a time-kill model, the researchers evaluated in vitro efficacy and synergy of gentamicin, tobramycin, moxifloxacin and vancomycin alone and in various combinations against methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant S. epidermidis (MRSE), methicillin-sensitive or -susceptible S. aureus (MSSA), methicillin-sensitive or -susceptible S. epidermidis (MSSE), and Pseudomonas aeruginosa. Each drug was tried alone against each isolate. And, combinations of vancomycin and moxifloxacin, and vancomycin and gatifloxacin were tried against the Staphylococci. The combination therapies moxifloxacin and gentamicin, and gentamicin and tobramycin were teamed up against P. aeruginosa.
Amniotic Membrane Transplant Treats Bacterial Conjunctivitis
The researchers found that gentamicin had a kill rate four times that of both vancomycin and moxifloxacin when it came to the Staphylococcus isolates. But, when moxifloxacin and vancomycin were used together, kill rates increased significantly. Kill rates increased four-fold to 12-fold against P. aeruginosa when moxifloxacin was used in combination with either gentamicin or tobramycin.
Treatment with topical azithromycin resulted in a reduction of common eyelid bacterial flora and improved symptoms in patients with blepharitis, say study leaders in Massachusetts, Pennsylvania, North Carolina and Texas.2661/D893 The eight-week multi-center study examined the efficacy of a four-week treatment regimen of topical azithromycin 1% ophthalmic solution. Researchers measured reduction in eyelid margin bacterial load, tear cytokines, and signs and symptoms. After a dosing regimen of b.i.d. for two days and q.d. through day 28, patients eyelid margin cultures demonstrated significant decreases in bacteria, but tear cytokine concentrations were unaffected. Median scores for all symptomsitching, foreign body sensation, swelling, dryness and painwere significantly decreased from baseline. Median scores for clinical signseyelid margin and palpebral conjunctival redness and meibomian gland pluggingwere also significantly reduced.
Over a keratoconus patients lifetime, he or she may spend an average of $25,543 on treatment and management.3525/D911 Researchers from Washington University in St. Louis and Ohio State University modeled a hypothetical cohort of patients on the findings of the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) study to develop a range of costs, including clinic visits, fitting fees, contact lenses, surgical procedures and possible complications. A patient could be expected to pay more than $25,000 over his or her lifetime post-diagnosis, with a standard deviation of $19,396. Costs could potentially range from $6,341 to $94,007 over an average period of 37.08 years after diagnosis at age 40. The patient could potentially afford the necessary treatment, say researchers, but as costs increase and the patient ages, this could become more difficult.
Keratoconus and Stromal Cross-Linking
The Financial Burden of Keratoconus
Researchers are now beginning to understand the breadth of keratoconus, as well as other factors that it affects. Morbid complications can impact quality of life significantlyfrom reduced acuity as a result of corneal scarring to the inability of patients to wear contact lenses.
Researchers from Johns Hopkins University in Baltimore found that tears of patients with advanced keratoconus contain markedly decreased levels of several cytokinesin particular, interleukin-4 (IL-4).3533/D919 The researchers examined tear fluid samples of 18 keratoconus patients and 11 control subjects. Levels of IL-1 beta, IL-4, IL-6, IL-12, IL-13, interferon-gamma and tumor necrosis factor alpha were significantly decreased in patients with keratoconus. Also, contact lens use was associated with greater decreases in IL-4, tumor necrosis factor alpha and interferon-gamma. Researchers speculate that these lower levels may play a role in disease pathogenesis.
Sleep apnea may occur much more frequently in the keratoconic population, say researchers from Illinois College of Optometry.3538/D924 Through a questionnaire, patients risk was assessed. Of the control patients surveyed, only 19.6% were at risk for sleep apnea; but, in the keratoconus group, 32.5% scored at the high-risk level, resulting in a 166% higher risk for patients with keratoconus vs. those without. Gender, though a factor in the control group, was irrelevant in the keratoconic population.
C3R
Corneal cross-linking with riboflavin (C3R) was also widely studied this year at ARVO. Several studies examined its capabilities for wound healing, abrasion improvement and reduction of swelling. This new treatment option holds potential for treating infectious and non-infectious corneal ulceration. The procedures effect on keratocytes and dendritic cells is being watched closely; it may have some impact on any injury or infection to the treated patient months or perhaps even years after the procedure is performed.
In cases of keratoconus, C3R may be a way to slow the progression of keractasia, say researchers in Germany.5492/A463 Rather than a full epithelial removal before treatment, which would increase the patients risk of infection, researchers used a linear abrasion technique, creating five or six abrasions that were each 1mm or 2mm wide. Within the follow-up period of 12 months, no patient experienced any complications. Each patients epithelium was completely closed within two days, and keractasia was stable. Best-corrected visual acuity returned to baseline by six or 12 months.
In a rabbit study, C3R was tested as a potential treatment for epithelial wounds.5496/A467 The
Researchers in
The risk of vision loss in one procedure of LASIK is equivalent to that of 10 years of constant contact lens wear, say researchers in Australia.1247 This 12-month prospective surveillance study used controls generated through available research and a telephone survey. LASIK risks were likewise generated through evaluation of FDA outcome and safety studies. The average incidence of vision loss in contact lens wear was 0.6 per 10,000 wearers per year, and it varied with lens modality and type. Vision loss following LASIK demonstrated an incidence of 42 per 10,000 cases, a risk equivalent to 69 years of any contact lens use, 102 years of daily wear and 10 years of overnight wear.
LASIK vs. CL Wear: What Are the Odds of Vision Loss?
Contact Lens Research
Especially now, when contact lens care regimens and efficacy testing protocols are under scrutiny, much attention at ARVO has been given to new contact lens research. In light of recent revelations with mini-epidemics of non-bacterial pathogens causing contact lens-related infections, regulatory agencies are taking a close look at ways to improve compliance by minimizing solutions under stress and improving efficacy against a wide range of potential pathogens.
Researchers in
The contact lens case can become contaminated after as little as one week of use, say researchers in Australia and Texas.6352/D990 More than 70 subjects in the study wore silicone hydrogel lenses on a daily basis and were randomized into two groups of solution usage (Group As solution used polyquaternium 1 and MAPD as a preservative, and Group Bs solution included PHMB). The different solutions, however, had no impact on contamination rates. Nearly 60% of cases and 34% of lenses were contaminated, and the researchers also found a significant correlation between contamination levels in each patients case and lenses. Case contamination was evident at one week, but more likely to be heavy after two weeks. Lens contamination was less frequent.
Researchers in
But, researchers in Australia found that most of these organisms cluster in a specific area of the lens casethe upper inner rim of the case; however, biofilm staining was most significant at the meniscus of the solution.5649/D958 These researchers evaluated 27 contact lens cases collected from asymptomatic lens wearers and took samples from one well each at the upper inner rim and the well bottom. The other well of each case was stained to visualize biofilm. Cases ranged in age from two weeks to one year, and contamination was uniformly higher at the upper inner rimmost likely due to the lack of contact in that area by solution, posit researchers.
Meibomian Gland Dysfunction
Meibomian gland dysfunction, one factor of dry eye, was another topic presented at this years meeting. Researchers discussed such factors as gland secretion capabilities and impact of fatty acid intake. MGD affects a large number of patients in clinical practice. These glands are essential to providing an ideal environment for the ocular surface and are easily affected by a whole host of outside influences.
A single meibomian gland is capable of secreting oil continuously over the course of the average working day, found researchers in Boston.4258/D861 The 10 patients in this small study were asymptomatic for dry eye and took no topical or systemic medications that could affect ocular dryness. After expressing the glands in the lower lid four times in three hours, researchers found that only 34% of glands were able to yield secretion at each expression. Of the nasal section, 69% secreted liquid each time vs. 31% of central glands and 22% of temporal glands. Researchers note that the nasal glands are most likely to function continuously for a period of nine hours.
Free fatty acids (FFAs), such as free linoleic acid and its oxidized derivatives, may have an adverse effect on the quality of the tear film, say researchers in Dallas.4254/D857 Using expressed human meibum samples, the study authors measured the reaction to FFAs in concentrations in excess of normal physiological levels; the FFAs quickly disrupted the layers of meibum. Effects of unoxidized mono- and polyunsaturated FFAs were similar. But, when oxidized, the effect is diminished and may even provide a possible protective mechanism, researchers note.
Dry Eye
This years research looks at such dry eye topics as age- and gender-specific treatment, concurrent ocular conditions and treatment efficacy. Many variables influence a dry eye state, and some sobering research points to the fact that most patients are going to show improvement, but not a complete cure.
Treatment with transdermal testosterone appears to have the best impact on women between the ages of 40 and 60, say researchers from Memphis, Tenn.4650/D900 These women, during menopause, respond far better to such androgenic treatment than do geriatric female patients, whose response is drastically reduced. Women under the age of 40 experienced some benefit, but not as much as the menopausal group. Women in this study cohort experienced a significant improvement in dry eye symptoms and tear film break-up time.
In a retrospective review of 12 pediatric patients, researchers in Florida, New Jersey and China found that demodicosis was the cause for all but one case of blepharoconjunctivitis.2606/D1026 For four to six weeks, patients were split into two groups; one received weekly lid scrubs with 50% tea tree oil (TTO), and the second received lid massage with 5% TTO. Before treatment, patients demonstrated bilateral ocular irritation and lid margin inflammation. Ten experienced bilateral meibomian gland dysfunction, four had multiple recurrent chalazia, three eyes had corneal infiltrates, two eyes evidenced superficial punctate keratopathy, two eyes showed phlyctenular keratoconjunctivitis and one eye demonstrated a corneal ulcer. After one week, all patients showed dramatic improvement in irritation and inflammation, and Demodex counts dropped. Corneal signs resolved in two weeks, with the exception of one residual anterior stromal scar and one incident of recurrence that was managed successfully with the same care regimen.
Lid wiper epitheliopathy is a reliable indicator for the presence of dry eye, say researchers in Massachusetts.4640/D884 Patients were recruited into two groups: symptomatic and control. After staining and comparing the lid wipers of all patients, researchers found that 88% of the dry eye symptomatic patients demonstrated lid wiper epitheliopathy, while only 18% of the control group showed it. Researchers point to the drastic difference between incidence in the two groups and suggest that lid wiper epitheliopathy may be a diagnostic indicator of dry eye.
Demodex Causes Pediatric Blepharoconjunctivitis?
The role of inflammation control and immunosuppression in dry eye management may currently be undervalued, say researchers in Germany.2613/D1033 Changes in cytokine concentrations could be an important indicator of ocular surface health. Researchers examined 50 patients with keratoconjunctivitis sicca and 50 control patients. Tear samples were analyzed through cytometric bead-based assay. Dry eye patients demonstrated significantly higher cytokine concentrations than those in the control group, suggesting that inflammation plays a role in the pathogenesis of dry eye.
Researchers in
Medical treatment may cure symptoms but not clinical signs of dry eye, say researchers in Spain and California.4667/D911 Twenty-one patients with no previous treatment for dry eye were examined and placed on an aggressive two-month regimen of lid hygiene, tears, steroids and doxycycline. At follow-up, patients demonstrated an improvementbut not resolutionin clinical signs, though their symptoms, they said, were much improved. Researchers note that in a population such as this, in which no prior disease history exists, symptoms are the most effective method to measure the efficacy of treatment.
For the text of each abstract, referenced here by presentation number, please go to www.arvo.org.
