Fluoroquinolone efficacy; new treatments for neovascularization, inflammatory conditions and infectious diseases; new information on dry eye; and quality-of-life perspectives were just a few topics covered at this years Association for Research in Vision and Ophthalmology (ARVO) meeting.
Research on the emerging resistance rates and effectiveness of fluoroquinolones is a topic of both interest and importance for optometrists.
With that in mind, researchers from Boston compared the in vitro effectiveness of fourth-generation fluoroquinolones (moxifloxacin and gatifloxacin) with that of third-generation (levofloxacin), and second-generation (ofloxacin and ciprofloxacin) versions. They used these agents on 22 Staphylococcus species cultures; half of these were methicillin-resistant Staphylococcus aureus (MRSA).2770
Moxifloxacin and gatifloxacin were equally effective to each other against MRSA. Levofloxacin, ciprofloxacin and ofloxacin were equally effective to each other against MRSA, but overall, moxifloxacin and gatifloxacin were more effective. Moxifloxacin was most effective against all Staphylococcus species, followed (in order of effectiveness) by gatifloxacin, levofloxacin, ciprofloxacin and ofloxacin.
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| Fourth-generation fluoroquinolones may be the most effective option against MRSA, which caused this patients corneal ulcer, new research suggests. |
Despite the effectiveness of fourth-generation fluoroquinolones, a study at Bascom Palmer Eye Institute in Miami revealed that nonbacterial pathogens and mycobacteria were more frequently linked in cultures of patients who were pretreated with fourth-generation fluoroquinolones than those who were pretreated with a non-fluoroquinolone antibiotic.2777
This same group of researchers observed emerging resistance against the fourth-generation fluoroquinolones in common ocular isolates of Streptococcus and Pseudomonas aeruginosa.
Keratitis
Several studies at this years meeting looked at the course and treatment of various forms of keratitis.
Researchers from the University of Pittsburgh studied the clinical outcomes in 20 patients treated for infectious keratitis caused by MRSA and 14 patients treated for infectious keratitis caused by methicillin-sensitive Staphylococcus aureus (MSSA).2624 All 34 cases cleared up without adverse events. The time range for re-epithelialization was one to 88 days for infections caused by MRSA and three to 55 days for those caused by MSSA. The median/mean time for the infiltrates to resolve was 19/39 days for MRSA and 19/27 days for MSSA. There were no statistical differences between patient gender or age in terms of resolution.
Meanwhile, researchers at Wills Eye Hospital in Philadelphia discovered that patients who have bilateral recurrent interstitial keratitis of unknown etiology are more likely to have recurrences than patients who have unilateral disease.2631 They also discovered immunoglobulin antibodies against Epstein-Barr virus in three patients and against Lyme disease in three patients, suggesting that you consider these in your differential diagnosis, even though the etiology of both forms of keratitis is often unknown. In addition, they conclude that, during the treatment of acute disease and flare-ups, steroids should be used carefully with slow taper to preclude recurrences.
When treating ocular inflammation, we cannot allow ourselves to be restricted to one treatment. For example, amphotericin B, an antifungal agent, has long been considered the gold standard in the treatment of Candida albicans keratitis. However, a study on 44 rabbits suggests that voriconazole may be the new drug of choice.2623 In the initial homogenized samples, only those given voriconazole had significantly reduced colony-forming units when compared to the control group. Also, those given ampho-tericin B experienced significant increases in mucous discharge and conjunctival hyperemia when compared to the other groups, including rabbits who received flucanozole, another antifungal agent.
New Treatments
Researchers presented several new treatments for neovascularization and various corneal diseases at this years meeting. For example, a French and Israeli study showed that selective photodynamic therapy using WST11, a new hydrosoluble photosensitizer, results in the efficient, safe and continuous occlusion of rabbit corneal neovessels.4498 The researchers also discovered that the effectiveness of WST11 is closely linked to the distance to light illumination of the laser fluence usedmost likely because of its fast elimination from the circulation.
Meanwhile, a New York study showed that the systemic administration of VEGF Trap, a potent inhibitor of vascular endothelial growth factor, curbs the development of corneal neovascularization, edema and inflammation following injury in male miceeven when administered at low doses.4497 Also, when used at higher doses for a brief amount of time following injuries, VEGF Trap may be relatively effective, the researchers say.
Also in New York, researchers discovered that topical cyclosporine, normally used to treat severe dry eye, may also be effective for treating chronic, active ocular rosacea that is unresponsive to standard treatment.2660 Out of 55 patients who were prescribed topical cyclosporine for a minimum of six months, 17 reported mild to moderate relief of symptoms, and there was improvement on clinical exam. Another 25 patients reported significant relief or complete resolution. Eleven patients withdrew prior to six months due to poor response. Two patients discontinued topical cyclosporine without recurrence, but two others (4%) developed recurrence. At final follow-up, 30 of the responsive patients were no longer taking any other medications, and 12 were taking low-dose tetracycline.
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| Topical cyclosporine may be effective for treating chronic, active ocular rosacea. |
A University of Florida study showed that a replication-defective herpes simplex virus cannot only be used to grant local immunity to the cornea of the herpes simplex keratitis patient, but can potentially act as a corneal vaccine against herpes simplex infections.2617
Finally, researchers from New York discovered that riboflavin/ UVA-induced collagen crosslinking may stabilize the progression of keratoconus by reducing corneal elasticity.4964 In turn, this stability may allow for excimer laser correctionsomething that has been contraindicated in keratoconus patients. Also, 65% of the participants had slight visual acuity improvements. Still, the researchers say that long-term studies are necessary to evaluate the duration of stiffening effects and exclude any long-term side effects of therapy.
Keratoconus Progression
Keratoconus affects one in every 2,000 Americans, especially young adults, making it the most prevalent corneal dystrophy in the United States, according to statistics from the National Eye Institute. Research presented at this years meeting offered new insight on disease progression and patients quality of life.
One study used seven years of follow-up data from 953 keratoconus patients who participated in the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) study. These patients did not under-go penetrating keratoplasty in either eye at baseline. The researchers found that better best-corrected visual acuity at baseline, steeper corneas, corneal scarring and fundus abnormalities were predictive factors for increases in reduced visual acuity.4947
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| Continued progression of keratoconus results in continued decline in vision-related quality of life, according to new findings from the CLEK study. |
Researchers also used eight years of follow-up data from 1,032 CLEK participants (those who had penetrating keratoplasty in either eye at baseline were excluded) to predict longitudinal increases in corneal curvature using the first definite apical clearance lens and the flatter keratometric curvature measurement. Results showed that younger age in a keratoconus patient and poorer visual acuity on high-contrast manifest refraction at baseline are predictive factors for the rate of change in corneal curvature.4949
New findings from the CLEK Study offer insight on the quality of life of keratoconus patients. CLEK researchers administered the National Eye Institute Visual Function Questionnaire (NEI-VFQ) annually to keratoconus patients for seven years.4945 The researchers found that:
On average, patients who reported lower NEI-VFQ scores at baseline, reported improvements in quality of life over time.
An increase in corneal curvature was significantly linked to a decline in the NEI-VFQ scores of dependency, mental health, ocular pain and role difficulties in those who reported high NEI-VFQ scores at baseline.
Decreases in visual acuity were associated with significant decreases in NEI-VFQ scores of dependency, driving, mental health and near activities scales.
There is preliminary evidence that keratoconus patients who have impaired vision-related quality of life accommodate to their disease, the researchers say. But, progression of disease, as measured by changes in visual acuity and corneal curvature, results in continued decline in vision-related quality of life.
Dry Eye Gender Difference
Why are female patients more affected by dry eye syndrome than male patients? Higher amounts of meibomian gland triglycerides in the lipids of female patients than in male patients could be the reason, say researchers from Texas.
In analyzing meibomian gland secretions from 13 males and 12 females, they found that the trigylceride mean of the total meibomian liquid was 61% (38.5%) for the female patients vs. 2.3% (1.7%) for the male patients. While higher levels of triglycerides result in greater stability in the tear film lipid layer, triglycerides may be more vulnerable than other lipids to destruction by enzymes, such as those from bacteria, the researchers say.4472
Contact Lens Infiltrates
Silicone hydrogel contact lenses have been shown to significantly decrease the complications associated with hypoxia when compared with traditional low Dk/T hydrogel contact lenses. However, there has not been a clear comparison of the risks of inflammatory and mechanical complications between the two lenses.
Researchers from Case Western University analyzed results of 22 studies to evaluate the risks of corneal inflammatory events and contact lens papillary conjunctivitis between silicone hydrogel and traditional extended-wear lenses.2067 The probability for infiltrates was 4.34 per 100 eyes in the group wearing low Dk/t lenses. The probability for contact lens-induced peripheral ulcer in this group was 2.24 per 100 eyes. The pooled estimates of infiltrate events were not significantly different between those patients who wore silicone hydrogels and traditional hydrogels. However, contact lens papillary conjunctivitis was more likely to be seen in the silicone hydrogel group than in those patients wearing traditional lenses (odds ratio of 1.48).
Dr. Shovlin is in group practice in Scranton, Pa. He edits Review of Optometrys Cornea and Contact Lens Q&A column and is clinical editor for Review of Cornea and Contact Lenses. Check out Highlights of ARVO 2005 in the May and June issues of Review of Cornea and Contact Lenses for more abstracts.
2067. Szczotka-Flynn LB, Diaz-Insua M. Risk of infiltrates and CLPC with traditional hydrogel and silicone hydrogel extended wear: a meta analysis.
2623. Botelho PJ, Zhang C, Kuo IC, et al. Comparative efficacy of topical voriconazole with amphotericin B and fluconazole in the treatment of Candida albicans keratitis in an animal model.
2624. Happ EM, Kowalski RP, Mah FS. Can MRSA (methicillin resistant Staphylococcus aureus) keratitis be successfully treated?
2631. Ribeiro M.F., Cohen E., Hammersmith K. Laibson P.R., et al. Clinical outcomes of recurrent interstitial keratitis of unknown etiology.
2660. Perry HD, Wittpenn JR, DAversa G, Donnenfeld ED. Topical cyclosporine 0.05% for the treatment of chronic, active ocular rosacea.
2770. Kim EC, Charukamnoetkanok P, Poothullil AM, et al. Second, third, and fourth generation fluoroquinolone susceptibilities of methicillin resistant Staph aureus (MRSA) cultures collected at the Massachusetts Eye and Ear Infirmary.
2777. Miller D, Alfonso EC, Perez EM, Diaz MG. Trends in use, frequency, culture positive rates, pathogen selection, and emerging resistance among patients presenting on moxifloxacin and gatifloxacin.
4472. Shine WE, Aronowicz JD, Butovich I, McCulley JP. Sex differences in meibomian gland triglycerides.
4497. Song H, Cao J, Liu Y, et al. Low dose or transient administration of VEGF trap suppresses corneal neovascularization and inflammation.
4945. Kymes SM, Walline JJ, Zadnik K, et al. A longitudinal study of the quality of life of people with keratoconus: a report from the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study.
4947. Zadnik K, Schechtman KB, Davis LJ, et al. Predictors of visual acuity loss in keratoconus.
4949. McMahon TT, Edrington TB, Szczotka-Flynn L, et al. Longitudinal changes in corneal curvature in keratoconus.
4964. Braun E, Kanellopoulos J, Pe L, Jankov M. Riboflavin/ultraviolet A-induced collagen cross-linking in the management of keratoconus.
