Report from ARVO

What’s New in Cornea and Contact Lenses

This year’s meeting brings us new knowledge in treating corneal infections and about the effects of contact lenses.
By JOSEPH P. SHOVLIN, O.D., Associate Clinical Editor

Sidebar: What's New in Contact Lenses
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A patient presents with severe corneal pathology. You don’t want to withhold appropriate treatment, nor do you want to overmedicate the patient. What is the most appropriate course? And, how do you treat the patient whose infection is resistant to the seemingly strongest of medications? These are some of the questions researchers discussed at this year’s ARVO meeting.

The Antibiotic Debate

When treating corneal infections, the question remains: How aggressive should therapy be? Clinicians from Wills Eye Hospital in Philadelphia studied the effectiveness of aggressive topical antibiotic therapy (at least every hour) in 49 patients with infectious keratitis and visual acuity of 20/40 or worse.¹⁹² Visual acuity returned to 20/25 or better in 19 patients (40%), but 10 patients suffered further decline in acuity, to 20/200 or worse. Also, five patients suffered vision loss due to scarring and eventually needed therapeutic or penetrating keratoplasty. So, while aggressive topical antibiotic therapy can treat vision-threatening infections and restore visual acuity in some patients, we still need something more effective for many others.

Incidentally, researchers from Ontario’s University of Waterloo studied the ability of high-DK silicone hydrogel contact lenses to absorb and release topical ocular medications—in this case ciprofloxacin—to the eye.³¹⁷⁹¹ Their action was comparable to that of conventional soft lens materials. However, when you consider the oxygen transmission characteristics of silicone hydrogels, these researchers say, these lenses warrant further study into their applicability as sustained-release drug delivery devices and/or therapeutic/bandage lenses.

Even with some good news about antibiotic therapy, many of us are concerned about increasing bacterial resistance to the meds we have available. Researchers at Massachusetts Eye & Ear Infirmary reviewed charts of patients who presented with keratitis over a 22-month period.¹³⁷³ They found that most gram-negative organisms and a growing number of gram-positive ones were resistant to cefazolin. There were also emerging patterns of resistance to ciprofoxacin, especially among gram-negative organisms, including Pseudomonas aeruginosa.

With severe bacterial keratitis, we cannot rely on fluoroquinolones alone, they say. Rather, we should consider combination therapy with fortified antibiotics.

Researchers from Alcon Laboratories and Johns Hopkins University found that another antibiotic, moxifloxacin, was more active in vitro against quinolone-resistant isolates of Staph. aureus and Staph. epidermidis than were ofloxacin and ciprofloxacin.¹³⁷⁷

New Treatments

Preserved human amniotic membrane transplants may offer us an important new option for treating pathology. Researchers performed transplants on 14 eyes with pathologies that failed to respond to conventional treatment.¹⁴⁹ Corneal repair was successful in 11 patients, and the regenerated conjunctiva was less swollen. What’s more, none of the patients rejected the grafts or developed infection, probably due to the membrane’s antimicrobial properties.

Amniotic membrane transplants also show promise as a herpes treatment. Two studies found that amniotic membrane transplants improved HSV-induced ulceration and stromal inflammation.^254,255

Meanwhile, researchers from New York found that polyvalent, polyclonal antibodies showed promise as an antiviral in rabbit eyes infected with HSV.²⁵¹The drug works by targeting HSV-recombinant glycoprotein D. The researchers found that qid dosing appears most effective.

A new treatment for corneal dystrophies may also be on the way. Taiwanese researchers hope that by inducing a viral mediated transgene into the endothelial cells, they can treat and even prevent certain endothelial diseases.¹⁴⁷³

Dry Eye

Presentations at this year’s ARVO meeting also added to the growing body of information on dry eye. Researchers in Boston offer clues about the causes of computer-induced eye discomfort syndrome. They say that reduced blink frequency over a prolonged period results in thinning of the lipid layer, leading to dry eye symptoms.¹⁸²However, high periocular humidity, achieved in test subjects with Speedo swim goggles, appears to increase the lipid layer thickness, minimize evaporation, improve tear film stability and decrease the necessity to blink.

Dry eye may play a role in the development of neurotrophic keratitis, a difficult-to-treat condition that often requires very aggressive, disfiguring therapies.¹⁷²Researchers found that patients with neurotrophic keratitis had substantially diminished aqueous tear production. Punctal occlusion and artificial tears were successful treatments in these patients, indicating that more disfiguring therapies such as tarsorraphy and conjunctival flaps might best be reserved for refractory cases.

Meanwhile, researchers in England learned that dry eye mucins are less glycosylated, less sialylated and lack MUC2 when compared with normal ocular surface mucins.¹⁸⁸And, researchers from the State University of New York State College of Optometry found variations when comparing normal tear samples to those from dry eye patients. They found that patients with chronic external ocular symptomatology have higher levels of gelatinases, especially MMP-9 and MMP-2, in their tear samples.¹⁴²²These findings may one day lead to new dry eye therapies.

Much attention now focuses on wavefront technology for improved LASIK results, and the wavefront sensor might one day help you evaluate the severity of dry eye. Japanese researchers compared 17 dry eye patients (30 eyes) with 15 control subjects (15 eyes). Dry eye patients had increased higher-order aberrations, and their optical quality was deteriorated.¹⁸⁹

Unconventional Wisdom

Besides offering new insight on combating ocular pathology, researchers at this year’s ARVO meeting challenged what we might otherwise consider conventional wisdom about different ocular surface disorders. Some of those beliefs they challenged:

Xalatan reactivates ocular herpes simplex. Researchers from the University of Pittsburgh studied rabbit eyes and found that neither Xalatan (latanoprost) nor any of its components induced or promoted reactivation of latent HSV type 1.²⁵³
Helicobacter pylori infection causes ocular rosacea. Scientists in Paris found similar incidence of H. pylori in two different groups, one with ocular rosacea, the other without.⁴⁸⁷⁴They’ve concluded that this infection does not play any major role in the development of ocular rosacea.
Meibomitis is bacterial. Actually, it isn’t, say Japanese researchers. Rather, they suggest that most cases are not infections, but consist of lipogranulomatous inflammation.²⁰¹
Tamoxifen causes ocular toxicity. Israeli researchers asked if women treated with tamoxifen for breast cancer risk ocular toxicity, including vortex keratopathy.⁴⁰⁴Patients on lower doses rarely showed signs of toxicity, but four of five patients treated with a high dose (cumulative dose >85 grams) showed signs of toxicity within a year. This was partially reversible after cessation of the drug. Careful assessment and periodic follow-up are essential in patients who use tamoxifen.

Corneal Imaging

We’re learning more about how to obtain images of the cornea, especially in the endothelial cells. Japanese researchers studied six patients with normal eyes and six patients with Fuchs corneal endothelial dystrophy.¹⁵⁰⁸A specular microscope and a confocal biomicroscope were equally effective in obtaining images and calculating cell density of intact corneas, but confocal biomicroscopy was more effective in obtaining images of endothelial pathology.

Confocal microscopy also provides an alternative and immediate means of diagnosing fungal keratitis, which doctors often initially misdiagnose as bacterial keratitis.⁴⁸⁶⁰Given that cultures often prove unreliable, earlier diagnosis with confocal microscopy might lead to significantly improved visual prognosis, as was the case with the four patients in this study.

Researchers in Grand Rapids, Mich., meanwhile, found that atomic force microscopy, a new imaging tool, produced images of live corneal cells within a liquid median with a resolution comparable to scanning electron microscopy.¹⁵²³They say that’s an important indicator that this method will be useful for morphologic studies of corneal cells in pharmaceutical and toxicologic applications.

Meanwhile, researchers from Mexico learned more about endothelial cell density changes in penetrating keratoplasty.¹⁵⁰⁴It’s long been known that cell density is lost after penetrating keratoplasty. This study shows a nearly 20% cell loss after PK. And, it shows that endothelial cell density changes are directly correlated with the patient’s preoperative cell density and not with the donor’s age.

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What’s New in Contact Lenses
Papers at this year’s ARVO meeting tell us more about new contact lens materials and the cornea’s response to contact lens wear. Here are some of the highlights:
Corneal swelling. Researchers at Indiana University School of Optometry found variation in corneal swelling among eight subjects wearing soft contact lenses, and a positive though not significant correlation between swelling and oxygen consumption.³¹⁶⁶ There were no correlations between swelling and endothelial cell density or epithelial thickness. The overall corneal metabolic rate and endothelial function may influence the variations among subjects, they say.
Meanwhile an Australian study compared corneal swelling before and after seven months of extended wear (six nights) with both high- and low-Dk soft lens materials.³¹⁶⁸ The study, sponsored by Bausch & Lomb, found that the low-Dk lenses significantly changed the corneal physiological response to hypoxia—a reduction in corneal swelling indicated this—but the physiological response remained unchanged with the high-Dk lenses.
Also out of Australia, researchers conducted a 12-month clinical trial of 154 patients who wore high-Dk soft contact lenses on a six- or 30-night extended wear basis.³²⁰⁹There were no significant differences in physiological response or lens performance between the two groups.
SEALS. These same researchers found that superior epithelial arcuate lesions (SEALs) tend to occur both limbally and paralimbally with high-DK extended wear.³¹⁹⁵The paralimbal group reported a higher proportion of symptoms and had a higher recurrence rate in the same eye; however, this did not reach statistical significance.
Overnight orthokeratology. Clinicians from Ohio State University and New England College of Optometry studied the long-term safety and effectiveness of this method of vision correction.³¹⁸⁰The LOOK Study (Lenses and Overnight Orthokeratology Study) involves 43 patients fit with reverse-geometry RGP lenses. Three-month follow-up data on 11 subjects showed “significant improvements in unaided acuities and reduction in myopic refractive error,” that can be maintained during waking hours. Overnight ortho-K, the researchers say, is safe and effective, but they acknowledge that more long-term data is needed.
In another study, seven patients wore reverse geometry lenses overnight and removed them during the day for three months. Investigators found significant central epithelial thinning and slight midperipheral corneal thickening.³²⁰⁷
Corneal topography. Information from 3-D topography data apparently optimizes fitting characteristics of RGP contact lenses in normal eyes. Researchers say that in normal eyes, “the measurement of corneal shape, especially in the mid-periphery, is of importance to optimize the fit and initial comfort of RGP contact lenses.”³¹⁷³
Contact lens care. The Purilens contact lens cleaning unit successfully eradicated such organisms as Staphylococcus aureus and Pseudomonas aeruginosa, but left viable Acanthamoeba cysts even after the 15-minute cycle, researchers at Johns Hopkins’ report.³¹⁸²—J.P.S.

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