GSLS REPORT

An Update on Specialty Contact Lens Research

A look at research highlights presented at the 2012 Global Specialty Lens Symposium.

By Gretchyn M.Bailey, NCLC, FAAO

Gretchyn M. Bailey, NCLC, FAAO, is a longtime editor and writer for ophthalmic publications. She has more than 20 years of ophthalmic experience and is based outside of Philadelphia. Reach her at gretchyn@me.com.

The 2012 Global Specialty Lens Symposium (GSLS) was held Jan. 26 to 29 in Las Vegas. Presented by the Lippincott, Williams & Wilkins Health Care Conference Group and with Contact Lens Spectrum as the exclusive media partner, the meeting attracted 460 attendees from 31 countries, 42 exhibitors, and a new record of 65 posters. In addition, this year’s meeting featured a photo contest for the first time.

The fourth annual symposium included lectures, free papers, industry breakfast seminars, and breakout sessions as well as a pre-conference fundamentals track that reviewed key fitting concepts and patient management tips. Topics covered included myopia control, large-diameter lenses, ocular surface disease, irregular cornea management, safety in contact lenses, dry eye, presbyopia, corneal surgery, and contact lens comfort.

The GSLS Education Planning Committee (Figure 1) included Patrick J. Caroline, FAAO, FCLSA; Jason J. Nichols, OD, MPH, PhD, FAAO; Craig W. Norman, FCLSA; Edward S. Bennett, OD, MSEd, FAAO; and Eef van der Worp, BOptom, PhD, FAAO, FIACLE, FBCLA.

Figure 1. The GSLS Education Planning Committee from left to right: Ed Bennett, OD, MSEd; Craig Norman, FCLSA; Jason Nichols, OD, MPH, PhD, FAAO; Eef van der Worp, BOptom, PhD, FAAO, FIACLE, FBCLA; and Patrick Caroline, FAAO, FCLSA.

This year’s report provides a deeper look at some of the meeting highlights. To see the full meeting agenda, visit www.gslsymposium.com.

Competing Theories of Myopia Control

Jeffrey J. Walline, OD, PhD, reviewed several studies about the “outdoors preventive effect”—the theory that outdoor activity makes people less likely to be myopic. Jones (2007) and Dirani (2009) both showed that subjects who reported more hours of outdoor activity were less likely to be myopic, and Rose (2008) showed that greater hyperopic refractive error was associated with more outdoor activities. These studies also showed that activities such as reading, watching television, and playing computer games were not predictive of myopia. The question Dr. Walline then posed for the following presenters was, “What is it about outdoor activities that prevents myopia?”

Donald O. Mutti, OD, PhD, discussed the effects of vitamin D on myopia. Vitamin D has a long list of benefits, and researchers are learning that it plays a role in overall health. Sunlight exposure increases the level of vitamin D in the blood. In fact, vitamin D levels can shift 40 percent from summer to winter in North America.

Dr. Mutti reported that vitamin D blood levels were about 20 percent lower for myopes than for non-myopes, a statistically significant difference (Mutti, 2011). Plus, there are differences seen only in Caucasians between myopes and non-myopes in the vitamin D receptor gene. About 18 percent of the variation could be explained by the receptor gene differences; these effects are significant, but what they mean is yet unknown. In addition, myopes consume less dietary vitamin D per day compared to non-myopes.

Vitamin D participates in cell signaling, works with retinoic acid—which changes the rate of eye growth—and potentially affects refractive error. Dr. Mutti hypothesized that vitamin D exerts an effect on the eye through an improvement in muscle function, specifically the ciliary muscle.

Dr. Mutti disagreed with the hypothesis that the outdoors exert a general effect on the growth of the eye—it seems to be inhibitory before the onset of myopia but not after. He asserts that light does not exert a general effect on the growth of the eye, but Earl L. Smith III, OD, PhD, made compelling arguments for that basis.

Dr. Smith gave two reasons why the more time kids spend outdoors, the less chance they have to be myopic. First, outdoor scenes are very different from indoor scenes. If the eye is focused on infinity, as it is when outdoors, there is very little change in focus across the retina. Indoor environments feature a variety of dioptric demands that are irregularly distributed across the visual field. Dr. Smith proposed that near-work demands while indoors cause the eye to become myopic.

Second, outdoor environments are approximately 100 times brighter compared to indoor environments. An outdoor overcast day is about the same brightness as a brightly lit office for detailed near work. This raises the question as to whether substantial therapeutic benefits could potentially be achieved by manipulating indoor lighting levels. Parameters of light (threshold levels, duration and frequency of exposures, spectral characteristics) need to be studied. In addition, still requiring an answer is the question of whether use of sunglasses promotes the development of myopia by reducing retinal illuminance.

Dr. Walline discussed the causes of myopic eye growth. There is a genetic predisposition to myopia: children who have one myopic parent are two times more likely to develop myopia; children who have two myopic parents are five times more likely. Many genes have been implicated in myopia.

There may also be an environmental cause of myopia. Children who read more have longer eyes compared to children who read less. Myopic children also have greater accommodative lags compared to non-myopic children, which may act as a signal to increase myopic eye growth. Furthermore, inner city children are more likely to be myopic compared to those in rural areas, which may be attributed to differences in visual stimuli or amount of sunlight exposure. Myopia is likely a combination of nature versus nurture, so the question is: how can we control myopic eye growth? Drs. Mutti and Smith provided some answers.

Dr. Mutti looked at accelerated eye growth in terms of mechanical restriction. Defocus modulates the growth of the eye, and peripheral defocus stimulates growth. He argues that accommodative lag is a result of myopia, not a cause, and once a person become myopic a lot of accommodative lag follows, but there is no correlation with progression.

Myopia research is attempting to explain the relatively prolate shape of the myopic eye, accelerated axial elongation, accommodative dysfunction (higher AC/A ratio and higher lag), and a sudden lack of crystalline lens compensation for growth. Ciliary mechanical restriction—that is, restriction to equatorial expansion from ciliary muscle hypertrophy—can explain each of these findings.

In myopic eyes, the ciliary muscle becomes bigger and stiffer than in emmetropic eyes, and the muscle contracts less easily. Myopia, to some degree, is influenced by the mechanical properties of the ciliary muscle through the loss of equatorial stretch.

Dr. Smith explored the question of peripheral hyperopia as a risk factor for myopia progression. Evidence from animal studies indicates that the retinal periphery can have a significant influence on central refractive development. Foveal signals are not essential for normal refractive development. Some evidence from human studies is in agreement with the hypothesis that peripheral hyperopia is a risk factor for myopia. Young adults with peripheral hyperopia are more likely to exhibit myopic shifts, and children who became myopic exhibited more peripheral hyperopia two years before the onset of myopia.

However, evidence from human and animal studies indicates that the relationship between peripheral hyperopia and central myopia is complex and not necessarily causal in nature. The degree of peripheral hyperopia varies between meridians, with eccentricity, and with the degree of central myopia. Relative peripheral myopia may slow axial growth. Overall, imposed relative peripheral hyperopia can produce axial myopia in animals, but a causal relationship in humans has not been clearly defined and many critical factors are not well understood.

Safety Factors in Contact Lenses

Fiona Stapleton, BSc, MSc, PhD, MCOptom, DCLP, FAAO, presented a safety comparison of refractive corrections. Many practitioners are worried about the likelihood of vision loss (a loss of two or more lines of best-corrected visual acuity) with contact lens wear. This would most likely result from microbial keratitis (MK), of which the risk to individuals is very low. With laser assisted in-situ keratomileusis (LASIK), vision loss from procedures prior to 2000 was 1.38 percent; due to improvements, vision loss from procedures performed during 2000 to 2003 was 0.61 percent.

Winning Photos and Posters

For the first time, the 2012 GSLS featured a photo contest. Winners were chosen in two categories and are pictured here: CONTACT LENSES Halina Manczak, MD, PhD, ClearKone in Optic Section View CORNEA, CONJUNCTIVA, AND LIDS Sakurako Takeda, A Red Dragon Is Climbing Posters were categorized into research or clinical categories at GSLS 2012. Once again, a record number of posters were submitted. Sixty-five posters were displayed, and two winners were chosen in each category. Research, First place: Roxanne Achong-Coen, OCT Differences Between Normal and Keratoconic Eyes First place in the GSLS 2012 Photo Contest for the category of Cornea, Conjunctiva, and Lids: A Red Dragon Is Climbing by Sakurako Takeda. First place in the GSLS 2012 Photo Contest for the category of Contact Lenses: ClearKone in Optic Section View by Halina Manczak, MD, PhD. Second place: Ashley Wallace Tucker, Endothelial Cell Density and Morphology in Overnight Orthokeratology Clinical, First place: Natalie Santelli, Scleral Contact Lens Use over the Postoperative Boston Type I Keratoprosthetic Corneal Surface Second place: Mark W. Roark, The Use of Corneal Refractive Therapy for Residual Myopia Following LASIK

Dr. Stapleton looked at estimating the risk of vision loss following contact lens-related MK and compared this with the one-time risk of vision loss measured months after contemporary LASIK surgery. She conducted a review of U.S. Food and Drug Administration (FDA) studies on LASIK completed since 2003: 13 prospective studies looked at 3,534 eyes; refractive error was +6.00D to –15.00D. She looked at the prevalence of vision loss per 10,000 eyes and 95 percent confidence interval. Results showed vision loss in 57 per 10,000 eyes.

To compare this result with the rate of vision loss from contact lens-related MK, she conducted a national surveillance study in Australia with population-based controls (Stapleton, 2008). Results showed 39 cases of vision loss. Overnight hydrogel wear, silicone hydrogel lens wear, and any contact lens type showed a rate of loss of 4.0, 2.8, and 0.6, respectively. Overall vision loss is 0.28 percent per 10,000 eyes per year with a significantly higher rate during the first six months of lens wear. In per-eye terms, the risk of vision loss with contact lens wear is 3 per 10,000 eyes per year as compared to LASIK with a one-time risk of 57 per 10,000 eyes. The risk with LASIK is equivalent to 70 years of any lens use and 11 years of hydrogel lens use.

Corneal Surgical Update 2012

David Schanzlin, MD, explored riboflavin and corneal cross-linking for keratoconus and post-LASIK ectasia. Cross-linking is well known in materials sciences—it’s the addition of molecular bonds to increase the mechanical strength of tissue. Cross-links can be induced enzymatically by means of aldehydes, chemical fixatives, and photosensitizing radiation. In-vivo experiments reveal that ultraviolet (UV) radiation and riboflavin are the most effective and the least harmful.

Riboflavin, which is vitamin B2, is the prime photosensitizer used in cross-linking. The riboflavin molecule absorbs the UV radiation and causes a cleavage of the oxygen, which splits off and causes the cross-linking in the tissue. Increasing the number of cross-links adds strength to the tissue. Cross-linking works at more than the basic collagen/molecular level; there are also changes between the fibrils of collagen. Interestingly, diabetics have a very low incidence of keratoconus or corneal ectasia, perhaps because glucose induces cross-linking.

In treated rabbit corneas, a decrease in the ultimate strain (of 0.57 percent to 78.4 percent) was found over a time period of up to eight months after cross-linking treatment. Riboflavin/ultraviolet radiation-induced collagen cross-linking leads to a long-term increase in biochemical rigidity that remains stable over time—the benefits last at least two years. It also leads to a significant increase in corneal collagen diameter. Morphologic correlate of the cross-linking process leads to an increase in biomechanical stability.

This treatment also results in dose-dependent keratocyte damage that can be expected in human corneas down to a depth of 300µm; repopulation occurs at six months. It causes apoptosis at the front of the cornea. As the amount of energy is increased, the depth of the cell death increases.

Confocal microscopy of treated corneas shows early diffuse hazing that dissipates with time—this is likely due to the linking and spacing of fibers. A cytotoxic effect on endothelial cells was demonstrated at a thickness of <400µm; therefore, patients whose corneas are less than 400µm should be excluded from treatment. The obvious goal is to not kill all of the endothelial cells with the treatment. Direct application of this wavelength to the endothelial cells causes damage. Without riboflavin, safety zones are decreased at 400µm.

Early studies indicated that the procedure could not be conducted without removing the epithelium— an intact epithelium results in only a 28-percent effect—because not enough energy was reaching the cornea. However, there are other ways to get riboflavin into the eye.

When the first study on cross-linking for keratoconus was conducted several years ago, researchers needed cases that were showing progression. Preliminary results were significant: untreated eyes continued to progress, while treated eyes had a statistically significant decrease over six, then 12 months. This set the stage for a U.S. FDA clinical trial.

This prospective, randomized clinical trial included 160 progressive keratoconus patients and 160 patients who developed corneal ectasia after refractive surgery. It began in February 2008 with a one-year follow-up period. Inclusion criteria were post-LASIK or post-photorefractive keratectomy (PRK) ectasia, progressive keratoconus over 24 months (increase of ≥1.00D in steepest K, increase of ≥1.00D in manifest refraction (MR) astigmatism, myopic shift of ≥0.50D manifest refraction spherical equivalent (MRSE), or decrease of ≥0.1mm in the base curve radius (BCR) for GP wearers when no other information was available. K_max, the area in which the maximum curvature was obtained, was the assessment point. The trial followed the Dresden technique: remove 9mm of the corneal epithelium, saturate the cornea with riboflavin drops for 30 minutes, and assess pachymetry (if <400µm, proceed with 30 minutes of UV radiation; if <400µm, administer riboflavin until the cornea swells to ≥400µm, then proceed to UV radiation).

At the six-month point, significant differences were noted in the K_max, meaning that corneas were flatter. In addition, corneas thinned after the procedure, and BCVA with spectacles improved. Complications were minor: four infiltrates, four cases of delayed re-epithelialization, and one uveitis.

One-year results at Dr. Schanzlin’s site at the University of California, San Diego, included 26 treated eyes, 21 keratoconus, and 11 ectasia. The sham control group received riboflavin drops only and crossed over to the cross-linking treatment at three months. At one year, uncorrected VA in keratoconus patients improved, and ectasia patients had more dramatic improvement. Ectasia patients also had statistically significant decreases in K_max. At three months, patients in the sham control group exhibited decreased UCVA and BCVA plus increased K_max.

What happened to this study? Data collection was completed in 2009, but there was a delay in reporting the data to the FDA. The database was sold to Avedro, a Waltham, MA-based device manufacturer, and the data was verified and submitted to the FDA in late 2011. The company hopes for approval soon.

Looking to the future, a new generation of products for cross-linking treatment attempts to decrease the treatment time. Researchers are trying to reduce the riboflavin instillation time to a total of five to 10 minutes and use the same amount of energy in a stronger wavelength to reduce UV radiation treatment to the same time frame. Tests to date show that this works, and in fact the higher energy for a shorter time actually decreases endothelial cell death rather than increasing it. A new trial launched in February with a new delivery device and protocols of three- and five-minute treatment exposure times.

Avedro researchers want to develop a procedure to treat patients during LASIK by administering riboflavin drops prior to flap repositioning, then applying UV radiation. Because the flap weakens the cornea by up to 30 percent, patients were vulnerable to ectasia. Cross-linking can increase the corneal strength three to four times.

Cross-linking also opens up new directions of treatment for other conditions such as lamellar corneal transplants. Treatment in Europe has shown cross-linking to be effective for corneal edema and eliminating bullae. Using cross-linking with Intacs (Addition Technology) provides a statistically significant increase in corneal rigidity over the procedures separately. Current international indications for cross-linking include progressive keratoconus, induced ectasias, pellucid marginal degeneration, intrastromal rings, bullous keratopathy, corneal ulcers and melting, and scleral cross-linking to prevent the progression of axial myopia. The treatment halts progression of keratoconus and ectasia after LASIK, decreases corneal curvature and thickness, improves manifest refraction and BCVA, and has an excellent safety profile. Corneal cross-linking will become a standard of care for keratoconus and will continue to evolve to be used early in the disease management to halt progression when it starts.

Don’t Miss the Next GSLS

Contact lens fitters are discovering that the GSLS is one of the leading meetings for specialty lens research and information. Join us next year for the fifth annual Global Specialty Lens Symposium to be held Jan. 24 to 27, 2013, in Las Vegas. CLS

For references, please visit www.clspectrum.com/references. asp and click on document #197.