Creating the "Spectacle Killer"
Contact Lens

BY BRIEN HOLDEN, B.OPTOM., PH.D., D. SC.
JULY 1996

Our surface scientists have their work cut out for them. Here, Dr. Holden details what they must achieve to produce the ideal "spectacle killer" contact lens. Where are we with contact lenses at present? How well do contact lenses perform? To address these issues, I have "invented" the OSCARs: the Overall Spectacle and Contact Lens Acceptability Rating or HPRs (Holden's Performance Ratings). To achieve a perfect score, a device or procedure has to be truly simple, safe and effective.

SIMPLE MEANS CONVENIENT

An inconvenient system requires lots of patient time and trouble. For example, conventional daily wear (DW) requires time for purchasing (fitting), complex lens cleaning and disinfection every day, and the inconvenience of adverse effects and trips to the practitioner. (Brennan and Lakkis actually counted 66 separate steps in conventional DW nightly care and maintenance.)

Safety is judged by having no significant effects on the eye, no adverse responses, and by not increasing the risks of infection.

Effectiveness includes both vision and comfort. A perfect score for vision requires excellent performance for day and night, and correction of spherical and astigmatic refractive errors under near, intermediate and distance vision conditions with low, medium and high contrast tasks. Perfect comfort would involve an extremely comfortable device that did not induce "dryness" and where comfort was maintained under all environmental conditions.

In my system, spectacles rate an OSCAR of 86 percent. They lose points for removal at night, poor response to environmental conditions (they fog up easily) and visual disadvantages compared to contact lenses such as reduced field of vision and limited visual mobility.

Conventional daily wear contact lenses are not simple to use due to the need for cleaners, rinsing solutions, disinfectants, protein removers and storage cases, and because they need morning and nightly handling and lens care. They are also associated with chronic hypoxia and inflammatory effects such as GPC. Although conventional lenses provide good vision and reasonable comfort, if you compare this contact lens system to the convenience and simplicity of spectacles, they aren't that impressive. I give them an overall rating of 51 percent -- barely half a product!

Daily wear disposable lenses that are replaced weekly or biweekly rate reasonably well for convenience, however, they still need cleaning, rinsing and storage each morning and night. Attempts by manufacturers to imply that they do not need cleaning have also significantly reduced their inherent good level of safety. They have, however, consistently provided adequate daily wear oxygen levels (as defined by Holden and Mertz). They rate 63 percent in my OSCAR system.

Daily disposables (DD) are the ultimate form of daily wear lens. The only disadvantages to the patient are cost and that they must be inserted every day. They are not perfect. Dryness and redness still occur at the end of the day; and we do not yet have toric disposables. However, considering their overall simplicity, safety (which is excellent) and efficacy, I give them an OSCAR rating of 78 percent.

Disposable extended wear (DEW) rates poorly in every category because, although patients love the concept and convenience, the hypoxic (and therefore infective) and inflammatory side effects means serious trouble for a substantial number of patients. The microcysts, polymegathism, ulcers and other adverse effects cause not only significant breaches in safety but also inconvenience. Only six percent of corneas are unaffected by extended wear of disposable contact lenses and even though they can be visually efficient and comfortable, they fail as a product, rating only 44 percent. In reality, they rate this well only because of the concept, not because of performance.

THE SPECTACLE KILLER (SK)

This brings me to continuous wear, the Holy Grail of contact lenses. Almost every patient when asked, "if you could wear a lens safely, effectively and continuously, would you?" replies with an enthusiastic "yes." Only when we've developed a lens with excellent safety and comfort that can be worn continuously for at least 30 days will we have a lens that can compete for the 2.5 billion people in the world who wear eyeglasses.

The true Spectacle Killer lens will provide better and more convenient vision than spectacles. It should be more comfortable than no lens. As Stan Yamane used to say, it should "look good, feel good and see good."

Ed Goodlaw pointed out nearly 50 years ago that the perfect contact lens would need high levels of O₂ and CO₂ transmission. George Mertz defined that level for EW over 10 years ago, as an oxygen transmissibility of 87 x 10^-9.

After 30 years of soft lenses, the polymer chemists have "come in from the cold" and provided us with this high level of oxygen permeability. Many prototype lenses that we have tested from various companies and sources consistently show not only overnight swelling equivalent to "no lens," but according to Papas, Sweeney, Vajdic, Austen, Covey and earlier, Robboy, a reduced limbal vascular response. These lenses also move well, are comfortable and avoid physical trauma.

WETTABILITY

It's now up to the surface scientists to contribute to the SK lens. In addition to high oxygen permeability, the lens of the future needs excellent wettability and controlled deposition and bacterial adherence. These are not easy challenges.

One approach to achieving the required wettability is to try to mimic the animal eye. As the Guillon brothers have pointed out, the average ocular drying time of the human eye is about 27 seconds. In numerous studies, including testing the 10 leading soft contact lenses, we found that none could provide better break-up time than seven to 10 seconds. The human eye achieves normal wetting via the glycocalyx emanating from the epithelium, chemically "trapping" an adherent mucous layer on which the aqueous layer is stabilized, according to Ilene Gipson and others.

How do we achieve a 27-second break-up time on a contact lens? We could benefit from studying how the animals do it. According to Rosemary Austen, Helen Swarbrick and Joseph Huff, animals do it much better than we do. They demonstrate about a 5-minute break-up time which in turn enables them to blink infrequently. A typical cat might blink twice in five minutes compared with a human who blinks approximately 50 times over the same period. This is partly due to the fact that animals have highly carbohydrate-rich mucins, according to Carol Morris, Shirley Bolis, Maxine Tan and Stuart Davies at CRCERT.

THE EXTRAORDINARY BREAK-UP TIME THAT ANIMALS DEMONSTRATE MAY BE RELATED TO BLINK FREQUENCY, ACCORDING TO SOME RESEARCHERS. WE MIGHT BLINK 50 TIMES IN FIVE MINUTES, WHEREAS A CAT WILL BLINK ONLY TWICE.

BACTERIAL CONTAMINATION AND LENS DEPOSITION

The two most frequent extended wear complications are at least partly associated with bacterial contamination, according to Mark Willcox and colleagues at the CCLRU and Savitri Sharm and colleagues at LV Prasad Eye Institute. Certainly contact lens acute red eye (CLARE) seems to be highly statistically significantly associated with pathogenic gram-negatives that adhere to the surface of contact lenses. Staphylococcus aureous and other gram-positive pathogens appear to be associated with the culture-negative peripheral ulcers (CNPU) caused by extended wear.

RESEARCHERS HAVE IDENTIFIED CONTACT LENS RELATED ACUTE RED EYE AS BEING A DIRECT RESULT OF GRAM NEGATIVE ADHERANCE TO THE SURFACE OF CONTACT LENSES.

Why are there so many pathogens on our lenses when we have so few in our normal microbiota? The current hypothesis is that CLARE is caused by gram-negative bugs from our tap water. The gram-positive bugs that are associated with the CNPUs are probably harbored on the eyelids and attach to lenses.

We have also learned, as Suzanne Fleiszig, O.D., Ph.D., suggests, that "bacteria aren't just bacteria." They are very individual and specific. Thus bacterial adherence to contact lenses is specific to certain species. Many virulent pathogenic bacteria are poor at adhering to contact lenses, however, according to Wilcox, clinical isolates from our CLARE patients are very good at adhering to contact lenses. Patients are also different. If you expose individual patients' lenses to highly adherent pseudomonas, some lenses will pick up thousands of pseudomonas, while others will pick up relatively few.

Another interesting finding is that the clinical isolates like different aspects of the open and closed eye environments. Brigette Cowell at CRCERT suggests that in the open eye environment, the increase in the salt concentration of the tears keeps pseudomonas adherent during the open eye phase of contact lens wear. The change in temperature of the closed eye allows growth of the adherent bacteria. She's also found that the output of the toxic substances that produce acute red eyes increases when the bacteria are under threat, so that pseudomonas protease production is regulated to respond to nutrient limitation.

Emma Hume at CRCERT is looking at how bacteria invade the normal defense systems of the eye. Using Serratia marcescens, she found that CLARE bacteria are more resistant than other bacteria to complement. In additon, CLARE bacteria are able to grow in an artificial tear formulation, whereas other isolates are not.

When we look at recruitment of PMNs (white blood cells), there's also a significant difference between standard bacteria in culture collections and clinically isolated organisms. CLARE bacteria do not stimulate PMNs to the site to do battle.

BACTERIA ADHERENCE ON CONTACT LENSES MAY BE VERY PATIENT SPECIFIC. WHAT IS PREVALENT IN ONE INDIVIDUAL, MAY BE VERY RARE IN ANOTHER.

RESEARCHERS SUGGEST THAT THE INCREASE IN SALT CONCENTRATION OF THE TEARS KEEPS PSEUDOMONAS ADHERENT DURING THE OPEN EYE PHASE OF CONTACT LENS WEAR. THE TEMPERATURE OF THE CLOSED EYE KEEPS BACTERIA ADHERENT AT CLOSED EYE ENVIRONMENTS.

SO WHAT DOES IT ALL MEAN?

The key bacteria, because they like the ocular environment, are very good at resisting the ocular defense systems, and thus cause CLARE. The response of the eye not only involves lens and protein interactions hooking on the bacteria, growth of bacteria and the release of toxins, but it is also affected by the individual host defense systems. These rare but significant events for the extended wear contact lens patient are certainly modulated by all of these influences.

Can we eliminate bacteria? Probably not. We will always be exposed to pathological gram-negative and gram-positive bugs. To control them, we need to identify the factors that bind them to the lens and then prevent them from adhering to the lenses by blocking the receptor sites of the bugs we don't like.

So what we want from our surface scientists are surface treatments that avoid spoilation with critical proteins and bacteria.

Thus the Spectacle Killer contact lens needs not only excellent levels of oxygen transmissibility -- which in my opinion will go a long way to preventing infections by maintaining a healthy epithelium -- but a true biocompatibility where the interaction of the material with the ocular surface does not produce contamination that challenges the eye's integrity.

To develop such lenses, we must understand the fundamental mechanisms that control the inflammatory state of the eye. The polymer chemists and surface scientists must combine their efforts to produce a lens whose bulk and surface properties enhance the ability of contact lense to hold a stable, cleansing tear film and promote tear exchange at a rate that will remove potentially harmful debris and bacteria. CLS

Adapted from Dr. Holden's lecture, "What the Surface Scientist Must Achieve," at the 1995 North American Research Symposium.