Passing the Torch in Cornea and Contact Lens Research

BY MICHAEL G. HARRIS, O.D., J.D., M.S.
DEC.1996

In this excerpt from his 1995 Max Schapero Memorial Lecture, Dr. Harris takes us on a tour of his career as a cornea and contact lens researcher and pays homage to the mentors and colleagues who influenced him along the way.

When I entered the contact lens field in the mid-1960s, I was one of many bright and eager young clinicians and researchers who were guided by more experienced professionals in the nuances of contact lens research. Throughout my career, I approached a clinical problem or phenomenon by trying to understand the mechanism behind the problem, why it occurred and how it could be prevented or dealt with more effectively. I learned this from my mentors, the previous generation of cornea and contact lens researchers.

Now that it's time for my generation to pass the mantle to the next generation, I reflect on my 33 years in the field, and I dedicate this lecture to those who passed the mantle to me, Dick Hill, Mort Sarver, Bob Mandell, Irv Fatt and Bob Lester.

My first lesson in research was from Dick Hill, who asked me to help in a study of the temperature of rabbit corneas while I was an optometry student. After spending eight hours measuring corneal temperatures of rabbits that I was allergic to with a thermistor that I failed to properly calibrate prior to the experiment, I learned the importance of precision in scientific research.

SPECTACLE BLUR AND PMMA LENS DIAMETER

During my second year as an optometry student, I met the man who had the greatest influence on my career, the late Mort Sarver. Mort was the quintessential professor and researcher.

In the days before soft lenses or gas permeable lenses, many patients reported spectacle blur after contact lens wear. Mort and I compared the relationship between spectacle blur and PMMA lens diameter, and in my first published paper, we showed that a significantly greater number of patients who wore large diameter lenses experienced spectacle blur versus those who wore smaller diameter lenses. While not monumental, this first effort into patient-based clinical research stimulated me to make contact lens research a major part of my career.

PMMA LENS ADAPTATION AND TEARING

As a graduate student at The University of California, I first had the opportunity to work with Bob Mandell, my advisor and collaborator in research on contact lens adaptation. For years it was known that PMMA contact lens wearers adapted to their lenses over a period of several weeks. We suspected that physiological adaptation was related to one of the mechanisms that controlled corneal hydration.

Using an optical beam splitter developed by Bob Mandell and Irv Fatt as a primitive pachometer, I established baselines of corneal thickness on four unadapted subjects. One subject wore a contact lens for three hours each day for three weeks. The cornea thickened each day with lens wear but returned to normal thickness after lens removal. The rate and time of thickening diminished each day and the recovery period shortened over the three-week period, but there was little change after that time up to full-time wear over four months.

We stimulated a contralateral tearing response in the right cornea of one unadapted subject by placing a contact lens on only the left cornea. After 30 minutes of lens wear, we found a three percent increase in thickening of the right cornea which returned to normal within one hour after lens removal. Placing a contact lens on the nasal sclera of the right eye itself induced the same amount of corneal thickening.

We repeated these procedures after the subject had achieved full-time contact lens wear for three months and found no corneal thickening with contact lens wear on the contralateral eye. From this study, we concluded that tearing contributed to corneal thickness during adaptation, and that this occurred because excess lacrimal fluid at a tonicity which was lower than that of normal pre-corneal tear film caused water to move into the cornea. We theorized that the adaptation process may be caused by the decreased tearing that accompanies the normal adaptation of the receptors and lids margins to contact lens stimulation, thus producing a more normal tear tonicity.

LENS FLEXURE AND RESIDUAL ASTIGMATISM

As a graduate student teaching in the contact lens clinic with Bob Mandell and Bob Lester, I discovered that on highly toric corneas, thin PMMA lenses often flexed and can correct more astigmatism than predicted. We began a series of studies evaluating the effects of contact lens thickness, diameter, material and corneal toricity on flexure and residual astigmatism. The bottom line is that the thinner the lens, the more toric the patient's cornea and the more flexible the lens material, the more the lens will flex.

We found that we could determine the amount of increased flexure by measuring the anterior surface toricity of the contact lens while it was on the patient's eye. The most critical factor was the lens thickness. For PMMA lenses to flex at all, they had to be thinner than 0.13mm. This series of studies still has practical application in correcting high astigmats with spherical rigid lenses.

DEFINING CONTACT LENS SUCCESS

In the late 1960s, I resumed my research association with Mort Sarver to study the factors that led to success in wearing contact lenses. We designed and tested a standard for defining a successful contact lens patient.

We evaluated the responses of 122 contact lens patients four to six months after their initial examination and fitting. Table 1 illustrates our definition of a realistic, successful PMMA contact lens wearing response, considering the limitations of the material and fitting techniques available at the time. If a patient failed to meet any of these criteria, he was considered unsuccessful. Using our standard, we found that 73 percent of the patients evaluated were successful.

SOFT LENSES DEBUT

In the early 1970s, Bausch & Lomb debuted Soflens, the first soft contact lenses approved for marketing in the United States. Mort, Bob, a young graduate student named Barry Weissman and I had noticed that most of our myopic patients seemed to be overcorrected with their Soflens lenses. For example, a three-diopter myope who was fitted with a Soflens that was marked -3.00D often showed a half-diopter to a full diopter overrefraction.

In our study, we measured power on the lensometer after blotting the lenses on a lint-free tissue and air drying them for 15 to 30 seconds (we had approximately 10 minutes before the lenses started to dehydrate and change power). Using a random sample of 35 F, N and C series Soflenses, we found a mean difference of approximately 0.8D between the lensometer powers and the powers marked on the vials. The lensometer powers were generally higher in minus than those indicated on the lens vials.

We then evaluated the power effect of the Soflenses by placing them on the eyes of patients with known refractive error and determining the overrefraction. The power by overrefraction averaged one-half diopter more minus than the power given on the lens vials. Shortly after the publication of that paper, B&L started identifying its lenses with both a vial power and a back vertex power, and the company eventually dropped the vial power completely.

PROFILE OF A CONTACT LENS WEARER

With one of my students, Jay Messinger, and with the help of a member of our department of psychology, I developed a study to determine if the personality profile of a prospective contact lens wearer differed from that of someone seeking spectacles and if certain personality traits were associated with failure in wearing contact lenses. We assessed the personality characteristics of 120 patients, half of whom were seeking spectacles and half of whom were seeking contact lenses. Using the Adjective Checklist, a self-administered personality inventory, we asked patients to indicate which words from a list of 300 adjectives described attributes that apply to them. We found no differences in the personality traits of those patients seeking spectacles and those seeking contact lenses.

After the contact lens patients adapted to their lenses, we evaluated patient success using the criteria that Mort and I had developed and compared the successful patients with the unsuccessful patients on the basis of the Adjective Checklist. The most significant finding of this study was that unsuccessful females scored higher in 'abasement' and lower in 'aggression' than their successful counterparts. People scoring as such tend to be submissive, shy and unsure of themselves, and they often see themselves as being weak and undeserving.

This paper was picked up by some major U.S. newspapers including the San Francisco Chronicle and the Los Angeles Times, and much to my dismay, I was being interviewed on radio and television on what I considered to be one of my less important research projects.

CORNEAL EDEMA AND VERTICAL STRIAE

Around this same time, Mort Sarver, Ken Polse and I conducted a series of research projects involving soft and RGP lenses that resulted in almost 20 published papers. The first series of studies was stimulated by the observation of what looked like fine, short white lines in the deeper layers of the corneas of Harvey Arnold, one of my colleagues who had been wearing early model soft contact lenses. This phenomenon, which we initially named 'Harvoid Lines' after Harvey but later renamed 'vertical striae' or 'vertical striate lines,' appeared quite commonly in patients who wore their soft lenses for longer periods of time.

We fitted 27 patients with both F and N series B&L soft lenses and measured corneal thickness every two hours over an eight-hour period each week for two months. On some of the subjects, we measured the changes after 12 hours of lens wear and after lens removal. We found that approximately 50 percent developed vertical striae and that it was correlated with the development of corneal edema. Striae generally appeared after six hours of lens wear and were associated with an average change in corneal thickness of seven percent. This was significantly higher than the three percent mean increase for the group that did not show vertical striae. Once striae developed, they did not disappear unless the lenses were removed, even if corneal thickness diminished while the lenses were still worn.

We found a method of evaluating edema with soft contact lens patients using a simple slit lamp, much the same way Don Korb found a way of monitoring edema on PMMA wearers by observing central corneal clouding. By looking for vertical striae, a clinician could determine if a patient's cornea was thickening due to metabolic interference from wearing soft contact lenses. We later determined that the number and visibility of the striae increased as the amount of corneal edema increased.

In other studies, we found that both vertical corneal striae and corneal edema were reduced when the thickness of the hydrogel lenses was reduced. Thus, we documented one of the two major factors affecting oxygen transmission -- contact lens thickness. The other factor is the permeability of the material.

In a 1975 study with Tim Sanders and Frank Zisman, we showed that a half-hour nap while wearing soft lenses caused more than a five percent increase in corneal thickness. This was two percent greater than the thickening caused by a half-hour of open-eye wear.

EVALUATING THE RGP PROTOTYPE

In the mid-1970s, Mort, Ken and I started to evaluate patient responses to rigid gas permeable contact lenses. We initially worked with the Polyperm lens (later renamed the Polycon lens), which had an oxygen transmissibility of five and became the first successful RGP lens.

To determine how useful oxygen transmission was in patient success, we refit 46 patients who were unable to wear PMMA lenses because of corneal edema and associated symptoms with Polycon lenses of the same dimensions as their unsuccessful PMMA lenses. After adaptation, 67 percent of these patients were able to wear the Polycon lenses. None of them exhibited observable edema while wearing the Polycon lenses and the mean corneal thickness change after eight hours of contact lens wear was insignificant.

On average, the Polycon lenses showed no changes in corneal thickness while the PMMA lenses showed a four percent increase. Even though the hydrogel lenses transmitted more oxygen than the Polycon lenses of the same thickness, the hydrogel lenses generally produced more edema. This suggested that the tear pump was more effective with rigid lenses than with soft lenses.

We concluded that paper by stating "the Polycon lens provides a superior physiological environment for the cornea and it is likely that this lens and other gas permeable hard lenses will eventually replace PMMA lenses." Ken, Mort and I spent hours discussing whether or not this was an appropriate conclusion based on the results of this study. Mort, with his clinical wisdom, convinced us that our findings were truly monumental. While Mort taught me never to jump to conclusions unless you have the scientific facts, he also taught me that true clinical insight is the ability to go beyond results of a particular study or clinical observation to help all practitioners and patients.

THE CONSEQUENCES OF EXTENDED WEAR

We also evaluated corneal edema with hydrogel lenses during eye closure using an investigational ultra-thin B&L lens which had a center thickness of 0.06mm, less than half that of the standard Soflens. Placing an investigational lens on one eye and using the other eye as a control, we found that central corneal thickness increased gradually for both eyes during the first four hours and then remained fairly constant up to a wearing time of six hours.

However, for the control eye without a contact lens, we found an increase of about four percent at the end of four hours. For the experimental eye, the maximum thickness increase was over nine percent. The control eye returned to its baseline corneal thickness 80 minutes after eye opening, while the experimental eye returned to baseline two hours after the contact lenses were removed and the eyes opened. These findings had great implications as the era of extended wear began.

TASK PERFORMANCE WITH DIFFERENT MODALITIES

Jim Sheedy, a good friend and colleague on the Berkeley faculty, developed a method of using occupational tasks to evaluate how well people perform while wearing different visual corrections. We compared time and error performance on three tasks (pointers and straws, card filing and letter editing) of 18 presbyopic patients with monovision to their performance on the same three tasks wearing distance contact lenses and reading spectacles. We found that performance with monovision resulted in more errors and a slower performance time than with distance contact lenses and reading spectacles.

In later studies, we measured task and visual performance with bifocal contact lenses as well as monovision. At dispensing and after eight weeks of simultaneous vision, concentric bifocal wear, performance times with concentric bifocals was significantly slower than with distance contact lenses and reading spectacles for all three tasks. Bifocal contact lenses also generally resulted in more errors per trial. Compared to distance contact lenses, visual acuities with the bifocals were reduced significantly by 0.8 to 0.14 Snellen lines and stereopsis was reduced significantly by 32 to 36 seconds of arc.

We concluded that the decreased task performance with the simultaneous vision, concentric bifocals was caused by decreased acuity with these lenses. Nonetheless, 67.5 percent of those patients fitted with the bifocals chose to continue to wear them at the end of the study, showing that thoroughly screened and properly fitted presbyopic patients could wear these lenses successfully.

With the help of Cheslyn Gan, we measured vision and task performance of 26 presbyopes fitted with diffractive bifocal contact lenses, monovision, and distance lenses combined with reading glasses. Performance times for all three tasks were six to eight percent longer with the bifocals, and two to six percent longer with monovision, compared to the distance contact lenses. There was a significant reduction in distance visual acuity with the bifocals (0.4 to 0.5 Snellen lines) and monovision (0.5 to 0.8 Snellen lines) compared to distance contact lenses.

At the conclusion of the study, given a choice between diffractive bifocals and monovision, two of the subjects chose to continue wearing the bifocals while 18 of the 20 chose monovision. Despite the compromises associated with diffractive bifocal contact lenses and monovision, we must not forget the advantages of contact lenses over spectacles, including the improved appearance, decreased peripheral distortion and increased peripheral field.

UNCONVENTIONAL DISINFECTION METHODS

In the late 1980s, I became increasingly interested in contact lens care and compliance. My colleagues and I performed a series of studies at Berkeley and at the Cornea and Contact Lens Research Unit in Australia to evaluate the effectiveness of microwave irradiation to disinfect soft lenses. We also evaluated the effect of microwave irradiation on soft contact lens parameters.

Using a vented, microwaveable storage case, we microwaved hydrated soft lenses without significantly affecting the lens parameters. If the oven had a rotating glass plate, we could disinfect up to 40 lenses at a time and ensure that all were exposed to the same amount of microwave irradiation.

We also exposed the cases containing the lenses and six FDA test-challenged microorganisms to high intensity microwave irradiation from zero to 15 minutes. None of the microorganisms survived beyond two minutes of microwave exposure and some were killed in as little as 60 seconds.

Our findings indicated that microwave irradiation can be an effective, rapid and convenient method of disinfecting as few as one or as many as 40 soft contact lenses at one time and thus was adaptable for both in-office and at-home disinfection.

My interest in contact lens disinfection stimulated me to look into another method of disinfecting lenses -- ultraviolet radiation. With the assistance of Larry Fluss and others, we evaluated how exposure to 253.7nm wavelength UV radiation acted as a disinfectant to rigid and soft lenses and their storage solutions.

Using three different microorganisms as contaminants, we found that UV radiation is a rapid and effective method of disinfecting soft and rigid contact lenses and their storage solutions. For E coli, sterilization was achieved after 100 seconds of exposure. For Staphylococcus epidermis and for Serratia marcescens, sterilization occurred after 300 seconds of exposure. We concluded that UV radiation disinfection could eliminate the need for preserved disinfection solution and therefore, might help decrease allergic and toxic reactions in contact lens patients.

We also evaluated the effects of UV transmission on the contact lens parameters and found little or no adverse effect except with high water, nonionic (Group II) contact lenses, which showed an increase in power, center thickness, diameter and water content.

RECENT UV RESEARCH

I recently collaborated with a group of my students to investigate the protective ability of contact lens materials to UV transmittance. We found that lenses containing UV absorbers provided excellent protection and transmitted significantly less UV radiation than untreated lenses. Therefore, we recommend that contact lenses with UV absorbers be considered for all patients, especially aphakes, patients taking photosensitizing pharmaceutical agents and patients who are outdoors a lot.

PASSING THE TORCH

Over the years, I've had the good fortune to work with many promising, bright and talented contact lens practitioners and researchers. Many of these individuals are my contemporaries, while others are the next generation of contact lens researchers. My generation has made major strides in our knowledge of the cornea and contact lenses, but there is much more to learn. So, to the next generation of cornea and contact lens researchers, I pass the torch. May they enjoy the journey as much as I have. CLS

occocus epidermis and for Serraca marcesis, sterilization occurred after 300 seconds of exposure. UV radiation disinfection could eliminate the need for preserved disinfection solution and therefore, might help decrease allergic and toxic reactions.

We also evaluated the effects of UV transmission on the contact lens parameters and found little or no adverse effect except with high water content (Group 4) contact lenses.

RECENT UV RESEARCH

I recently collaborated with a group of my students to investigate the protective ability of contact lens materials to UV transmittance. Our findings indicated that contact lenses containing UV absorbers provided excellent protection and transmitted significantly less UV radiation than untreated lenses. Based on our findings, we recommend that contact lenses with UV absorbers be considered as a viable option for all patients, especially for aphakic patients, patients taking photosensitizing pharmaceutical agents and patients who spend a great deal of time outdoors.

Over the years, I've had the good fortune to work with many promising, bright and talented contact lens practitioners and researchers. Many of these individuals are my contemporaries, while others are the next generation of contact lens researchers. My generation has made major strides in our knowledge of the cornea and contact lenses, but there is much more to learn.

So, to the next generation of cornea and contact lens researchers, I pass the torch. May they enjoy the journey as much as I have. CLS

Dr. Harris is a clinical professor, an associate dean and the chief of the Contact Lens Clinic at the University of California School of Optometry.