Article Date: 9/1/2010

Bio-inspired and Synergistic
HIGHLIGHTS FROM AROUND TABLE DISCUSSION

Bio-inspired and Synergistic

Panelists discuss how the formulation of Biotrue leads to beneficial clinical findings and patient satisfaction.

Biotrue contains a unique new formulation that is inspired by the natural biology of the eye. As the roundtable panelists discovered during their performance evaluation of this product, patients were able to appreciate its biomimetic properties and benefits, and the practitioners' clinical examinations validated this subjective patient feedback.

BALANCED PH FOR COMFORT

As we know, pH is a measure of acidity (low pH) or alkalinity (high pH). In ophthalmic solutions, a pH in the range of healthy tears — 7.3 to 7.7 — is essential for the patient's comfort.1,2 Biotrue multi-purpose solution, with its pH of 7.5, is formulated to match healthy human tears (Figure 1).3 The formulation uses a dual buffering agent system, sodium borate and boric acid, to optimally balance pH. These buffering agents, which are the salt and acid forms of the compound BO3H3, drive pH to the desired range and the stability to resist fluctuations in pH.4 According to the panelists, pH balance in this healthy human tear range is important in helping to ensure comfortable contact lens wear.

"Patients may not understand pH, but they definitely understand stinging," Dr. Anderson says. "If the pH of a solution is unstable and shifts, it can sting the eyes when patients apply their contact lenses. A solution that remains stable in the pH range of tears should be a much more comfortable solution. Because of the way Biotrue is formulated, I can tell my patients it's a comfortable solution and not likely to sting when they use it."

Biotrue also matches other attributes of healthy human tears, namely osmolality, viscosity and surface tension.5-7 Osmolality is a measure of the salt concentration of a solution, a property that is rigorously maintained between 244-344 mOsm/kg in the aqueous layer of tear film. This function helps avoid imbalances in electrolytes, which may be associated with adverse symptoms, such as dryness. Biotrue is in the range of healthy tear osmolality at 285 mOsm/kg. It is also similar in viscosity (healthy tear viscosity: 1-10 cP; Biotrue: 1.15 cP) and surface tension (healthy tear surface tension: 42-46 nN/m; Biotrue: 44.4 nN/m) (Figure 2).

Figure 1. pH range of healthy tears for Biotrue compared to various contact lens care products.

Figure 2. Osmolality, viscosity and surface tension of Biotrue compared to various multipurpose solutions.

The result is a contact lens care solution that closely replicates the eye's natural environment and is designed to induce minimal physiological change when introduced to the eye, helping eyes stay comfortable upon lens application.4

In addition to helping to promote comfort, the pH of Biotrue also optimizes the efficacy of its disinfectants.

As Dr. Giedd notes, "Patients may not fully understand the science behind pH, just as they may not understand the meaning of 20/20 as it relates to their vision. But pH balance implies biocompatibility, which has a positive connotation."

"The most frequent complaints I hear from contact lens wearers relate to dryness and lens awareness. If we can tell patients a product was formulated specifically to help keep their lenses moist and feeling comfortable — even at the end of the day — I think that will hit a home run as far as their willingness to try it, and more importantly, to stick with it."

Ron M. Cedrone, OD, FAAO


"When I explain to patients that Biotrue contains a natural lubricant, this point really hits home. People embrace that concept more than I would have expected, and they respond very favorably to the idea of natural lubrication ."

Kerry Giedd, OD

NATURE'S LUBRICANT

A key ingredient in Biotrue is hyaluronan, a natural lubricant that's found throughout the body, in the connective tissue of the skin, inside the umbilical cord, in synovial fluid in joints and in the eye, specifically in the vitreous, lacrimal gland, cornea, conjunctiva and tear film.8-12 A naturally occurring glycosaminoglycan, hyaluronan is thought to have anti-inflammatory properties and to play a role in wound healing.11-13 In addition, it's reported to have a protective effect against oxidative damage to cells because of its ability to inhibit free radicals.13-15

In addition, hyaluronan has a unique capacity to retain water, with each molecule capable of holding up to 1000 times its weight in water.8,16 This property is important for keeping the corneal epithelium hydrated and stabilizing the preocular tear film.11

One of hyaluronan's essential functions is to keep the ocular tissue lubricated during blinking. Tears are viscous and coat the eye without draining, which improves the tear-film breakup time.15 When a blink occurs, this results in tear film lubricants, such as hyaluronan, spreading across the eye, providing a smooth, lubricating coating.10,14 The ability of hyaluronan to hydrate and lubricate has led to its use in numerous ophthalmic products, such as artificial tears, contact lens rewetting drops and viscoelastic agents.17

Biotrue is the first multi-purpose contact lens care solution in the United States that's formulated with hyaluronan. By creating a free-flowing, hydrating network on the lens surface and naturally attracting and retaining water molecules, the hyaluronan in Biotrue envelops lenses in a moisture-rich cushion and remains on hydrogel and silicone hydrogel lenses for up to 20 hours, likely contributing to allday comfort and moisture (Figure 3).3

Figure 3. Percentage of hyaluronan that remains on silicone hydrogel and hydrogel lenses over time.

"When I explain to patients that Biotrue contains a natural lubricant, this point really hits home," Dr. Giedd said. "People embrace that concept more than I would have expected, and they respond very favorably to the idea of natural lubrication. It goes back to the bio-inspired concept. The fact that we're doing something that the body already does naturally, and simulating and augmenting that process is perceived as a positive."

According to Dr. Anderson, "One of the major benefits patients appreciated during the study was that their lenses stayed wet throughout the day. The hyaluronan in Biotrue lubricates, hydrates and coats lenses for up to 20 hours.

"I was somewhat familiar with hyaluronan and its use in ophthalmic surgical procedures," Dr. Anderson continues. "Knowing its properties, how it's incorporated into the solution and its ability to hydrate and stay on the lenses is impressive to me. With that ability, I would expect patients to have more comfortable lenses, and if that idea can be communicated, I think patients would be more likely to use the product and stay with it. It's a very impressive property."

Adds Dr. Cedrone: "The most frequent complaints I hear from contact lens wearers relate to dryness and lens awareness. If we can tell patients a product was formulated specifically to help keep their lenses moist and feeling comfortable — even at the end of the day — I think that will hit a home run as far as their willingness to try it, and more importantly, to stick with it."

A NEW VIEW OF PROTEIN MANAGEMENT

For eyecare professionals who prescribe contact lenses, protein has always been considered the enemy, something to be avoided or eliminated. However, there are more than 400 proteins found in the tear film, some of which are vital to the eye's natural defenses. An analogy can be drawn to cholesterol in general health care. In the past, it was believed that all cholesterol needed to be eliminated, but today it is known that in a natural, healthy system, there is good cholesterol and bad cholesterol. Similarly, it is now known that some proteins in the tear film are beneficial and that protein management, not elimination, should be our goal.

Lysozyme and lactoferrin, prominent beneficial proteins in the tear film, have important antimicrobial properties.19 They form a natural first line of defense for the eye against invading microorganisms, whether or not an eye is exposed to a contact lens.

Lysozyme hydrolyzes the bonds of bacterial cell walls and kills a variety of bacteria, including Streptococcus and Staphylococcus. Lactoferrin binds to gram-positive and gram-negative bacteria, inhibiting the growth of bacteria, including Escherichia coli, Haemophilus influenzae, Streptococcus, Staphylococcus and Pseudomonas spp.

One key point, however, is that these proteins are most effective in their unaltered native state.20 External stressors, such as heat and oxidation, transform them to a denatured state, rendering them ineffective against miroorganisms.

To help prevent denaturation, Biotrue multi-purpose solution surrounds and protects tear proteins, allowing them to maintain their inherent antimicrobial activity longer. In fact, laboratory data show that Biotrue keeps more lysozyme active than any other competing multipurpose solutions (Figure 4).3,21

Figure 4. Percentage of protein activity for Biotrue compared to various other contact lens care products.

"Nature provided us with these antimicrobial tear proteins for a good reason," Dr. DePaolis says. "Denatured proteins not only compromise the tear film's defenses but also contribute to lens spoilage and potentially attendant inflammatory responses. Keeping proteins in their native state can help mitigate against these complications."

In addition to preventing denaturation of beneficial tear film proteins, Biotrue seeks proteins that have already denatured and bonded to the surface of contact lenses, lifting and dissolving them to keep lenses free of deposits.

"I find it incredibly amazing that this care solution can stabilize a protein in its normal state and can eliminate or lift denatured proteins," Dr. Anderson says. "I'm impressed that it has that ability."

Adds Dr. Cedrone: "The fact that Biotrue prevents the beneficial protein from becoming denatured as rapidly, so that it stays active and continues to provide that benefit, is definitely a plus."

While some clinicians believe protein equals lens deposition, Dr. Giedd notes, "We definitely had no problems with deposits during our study of Biotrue." Dr. Anderson also noted protein deposition was minimal during the study. The panelists' experiences were consistent with those reported by all clinicians in the study; 89% of clinicians reported that Biotrue keeps lenses clean.3

Returning to a Rub Regimen
Biotrue has excellent disinfection efficacy data, but Bausch + Lomb chose not to pursue FDA clearance of a no-rub regimen — a decision the roundtable panelists applauded. "I commend Bausch + Lomb for taking that step, because I think it's in the best interests of our patients, and it's what eyecare practitioners want," Dr. Giedd says.
Dr. Anderson notes, "The no-rub lens care regimen has always been a pet peeve of mine. I find that very few patients follow the instructions on a no-rub solution to thoroughly rinse each side of the lens for 5 seconds. So I've been dispensing no-rub solutions as a rub regimen anyway. Having a rub regimen is the responsible thing to do, and as a result, I think we'll see cleaner lenses."
Dr. DePaolis also agrees with B+L's decision to market Biotrue as a "rub-recommended" regimen. "I've always felt the efficacy of multipurpose solutions is enhanced with a rub regimen," he says. "As a clinician who sees patients every day, I'm well aware of our patients' tendencies toward noncompliance. Therefore, I believe it's critical for us to continually educate them on the importance of complete lens care, rubbing included."

NEW APPROACH TO DISINFECTION

Biotrue contains two proven disinfecting agents — polyaminopropyl biguanide (PHMB) and polyquaternium-1 (PQ-1) — both of which have been used successfully in other ophthalmic products. For the first time, however, they've been combined in a unique bio-inspired formulation. While the PHMB and the PQ-1 combine for optimal disinfecting power, the pH of Biotrue enhances their performance. This combination of dual disinfectants and the bio-inspired properties of the formulation have demonstrated unsurpassed disinfection efficacy in laboratory studies, including FDA/ISO stand-alone testing, clinical isolate testing and FDA/ISO elimination.3

FDA and ISO stand-alone testing evaluates the disinfection efficacy of multipurpose contact lens care solutions based on log reductions of established challenge organisms, known as American Type Culture Collection (ATCC) strains. These strains include fungi and bacteria.

To meet the criteria to pass the stand-alone test for disinfection of fungi, solutions must achieve a 1-log reduction of Candida albicans and Fusarium solani. For bacteria, solutions must achieve a 3-log reduction of Serratia marcescens, Pseudomonas aeruginosa and Staphylococcus aureus. Biotrue was shown to provide superior disinfection against competing multipurpose care solutions, even with organic soil added to create more rigorous testing conditions.3 Figure 5 illustrates these results.

Figure 5. Mean log reduction of organisms tested using FDA/ISO stand-alone testing.

"The way Biotrue performed against the ATCC strains currently used for FDA testing is very impressive," Dr. DePaolis says. "Even more impressive is its performance in soil simulation testing."

Upon reviewing these data, Dr. Anderson notes, "Two things impressed me. One is that Biotrue did incredibly well against the other cleaning and disinfecting products, even the peroxide system, which, in my mind, has been the gold standard. Two is that Biotrue has the ability to achieve a mean log reduction of 4.1 for Fusarium. Those two facts alone are impressive to me."

Clinical isolate testing provides an additional method of disinfection evaluation beyond the standardized measures of FDA/ISO stand-alone testing. Clinical isolates are microbial strains collected from clinically worn lenses, lens cases or infected eyes. Testing against them can provide insights as to how well a multipurpose solution disinfects against microbes different from or not included in the panel of FDA/ISO challenge organisms. Study results of clinical isolate disinfection efficacy showed that Biotrue achieves consistently high log reduction against Staphylococcus aureus, MRSA and Fusarium solani (Figure 6).1 In addition, Biotrue is equally effective against trophozoites and cysts (Figure 7).3

Figure 6. Mean log reduction of clinical isolates of S. aureus, MRSA and F solani for Biotrue compared to various contact lens care products.

Figure 7. Log reductions of clinical isolates of Acanthamoeba polyphaga trophozoites and cysts.

"Historically, I think many of us felt hydrogen peroxide was the best lens care product for prophylaxis against Acanthamoeba infections. I believe Biotrue has the potential to create a paradigm shift in this area."

Michael DePaolis, OD

"Most of the multipurpose solutions, as well as the peroxide system, perform well against trophozoites," Dr. Cedrone says, "but if you review the performance against cysts, some of the products had negligible action, while Biotrue had equal action against trophs and cysts."

As Dr. DePaolis notes, "Historically, I think many of us felt hydrogen peroxide was the best lens care product for prophylaxis against Acanthamoeba infections. I believe Biotrue has the potential to create a paradigm shift in this area."

"It's amazing how Biotrue has the whole package," Dr. Giedd says. "Not only does it exhibit exceptional disinfection, even when compared to a peroxide system, but it also provides comfort because of the bio-inspired components. I think we all would agree that if a multipurpose solution has great disinfecting ability but doesn't provide comfort, patients aren't likely to use it. So to have comfort and efficacy in one product makes Biotrue unique."

Dr. Anderson notes, "What impresses me is that all of the ingredients in Biotrue are synergistic so that it performs well in terms of lubricating, disinfection and its ability to keep lenses comfortable."

"I believe Biotrue is efficacious against all of the bacteria and other organisms we see in private practice," Dr. Cedrone says. "A product that has effective disinfecting action but is gentle on the eye and comfortable is a great breakthrough."

TANGIBLE, SUBSTANTIVE BENEFITS

After examining the scientific data, reviewing their own clinical experiences and learning what patients had to say, the panelists agree that Biotrue is an innovative new contact lens care product. Its bioinspired features provide tangible, substantive benefits that have been proven through scientific evaluation and patient testimony.

"I'm a firm believer that lens care is as important as lens type and wear," Dr. DePaolis says. "For me, the biggest challenge is getting patients to see the value of brand-name multipurpose solutions and not simply select the least expensive privatelabel product on the shelf. The concept of bio-inspiration, as well as the impressive performance of Biotrue will help me keep my patients on track." CLS

Cultivating Trust to Ensure Compliance
Of the 400 people who participated in the Biotrue performance evaluation study, 75% indicated they intended to continue to use Biotrue based on their eyecare professional's recommendation. According to the roundtable panelists, this percentage is higher than what they usually experience in practice. "You hope patients will follow your recommendations, but they don't always do that," Dr. Anderson said.
The panelists believe, however, that the bio-inspired attributes and proven efficacy of Biotrue will continue to help improve compliance. "When a product performs to a level where patients can tell the difference — when it's more comfortable, for example — they're more likely to continue using it or to come back to it if they tried something else," Dr. Anderson says.
A patient's trust and confidence in his eyecare professional are also reinforced when a product performs as the doctor says it will, according to Dr. Giedd. "When you communicate a product's benefits and accurately predict how it will perform for patients, that builds trust," she said. "When patients trust your recommendation, they're more apt to follow it."

Patient Education…Bio-inspired
Typically, patients understand lens-to-lens comparisons — soft vs. rigid, for example — because these attributes are relatively easy to understand. But differentiating lens care products, other than by price, can be difficult for patients.
With the introduction of Biotrue, which is inspired by certain natural processes of the eye, practitioners can educate their patients about efficacy and comfort in familiar terms that are easily understood and appreciated.
"I have a standard speech that I use with my patients," Dr. Giedd says. "I tell them that part of my job each year is to educate them about what's new and different in the world of contact lenses and lens care products. This gives me the opportunity to introduce them to a new product and explain what makes it different.
"In the case of Biotrue, that leads very naturally into a conversation about its bio-inspired aspects and attributes, including how it matches the pH of healthy tears, how it contains a natural lubricant and its ability to work with tear proteins to maintain their antimicrobial effects."
Dr. Anderson also embraces his role as educator, emphasizing a product's pluses. "When I introduce a patient to a new product, I talk about its advantages and what is different about it," he says. "I have a very busy practice, so I don't have a lot of time to talk about it, but I do discuss its positive attributes. More importantly, I give patients a sample and let them try it. If they do well and the lenses feel better, which I'm sure they will with Biotrue, then they're more likely to continue using the product. So my advice is 1) give patients information about what's positive about the product, and 2) give them a chance to use it."
Dr. Giedd agrees that homing in on key points that will resonate with patients is the most efficient way to educate. "We don't want to overwhelm patients with information," she says. "Based on a patient's history, we can tune in to what's important for him — initial discomfort or end-of-day dryness, for example — and communicate the various aspects of Biotrue that he will appreciate."
According to Dr. Anderson, even patients who claim they have no problems with their contact lenses will appreciate learning about a new product, especially if you feel it's an improvement over what they're using. "I may have these patients switch to something I perceive is a better product and has been shown to work better. If they have a better experience with the new product, they'll be pleased with it, and possibly more compliant. I always try to make improvements for the patients. Even if they're doing well, I try to have them even do better."
Dr. Giedd notes, "If patients truly are happy and they don't have any specific complaints, then I'll mention Biotrue's unsurpassed disinfection, even when compared to a peroxide-based system. I tell patients they'll have the ease of a multipurpose solution with exceptional disinfection. That's another message they can take home — that they could still do better in terms of lowering their infection risk — even as a happy contact lens wearer."

REFERENCES

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Contact Lens Spectrum, Issue: September 2010