Article Date: 4/1/2002

strategic skill builders
Solution Chemistry
A care system's components and interaction with the lens and the ey are essential to successful contact lens wear.
BY PETER A. SIMMONS, PH.D., F.A.A.O., IRVINE, CALIF.

Contact lens care solutions have evolved recently. Several multipurpose products claim to be as effective at disinfection as hydrogen peroxide products and to be more convenient, particularly since the approval of no-rub indications. Multipurpose products have also enjoyed the greatest growth (+30%). I'll review multipurpose care products and discuss the interaction of their chemistry with the lens and the eye.

BALANCING EFFICACY AND COMFORT

Multipurpose solutions (MPSs) for disinfecting contact lenses must have sufficient antimicrobial activity yet be non-toxic to the eye. This need for balance has encouraged development and selection of MPS disinfectants. Most MPS products bind to the microbe cell surface, destroying cell membrane function. Common disinfectants in these products are:

Polyhexamethylene biguanide (PHMB). Also known as polyhexanide and polyaminopropyl biguanide, PHMB is the most popular disinfectant in MPS products. It's found in Complete, ReNu MultiPlus, SOLOcare and numerous generic products, at concentrations of 1 part per million (ppm).

The biguanide group has a strong cationic (+) charge, which accounts for its high activity and usefulness at low concentrations. Other ingredients (e.g., buffers, surfactants, salts, etc.) can affect its activity, which is why antimicrobial effectiveness differs between products. Overall, PHMB is effective and well tolerated.

Polyquad (Polyquartenium-1). Unique to Alcon products, this is a large cationic (+) polymer (larger than PHMB). The quaternary ammonium group has a lower cationic (+) charge than PHMB's biguanide group, so we use Poly-quartenium-1 at higher concentration levels (10 ppm ).

Aldox (myristamidopropyl dimethylamine). Aldox is an additional disinfectant found in Opti-Free Express at 5 ppm. It's a fatty acid modified with a cationic group and mainly demonstrates anti-fungal activity. It's a much smaller molecule than the two polymeric disinfectants and more likely to irritate the eyes.

PROVING THAT THEY WORK

In the United States, two recognized pathways exist for demonstrating that an MPS disinfects adequately. One is to test it by loading lenses with microorganisms and then performing each disinfection step as specified in the product labeling. This testing, called Regimen Qualification, must demonstrate that at the end of the disinfection process, fewer than 10 microbes of an initial inoculum of 100,000 to 1 million viable cells remain on the lenses and in the solution (at least a 5 log reduction of three types of bacteria). The manufacturer specifies the regimen used; it may or may not include a rub step.

The second method is "stand alone" testing. It was developed to expedite industry testing of MPS products that are used in a "standard" regimen, including rubbing and rinsing steps as well as a lens soak period. In this test a volume of MPS is inoculated with micro-organisms soaked for the time specified by the product labeling. Then the disinfectant is neutralized and the number of surviving organisms is determined. To pass the test, there must be at least a 3 log reduction in bacteria and a 1 log reduction in fungi. Passing "stand alone" testing doesn't demonstrate cleaning or disinfection of lenses since no lenses are involved in the test.

The only requirement is a specific reduction in microbial viability numbers, expressed as log reduction, within the specified soak time. For example, if the test inoculum is 500,000 (5x 105) organisms, a 1 log reduction would have 50,000 (5x104) organisms surviving, and a 3 log reduction would have 500 (5x102). If the MPS passes the "stand alone" test, regimen testing is unnecessary, and the product may be labeled a multipurpose disinfecting solution (MPDS).

Products that qualified as adequate disinfectants using regimen testing include Complete Brand and SOLOcare. Products that qualified using the stand alone test are ReNu MultiPlus and Opti-Free Express.

NO-RUB MULTIPURPOSE USE

Because a no-rub regimen isn't a "standard" regimen, the MPS must pass a modified regimen test (including a special test using organic soil added to the lenses) to be cleared by FDA. Products that have no-rub labeling are Opti-Free Express, Complete, and ReNu MultiPlus.

How does a no-rub multipurpose product clean and disinfect adequately? A lens taken from a healthy eye has few microbes when put away in its case. Rinsing before and after the soak removes at least 90% of the debris and contaminants, and the disinfection action of the MPS kills remaining organisms and prevents new growth. While rubbing a lens helps remove deposits and particulate matter, it adds contaminants from the hands, grinding them onto the lens surface. If you follow a no-rub regimen, the lens could have less microbial contamination.

Rinsing is crucial to the success of a no-rub regimen. No rub hasn't been shown to be safe or effective without it. Recent contact lens industry data suggest that only 66% of patients rinse their lenses.

Before recommending a no-rub regimen, evaluate the patient's level of compliance (inspecting the cleanliness of the lens case brought from home may provide an objective clue). If you think he or she's a good candidate, thoroughly explain the importance of adequate rinsing.

BIOCOMPATIBILITY

Although the disinfectant in an MPS product is its active ingredient, all such products have a complex mixture of other ingredients to clean lenses and keep the solution compatible with the eye (see Table on page 75). These ingredients include:

EDTA (edetate disodium). Found in all MPS products, EDTA enhances the anti-microbial effectiveness of the primary disinfectant. It chelates divalent cations (usually calcium and magnesium), leaving the microbe more vulnerable to the disinfectant. Because EDTA chelates calcium and magnesium ions, it's also slightly toxic to corneal cells, which need these ions for metabolism. Thus products with lower levels of EDTA may be preferable, provided they demonstrate adequate anti-microbial performance.

Surfactants. Surfactants are essential to cleaning ability. They're particularly important for emulsifying lipid-based soils on lenses and preventing re-attachment of proteins or other materials to the lens.

All surfactants have a structure composed of lipophilic (nonpolar) and hydrophilic (polar) domains. While classic surfactants are small molecules, modern MPS surfactants are polymers large enough to avoid penetration into the lens matrix, so that carry-over to the eye during lens application is minimized. Two classes of these polymers are:

Polyoxyethylene-polyoxypropylene block copolymer in SOLOcare and Poloxamer 237 in Complete are examples of pluronic surfactants. Poloxamine in ReNu MultiPlus and Tetronic 1304 in Opti-Free Express are tetronic surfactants. Pluronic surfactants may have a lower potential for ocular irritation.

Buffers. A buffer is essential for maintaining a pH compatible with the eye. It must also be chemically compatible with the other formula components. Several buffers are used in MPS products, including borate, which can work synergistically with the disinfectant, boosting the overall disinfection. However, as with EDTA, the trade-off for enhanced anti-microbial effect is increased potential for eye irritation.

Phosphate and citrate buffers, found in Complete and Opti-Free Express, are more like physiological buffers and gentler on the eye.

Chemically, buffers must match with eletrolytes to provide isotonicity. This balance of concentration is necessary for compatibility of the solution with the contact lens and the eye. Sodium and chloride are the primary electrolytes. Potassium is found in Complete Brand; potassium ions are believed to be particularly beneficial to the ocular surface.

Several in vitro tests measure biocompatibility. They expose a standard cell model to the MPS and measure cellular integrity and survival. In one test, the vital dye neutral red is taken up by cells of a standard cell line. Then the cells are exposed to the test products. Released dye is washed out, and the dye remaining in the cells is measured by a colorimeter. More toxic solutions will damage the cell membranes, causing more dye loss. Opti-Free Express causes more dye loss and so is more cytotoxic than ReNu MultiPlus or Complete.

Multipurpose solutions are all qualified for use with any hydrogel lens, including toric and multifocal designs as well as opaque and tinted lenses. However, some evidence indicates that certain match-ups between lens and solution may be better than others.

In a French study on MPS use and polymer selection, 3,066 subjects, both existing and new wearers, were recruited from more than 300 ophthalmological practices. All were fit with Acuvue 2 lenses and given Complete Brand Multi-Purpose Solution. After 28 days, they were questioned.

Key findings included a higher score for comfort during the 2 or 3 days before lens replacement with the new combination than with the previous lens and solution. Furthermore, about 8 out of 10 users overall (and 9 of 10 new wearers) stated that they would continue to use the new combination after the study.

In a similar U.S. study, 284 wearers compared Acuvue2 lenses and Complete with their usual lens/solution in an open-label, randomized, crossover test design. They preferred Acuvue 2 lenses and Complete Brand MPS over their usual combination for initial and all-day comfort as well as overall comfort, giving the new combination superior scores for satisfaction and intent to purchase the after the study.

SUBCLINICAL EFFECTS OF MPS'S

What could be the mechanism for interaction of the contact lens and the care system? Remember that the soft contact lens is a delivery device for MPS components to the eye. Disinfectants and surfactants in particular may have subtle irritating effects on the eye, not as stinging and burning, but as a slight decrease in overall lens wearing comfort or reduced wearing time.

One doctor reported significantly higher levels of corneal staining in patients using an MPS with a relatively high level of PHMB. This effect was particularly evident in patients wearing Group II lenses. Subjects with more staining also reported less comfort and satisfaction. The proposed mechanism for this effect is enhanced binding of PHMB to lipid deposits on the group II lens, causing delivery of more PHMB to the corneal surface as the lens ages.

PHMB is a poly-cationic molecule that binds to anionic sites on the eye surface (and on microbes) to exert its disinfectant or cytotoxic action. Blocking poly-cationic sites may reduce its effect, de-activating it by ion-pair binding with a suitable poly-anionic molecule.

One such moledule is Carboxymethyl cellulose (CMC), the active ingredient in some rewetting drops. It's also an ophthalmic demulcent in some dry eye preparations.

The proposed actual use of this effect would be insertion of a drop of the tear product in the eye before lens application, or direct placement of the CMC tear inside the lens before application. The relative volumes of tear and MPS would be close to 1:1, so there would be substantial excess CMC in the mixture (up to 200:1 relative to PHMB) due to its relatively higher concentration.

Market value of contact lens care products

THE FUTURE OF MPS PRODUCTS

MPS products provide excellent disinfectant and superior convenience, but areas for improvement remain. I'd like less potential for ocular discomfort, with modifications in formula components. As new lens types are introduced, MPS products may need to evolve to maintain their lens compatibility.

One possible direction for evolution is toward comfort components. Hydroxypropyl methylcellulose (HPMC) is one FDA-specified ophthalmic demulcent that may be used to treat dry and irritated eyes in artificial tears. It's a common ingredient of dry eye drops. In the tear film it supplements the natural tear layer by attracting and holding additional water on the ocular surface, improving wearing comfort.

In an MPS, HPMC is taken up to hydrogel lenses during overnight soak, and then released from the lens surface. It improves lens surface wettability and is associated with a small but significant increase in tear break-up time in lens wear. Adding HPMC to an MPS improves wearing comfort in clinical tests.

In the future, more products will be formulated to enhance the wearing experience.

Dr. Simmons conducts research within the Consumer Eye Care group at Allergan, Inc., with particular interests in contact lens care products and dry eye formulations.

This Strategic Skill Builders Continuing Education article is made possible by a grant from Vistakon. The content is independently produced by Optometric Management.

 


Optometric Management, Issue: April 2002