25th Anniversary Perspective
Soft Contact Lens Solutions Over the Last 25 Years
By William J. Gleason, OD
In the last 25 years, lens manufacturers have faced challenges of finding the perfect design for astigmatic or presbyopic patients. Material research has been looking for a polymer that the eye doesn't reject as a foreign object, while at the same time having adequate optical and manufacturing properties.
Considerations for Solutions
Contact lens solutions development has faced similar multifaceted challenges. How does a solution hydrate the lens material, coat the surface, cushion the application process, stick to the surface, provide lubricity, contain surfactants to clean the lens surface, and at the same time not be too viscous?
At the same time, solutions have to be effective enough to kill known pathogens on the lens and in the storage case. More recently, they have been expected to be effective against pathogens of which no agreement exists as to a validated test method or the magnitude of kill necessary to reduce the patient risk.
Now let's consider putting this highly effective disinfectant into the eye where it has to be gentle to and compatible with the various corneal and conjunctival tissues. All of this has to be accomplished while not interfering with the delicate balance of the tear layer or the “normal” ocular flora.
Having met all of these attributes, this formula has to be compatible with the various lens polymers, surface wetting and non-wetting components, pore size, water content, and UV absorbers, and lastly not bleach out the tints and dyes that make the lenses cosmetically appealing.
Manufacturers of one-bottle solutions face big challenges. Let's examine what the hydrogel solution developers have accomplished and where they have fallen short in the last 25 years.
Soft Lens Solution Beginnings
First let's go back even further to understand how we got to the 1986 starting point. In the early 1970s, three-bottle solution systems were the norm for PMMA lenses. This model strongly influenced the original chemical systems approved in the late 1970s for soft lenses. There was a separate cleaner for use after lenses were removed from the eye, a storage solution with higher concentrations of disinfectants, and rinsing solutions to use prior to putting the lenses onto the eye. The thought was to keep the strong cleaners and disinfectants out of the eye. The primary preservatives used in the early solutions were, in combination or independently, chlorhexidine and thimerosal along with the ever present ethylenediaminetetraacetic acid (EDTA). Irritation, sensitivity, and even toxicity occurred with these systems as the concentrations of the preservatives or their toxic fragments built up in the lens matrix.
First change came with the combining of the cleaning and disinfecting solutions into one bottle. During the early-to-mid 1980s, the evolution of the disinfectant components began with the introduction of polyaminopropyl biguanide and polyquaternium-1. It was hoped that these preservatives would result in better lens and ocular tissue compatibility.
Polyaminopropyl biguanide has since been used by multiple solutions companies under various chemical names. Until recently, polyquaternium-1 has remained the property of a single manufacturer. Products with these preservatives along with the addition of various demulcents and surfactants were cleared and marketed as multipurpose solutions (MPSs) by every major manufacturer. In 2000, Aldox was added to the polyquaternium-1 preservative system for broader disinfection efficacy. Shortly thereafter, Alexidine was used as the primary preservative in an MPS product.
One of the driving forces behind the development of MPS products was wearer noncompliance. The hope was to combine all of the major components for cleaning and disinfection of the lenses into one bottle. To further accommodate patient noncompliance, companies applied for and were granted clearance for norub instructions for cleaning and overnight disinfection. Following a series of unfortunate adverse events and the associated recall of two MPS products, the FDA, the Ophthalmic Panel, and various professional organizations have recommended that using the rub-and-rinse method prior to overnight storage in a clean case with fresh solution and again rinsing with fresh solution prior to application is the best practice and safest method for lens care. An FDA guidance issued on Aug. 15, 2010 recommended that manufacturers of MPS products that include no-rub directions remove the “No Rub” from product labeling and emphasize the importance of “rubbing and rinsing” in caring for contact lenses.
Two MPS products have been cleared under the 510(k) process since the recalls of 2006 and 2007. The first product cleared is an MPS that uses polyaminopropyl biguanide and polyquaternium as the preservative system with various buffers, viscosity agents, demulcents, and surfactants. The second solution cleared contains a preservative combination of polyquaternium and alexidine.
During the last 25 years, hydrogen peroxide systems have been available with a platinum catalyst for neutralization or with a catalase neutralizer. Upon completion of the neutralization, the lenses sit in a nonpreserved solution. While these products have not maintained a large section of the market, they are the go-to products when practitioners have problems with preservative sensitivity and reduced wearing time with MPS products.
To be consistent with the guidance for MPS products, most of these systems need to include a separate saline solution to rinse away the dead organisms and debris before applying the lenses.
Soft Lens Solution Goals
Hydration of the lens material is a fairly easy goal for all solutions. Maintaining surface hydration and wettability is also easy these days, but mostly because we discard lenses with relative frequency. Surface compatibility has been a challenge of the last 10 years with the introduction of silicone hydrogel lenses that have various surface treatments and wetting agents. As lens manufacturers introduce new surface treatments and material components, the challenge will remain for all solutions currently on the market to prove that they still work with the new technology.
Preservative combinations are evaluated during clinical studies to determine whether they are compatible with the eye and its surrounding tissue. We look only at gross issues such as evidence of toxicity with staining and redness. We may need to develop better ways to clinically quantify the effect on goblet cells and other cells that produce tear components. There is more to a successful product than simply a stain-free cornea. At the same time, we may need to monitor the natural flora to make sure the preservative combinations of the future don't disrupt this important balance.
Disinfection efficacy for the storage case is still a moving target. Much of the problem could be eliminated by simple routine disposal of dirty cases. New test procedures for rare organisms have yet to be agreed upon. Even when we do have a testing method that everyone accepts, we still don't know enough about the mechanism of these rare infections to know whether the standard acceptable reductions are appropriate.
Twenty-five years ago, no one thought it was a good idea to put a disinfectant or surfactant into a patient's eye. Maybe it still isn't a great idea, but we have made significant progress in understanding what does and doesn't work for each of the product attributes.
There will be new compatibility issues as new materials are approved. There may even be products specifically designed to work exclusively with a new material. For now, solution chemists should feel comfortable that their jobs are not done and their employment is secure for the near future. CLS
For references, please visit www.clspectrum.com/references.asp and click on document #186.
Dr. Gleason, founder of Foresight Regulatory Strategies Inc., has greater than 35 years of experience in basic research and management of clinical trials for medical devices. He has extensive experience in design control, product development requirements, and regulatory submissions for both the U.S. and international markets. He is also a consultant or advisor to and has received research funds from Allergan Pharmaceuticals, Ciba, Vistakon, CooperVision, Menicon, and Sauflon Pharmaceuticals.