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This Blog contains the comments and opinions of Dr. Gary Andrasko relating to
lens/solution biocompatiblity, the Staining Grid study and other developments on these or related topics.
This blog does not reflect the views or opinions of anyone else.
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A Logical Approach to Diagnosing SICS - 12/9/2011
An article in the December, 2011 issue of Contact Lens Spectrum entitled, "Communicating the Importance of Lens Care" by Bruce W. Anderson, OD, FAAO recently caught my attention. Dr. Anderson discusses two cases illustrating common lens care-related issues that you are likely to encounter in your practice.
I would like to bring your attention to the first case which he discusses, "Discomfort Upon Lens Application" which is particularly relevant to the information on this web site. Dr. Anderson lays out a typical scenario in which a patient presents with discomfort and stinging soon after soft lens insertion. He then walks the reader through his thought process in arriving at the diagnosis and ultimate recommendations for the resolution of the problem.
In my opinion this short, but well written, article offers the eye care practitioner one of the best resources to solving this common, yet often overlooked condition ... solution-induced toxic corneal staining. The only two points which I would like to add to this article are:
1) Consult the Staining Grid to determine the expected biocompatibility (i.e., SICS) of the lens/solution combination being used by the patient.
2) Use the Staining Grid as a teaching tool when discussing with the patient the importance of not arbitrarily switching solutions without consulting your office.
I strongly encourage you to take a few minutes to read Dr. Anderson's article and adopt his logical diagnostic approach to solving this common patient complaint.
| Real Staining or an Artifact: Let's Look at the Evidence - 10/23/2011
Some of you may have seen the recent supplement in Review of Optometry entitled "The Science Behind the Stain". This supplement, sponsored by Bausch+Lomb, discusses in great detail what they call "PATH " Preservative Associated Transient Hyperfluorescence. Although I've covered this topic extensively in my 5/14/11 blog I'll review it briefly here since the Review supplement references the Staining Grid with some confusing and incorrect statements.
PATH is the brainchild of Dr. Frank Bright, a chemistry professor from Rochester, NY. His theory states that those little green dots that we may see on the corneal surface after our patients use a non-biocompatible lens/solution combinations are not really corneal staining but the result of the interaction between fluorescein, PHMB (preservative), and the corneal epithelial cell. Dr. Bright postulates that fluorescein binds with PHMB causing it to hyper-fluoresce and appear as tiny green dots attached to the corneal surface. Coincidentally, this PHMB/fluorescein complex looks exactly like corneal staining!
Since most of us are not PhD chemists we might be tempted to give this theory the benefit of the doubt. However, PATH has a few problems based on the clinical evidence. I promised to keep this short so I'll discuss only 2 points here.
1) Visual evidence: Keep in mind Dr. Bright's theory states that PATH is observed due to the attachment of PHMP and sodium fluorescein sticking on the corneal surface. With that explanation please look at this hyperlink showing 2 photos of the same cornea after wearing a non-biocompatible lens/solution combination. The left photo shows the cornea photographed with white light BEFORE fluorescein was instilled. Grayish areas in the anterior cornea can easily been seen against the black pupil. The photo on the right shows the same cornea AFTER fluorescein was instilled. Dense corneal hyper-fluorescence (i.e., PATH or staining) can be seen exactly corresponding to the grayish areas in the photo on the left. So is it PATH or staining? If it were PATH why would we see anything in the left photo since fluorescein had not yet been instilled? On the other hand, heavy corneal staining, from any cause, can often be seen as grayish areas on the corneal surface before fluorescein is instilled representing the disruption of the epithelial surface.
2) Discomfort Evidence: Some are attempting to portray PATH as a "benign" phenomenon that we should simply ignore. In the Staining Grid study we not only assess the amount (area) of staining but we also ask our subjects to rate subjective comfort with the lens solution combination being tested. By definition a "benign" phenomenon (PATH) would have no effect on subjective comfort while real corneal staining would reduce comfort as staining increases.
To answer the comfort question I've plotted the staining vs. comfort values for a highly staining lens (Purevision) with each dot representing a different solution which it was pair. This graph indicates that as staining area (shown on x-axis) increases the average comfort scores (shown on y-axis) decrease. The slope of the trend line indicates that increasing the numbers of those little green hyper-fluorescent dots on the cornea is associated with a consistent and systematic decrease in the subject's comfort ratings (22 points when going from none to excessive staining in the case of Purevision).
So let's summarize, looking not at theory, but at evidence. A chemistry professor (non-OD, non-MD) claims to have discovered a new ocular condition that is morphologically indistinguishable from corneal staining. According to his THEORY, when little green dots are observed on the cornea after wearing a non-biocompatible lens/solution combination it's a benign artifact (PATH) that eye care practitioners should ignore. However, when identically appearing green, fluorescing dots are observed from any other cause then it's still corneal staining!
What does the clinical EVIDENCE say? Subjects from the Staining Grid study (and your practices) typically report discomfort while using non-biocompatible lens/solution combinations that are responsible for inducing multiple green, hyper-fluorescing dots on the cornea. Also, damaged epithelial cells can be seen as small grayish areas before fluorescein is instilled (using white light) and as bright, hyper-fluorescing green dots after fluorescein has been instilled, both in the same corneal location.
Although PATH is an intriguing theory it doesn't stand up to clinical evidence. Corneal staining represents what it has for over 100 years, damage to the corneal epithelium. As Dr. Laurent said about the current research being done in this field, "...induced corneal staining, regardless of the cause, indicates the premature initiation of programmed cell death. Cells are dying earlier than Mother Nature intended."
| Corneal Staining - Understanding its True Significance - 7/10/2011
In our fast moving, high tech society the way we think about almost anything can change in a heartbeat. Take corneal staining for instance. We've been using sodium fluorescein for over 100 years to assess the health and integrity of the corneal epithelium. We learned in our ophthalmic training that corneal staining is the sign of an injured epithelial cell. We also learned that an intact corneal epithelium presents a formidable barrier against the invasion of unwanted microorganisms into the deeper layers of the cornea.
Our research (and this web site) quantifies one specific type of corneal staining; staining induced by multipurpose solutions following lens insertion. This is commonly called solution-induced corneal staining or SICS. From the beginning of our research there has been discussion as to what SICS means and how eye care practitioners should think about this staining. To better understand corneal staining in general and SICS in particular I've interviewed Dr. John Laurent. Dr. Laurent is currently an associate professor at University of Alabama-Birmingham school of Optometry. His PhD research in the mid 1990's involved an evaluation of the surface cells of the corneal epithelium. He also looked at corneal staining at the cellular level and is one of a handful of people who has observed the fluorescein stained cornea with the high magnification of a laboratory microscope. He has graciously agreed to share his knowledge with the readers of this web site.
Q: Dr. Laurent, before we talk about corneal staining it would be useful to understand the nature and function of the corneal epithelium. What can you tell us about this important structure that might help us better understand the significance of staining?
A: I think everyone probably has a basic appreciation of the protective/barrier function of the corneal epithelium as well as its relatively fast regenerative potential. However, to understand what is happening on the corneal surface, I think it would be good to review the life cycle of corneal epithelial cells. Most epithelial cells are produced by the stem cells located in the limbal region. They begin life as columnar cells in the basal layer, slowly migrating toward the center of the cornea. Some of these cells also start migrating anteriorly as they move centrally. Depending on the physiological "wear and tear" on the surface and the demand for new replacement cells, some basal cells may not get very far in their journey towards the central cornea before they start to move anteriorly, losing their columnar characteristics and becoming wing cells. At this point, they are probably committed to further anterior migration, becoming flattened wing cells, then squamous cells, and ultimately shedding from the corneal surface. So the big picture is one of a mass migration of cells centrally and anteriorly with the shedding of several hundred surface squamous cells every hour.1,2
To understand fluorescein staining of the cornea it is particularly helpful to understand the nature of the cells in the top 1-3 layers of the epithelium. These are squamous cells and are similar in shape to tiny leaves or miniature taco chips, flattened out and overlapping one another in an irregular fashion. This is distinctly different from the columnar cells in the basal layer of the epithelium that touch but do not overlap. At the surface, these squamous cells are only 1-2 microns (micrometers - 0.001 mm) thick but have a longest dimension averaging around 35 microns. Most clinicians have probably used the high magnification on their slit lamps to observe individual red blood cells (RBC's) moving through the conjunctival capillaries just beyond the limbus. RBC's are approximately 8 microns in diameter. Individual corneal epithelial surface cells are 4-5 times larger than RBC's and, with the proper stain and lighting, should be visible with the slit lamp.3
I would divide the squamous cells of the anterior corneal epithelium into three groups. The first group is composed of the cells that are completely exposed on the corneal surface. Probably most of these cells are dead or dying and will be the next cells to be shed from the surface. Some of these cells are easily removed with irrigation. They do not stain with fluorescein but can often be seen to overlap other cells that do stain with fluorescein. When these cells leave the corneal surface, there is no underlying depression or "footprint" left on the surface. A good analogy is to think of a deck of cards spread out into a small pile - if you picked up one of the topmost cards it would not leave a depression, there would simply be more cards beneath it.
The cells in my second group are those immediately beneath the surface-most cells.These cells are partially exposed to the surface and partially covered by the first category of surface cells. They are not quite ready to shed, although that condition can change quickly as the cells that are partially covering them leave the corneal surface. I believe it is these partially covered cells that have the potential to take up fluorescein and become the hyperfluorescent cells we see with the slit lamp as micropunctate staining. The dead/dying surface cells that are partially covering them do not stain and are transparent in the slit lamp view.
My third group of squamous epithelial cells is comprised of the cells immediately beneath the partially exposed cells in the second group. These cells are not exposed to the corneal surface and probably take up little or no fluorescein. However, as more surface cells shed, this third group will "graduate" and become the new partially exposed cells. I do not think any of these cells can become hyperfluorescent until they are at least partially exposed to the surface and a tearfilm containing fluorescein. An exception to this observation occurs in the case of injury, when epithelial cells that are below the surface become exposed to the fluorescein in the tearfilm when the cells in front of them are removed, as in the case of a corneal abrasion. Many of these mechanically compromised cells will then become hyperfluorescent.
An additional subject that should be addressed here is the meaning of "hyperfluorescence." Stedman's Medical Dictionary, among others, describes hyperfluorescence as the "Increased fluorescence of fluorescein dye observed in the ocular fundus during fluorescein angiography," which refers to the appearance of fluorescein in solution in blood. In our 1995 paper (Wilson, et al.) we used the term "hyperfluorescence" to describe the brightness of the small spots on the corneal surface viewed with the slit lamp in cases of "micropunctate staining", "superficial punctate staining", or "superficial punctate keratitis". For the purposes of our paper, we assumed these three terms were generally used to describe the same phenomenon.4 A hyperfluorescent spot on the cornea is bright enough to stand out from the adjacent epithelium and be distinctly visible with the slit lamp even when viewed through the fluorescein-laden tear film.
Q: Our ideas concerning what occurs at the cellular level when we observe corneal staining has evolved over the last few decades. What were some of the original theories concerning staining?
A: One of the most influential papers concerning the nature of corneal fluorescein staining was written by M. S. Norn. His paper, Micropunctate fluorescein vital staining of the cornea, was published in 1970 and stated that "The dots [micropunctate] are so minute that they must be due either to dropping out of a single cell or to a defect between two epithelial cells, which allows dye to penetrate into the intercellular space."5 Norn's view of corneal fluorescein staining was reinforced in a 1982 paper by K. G. Romanchuk, who wrote that "Micropunctate staining of the cornea may be due to drop-out of a single surface epithelial cell, allowing the dye to penetrate into the intercellular spaces of the surrounding cells ... "6 A 1997 paper by H. M. Tabery also agreed with Norn, stating that "The findings indicate that micropunctate fluorescein staining probably reveals disruptions of intercellular junctions permitting penetration and accumulation of stained fluid beneath diseased cells in situ."7 These papers contributed to what some people call the "footprint" theory of corneal fluorescein staining, which explained the hyperfluorescence we see with the slit lamp as spaces with an accumulation of fluorescein.
Q: Your work with Wilson in the mid-1990's provided a new understanding of corneal staining. What did you find?
A: While I was a graduate student working with Dr. Graeme Wilson and Dr. Hongwei (David) Ren at UAB, we used a rabbit model to investigate the nature of fluorescein staining on the corneal surface. (Animals were treated according to ARVO guidelines and research protocols were approved by a Laboratory Animal Care and Use Committee.) Our specific goal was to discover the anatomical source of a single micropunctate hyperfluorescent spot on the corneal surface as viewed with the slit lamp. Corneas were treated with exposure to chemical preservatives known to cause staining in humans as well as mechanical trauma, creating slit lamp views similar to those seen in clinical practice in cases of contact lens solution sensitivity or corneal abrasion. After slit lamp verification of the fluorescein staining pattern, animals were euthanized and the corneas excised for viewing with high magnification on a fluorescent laboratory microscope. I am not sure if we were the first ones to discover it, but I think we were the first to publish it: hyperfluorescent staining of the cornea is due to the uptake of fluorescein by individual cells. We found no evidence of any accumulation of fluorescein on the corneal surface or in intercellular spaces that resulted in hyperfluorescence.4 A recent paper by Mokhtarzadeh et al. seems to agree with us, stating "Punctate epithelial erosions correspond to enhanced fluorescence in epithelial cells predominantly in superficial layers of the cornea and would be more aptly named fluorescent epithelial cells (FLECs)."8
Q: Some recent work by Papas, et. al. on the cellular nature of corneal staining was presented at ARVO this year. What did Papas' group find and does it agree with your work?
A:
Bandamwar, Garrett, and Papas presented an excellent poster at ARVO that I think is a continuation of the work I was involved with at UAB. Using a rabbit model, they also showed that hyperfluorescence on the corneal surface is due to the uptake of fluorescein by individual cells. With a series of different stains, they were able to identify three groups of stained cells: 1) healthy cells that stain with fluorescein but not at a level to cause hyperfluorescence, 2) apoptotic cells that take up fluorescein and are hyperfluorescent so they can be visualized with the slit lamp as micropunctate staining, and 3) dead cells that take up minimal fluorescein and would not be visible with the slit lamp. They concluded that "Superficial punctate fluorescein staining of the corneal epithelium visualized with the slit lamp corresponds to the presence of damaged epithelial cells."9
The work I was involved with at UAB did not utilize stains that would have allowed us to label the hyperfluorescent cells we observed as being apoptotic. I am impressed that Bandamwar et al. was able to accomplish this and I find no disagreement between our two studies.
Q: At this year's BCLA meeting Papas also presented some research regarding the inflammatory nature of corneal staining. Did his findings make sense to you based on the current theories of staining?
A:
I did not attend the BCLA meeting but I read a synopsis of Eric Papas' presentation and I find myself once again very impressed with his work. He found an increase in cytokines (protein inflammatory markers) with contact lens wear and an additional increase in those patients exhibiting solution-induced corneal staining (SICS). Although he did not find a correlation between the degree of stain in those patients with SICS and the level of cytokines, I think the basic principle is clear: Some multi-purpose solutions can cause SICS and SICS is associated with an increase in inflammation compared to contact lens wearers without SICS. I think it is almost self-evident that the physiology of the corneal epithelium has been altered when we see fluorescein staining of the corneal surface - whether it is associated with dryness, mechanical abrasion, or some type of chemical insult. That this altered physiology is also associated with an increase in inflammatory markers should not be surprising.
Q: Dr. Jerry Paugh has found some interesting results correlating solution-induced corneal staining with a leaky barrier function. What does this mean to us as clinicians?
A: Dr. Paugh's excellent work with the amount of fluorescein that can penetrate into the corneal stroma and the anterior chamber seems like another piece of evidence that fluorescein staining of the cornea indicates a compromise of the corneal epithelium. Dr. Paugh's work does not necessarily tell us the long-term significance of the compromise of the epithelial barrier function after exposure to polyhexamethylene biguanide (PHMB), but once again, I think the basic principle is quite clear: corneal staining indicates that the corneal epithelium is not able to perform its protective function as well as a cornea without significant stain.10
Q: Based upon all the research that we have just discussed, please tell us how you view solution-induced corneal staining and if it is important to avoid it.
A: I think all hyperfluorescent corneal fluorescein staining is negative. The results of Bandamwar et al. indicate that hyperfluorescence of the cornea signifies apoptotic cells. One could conclude from this work that induced corneal staining, regardless of the cause, indicates the premature initiation of programmed cell death. Cells are dying earlier than Mother Nature intended. The question then becomes: how much staining/additional cell death is acceptable? Certainly the corneal epithelium is capable of replacing lost cells under normal physiological conditions as well as in cases of injury. How much physiological compromise can a cornea tolerate on a chronic basis? Could we relate the amount of corneal staining to some measure that in turn could be related to negative long-term consequences for the cornea? I do not know when we will be able to properly answer these questions, but at this point I think we can safely say that corneal staining is not good - we are just uncertain of how bad it is.
Thanks Dr. Laurent.
References
1. Thoft RA, Friend J. The X, Y, Z hypothesis of corneal epithelial maintenance. Invest Ophthalmol Vis Sci. 1983 Oct;24(10):1442-3.
2. Ren H, Wilson G. The cell shedding rate of the corneal epithelium--a comparison of collection methods. Curr Eye Res. 1996 Oct;15(10):1054-9.
3. Laurent J. Evaluation of the cornea through the use of contact lens cytology. PhD dissertation, University of Alabama Birmingham, 1996.
4. Wilson G, Ren H, Laurent J. Corneal epithelial fluorescein staining. J Am Optom Assoc 1995;66(7):435-41.
5. Norn MS. Micropunctate fluorescein vital staining of the cornea. Acta Ophthalmol (Copenh). 1970;48(1):108-18.
6. Romanchuk KG. Fluorescein. Physiochemical factors affecting its fluorescence. Surv Ophthalmol. 1982 Mar-Apr;26(5):269-83.
7. Tabery HM. Micropunctate fluorescein staining of the human corneal surface: microerosions or cystic spaces? A non-contact photomicrographic in vivo study. Acta Ophthalmol Scand. 1997 Apr;75(2):134-6.
8. Mokhtarzadeh M, Casey R, Glasgow B. Fluorescein punctate staining traced to superficial corneal epithelial cells by impression cytology and confocal microscopy. Invest Ophthalmol Vis Sci. 2011 Apr 5;52(5):2127-35.
9. Bandamwar K, Garrett Q, Papas E. Sodium Fluorescein Staining Of The Corneal Epithelium: What Does It Mean At A Cellular Level? ARVO Meeting Abstracts April 22, 2011 52:6496.
| Debunking the Hyperfluorescence Myth - 5/14/2011
Let me start this blog with a little history to provide some perspective. Since the introduction of the Staining Grid in 2006 the critics (actually one critic) has offered the following rationalizations, in chronological order, as to why the findings are insignificant (i.e., you should ignore them):
1) Solution-induced staining doesn't really exist (the website photographs proved otherwise)
2) Solution-induced staining exists but has no consequences (what about insertional discomfort?)
3) Visible staining is mostly gone by the end of the day (what about during the CL wearing period?)
4) Staining Grid study was sponsored by industry (Alcon and CooperVision) so it's biased
5) Results haven't been published in a peer-reviewed journal (see Journal of American Optometric Assoc., August 2008)
Now, there is an interesting (and imaginative) theory being proposed by the same critic that again attempts to cast doubts on the Staining Grid research. They state that what we are seeing, measuring, and photographing after 2 hours of lens wear isn't really solution-induced toxicity staining. Instead it is what they call "corneal hyperfluorescence". Hyperfluorescence, according to their theory, is the intense glowing of spots on the cornea caused by the binding of the PHMB (preservative) molecules with sodium fluorescein. This occurs after wearing hydrogel contact lenses soaked in a lens care solutions preserved only with the PHMB preservative. Conveniently, the appearance of these spots is identical to solution toxicity staining.
With the latest theory we've now come full-circle. We're back to:
6) Solution-induced staining doesn't really exist (now it's hyperfluorescence).
When I first heard of the "hyperfluorescence theory" I was more than a little skeptical. I was pretty sure that my optometric training and nearly 30 years of clinical experience had prepared me to diagnosis a condition as straight forward as corneal staining. Also, since the first solution-induced corneal staining article appeared in 1993 and there have been dozens of publications on this topic all referred to "corneal staining." None mention "hyperfluorescence." Could all of these scholarly researchers and authors have been fooled by hyperfluoresence for the last 18 years?
The short answer is that all of the researchers, authors, and eye care professionals were not wrong! What we are observing in our Staining Grid study and our practices is really solution-induced corneal staining. How can I be sure? I could give you my opposing theory but instead let's look beyond theories at real evidence.
1) Appearance Evidence
The little green spots which we see on the cornea after the use of some PHMB-based solution have an identical appearance to corneal staining which we commonly observe from other causes such as dry eye, BAK toxicity, and unneutralized hydrogen peroxide. The hyperfluorescence theory states that for most of these conditions what looks like staining is still staining. However, in the case of PHMB-preserved solutions what looks like staining is now hyperfluorescence. Apparently you have to know the cause to differentiate staining from hyperfluorescence.
2) Comfort Evidence
When large numbers of these green spots are observed on the cornea, as seen in red zone combinations on the Staining Grid, the comfort ratings of the subjects are correspondingly decreased by 20 or more points on a 100-point scale (see Comfort Analysis tab of this web site). This comfort decrease is exactly what would be expected as a result of widespread corneal staining and not addressed by the hyperfluorescence theory.
3) Risibility Evidence
The hyperfluorescence theory states that sodium fluorescein has a strong affinity to the PHMB molecule and these PHM/bfluorescein "clumps" stick to the corneal surface mimicking the appearance of solution-induced corneal staining. If this theory were correct one would expect to be able to dislodge most or all of these "molecular clumps" with vigorous irrigation of the corneal surface. To test this, I instilled fluorescein and observed widespread staining on the corneas of several subjects after wearing a non-biocompatible lens/solution combination. Then I vigorously irrigated their corneas using a powerful stream of non-preserved saline for several seconds. When I re-instilled fluorescein the appearance of the staining was identical to what was observed before irrigation. As expected, true staining cannot be irrigated off the cornea.
4) Moisture Loc Staining Evidence
When the Staining Grid was first being published in 2006 a multipurpose solution called Renu With Moisture Loc was being sold. Although this solution was recalled before we were able to complete testing with all lens materials, this 2007 version of the Staining Grid showed that Moisture Loc induced 25% staining area when paired with Acuvue 2 lenses. Interestingly, Moisture Loc contained Alexadine (0.00045%) in place of PHMB as its preservative. According to the "hyperfluorescence theory" small precipitates (resembling staining) occur as a result of the binding of sodium fluorescein with the PHMB molecule. Since Moisture Loc contained no PHMB how could hyperfluorescence still occur?
5) Photographic Evidence
Using our slit lamps (without instilling fluorescein) we have all observed small grayish spots on the surface of the cornea. Then, with subsequent instillation of fluorescein, we see corneal staining in the exact location of the original spots. This demonstrates that moderate to heavy corneal staining can be easily visualized even without the use of sodium fluorescein.
According to the hyperfluorescence theory, small precipitates (resembling staining) occur as a result of the binding of sodium fluorescein with the PHMB molecule. Consequently, if grayish spots are observed in the absence of fluorescein those spots cannot be hyperfluorescence and must be true staining.
As is often the case visual proof provides the most convincing evidence. Shown is the cornea of a patient who had worn Purevision lenses soaked in Walmart multipurpose solution. The photo on the left shows the corneal appearance before the instillation of fluorescein. Numerous small grayish spots can be observed on the surface. The photo on the right shows the same cornea after the instillation of fluorescein.
Since the same spots are observed WITH and WITHOUT fluorescein they cannot be due to hyperfluorescence and must be true staining.
In summary, what looks like ordinary corneal staining and has been called corneal staining by many learned eye care professionals for nearly 20 years is just that...SOLUTION-INDUCED CORNEAL STAINING.
The evidence described here confirms that the hyperfluorescence theory fails to stand up to clinical experience.
If you still have any doubts pull out one of your ocular pathology textbooks and look up corneal "staining".
Now try to look up "hyperfluorescence"!
| Some Questions/Comments Sent to the Web Site - 1/14/2011
Last September we added the biocompatibility results for the new Bausch Lomb multipurpose solution, Biotrue to our website. Over the last 4 months I have received several questions and some interesting comments regarding this new data as well as other biocompatibility-related issues. I'd like to share a few of these as well as my responses.
Q: Will you be testing the biocompatibility of the new Abbott solution, RevitaLens.
A:
Our goal with the Staining Grid is to provide an apple-to-apple comparison for all of the multipurpose solutions available in the U.S. As you can imagine the testing a new MPS with 9 different lens materials utilizing 30 subjects per material is a long and expensive proposition. (We spent 3 solid months testing Biotrue). I have had conversations with Abbott regarding the testing and inclusion of RevitaLens on the Staining Grid but at this point no commitment has been made. If you would like to see RevitaLens on the Staining Grid please share your thoughts with Abbott.
Q: There appears to be a relationship between the staining area observed with Biotrue compared to Renu Fresh for each lens material. Can you comment on that?
A: There is indeed a fairly consistent relationship in the staining area observed with Biotrue and Renu Fresh. As a general rule, for a given lens material Biotrue tends to induce slightly less staining area than Renu Fresh. This chart shows the ratio of Biotrue to Renu Fresh staining area for 6 lens materials in our study. The staining area of Biotrue with the 6 materials averages 68% of the Renu Fresh staining with those same materials. One interesting deviation from this pattern is the lens material, Biofinity, where the staining area was 4 times that found with Renu Fresh (17% vs. 4%).
These results point to a couple of interesting facts regarding the mechanisms of SICS (solution-induced toxicity staining). First, Biotrue contains a 30% greater concentration of PHMB preservative than Renu Fresh (0.00013% vs. 0.00010%) yet it generally stains only about two-thirds as much ... why?
Solution-induced staining is mainly related to the uptake (during overnight soaking); and subsequent release (into the tear film) of the preservative by the lens material. Beyond the preservative itself, all of the ingredients of multipurpose solution formulation (including the wetting/lubricating agents, buffers, etc.) can influence toxicity staining amounts. In the case of Biotrue it appears that the higher concentration of PHMB (compared to Renu Fresh) is possibly counterbalanced by other ingredients in the formulation, possibly the hyaluronan introduced as a lubricant.
Q: I'm curious about your personal opinions as to which disinfecting solutions you actually recommend for your patients. What criteria do you use?
A: Personally, I consider 3 factors in evaluating a disinfecting solution for use with my patients.
First and foremost, the solution must offer adequate disinfection. A few years ago I assumed that if a solution received FDA approval it would offer adequate disinfection. Obviously with the recalls of recent years I've become more skeptical. Unfortunately, as most of us aren't microbiologists, we must rely on outside sources for information to assess the disinfecting abilities of multipurpose solutions. This information is often available as comparative studies from the various manufacturers of these solutions. Personally, beyond that information I look for a long track record of success, with success being defined as a lack of solution recalls or reported infections. Fortunately most of the solutions which have currently been available to us for a few years satisfy this criterion in my mind.
Secondly, once a solution has passed my "disinfection criteria" I look at the biocompatibility of the multipurpose solution with the lenses that I typically use. Basically I look at the Staining Grid.
Finally, I look to see if any of the biocompatible solutions offer superior initial and long-term comfort for my individual patient. As we have all experienced, there is no one solution which offers superior comfort for 100% of our patients. Apparently individual patient factors dictate which solution works well for one patient but not another.
I have found that by using this 3-step system, often times combined with a little experimentation in the third step, that I can usually find an optimal solution for each patient.
| Clinical Research Intersects with Patient Care - 7/7/2009
Medical research, basic and clinical, provides us with insight as to how subjects react when exposed to a situation under tightly controlled conditions. The ultimate goal of this research, however, is to allow us as medical practitioners to better understand and predict how our patients will react under similar circumstances. It was the goal of the Staining Grid study to do just that; predict staining amounts and any resulting discomfort when corneas were exposed to various combinations of lenses and multipurpose solutions.
Since Kelly Ryen and I first published our research and this web site I have received hundreds of comments from eye care practitioners relaying their experiences with solution incompatibility in their own practices. One particularly noteworthy experience was recently published by Debbie S. Murnan, OD in the June 2009 issue of Contact Lens Spectrum (page 50) entitled Corneal Staining: Dry Eye or Something More?
This case is particularly interesting in that it points out many aspects of a solution incompatibility diagnosis including some complicating factors which could have easily resulted in a misdiagnosis. At her annual contact lens exam the patient reported recent onset of dry eyes and blurred vision. The patient was prescribed Proclear lenses and Clear Care solutions. Although Clear Care, when used correctly, is compatible with all materials we have tested the patient admitted that recently she began using a "Wal-mart store brand multipurpose solution." Fortunately at the time of the exam the patient had only worn her lenses for 2 hours. Ocular examination with fluorescein showed significant, diffuse superficial punctuate keratitis in both eyes. Upon refitting the patient with Oasys lenses and prescribing a compatible, branded solution (Replenish) the patient immediately noticed improved comfort, vision and the elimination of dryness symptoms.
Dr. Murnan points out in her article that the Staining Grid predicted 61% staining area (Red Zone) with the patient's habitual lens/solution combination (Proclear/Walmart brand MPS). She switched the patient to a highly compatible combination (Oasys/Replenish) which predicted 5% staining area (Green Zone). The patient's immediate improved wearing experience directly corresponded with the predicted results from the Staining Grid and validates the clinical usefulness of the color coding employed there.
I thank Dr. Murnan for investing the time and effort to publish this interesting and relevant case report. It points out several of the obvious as well as subtle aspects of solution toxicity which we often encounter in clinical practice.
| Staining Mechanisms Confirmed - 9/13/2008
For 3 years we have been investigating and reporting solution-induced corneal staining by systematically testing various popular lens materials with all of the multipurpose solutions available in the U.S. market. The amount of staining observed varies greatly depending upon which lens/solution combination was used. One trend which does not vary is that solutions based upon a PHMB preservative induce larger amounts of staining compared to Polyquad-based solutions. For this reason it has been postulated that the staining observed is a direct result of the type and concentration of preservative in the solution. Now, our most recent testing results have provided further evidence to support this theory.
We have just finished testing Renu (Original) MultiPurpose solution which is still available in the U.S. market. This solution, originally introduced in the early 1990's, lists its preservative as 0.00005% Dymed (polyaminopropyl biguanide). This is exactly one-half the concentration of preservative found in Renu MultiPlus solution (0.0001% Dymed). If Dymed is the main cause of solution-induced staining then Renu MultiPurpose should consistently induce less staining than Renu MultiPlus.
Inspection of the Staining Grid shows that this trend consistently holds true. Interestingly, the Renu Multipurpose-induced staining area is often about half of that found with MultiPlus. This chart shows the ratio of MultiPurpose/Multiplus staining area for each lens brand tested (with the exception of Acuvue 2 showing negligible staining). The MultiPurpose/Multiplus staining ratio ranges from 29% to 59% and averages 44%.
Two other areas of the web site also provide useful information. The Comfort Analysis tab shows information about the overall effect of staining on subjective comfort. The Photo Gallery tab displays (in the slide show) a series of staining photos of many of the combinations tested. Clicking through this slide show will give you an idea of the appearance and extent of solution toxicity staining. If you want to receive free email updates when significant additions are made to the web site go to the Contact/Updates tab and fill in our name and email address in the form.
These results confirm that Dymed plays a significant role in solution-induced staining and highlights two interesting facts. One, solution-induced corneal staining follows the typical dose-response curve found throughout pharmacology. Two, the staining area measured in a controlled clinical study with a reasonable sample size (n=30) correlates highly with the solution preservative concentration.
| Setting the Record Straight - 3/6/2008
This blog is long overdue. There has much written and spoken concerning our study over the last couple of years. Most has been accurate, but some not. In this blog I want to set the record straight concerning our study design, the results and even the consequences of solution-induced staining. I've listed 9 common misstatements or points of confusion and articulated what I hope is a common sense, clinically sound response. Throughout the blog I've placed hyperlinks referencing facts and study results, not just opinions. Also, especially relevant statements have been italicized for emphasis.
1) The vast majority of patients, even non-CL wearers, exhibit corneal staining.
This argument has been frequently proposed as proof that staining is "natural phenomenon" and is therefore not important. The answer lies in quantity.
Let's consider what is meant by "STAINING". At our baseline examination we examine all subjects who have abstained from lens wear for at least 12 hours. Within this group I often see some staining, typically a few dots. An analysis of our baseline data shows that the average population of subjects entering our study shows 0.6% staining area. Of course, this level of staining spread over an entire corneal is barely noticeable and most likely clinically insignificant, yet in the above argument it is still staining.
Our study shows that solution-induced staining can vary widely, ranging from a few insignificant dots to many thousands of dots spread densely over the cornea. For this reason on the Staining Grid we chose to report, not only the presence or absence of staining, but the amount of staining (i.e., percentage of corneal area covered with staining). Beyond that, the Staining Grid is color-coded so the user can easily identify which lens/solution combinations are inducing moderate (yellow) and high (red) amounts of staining. Finally, the web site includes photos of actual stained corneas observed in our study allowing the readers to apply their own criteria of clinical significance. While I agree that most people will exhibit a few dots of staining it is the goal of our study to identify cases where staining is severe enough to be a clinical concern.
2) Most staining is grade 1, micropunctate, and therefore clinically insignificant.
This statement tries to equate 3 different terms commonly used in ophthalmic practice; "grade 1", "micropunctate", and "clinically insignificant". Let's discuss each term.
The confusion starts with the term "Grade 1" which really has two meanings. To the eye care practitioner Grade 1 is a loosely used term to imply a condition which is minor, irrelevant and insignificant. On the other hand to researchers (including us) and the FDA Grade 1 denotes a type of staining, in this case "micropunctate" (i.e., individual dots). It says nothing about the quantity of that staining. These two, very different meanings of Grade 1 can create confusion. These photos from our study show that micropunctate (i.e., individual dots) staining can be either clinically insignificant or extremely significant depending upon the quantity of that staining. Again, that is why we report the quantity (i.e., staining area) versus a more simple, yet more confusing "Grade x" scale on the Staining Grid.
3) Solution-induced staining is asymptomatic and therefore not important.
Some (not all) early published reports of solution-induced staining described it as "asymptomatic". Our research has shown that low to moderate amounts of staining (i.e., less than 20% corneal area) are relatively asymptomatic, due in part to the bandage lens-effect. However, as staining becomes more widespread across the cornea subjective irritation is nearly universally experienced. This is conclusively shown in a chart of staining area versus subjective comfort. The trend line shows that, in general, as staining area (X-axis) increases subject comfort ratings (Y-axis) decreases. This difference is often more than 20 point (on a 100-point scale) for heavy staining.
4) Solution-induced staining is transient and therefore not important.
Fortunately, it is correct that the solution-induced staining which we observe is transient. But if you think about it, all staining eventually resolves. The real issue lies in the frequency of this staining and the time required for resolution.
We have measured this time to resolution over a 12-hour wearing period for one highly staining lens/solution combination, Renu Multiplus and Purevision. An analysis of staining area over time shows that staining peaks 2 hours after lens insertion and then begins to gradually resolve. However, the staining remains statistically greater than saline-induced staining for 12 hours. More clinically relevant is that fact that Renu/Purevision staining remains at or above 10% staining area for approximately 7 hours EACH DAY.
5) Solution-induced staining has not been definitely proven to be a direct risk factor in microbial keratitis and therefore is not important.
It is correct that there has been no definitive, peer-reviewed study proving that solution-induced staining directly increases the risk of corneal infection. On the other hand there has been no study showing that it doesn't. Realistically, there will probably never be such a prospective study since infection rates are so low (i.e., a few cases per 100,000 wearers per year) that a prohibitively large study would be required.
With our admittedly incomplete knowledge of the risk factors and mechanisms for corneal infection we, as highly trained professionals, are therefore required to rely on our ophthalmic education, clinical experiences, textbooks on corneal pathology, and common sense in determining how we view staining in the scheme of maintaining ocular health. Keep in mind that GPC, contact lens-induced dry eye, conjunctival injection, and excessive 3 to 9 o'clock staining are all conditions which do not appear to increase the risk for infections yet we try to minimize them whenever possible. How is solution-induced staining different?
6) Staining measured at 2 and 4 hours after lens insertion does not reflect long-term results.
Our study and several others have conclusively shown that solution-induced staining peaks around 2-hours after lens insertion. This early day timing is not surprising since the mechanism of this staining is irritation from preservatives released from the lens after overnight soaking. Previous published research by Jones (see Table 2) has shown that solution-induced staining is similar at day 1and day 14. Therefore, we chose to measure staining early in the wearing period and report 2-hour results on the Staining Grid.
Recently, a study was published by the Institute for Eye Research (IER) looking at staining induced by 16 lens/solution combinations used for 3 months. In the scatter plot comparison of the IER study with our study the relatively close alignment of the points to the trend line indicates that their study results correlate highly with ours. Based upon studies by both Jones and the IER group it has now been conclusively established that staining observed after 2-hour on the first day of lens wear is an excellent predictor of long-terms staining results.
7) Our study (sample size) is too small to be meaningful.
It has been occasionally misstated that our study includes 30 subjects. In reality our study tests 30 subjects for EACH lens/solution combination. To date, a total of 2,807 non-unique subjects have been tested over a 2-year period. Very few ocular studies include a sample size this large.
8) Our study population represents a cross-section of a typical practice.
At first glance one would think that a study of over 2,000 subjects would represent a good cross-section of a typical clinical practice. However, due to restrictions of the Institutional Review Board (IRB) which oversees our study, subjects experiencing several relatively common conditions must be excluded. Some of these conditions include:
a) baseline staining in two or more corneal regions
b) macropunctate staining anywhere on the cornea
c) active and/or clinically significant anterior segment conditions including dry eye, ocular allergies, GPC, conjunctival injection, blepharitis, iritis, etc.
d) hypersensitivity to any components of a multipurpose solution
e) evidence of active viral or bacterial infections
f) functionally monocular subjects
g) pregnant for lactating subjects
h) diabetic subjects.
Therefore, our subject population is indicative of the "healthiest" subset of patients in your practice. Due to these IRB restrictions our results probably represent a best case scenario of staining results. In clinical practice you do not have the luxury of pre-screening and excluding high-risk patients.
9) Bausch & Lomb sued Dr. Andrasko over this study.
In 2007 Bausch & Lomb sued Alcon Laboratories over their interpretation of our study results in their promotional materials. One of the main points of contention was the particular colors used to denote high amounts of staining. Alcon and B & L eventually settled the suit. For details of lawsuit and settlement.
I have not been sued over our study or its results. On our web site and in my lectures and writings I am careful to base any conclusions on results from either our study or other peer-reviewed publications. Eye care practitioners should consider our study results as well as the totality of their clinical experiences when prescribing an appropriate lens care products for each patient.
There will undoubted be more written concerning our study debating both sides of the issues. However, I hope that this admittedly lengthy blog will serve as reference conveying the facts about our study and a common sense approach to apply them.
| Greetings and Happy Holidays - 12/9/2007
It's been about 2 years since we began testing the biocompatibility of various lens/solution combinations. This web site just passed a milestone, 75,000 hits. We have just completed testing of the "relaunched" Complete MPS® Easy Rub. To-date we've tested 94 different combinations. More testing is planned for 2008.
Excluding saline and the recalled solutions, 67% of the combinations fell in the Green zone (<10% staining area), 11% fell in the Yellow zone (10% - 20% staining area), and 22% in the Red zone (>20% staining area). By observing the amount of green on the Staining Grid it is obvious that there are plenty of biocompatible choices available. My hope for the future is that the next generation of multipurpose solutions will entirely fall within the Green zone. We're already seeing that trend with AMO's recently launched Complete® EZ Rub solution showing better biocompatibility than its recalled predecessor.
At a recent seminar I presented our study results and was then followed by a speaker who mentioned that our work was "obviously suspect" since it was mainly sponsored by one company. That brings up an interesting question for discussion... In general, should industry-sponsored research be trusted?
In my opinion the short answer is... Yes, but understand all the variables. Over 27 years of performing industry-sponsored contact lens research I'm happy to report that I've never been asked to manufacture, skew, or in any way influence results of a study to make a product look favorable. However, each eye care practitioner should understand how industry-sponsored research works. When a company suspects that one of their products is superior in some area to its competitor's it commissions a study using "independent" (non-company employee) researchers. (Who would believe research done by company employees?) If the company's theory is true and the research is done correctly it will likely show the suspected results. (Sometimes it doesn't possibly because the original hypothesis was wrong, the research was not done correctly, or the effect was too small given the sample size.)
Should you believe industry-sponsored research? That is a question each reader needs to answer for themselves on a case-by-case basis. Here is how I analyze all research results:
1) First and most important.....Listen to comments from industry (both pro and con) while understanding their agenda. Each company wants to sell their products...period! Their comments and opinions of the research typically reflect how their own products performed in the study. Examples from our study
2) Evaluate the credibility of the researchers. What is their research background? How long have they done clinical research? Was their previous work credible? Relevance to our study
3) Evaluate the study design. Did it follow the accepted principles of good study design including (double) masking, randomization, adequate sample size, etc. Relevance to our study
4) Evaluate the results for yourself. Do they seem consistent with your own clinical experiences? Can you duplicate the results, even on a smaller scale, in your practice? An easy demonstration
5) Have similar results been previously shown? List of previous staining literature
6) Are the results clinically relevant in your practice? An improvement in comfort ratings of 3 points (on a 100-point scale) may be statistically significant but not clinically relevant. Clinical relevance explanation
7) Do the researchers offer a credible explanation for the results? Do the results and explanation make sense based upon of your knowledge of the topic? Explanation of staining mechanisms
8) Discuss the research with your colleagues. What is their "take" on the results? Are they arriving at similar conclusions as you?
I encourage you to scrutinize all research, including ours, following these simple principles. Hopefully our research has made your task as a contact lens fitter a little easier. Your input to our web site via the Contact Us page is always welcomed.
| Staining From "Down Under" - 9/23/2007
I want to bring your attention to an article on Solution-Induced Corneal Staining (SICS) published in the September 2007 issue of Contact Lens Spectrum. This article by 8 prominent researchers from the prestigious Institute for Eye Research (IER) in Australia reports on corneal staining found in 16 lens/solution combinations. The main differences between the IER study and ours are the time in which subjects wore lenses and the outcome reported. Our study looks for staining during the first day the lens/solution combination is worn. The IER study looks at staining various times during a 3-month wearing period. Another notable difference is that the IER study measures the percent of subjects experiencing solution-induced staining while ours reports average corneal staining area for each combination tested. Other differences including masking, control solution, criteria for color coding, the time of day subjects were examined and number of observers are summarized in a comparison table.
Even noting these many differences between the two studies the results are amazing similar. The peroxide solution tested in both studies induces very little staining.The multipurpose solutions tested in the IER study (Aquify, Opti-free Express, and Opti-free Replenish) induce various degrees of relatively low staining depending upon which lens they are paired.
Since the IER study reports percent of subjects while our study reports staining area the results of these two studies cannot be compared directly. In order to determine if our 2-hour staining observations correlate with the IER long-term (3 month) staining results I preformed a data conversion and analysis of our data. For the 16 combinations tested by IER I calculated the percent of subjects showing either yellow or red zone staining from our study. (This information is readily available on the "details page" of each combination by clicking on the percentage shown in any cell of the grid.) I then plotted the IER results versus our results for each of these 16 combinations.
In a scatter plot when the points are aligned close to a trend line then the two studies are highly correlated. In the scatter plot comparison of the IER study with our study the relatively close alignment of the points to the trend line indicates that staining observed at 2 hours after insertion on the first day of lens wear (our study) is highly predictive of long-term staining results (IER study). The abilixty of 2 hour staining observations to predict longer term staining results was also shown in a recent study by Jones, et al entitled, "The Impact Of Post-Insertion Time On Corneal Staining And Comfort With Group II Hydrogel Materials Disinfected With Various Lens Care Regimens". My sincere thanks to the researchers of the IER and (all study sponsors) for undertaking such a demanding and extensive study.
| Color Coding Explained - 7/6/2007
I've just returned from the AOA Congress. Upon speaking with many practitioners I was struck by a couple of things. Nearly every practicing optometrist (as opposed to industry-based optometrists) commented that the Staining Grid was a very useful tool in their practice. Many told me that it is bookmarked on their computer and they routinely show it to patients to emphasize compliance. As you might expect, industry-based optometrists are either the biggest advocates or the biggest critics of the Staining Grid depending on which company they work for...No surprise there! One topic which has been somewhat misunderstood is the origin and meaning of the green-yellow-red color coding employed on the Staining Grid.
Why color-code the Staining Grid?
There were essentially two purposes for using a color coded instead of a black-and-white grid. First, color allows the user to quickly determine how a particular lens/solution combination fares compared to other combinations tested. Secondly, the color coding reveals patterns in the amount of staining area observed across the grid. For example, Polyquad and peroxide-based solutions staining typically stain less than biguanide-based (PHMB) solutions. Another pattern is that surface-treated silicone/hydrogel lenses tend to staining more than non-surface-treated ones. These trends would not be as evident simply by looking at a table of numbers.
How were the color-coding ranges determined?
In the 29 years since graduation from optometry school I've been an instructor in the contact lens clinic at OSU, director of that clinic for a few years, and director of a contact lens research practice for the last 17 years. Over my career I've observed the corneas of tens of thousands of hydrogel lens wearers. The color coding employed on the Staining Grid is a general observation of staining severity based upon the totality of my teaching, practice and research experiences.
How is the color-coding relevant to the needs of your individual patients?
The color coding on the web site represents a starting point for assessing the various degrees of staining area for each lens/solution combination. The actual percentage of staining area for each combination is also displayed. Using this information the eye care practitioner should determine the clinical significance of various levels of corneal staining for their patients based upon the consideration of individual factors. Just as 120/80 is considered an overall guideline for blood pressure, most physicians would apply a different standard for a healthy 16-year old boy versus an 85-year old diabetic man with pre-existing vascular pathology. The same is true for staining. The Staining Grid provides initial guidelines. You, as the eye care practitioner legally and ethically responsible for rendering eye care services, should apply your own "mental color coding" for each individual patient after considering several factors such as general ocular health, lens care compliance history, wearing schedules, and other pertinent risk factors.
| BCLA Buzz - 6/17/2007
I've recently returned from the British Contact Lens Association (BCLA) meeting in Manchester, UK. This is reported to be the largest meeting in the world focusing only on contact lenses. Not surprisingly the hot topic was the recent recall of AMO Complete MoisturePlus solution and its link to a disproportionate number of acanthamoeba infections. Several questions and themes tended to recur in the various lectures. Are other multipurpose solutions going to be implicated? Is No Rub really a good idea? Should all patients be switched to a hydrogen peroxide-based disinfection system? What can practitioners do to protect their patients from all types of microbial keratitis? Based on what I have come to understand here are some answers to these questions.
Are other multipurpose solutions going to be implicated?
As of this time the U.S. Center for Disease Control and Prevention (CDC) has not released any evidence that other multipurpose solutions are deficient in their ability to control acanthamoeba. In their update of June 8, 2007 they state, The preliminary analysis of the reported use of other brands of contact lens solution did not reveal any significant associations.
Is No Rub really a good idea?
No Rub method of lens care was an interesting experiment. Results of several studies indicate that rubbing and rinsing the contact lens before storage effectively removes several log units of microorganisms from the lens surface. The remaining bugs are then effectively killed by the disinfecting solution. Based upon what we know today Rub and Rinse should undoubtedly be the standard.
Should all patients be switched to a hydrogen peroxide-based disinfection system?
Hydrogen peroxide is effective against acanthamoeba if the disinfecting solution is at full strength for a 4-hour soak. Current one-step systems begin to neutralize immediately upon contact with the disk. A two-step system where the patient delays inserting a neutralizing tablet for at least 4 hours would be ideal but probably not practical based upon the history of dubious patient compliance.
What can practitioners do to protect their patients from all types of microbial keratitis?
In short there are no procedures or lens care regimens which offer 100% assurance that a patient won't suffer a microbial infection. As with all aspects of medicine we are limited to minimizing the risk factors, both known and suspected. Review and emphasize with patients the necessity of strict adherence to all cleaning and disinfecting instructions. Also review the importance of hand washing, sticking to the prescribed wearing schedule (i.e., daily wear, flexible wear, etc.) and other known risk factors such as smoking and ocular exposure to contaminated water supplies. Finally, carefully examine contact lens wearers for corneal staining, infiltrates, chronic hyperemia, and tear film deficiencies.
The surprising infections and recalls of the last two years indicate there is still much we don't understand concerning contact lens care and effective disinfection. It is more crucial than ever that we adopt a cautious and conservative approach to lens care. Minimizing all risk factors, staining being an obvious one, is essential to maintaining happy, healthy patients.
| More Evidence - 5/12/2007
A new web site was recently launched, www.StainingGrid-Japan.com. Dr. Itoi, a highly respected Japanese ophthalmologist and researcher, has published his own lens/solution biocompatibility research. He has tested 3 lens materials (O2 Optix, Acuvue Advance, Acuvue Oasys) with 8 multipurpose solutions available in Japan. He tests 15 subjects for each combination and reports a score representing Staining Area X Density. He also codes his results using the same colors as we use but adds BLUE representing very low, saline-like staining. The third tab on his site shows his actual staining grid.
Where identical products have been tested, Dr. Itoi's results basically mirror ours. The hydrogen peroxide solutions (Clear Care on our site, AOSept on his) induces very little staining with all lenses. The Optifree product which he tests (essentially Optifree Replenish without Aldox) also induces very little staining. The various PHMB (biguanide) results, like ours, show a range of staining.
With all due respect to Dr. Itoi, you may be reading this and thinking, "So what?" The true test of the validity of any research is whether it can be duplicated by independent researchers. Dr. Itoi's work was done on a different continent using a slightly different grading metric. Despite these differences the bottom line is...Where similar products were tested, similar results were found. Dr. Itoi and I may occasionally differ in a red or yellow zone (his color coding is stricter than mine) but the overall trends are very consistent.
Dr. Itoi's excellent work is the third independent study showing similar lens/solution biocompatibility results. (A paper entitled, Evaluation of Solution Toxicity with Lens Care Products During Silicone Hydrogel Lens Wear by Tilia, Jalbert, Keay, Naduvilath, Wilcox, Holden, Papas, and Carnt presented at the 2006 American Acad. Of Optometry was the second study.) It's becoming increasingly difficult for the few (companies) denying that solution-toxicity staining really exists to maintain credibility. Should solution manufacturers step up and actively warn users (practitioners and wearers) when significant red zone staining exists with their product and a particular lens?
| Scales, Scales, Scales! - 4/10/2007
In the last couple of months two articles have been published in Contact Lens Spectrum discussing our study and the specifics of the grading scales which we use. Not surprisingly both articles were either written or funded by solution manufacturers whose products induce various degrees of corneal staining with some lens materials.
In the first article (written based upon a grant from Bausch & Lomb, manufacturer of Renu Multiplus) Dr. Milton Hom proposes some unlikely scenarios. In one example he concludes that the location of staining on the cornea affects our final grading amount. He also states that 29 dots of staining would be graded completely differently than 30 dots. For the record, neither of these statements are true. Surprisingly, Dr. Hom has never asked me about the specifics of our grading scale criteria or if his assumptions were actually true. Even more interesting is Dr. Hom's attempt to divert attention to cases of insignificant staining (i.e., 30 dots) while leaving the real problem unmentioned.
In a second, more balanced article Drs. Lasswell, Huth, and Tran, all employees of AMO (manufacturer of Complete MoisturePlus), discuss the various corneal staining grading scales available to researchers. They correctly point out that our study uses a modified version of the CCLRU scale. Since the vast majority of solution-toxicity staining is micropunctate (type) and superficial epithelial (depth) we chosen to make this modification to better focus on staining AREA. Dr. Lasswell also correctly illustrates one of the major strengths of our study design. With only one observer throughout the entire study we eliminate all inter-observer variability, a major source of error in other studies.
Dr. Lasswell does point out one apparent inconsistency in our study which bears explanation. The first published version of the Staining Grid (April 2006) was based upon a pilot study with a sample size of 9-14 for each lens/solution combination. We quickly realized the significance of our work and decided, at major cost and time commitment, to redo the entire study using a sample size of 30 subjects per cell. Today's Staining Grid is completely based on that larger sample size, thus providing confidence in the results of each lens/solution combination tested. As we switched from the pilot study to the final study results some lens/solution staining area results changed slightly. For example, Purevision/Optifree Express changed from 6% to 4%, still insignificant staining.
Both articles cite studies showing little or no staining with use of their own multipurpose solution - an apparent contradiction to our results. How can this discrepancy be explained? The answer lies in the time of day which the subjects were examined for corneal staining. Solution toxicity-induced staining peaks at or soon after lens insertion. For this reason subjects in our study were examined after 2 and 4 hours of lens wear, thus ensuring that staining, if present, would be detected. Results of our 12-hour study show that corneal heal commences soon after the initial insult and, even in cases of severe staining, is nearly complete by the end of the wearing period. On the other hand studies, like the ones cited by Dr. Hom and Lasswell, which recommend corneal examination near the end of the wearing period, are not likely to detect solution-induced staining. This does NOT mean that staining was absent during most of the wearing period. Bottom line...when a study is presented as evidence of lack of solution toxicity staining be sure to ask WHEN the subjects were examined.
I am truly impressed that the Staining Grid study has attracted so much attention, even spurring back-to-back publications. Soon I'll be discussing another staining grid-like study carried out on another continent. Stay tuned.
| An Exciting Year - 3/25/2007
It's been about a year since we first displayed our Staining Grid research during a poster session at ARVO. A lot has happened during that year. Poster sessions were also presented at AOA Congress (Las Vegas), BCLA (UK), AAO (Denver), and ARVO-Asia (Singapore). In addition this information has been presented by various speakers literally hundreds of times around the world. In March 2007 an article on our Staining Grid study was published in Review of Cornea & Contact Lenses. Sensing the enthusiasm which practitioners embraced our ongoing lens/solution compatibility research we decided to post the results on a web site for immediate access to practitioners around the world. Finally, the FDA is reassessing what criteria should be examined when approving multipurpose solution (MPS) products to be used with silicone hydrogel lenses.
Our work has also had many consequences. It's not surprising that several lens and solution manufacturers have pointed to our work as confirmation of the universal compatibility of their products. One company has continuously questioned our methodology, scales, and reliability in lectures and published articles...again not surprising. The consequence which I most like to hear is when a practitioner relates a story about a patient experiencing staining and symptoms which were solved by consulting the Staining Grid. I've heard dozens of those over the year.
My prediction for the future is this. Within the next one or two generations of MPS products we will be able to close this web site. By then all eye care practitioners will be aware of the issue and will favor using those products which offer the broadest biocompatibility. Sensing this (and the corresponding effect on sales of specific MPS) lens care manufacturers will have engineered ocular biocompatibility into all new products. Your voices will have been heard and another significant risk factor for patients will have been eliminated through sound scientific technique!
| Tricks and tips for using the web site - 3/18/2007
If you are a new or infrequent visitor to this web site please allow me to share some tips to maximize your experiences here. Obviously the initial page contains the Staining Grid which is fairly self explanatory. Only comments here are that each cell shows the average corneal AREA of staining found in a sample of 30 subjects tested in our study. It's NOT the percent of patients showing staining as some people mistakenly think. A lower number represents a more compatible lens/solution combination.
Clicking on any of the percentages within a cell opens what I call the details page. This page gives specific information about the selected lens/solution combination. The top of a detail page shows basic information about the lens and solution. The middle section shows the average staining area and its standard deviation. Next is a breakdown of the percentage of subjects in our study falling into each of the 3 staining zones (green=less than 10%, yellow=10-20%, red=greater than 20% staining area). This is useful in allowing you to predict how your patients might fare using the combination in question. Average comfort information (on a 100-point scale) of the lens/solution combination as well as averages of all lenses using this solution and all solutions using this lens is shown next. Finally, a representative staining photo from a subject in our study is shown, if available.
Other useful information on the web site is included under the FAQ and Learn More tabs. Check them frequently as we often add new info there. For example we recently completed a study measuring staining of one combination over 12 hours. This information is shown in the 12-hour study submenu under the Learn More tab. Also 3 short videos explaining various aspects of the web site are included in the Tutorials submenu.
Two other areas of the web site also provide useful information. The Comfort Analysis tab shows information about the overall effect of staining on subjective comfort. The Photo Gallery tab displays (in the slide show) a series of staining photos of many of the combinations tested. Clicking through this slide show will give you an idea of the appearance and extent of solution toxicity staining. If you want to receive free email updates when significant additions are made to the web site go to the Contact/Updates tab and fill in our name and email address in the form.
Since the staining grid study is an ongoing project this web site is constantly evolving and growing. Feel free to snoop around at your leisure.
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