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
click here.
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.