STAINING AND COMFORT
Solution-Induced Staining and Comfort During Lens Wear
Learn how controlling solution-induced staining can benefit your patients.
By Gary Andrasko, OD, MS
Dr. Andrasko is the director of a private contact lens clinical research practice in Columbus, Ohio. His interests include hydrogel lens end-of-day comfort and dryness, corneal physiological response to hydrogel solutions, and solution biocompatibility with various silicone hydrogel materials. He is also the publisher of the www.StainingGrid.com Web site.
Over the last two decades there have been many anecdotal and published reports of moderate to severe corneal staining (Figure 1) occurring when some hydrogel lenses and multipurpose solutions are used together. In one of the earliest reports, Jones et al (1997) described moderate to severe corneal staining when a PHMB-based multipurpose solution was used with the PureVision (Bausch & Lomb) lens.
Figure 1. Micropunctate and coalesced corneal staining observed after two hours of lens wear using an incompatible multipurpose solution.
Over the next decade, many additional reports documented clinically significant corneal staining with various combinations of hydrogel and silicone hydrogel lens materials and multipurpose solutions. These studies were undertaken by several different investigators using various corneal staining grading methods and scales.
In 2005, with the hope of standardizing the measurement of this staining and providing a broad snapshot of which lens/solution combinations offer less-than-optimal compatibility, we began systematically testing each FDA-approved multipurpose solution with all of the available silicone hydrogel materials and some select traditional hydrogel materials in what has become known as the "Staining Grid study."
While the existence of solution-induced staining is universally accepted, the exact consequences of this staining are still under investigation. Whether solution-induced keratitis causes measurable discomfort during lens wear has been debated in several previous publications with mixed conclusions. Lebow et al (2003) looked at staining and comfort preferences among Opti-Free Express (Alcon), Complete MPS (Advanced Medical Optics) and ReNu MultiPlus (Bausch & Lomb) with Acuvue 2 (Vistakon) and SofLens 66 (B&L) lenses. They concluded that "subjects experiencing significant corneal staining perceived (comfort) differences between the solutions tested."
On the other hand, Jones et al (2002) found no significant differences in comfort ratings between various lens care products but did find a significant difference (p<0.008) in "stinging on insertion." Garofalo et al (2005) failed to find significant differences in comfort or subjective symptoms with multipurpose solutions when used with some group II and group IV lenses.
This article will examine the relationship between staining and comfort, using data collected during the Staining Grid study whose most up-to-date results are available at www.StainingGrid.com.
The Staining Grid Study
The Staining Grid study is a series of randomized, double-masked, crossover studies in which investigators graded corneal staining type and area at a baseline visit before which subjects had abstained from lens wear for at least 12 hours. Investigators then applied lenses that had been presoaked overnight in various multipurpose solutions (or in saline as a control) to research subjects. After two hours of lens wear, investigators removed the lenses and evaluated corneal staining using sodium fluorescein in combination with a cobalt and Wratten #12 (yellow) filter. The lenses were then reapplied and worn for two additional hours, and upon removal investigators repeated the same grading procedure.
An ethics committee approved the Staining Grid study, and all subjects signed an informed consent in accordance with the Declaration of Helsinki. The staining results, based upon 30 subjects for each lens/solution combination tested, were averaged and reported in a previous publication.
The Staining Grid study also examined subjective comfort. Each subject rated comfort using a 100-point visual analog scale at 10 minutes after initial lens application and just prior to lens removal for the staining evaluations at two hours and four hours post-lens application. The labels anchoring the comfort scale were: 100 = excellent (lens cannot be felt); 80 = very comfortable (just felt occasionally); 60 = comfortable (noticeable but not irritating); 40 = slightly uncomfortable (just irritating or annoying); 20 = very uncomfortable (very irritating or annoying); 0 = causes pain.
The data reported in this article come from 35 individual studies making up the Staining Grid study, each of which examined one of eight different lenses and from two to five different solutions. Overall, 10 multipurpose solutions, plus saline, were examined. These 35 sequentially conducted studies involved 155 different subjects, with most subjects participating in multiple individual studies, producing 3,223 subject evaluations. The primary purpose of these studies was to examine the effects of lens/solution combinations on staining and comfort. The randomized, double-masked, crossover design, with subjects participating in multiple studies, is appropriate for that research question. However, this article examines the correlation between staining and comfort, and we can't use the statistical tools of correlation or regression with the entire data set, as these techniques require independence among the data points.
Examining Staining and Comfort
One way to ensure independence is to randomly select one set of data points (staining and comfort scores at baseline and after two and four hours of lens wear) for each subject. We applied this procedure to the larger data set after eliminating all data involving the control solution — saline — which is not a multipurpose solution. The lenses and solutions that are represented in this reduced data set were determined by this random selection procedure and mirror the distribution in the larger data set.
We can address the central question of this article — the relationship between staining and comfort — by examining the correlations among these measures within the reduced data set (n = 155) described above. The results show that staining and comfort are not correlated at baseline (staining assessed prior to lens application and comfort assessed 10 minutes after application), as the Pearson correlation is –0.04 (not significant). However, after two hours of wear staining and comfort are significantly correlated (r = –0.43, p<0.001) and after four hours the correlation increases to –0.56 (p<0.001). The conclusion is straight-forward: Across a variety of lenses and solutions, under controlled laboratory conditions and using standard measures, staining and comfort are moderately to strongly correlated. Those subjects who experienced more staining also experienced more discomfort.
The results of the Staining Grid studies show that the choice of lens and solution (and the combination of the two) may affect staining. This leads to the question: Do lenses and solutions affect the relationship between staining and comfort? Given the number of lenses (eight) and solutions (10) represented in these data, we decided to divide both lenses and solutions into two groups: those producing a below-average level of staining and those leading to an above-average level.
Based on the data from the entire Staining Grid, across the solutions tested, four lenses produced below-average staining (Acuvue 2, Acuvue Advance [Vistakon], Acuvue Oasys [Vistakon], Biofinity [CooperVision]) and four produced above-average staining (Proclear [CooperVision], PureVision, O2Optix [CIBA Vision], Night & Day [CIBA]). Separating the reduced sample of 155 into these two groups produced a low-staining lens group (n = 82, mean two-hour staining area = 4.80 percent) and a high-staining lens group (n = 73, mean two-hour staining area = 21.84 percent).
Following the same procedure for solutions led to a below-average solution staining group (Clear Care [CIBA], Opti-Free Express, Opti-Free Replenish [Alcon], Complete Multi-Purpose Solution Easy Rub Formula [AMO], Aquify [CIBA]; n = 98, mean two-hour staining area = 3.78 percent) and an above-average staining group (ReNu MultiPlus, Wal-Mart MPS, Target MPS, Complete Moisture Plus [AMO]; n = 57, mean two-hour staining area = 28.39 percent).
First, what are the effects of lenses on the relationship between staining and comfort? Within the high-staining lens group, the correlation between these two outcomes at two hours is –0.42 (p<0.001) and at four hours is –0.58 (p<0.001). However, among the low-staining lens subjects, there is no significant relationship between staining and comfort (r = –0.05 at two hours and r = –0.15 at four hours). So it seems that when the choice of lens produces above-average staining, then staining and comfort are related. But when the lens produces below-average staining, these two outcomes are unrelated.
Next, what are the effects of solutions on the relationship between staining and comfort? Within the high-staining solution group, the correlation between these two outcomes at two hours is –0.54 (p<0.001) and at four hours is –0.58 (p<0.001). However, among the low-staining solution subjects, there is no significant relationship between staining and comfort at two hours (r = –0.10) and a low, but statistically significant correlation at four hours (r = –0.22, p<0.05). As was the case for lenses, when the choice of solution produces above-average staining, staining and comfort are related. But when the solution produces below-average staining, these two outcomes are correlated at a much lower level.
Finally, what are the joint effects of lens and solution on the relationship between staining and comfort? Crossing the high- and low-staining lens groups with the high- and low-staining solution groups produces four subgroups: Low solution/low lens (n = 54); low solution/high lens (n = 44); high solution/low lens (n = 28); high solution/high lens (n = 29). When both lens-induced staining and solution-induced staining are below average, there is no correlation between staining and comfort (r = –0.10 at two hours and r = –0.26 at four hours). However, when the high lens/low solution, high solution/low lens and high solution/high lens groups are combined, the staining and comfort are significantly related (r = –0.42, p<0.001, at two hours and r = –0.56, p<0.001, at four hours). The conclusion here is that staining and comfort are not related when a low-staining lens is combined with a low-staining solution. However, these two outcomes are significantly related when either lenses or solutions (or both) produce an above-average level of staining. In other words, when a high amount of staining occurs, subjective wearing comfort may be subsequently decreased.
This analysis of the subjective comfort responses in the Staining Grid study demonstrates that reduced comfort significantly correlates with widespread solution-induced staining. Previous work has shown that the comfort reduction is most pronounced when staining is at its peak early in the patient's wearing period. Previous studies have also found mixed results when attempting to correlate staining and discomfort, possibly due to a failure to elicit comfort responses at the time of peak staining. However, the Staining Grid study elicited comfort ratings during the period of peak staining and found a highly statistically significant correlation between lens/solution-induced staining and reduced wearing comfort. CLS
Disclaimer: The Staining Grid study was primarily sponsored by Alcon Research Laboratories, Inc. with a supplemental grant from CooperVision. The author is the director of a private research practice that undertakes fee-for-service clinical investigations sponsored by various contact lens and solution manufacturers. The author is not a paid consultant to any company in the ophthalmic industry.
For references, please visit www.clspectrum.com/references.asp and click on document #154.