Article Date: 9/1/2011

Clinical Trial Experience with Opti-Free PureMoist MPDS
CLINICAL TRIALS

Clinical Trial Experience with Opti-Free PureMoist MPDS

The new solution was evaluated in two randomized, double-masked, clinical trials with 1,164 patients.

By Renee Garofalo, OD, FAAO and Jessie Lemp, MS

The Opti-Free PureMoist MPDS formulation (Alcon) was specifically designed to improve the wettability of silicone hydrogel and traditional hydrogel lenses. It has proven to be compatible with all soft contact lens materials tested and to be active against microorganisms defined by FDA and ISO standards. Following these important development steps, the new product was introduced to contact lens-wearing patients in the context of clinical trials. Here, we review the main clinical results gathered to date from two large clinical trials involving more than 1,100 contact lens-wearing patients, with a special emphasis on subjective assessments of comfort and moisture, removal of protein deposits and the maintenance of corneal integrity as evidenced by minimized corneal staining.1-3

Study Design and Methods

Some contact lens wearers may present with various complaints of discomfort associated with the use of contact lenses (symptomatic subjects), while others are generally satisfied with their overall experience. Patients who continually suffer with discomfort are more likely to drop out of contact lens wear.4 To fully investigate the range of clinical experiences, one study enrolled healthy contact lens wearers (study 1), while the other study enrolled symptomatic wearers (study 2). Ideally, new products should offer improvements over currently available products. The purpose of each of the trials was to evaluate the safety and efficacy of Opti-Free PureMoist MPDS compared to Renu Fresh multipurpose lens care solution (Bausch + Lomb). For both studies, protocols were approved by Institutional Review Boards (IRBs) and subjects completed informed consent.

In study 1, 573 subjects at 30 clinical practices participated in a 90-day, double-masked study. Subjects wearing one of six selected silicone hydrogel or soft lens brands (Acuvue Oasys, Air Optix, Biofinity, PureVision, Acuvue 2, Soflens 38) were randomized to either Opti-Free PureMoist MPDS (N=288) or to the control, Renu Fresh (N=285).2 Subjects had healthy eyes and had successfully worn their study lenses for at least 5 days prior to the study.

In study 2, 591 subjects wearing one of four selected silicone hydrogel lens brands (Acuvue Oasys, Air Optix, Biofinity, PureVision) were randomized to Opti-Free PureMoist MPDS (N=294) or Renu Fresh (N=297) at 42 clinical practices in a 30-day, double-masked study.2 All subjects in study 2 were symptomatic as determined by reports of end-of-day discomfort with their contact lenses.2

In both studies, lenses were replaced according to the manufacture's recommended schedule. Investigators instructed subjects to wear their lenses for at least 8 hours each day (study 1) or 4 hours each day (study 2). Rewetting drops, Bausch + Lomb Sensitive Eyes Drops, were provided for use only as needed.

A number of safety and efficacy measures were assessed on Days 0, 7, 30, 60, and 90 (study 1) or Days 0, 14 and 30 (study 2). Of particular interest were subjective evaluations of lens-wearing experience during the study. Subjects were presented with a series of Likert-style statements to which they noted their level of agreement on a 5-point scale. In study 2, symptomatic subjects were also asked to use a visual analog scale (from 0 to 100) to rank the intensity of ocular symptoms (dryness, irritation, scratchiness, burning, stinging).

All subjects also reported lens wear time (including comfortable wear time for study 2) and use of rewetting drops. Investigators evaluated and recorded unscheduled replacement of contact lenses; corrected Snellen visual acuity; and slit lamp findings including corneal staining, circumlimbal conjunctival staining (study 2), corneal edema, corneal neovascularization, conjunctival injection, corneal infiltrates and other clinical complications. In study 1, corneal staining severity and extent was graded for each of the five corneal regions.

On Day 30 in study 1 only, investigators collected the lenses of subjects wearing the Acuvue 2 and shipped them overnight to the sponsor for high-performance liquid chromatography (HPLC) analysis to determine the amount of lysozyme on the 2-week lenses.

Study Results

Advantages in Comfort and Patient Satisfaction

In study 1, answers to the Likert questionnaires showed that comfort and satisfaction remained at high levels throughout the study. Mean responses to all seven Likert statements at the end of the study (Day 90) were more favorable overall for the Opti-Free PureMoist MPDS regimen compared to the Renu Fresh regimen (P≤0.003) (Figure 1).2 Given the mechanism of action of Opti-Free PureMoist MPDS to improve wettability, of particular importance was subjective assessment of lens moisture. Responses to the statement “When I use this solution my lenses feel moist” showed higher agreement (1=Strongly Agree, 5=Strongly Disagree) with the Opti-Free PureMoist MPDS regimen compared to the Renu Fresh regimen with mean score (SD) of 1.9 (0.8) versus 2.1 (1.0) (P=0.003).2

Figure 1. Study 1: Mean response to acceptability and comfort statements at Day 90, scored on a Likert-style scale of 1 (Strongly Agree) to 5 (Strongly Disagree).2

Also in study 1, the lens insertion and removal comfort scores assessed over the five days before Day 90 (end of study) yielded differences that were more favorable (lower scores) with Opti-Free PureMoist MPDS. Five minutes after insertion, the mean (SD) scores were 1.6 (0.6) for Opti-Free PureMoist MPDS and 1.8 (0.7) for Renu Fresh (P<0.0001) (Figure 2).2 Likewise, at the end of the lens-wearing day, mean comfort scores within five minutes before removal were 2.0 (0.8) for Opti-Free PureMoist MPDS versus 2.2 (1.0) for Renu Fresh (P=0.0039) (Figure 2).2

Figure 2. Study 1: Comfort at lens insertion and lens removal (scored on a Likert-style scale of 1 (Strongly Agree) to 5 (Strongly Disagree); average of last 5 days on study.2

In addition, at least 80 percent or more subjects across lens brands who reported an average lens wear time of at least 16 hours agreed that their lenses were moist throughout the study (Figure 3).2,3 Together, these data indicate that the HydraGlyde Moisture Matrix provides comfort and moisture from contact lens insertion to removal.

Figure 3. Study 1: Subjects using Opti-Free PureMoist MPDS who agreed or strongly agreed that “My lenses are moist” comparing subjects with wear time less than 16 hours to subjects with wear time equal to or greater than 16 hours.2

For symptomatic subjects (study 2), ocular symptoms of irritation, scratchiness, burning, and stinging were all rated low (visual analogue scale) after 30 days use of Opti-Free PureMoist MPDS with reductions in severity observed from baseline to Day 30 for each symptom (Figure 4).2 Additionally, there was higher agreement with the statement, “When I use this solution, I can comfortably wear my lenses” for symptomatic subjects using Opti-Free PureMoist MPDS over those using Renu Fresh by Day 30 (P=0.047).2 This finding has particular implications for a patient population that typically experiences substantial discomfort with contact lenses.

Figure 4. Study 2: Symptomatic Subjects using Opti-Free PureMoist MPDS - Eye Irritation Symptoms scored on a Visual Analogue Scale of 0 (none) to 100 (worst imaginable) at Day 0 (Baseline) and Day 30.2

Removal of Protein Deposits

Deposits begin to form on lenses immediately upon insertion. These deposits can contribute to poor clinical performance, including diminished visual acuity, dryness, discomfort and papillary changes.5,6 Proteins deposit preferentially on Group IV lenses.7 HPLC analysis measures the amount of lysozyme, the primary protein in tears, on a contact lens.8

In study 1, Opti-Free PureMoist MPDS was highly effective at keeping lenses clean through 2 weeks of lens wear as measured by objective HPLC measurements of lysozyme on Acuvue 2 lenses (Group IV lens). Opti-Free PureMoist MPDS proved to be an effective cleaning care solution with notably less residual lysozyme compared to Renu Fresh (Figure 5). After 30 days, 37 percent less residual lysozyme remained on the Group IV lenses treated with Opti-Free PureMoist MPDS (mean = 898 μg/lens) compared to lenses treated with Renu Fresh (mean = 1416 μg/lens, P<0.0001).1,2

Figure 5. Study 1: Residual lens lysozyme on Group IV lenses (Acuvue 2) worn for 2 weeks and cared for with Opti-Free PureMoist MPDS or Renu Fresh.1,2

Minimal Staining

A care solution that effectively reduces the number of microorganisms must do so while remaining gentle to the ocular surface. The ingredients in the formulation must be compatible with the lens material in order to minimize the potential for cytotoxic effects, including corneal staining, upon lens insertion. In study 1, the cornea staining procedure was conducted using sodium fluorescein and a yellow filter. The extent of corneal staining (% area) was averaged across the 5 corneal regions, and the severity of corneal staining (0-4 scale) was summed across the 5 corneal regions. For each of the six lenses, the mean corneal staining area (%) averaged over all visits remained very low (Figure 6).2 Likewise, mean corneal staining area was also lower for Opti-Free PureMoist MPDS than for Renu Fresh at each visit for all lenses combined (P≤.0152).2 The mean sum severity score was also lower for Opti-Free PureMoist MPDS compared with Renu Fresh, at each visit for all lenses combined (P ≤.0002).3 Despite the high level of disinfection efficacy, the proven and patented Polyquad-Aldox dual disinfection system (Alcon) in Opti-Free PureMoist MPDS was shown to be biocompatible, resulting in minimal corneal staining with all lenses evaluated in the 90-day clinical study.

Figure 6. Study 1: Subjects using Opti-Free PureMoist MPDS: corneal staining area (average of five corneal regions) by lens type, averaged across all visits during the 90-day trial (Lenses replaced according to manufacturer's recommended schedules).2

In study 2, the bulbar conjunctiva was examined for presence of circumlimbal conjunctival staining with lissamine green. Severity of circumlimbal staining (0-4 scale) was summed for four regions of the bulbar conjunctiva. At Day 30, less circumlimbal staining was observed for symptomatic subjects on Opti-Free PureMoist MPDS compared to Renu Fresh (P=0.02).2 These results could be indicative of the care solutions impact on lens material properties.

Investigators observed no other clinically relevant differences in slit lamp findings between regimens during either study 1 or study 2.

Lens Replacements and Lens Wearing Time

In study 1, fewer subjects required unplanned replacement when using Opti-Free PureMoist MPDS (10%) than when using Renu Fresh (16%) (P=0.04).2,3 Most of the lens replacements in both regimen groups were due to damaged lenses, 24 for Opti-Free PureMoist MPDS vs. 30 for Renu Fresh. The largest numerical difference shown between regimens was for lens replacements due to deposits, eight in the Renu Fresh group compared to none in the Opti-Free PureMoist MPDS group.2 In study 2, likewise, more subjects in the Renu Fresh group required lens replacement, although the difference between the two groups was not statistically significant (4.5% versus 6.2%).2

There were no notable differences between care solutions in total lens-wearing time in either study 1 or study 2, and average lens wear times across lenses were between 12.1 and 12.9 hours at the end of both studies.2 This was an expected finding since a wear time of 12-14 hours is consistently observed in studies evaluating contact lens care solutions. Lens wear time is influenced by comfort of the lenses as well as lifestyle factors such as work and sleep schedules. A more important and sensitive measure, especially in symptomatic subjects, is the number of hours that lenses can be worn comfortably. When subjects in study 2 were asked how long they had comfortably worn their lenses, there was an advantage for Opti-Free PureMoist MPDS compared with Renu Fresh at Day 30 (10.2 hours versus 9.8 hours, P=.041).2 This represented an increase in nearly two extra hours (1.8 hours) of comfortable lens wear time compared to baseline for subjects using Opti-Free PureMoist MPDS (p<.0001, Figure 7).

Figure 7. Study 2: Symptomatic subjects using Opti-Free PureMoist MPDS: comfortable lens wear time at Day 0 (Baseline) and Day 30.2

Visual Acuity

Opti-Free PureMoist MPDS and Renu Fresh successfully maintained corrected visual acuity with baseline values throughout the 90-day study (study 1) or 30-day study (study 2). No differences were found between Opti-Free PureMoist MPDS and Renu Fresh in either study. However, subjects in study 1 using Opti-Free PureMoist MPDS reported a higher level of agreement compared to subjects using Renu Fresh to the statement related to clear vision at the end of the day (Figure 1; P=.0019).2

Safety

In these two large-scale clinical trials, both Opti-Free PureMoist MPDS and Renu Fresh were safe and well tolerated. However, in study 1, fewer subjects using the Opti-Free PureMoist MPDS regimen experienced adverse events assessed as related to the test article (2.4%) compared to those using a Renu Fresh regimen (5.3%).2

Similar to what was noted for study 1, in study 2 fewer subjects in the Opti-Free PureMoist MPDS group (2.7%) experienced adverse events that were deemed related to the test article compared to subjects using Renu Fresh (4.4%).2

Discussion

Two large, well-controlled clinical trials conducted with Opti-Free PureMoist MPDS have extended our current clinical experience to a total of 582 contact lens wearers, providing a solid base to assess the safety and acceptability profile of this new product. Results indicate that Opti-Free PureMoist MPDS offers an advance over the compared multipurpose care solution. The addition of the new proprietary multi-action surface active agent, HydraGlyde Moisture Matrix, acting as a wetting and lubricating agent, maintains a cushion of moisture on the lens surface. Opti-Free PureMoist MPDS care solution is designed to improve the wettability and moisture retention of silicone hydrogel lenses and traditional hydrogel lenses. The two clinical studies show that Opti-Free PureMoist MPDS care solution provides comfort from insertion to removal, removes protein deposits for clean, fresh lenses, and utilizes a proven dual disinfection system that results in minimal corneal staining. CLS

References

1. Napier L, Garofalo R, Lemp J, Ketelson H, Lally J. Clinical evaluation of an investigational multi-purpose disinfecting solution. Poster presented during CLAO meeting, September 2010 in Las Vegas.
2. Data on file, Alcon.
3. Garofalo RJ, Napier LD, Lemp JM, Ketelson HA, Stein JM, Lally, JM. Clinical performance of a new multi-purpose disinfecting solution. Poster presented during BCLA meeting, May 2011 in Manchester, England.
4. Pritchard N, Fonn D, Brazeau D. Discontinuation of contact lens wear: a survey. Int Contact Lens Clin. 1999;26(6):157-162.
5. Suttorp-Schulten MS, Luyendijk L, Kok JH, Kijlstra A. HPLC analysis of tear proteins in giant papillary conjunctivitis. Doc Ophthalmol. 1989;72(3-4):235-40.
6. Jones L, Senchyna M, Glasier MA, Schickler J, Forbes I, Louie D, May C. Lysozyme and lipid deposition on silicone hydrogel contact lens materials. Eye Contact Lens. 2003;29(1 Suppl):S75-79; discussion S83-84, S192-194.
7. Suwala M, Glasier MA, Subbaraman LN, Jones L. Quantity and conformation of lysozyme deposited on conventional and silicone hydrogel contact lens materials using an in vitro model. Eye Contact Lens. 2007;33(3):138-143.
8. Keith D, Hong B, Christensen M. A novel procedure for the extraction of protein deposits from soft hydrophilic contact lenses for analysis. Curr Eye Res. 1997;16(5):503-510.

Dr. Garofalo is associate director of clinical trial management for vision care at Alcon Research, where she is responsible for clinical research on new contact lens care products. Prior to joining Alcon, Dr. Garofalo was research optometrist for Wesley Jessen, served as adjunct professor at the Illinois College of Optometry, and was a scientific reviewer for the National Institutes of Health.
Ms. Lemp is a clinical trial manager for vision care at Alcon Research, where she is responsible for managing global clinical trials on contact lens care products. Ms. Lemp received her master's degree in Biomedical Sciences from the University of North Texas Health Science Center in 2004.


Contact Lens Spectrum, Issue: September 2011