Evaluating Silicone Hydrogel Multifocals
This study compared two silicone hydrogel multifocal contact lenses.
|Dr. Rappon is head, Clinical Trial Management, Alcon, Vision Care.|
|Dr. Brobst is a clinical lead for Alcon’s Vision Care R&D division and is responsible for conducting and managing clinical contact lens research regarding new product development.|
|Chiao-Hua Wang is a therapeutic area lead statistician at Alcon, and is responsible for designing, analyzing, and reporting of all contact lens clinical trials conducted by the Vision Care franchise.|
|Dr. Bergenske, a diplomate and past chair of the American Academy of Optometry’s Section on Cornea and Contact Lenses, is currently the director of Professional and Clinical Support at Alcon Laboratories, Inc.|
By Joe Rappon, OD, MS, FAAO; Anne Brobst, OD, FAAO; Chiao-Hua Wang, MS; & Peter Bergenske, OD, FAAO
It has been more than 25 years since Holden and Mertz (1984) published their landmark paper on critical oxygen levels to avoid corneal edema with contact lenses. Since that time, the benefits of high-Dk/t silicone hydrogel over traditional HEMA lenses have been extensively documented, including some key articles demonstrating reductions in corneal edema (Fonn et al, 1999), limbal redness (Papas et al, 1997), neovascularization (Dumbleton et al, 2001), and dryness symptoms (Chalmers et al, 2008).
Well established as the state-of-the-art in contact lens prescribing, an increasing number of practitioners turn to silicone hydrogel contact lenses for new fits and refits (Morgan et al, 2009). With more silicone hydro-gel options available, the question for many practitioners has shifted from whether to fit a silicone hydrogel lens to which silicone hydrogel lens to fit.
This question becomes increasingly critical when fitting presbyopes with contact lenses. Due to the dynamic visual needs of the presbyopic eye and the higher prevalence of dry eyes in this population (Abelson et al, 2009), a presbyopic system that is easy to fit, satisfactory in performance, and dependable is desirable. Individual practitioners, however, rarely have the opportunity to trial the same patient in several lens brands and thus get a true sense for which lenses perform better. To that end, it can be helpful to review clinical studies that compare the performance of multifocals in a controlled and randomized fashion.
We completed a comparative trial of two silicone hydrogel multifocal lenses: Air Optix Aqua Multifocal (Al-con) and Acuvue Oasys for Presbyopia (Vistakon).
Although the designs of the two lenses are proprietary, the Air Optix Aqua Multifocal (Air MF) lens system consists of three variations of a center-near aspheric design, providing different levels of “add” specified by the manufacturer as Lo, Med, and Hi. The Acuvue Oasys for Presbyopia (AVOP) lens system (as tested at the time) consisted of two variations on a center-distance concentric design, providing two levels of add power indicated as Low and Mid. (Since the time of this trial, a High add has been added to the AVOP system. As the High add was not available at the time, this trial was limited to subjects requiring +0.75D to +1.50D spectacle add power.)
A pilot trial with 38 subjects comparing the performance of Air MF lenses against AVOP lenses suggested that the Air MF lenses had clinical advantages over the AVOP lenses. Therefore, a larger confirmatory trial was conducted to substantiate those pilot findings with adequate statistical power.
The objectives of the trial included the comparison of visual acuity, range of clear vision, subjective visual quality ratings, overall satisfaction, and lens preference with the Air MF and AVOP lenses. In addition, other variables for successful multifocal contact lens wear were assessed.
Materials and Methods
This study was conducted under Institutional Review Board approval, and informed consent was signed by each subject before any study procedures were performed. This was a multi-center, prospective, subject-masked (product and sponsor), randomized, bilateral crossover clinical trial.
|Inclusion and Exclusion Criteria|
• At least 35 years of age.
• Able to read, understand, and sign Informed Consent.
• Best-corrected distance visual acuity of at least 20/40 in each eye.
• Spectacle add between +0.75D and +1.50D (inclusive).
• Able to be fit in available study sphere powers (−1.00D to −5.00D).
• Currently wearing soft contact lenses at least five days a week.
• Eye injury or surgery within 12 weeks immediately prior to enrollment.
• Pre-existing ocular irritation that would preclude contact lens fitting.
• Currently enrolled in an Ophthalmic Clinical Trial.
• Evidence of systemic or ocular abnormality, infection, or disease likely to affect successful wear of contact lenses or use of their accessory solutions.
• Any use of medications for which contact lens wear could be contraindicated as determined by the investigator.
• Aphakia, pseudophakia, or previous refractive surgery.
• Astigmatism ≥1.00D.
• Difference in refractive error between eyes (anisometropia) ≥2.00D.
• Clinically significant anisocoria.
• Currently wearing Air Optix Aqua Multifocal or Acuvue Oasys for Presbyopia.
Selection of Trial Subjects All trial subjects were selected from the patient population at the investigational sites and were screened to ensure suitability. Table 1 notes all inclusion and exclusion criteria.
Study Design A total of 20 clinical sites were engaged to conduct the study. Each study site was to enroll 13 subjects, with a target enrollment of 260 subjects. Each site received a study binder that included the protocol and methods for data collection. Grading scales for biomicroscopy findings were provided to all sites. Subjects were masked to the trial product brand(s) and to the sponsor throughout the trial. Investigators and coordinators were instructed to prepare the trial products for dispensing so that brand name(s) were not visible.
Each pair of study lenses was worn on a daily wear basis for one week ± two days. In a randomized fashion, each subject wore a pair each of Air MF (Test) and AVOP (Control) on a crossover basis. Lenses were fit and dispensed according to each subject’s spectacle prescription and add requirement, following the respective manufacturer’s fitting guidelines. Table 2 compares the lenses used in this study.
All subjects had spectacle adds between +0.75D and +1.50D (inclusive) based on a new spectacle refraction with add determination completed at the baseline visit. To more accurately reflect the overall presbyopic market, attempts were made for each site to have at least one and no more than five habitual monovision subjects enrolled into the trial.
The Air MF were fit in accordance with Air Optix Aqua Multifocal Fitting Guidelines. The AVOP were fit according to Acuvue Oasys for Presbyopia Stereo Precision Select Log. In accordance with the Acuvue Oasys for Presbyopia Stereo Precision Select Log, Acuvue Oasys spherical single vision lenses were also permitted to be fit on a unilateral basis as directed.
All subjects had their visual acuity at distance, near, and intermediate as well as near range of clear vision measured at each visit. Fitting characteristics (including number of lenses required) and lens surface characteristics were documented. Subjective ratings were taken on visual quality and initial comfort at dispense. Subjects were given Clear Care (Alcon) for daily cleaning/disinfection. When necessary, SoftWear saline (Ciba Vision, discontinued) was used for rinsing purposes, and lens rewetting drops were allowed at the subjects’ discretion. At follow up, purchase intent and subjective ratings (visual, comfort, satisfaction, ghosting) were collected by means of a questionnaire completed by the subjects. Visual and overall preferences were assessed at the final visit. At the completion of all subject visits, each site completed an investigator questionnaire.
|Test and Control Lens Parameters|
|Air Optix Aqua Multifocal||8.6mm||14.2mm||−1.00D to −5.00D
|Lo, Med, Hi|
|Acuvue Oasys for Presbyopia||8.4mm||14.3mm||−1.00D to −5.00D
|14.0mm||−1.00 to −5.00D
|* In accordance with the Acuvue Oasys for Presbyopia Stereo Precision Select Log, Acuvue Oasys spherical single vision lenses (14.0mm diameter, 8.4mm and 8.8mm base curves) were also permitted to be fit on a unilateral basis as directed.|
|Dispensed Subject Profile|
Mean age: 45.5 ± 4.3
Female/male ratio: 86% / 14%
Correction before study:
52.3% − Distance only contact lenses
Most Common Habitual Contact Lens Brands Prior to Study:
19.2% − Acuvue Oasys
Distribution of Spectacle Adds:
+0.75D − 16.3%
Visit Schedule The three planned visits for this trial were as follows:
• Baseline/Dispense Pair 1
• Follow-up Pair 1/Dispense Pair 2 after one week (± two days) of Pair 1 lens wear
• Follow-up Pair 2/Trial exit visit after one week (± two days) of Pair 2 lens wear
Baseline measures included habitual lens information, biomicroscopy, visual acuity with habitual lenses, and subjective refraction with add determination. Visual acuity at baseline was determined with routine clinical measure of Snellen acuity.
Distance visual acuity with the test and control multifocal lenses was determined with routine clinical measure of Snellen acuity and subsequently converted to logMAR notation for analysis purposes. For measurement of near and intermediate acuity, each site was provided with a handheld logarithmic visual acuity chart to which a 40cm string was attached. Investigators were instructed to use the string for near acuity test distance. A tape measure was also provided, with instruction to hold the chart at 100cm for the intermediate testing. All acuity testing was done under high-contrast conditions.
Lenses were dispensed according to guidelines provided by the manufacturers. The day that the lenses were dispensed was counted as the first day of lens wear. While lens replacement was permissible in this trial for lost or damaged lenses, refits were not allowed other than during the dispensing visit of either lens type. The need for refit was determined by investigator judgement regarding satisfactory vision, comfort, or fit. If a subject required a refit of Pair 1 after the dispensing visit, the investigator was to discontinue the subject from Pair 1 and dispense Pair 2. If the subject required a refit of Pair 2 after the dispensing visit, the subject was to be exited from the trial. Also, missed visits were not allowed. Subjects who failed to report for a follow-up visit within the specified window were discontinued from the trial.
At each follow-up visit, subjects were asked to complete a questionnaire that included a question regarding purchase intent: “Assume your eye doctor said you could use this product. How likely would you be to purchase the lenses you wore during the past week of the study?” Subjects answered by selecting from a five-point scale ranging from “Definitely would purchase” to “Definitely would not purchase.”
At the end of each trial week, subjects also rated lenses worn for that week. Responses were recorded on a 10-point scale, anchored with 1 labeled as “Poor/Difficult” and 10 as “Excellent/Easy.” Ratings were collected for Distance vision (e.g. driving or watching TV), Intermediate vision (e.g. looking at the car dashboard), Near Vision (e.g. reading), Night Vision (e.g. driving at night), Vision when using computer, Minimizing eye fatigue/eye strain, Ease of transition between close-up and distance vision, Overall vision, Overall comfort, and Overall satisfaction. When rating Night Vision and Vision when using computer, subjects were given the option of responding with “Not Applicable” in the event that this did not apply.
|Dispensed Lens Profile|
|Parameter||Air Optix Aqua Multifocal||Acuvue Oasys for Presbyopia*|
|Average Lens Power (D)||−3.02 ± 1.13||−3.02 ± 1.13|
|Lens Power Range (D)||−1.00 to −5.00||−1.00 to −5.00|
|Sphere Used* (%)||N/A||0.4|
|Lo / Low Add Used (%)||41.2||55.6|
|Med / Mid Add Used (%)||57.9||44.0|
|HI Add Used (%)||0.8||N/A|
|* Acuvue Oasys spherical lenses (per fitting guidelines in study methods)|
|Binocular VA (logMAR) and Near Range of Clear Vision|
|Parameter||Visit||Air Optix Aqua Multifocal (mean ± std)||Acuvue Oasys for Presbyopia (mean ± std)||Statistical Significance*|
|Binocular Distance VA||Dispense||−0.02 ± 0.05||−0.01 ± 0.06||p<0.001|
|Follow up||−0.01 ± 0.06||0.01 ± 0.07|
|Binocular Intermediate VA||Dispense||−0.04 ± 0.10||−0.02 ± 0.11||p<0.001|
|Follow up||−0.04 ± 0.10||0.00 ± 0.13|
|Binocular Near VA||Dispense||0.03 ± 0.10||0.08 ± 0.12||p<0.001|
|Follow up||0.06 ± 0.12||0.12 ± 0.14|
|Near Range of Clear Vision (cm)||Near (disp)||24.8 ± 7.4||26.2 ± 8.3||NP|
|Near (f/u)||25.6 ± 8.0||26.6 ± 8.6|
|Far (disp)||118.4 ± 19.9||115.3 ± 19.0||NP|
|Far (f/u)||118.5 ± 19.7||114.7 ± 19.8|
|Near to Far (disp)||93.6 ± 22.8||89.2 ± 22.3||p<0.001|
|Near to Far (f/u)||92.9 ± 22.7||88.1 ± 23.2|
NP – Per protocol, inferential testing not performed.
* p-value obtained from a Repeated Measures mixed effect model which included Lens, Sequence group, and Period as main effects. Visit and Lens-by-Visit interaction also included in the model for endpoints collected at multiple visits.
In addition, each subject rated “ghosting,” which was described on the subject form as “a faint, overlapping image next to the object you are looking at.” Ghosting was rated as None, Mild, Moderate, or Severe and included questions regarding ghosting with distance vision (driving or TV), intermediate vision (computer or dashboard), near vision (reading), and overall.
After completing one week of wear with each pair of lenses, subjects completed a form containing questions regarding lens preference. They responded on a five-point Likert scale ranging from “Strongly prefer Pair 1 lenses” to “Strongly prefer Pair 2 lenses” (middle box “No preference”). Preference was completed for Distance vision, Intermediate vision, Near vision, Overall vision, and Overall preference.
Statistical Methods A pilot clinical trial with 38 subjects had compared the performance of Air MF lenses against AVOP lenses and showed trends for superiority of the Air MF lenses. Of the subjective vision ratings (scale of 1 to 10) collected in the pilot trial, the maximum standard deviation of paired differences between lenses was 2.75. Using this result, a difference of 0.5 grade could be detected at 80 percent power (α = 0.05) with a sample size of 239 in a paired study design.
For this trial, the efficacy variables included visual acuity (distance, intermediate, and near), near range of clear vision, subjective visual ratings (distance, intermediate, near, night, computer, overall, minimize eye fatigue/strain, and visual transition), overall satisfaction, preference (distance, intermediate, near, and overall vision as well as overall), investigator future fitting questions with Test lenses, purchase intent, ghosting, and centration. Safety variables were biomicroscopy findings. All statistical tests were conducted at α = 0.05 two-sided.
Subjective preferences were evaluated using Exact Binomial Test. Clear near vision range was calculated as the difference between near and distant point of clear near vision as captured on the Clinical Report Form. Investigator fitting intent questions were analyzed based on the top-two box, whereby the percent of investigators responding to Strongly Agree or Agree was calculated. This percent was tested against 50 percent with Exact Binomial test, assuming that “no difference” would result in a 50/50 ratio.
A Repeated Measures mixed effects model (Proc Mixed/GenMod, SAS 8.2) was fitted to evaluate paired differences between Test and Control as crossover pairs. Period (Pair 1, Pair 2) and sequence group (Test followed by Control, Control followed by Test) were included in the model. Consistency in magnitude and direction of lens difference across scheduled visits (i.e. lens-by-visit interaction) was investigated first for endpoints collected both at dispense and follow-up visits. When found to be significant, Test versus Control comparison was done at each visit separately.
The number of subjects fit with the first pair of lenses was counted as the number of subjects who could be dispensed in both eyes with the first trial pair of study lenses and who could have completed the assigned wearing period with lenses of those parameters. A 95-percent, two-sided confidence interval was also constructed on the percent of subjects fit with the first pair of Test lenses.
Lens fit and surface characteristics were also collected in the study and were summarized with descriptive statistics.
Randomization Two sequence groups were defined: Test followed by Control and Control followed by Test. A computerized randomization table was generated for each site, adopting an equal randomization, whereby each treatment sequence is given with probability 1/2.
|Ghosting (Percentage Reporting “None”)|
|Parameter||Air Optix Aqua Multifocal||Acuvue Oasys for Presbyopia||Statistical All p<0.01 Significance*|
|*Inferential testing performed for all categories (i.e., None, Mild, Moderate, and Severe). P–value obtained from a Repeated Measures mixed effect model which included Lens, Sequence group, and Period as main effects.|
Two hundred fifty-nine subjects were enrolled at 20 sites to ensure that 239 completed the study. Two hundred fifty-eight subjects (222 female, 36 male) were dispensed lenses, and 252 completed the study.
Baseline Best-corrected acuity was 20/20 or better for all but five eyes, all of which had 20/25. Mean subjective refraction sphere was −3.03D ± 1.22D, range was −0.75D to −5.75D. Mean cylinder was −0.24D ± 0.27D. Baseline physiology was grade 2 or lower for all biomicroscopy signs, with the exception of one subject with a grade 3 pinguecula, which in the opinion of the investigator did not interfere with the subject’s ability to wear contact lenses.
Table 3 shows profiles of the subjects who were dispensed lenses for the trial, and Table 4 shows profiles of the dispensed lenses.
Visual Acuity and Range of Clear Vision Visual acuity (VA) measurements at the intermediate and near distances were obtained at 100cm and 40cm, respectively. While wearing Air MF, 90.4 percent of the eyes were found to have 20/25 or better distance VA at follow up versus 85.3 percent of eyes wearing AVOP lenses. Binocular distance, intermediate, and near VA were all found to be statistically superior with Air MF lenses versus AVOP lenses (p<0.001), but the differences were only clinically significant (i.e., three letters of acuity) for intermediate VA at follow up and for near VA at dispensing and follow up. Range of clear near vision was found to be statistically significantly larger for subjects when wearing Air MF lenses (Table 5).
Quality of Vision Subjects were asked to rate the quality of vision at distance, intermediate, near, at night, while using a computer, and overall on a scale of 1 to 10 where “1” was poor/difficult and “10” was excellent/easy. Subjects were asked to rate the study contact lenses for minimizing eye fatigue/strain and for providing ease of transition from close-up to distance vision. In all cases, Air MF were found to be statistically significantly superior to AVOP (p<0.01). For ratings collected at both dispensing and follow up, larger differences between Air MF and AVOP were found at follow up. See Figure 1 for vision ratings.
Subjects were also asked to rate the severity of ghost images in their vision at distance, intermediate, near, and overall where “0” was none, “1” was mild ghosting, “2” was moderate ghosting, and “3” was severe ghosting. Again, in all cases, Air MF lenses were found to be statistically superior to AVOP lenses (p<0.001) (Table 6.)
Figure 1. Quality of vision.
Figure 2. Lens preference.
Figure 3. Purchase intent.
Overall Satisfaction and Preference Overall satisfaction at follow up for Air MF was 7.4 ± 2.1 and for AVOP was 6.4 ± 2.4 (p<0.001). At the end of the study, subjects were asked their preference for the study lenses in terms of distance, intermediate, near, and overall vision as well as overall preference. Of subjects with a preference, Air MF lenses were significantly preferred over AVOP lenses in all cases (p<0.001) (Figure 2).
Purchase Intent After wearing each pair of lenses, subjects were asked if they would purchase the lenses. Statistically significantly higher purchase intent was found for Air MF compared to AVOP lenses (p<0.001) (Figure 3).
Number of Lenses to Achieve Final Fit Comparatively, 85.4 percent of subjects were fit with the first pair of Air MF versus 84.2 percent with AVOP lenses. This difference was not statistically or clinically significant.
Lens Fit and Surface Characteristics A higher percentage of subjects were found to have an optimal lens fit with Air MF compared to AVOP lenses (89.3 percent versus 82.5 percent at dispensing and 89 percent versus 82.1 percent at follow up, respectively). There was a significant difference in lens centration between Air MF and AVOP (p=0.005), most notably 93.7 percent of Air MF lenses were centered at dispense compared to 87.5 percent of AVOP lenses.
Safety Evaluation All enrolled and dispensed subjects were assessed on all safety endpoints. One subject was found to have grade 3 nasal and temporal asymptomatic pingueculae at baseline and at both follow-up visits. It was the investigator’s opinion that this did not interfere with the subject’s ability to wear lenses. For all others, there were no biomicroscopy findings greater than grade 2 at baseline and throughout the study. Limbal redness, bulbar redness, epithelial staining, and conjunctival staining were all similar for both lens types.
All safety variables were similar for the study lenses in this trial. One ocular adverse event (allergic conjunctivitis) occurred with the control product, otherwise there were no safety issues observed.
Investigator Questions At the end of the trial, each investigator was asked to indicate future fitting behavior based on their experience in this trial. In total, 80 percent indicated that they would fit Air MF over monovision and 85 percent indicated that they would recommend Air MF over AVOP (Figure 4).
Practitioners often rely on their own experience with a small number of patients to draw conclusions regarding product performance. From a practical standpoint, if a practitioner succeeds in fitting a given patient with a complex design, refitting that same patient in an alternate product makes little clinical or financial sense. Now that soft multifocals with different designs are available from a number of manufacturers, studies that compare the performance of different lenses in a large number of subjects may help guide practitioners in determining which lenses may be most likely to perform better on average.
Figure 4. Investigator questions.
In this study, both products performed well, although it became evident that the test (Air MF) consistently out-performed the control (AVOP). Often, clinical measures such as VA and lens centration do not correlate directly with subjective preference and purchase intent. For instance, although VA was statistically superior for Air MF (Table 5), the clinically significant difference (three or more letters) was limited to intermediate and near only. Despite small differences measured clinically, strong preferences were expressed based on the subjective impression of vision. It would appear that variables clinically documented in the examination room only tell part of the story when it comes to success with these products.
Manufacturer-conducted studies such as this one are inherently suspected of bias. As such, the sponsor bears a responsibility of going to all reasonable measures to rise above that suspicion. A number of such measures were taken in this study. Subjects were masked as to the sponsor and to the lens brands being tested. Investigator masking was not employed, as the investigators needed to assess lens fit and centration, and the characteristic inversion marking on the AVOP lenses would have effectively unmasked examiners. As this study involved a number of investigative sites (necessary to enroll this large a number of subjects in a reasonable time frame) it was not practical to employ separate masked examiners.
Conducting a trial at multiple locations raises questions regarding the consistency from site to site and whether the data from multiple sites can be combined. This trial had relatively small sites (n=13 per site, approximately), therefore, we did not have adequate power to detect treatment-by-site interaction, if any. However, the average paired differences between Test and Control at each site did not reveal any clinically significant difference compared to the pooled average.
Significant efforts were made to assure methodology concordance. Printed case report forms helped guide investigators to collect and record data consistently. VA charts were provided for all near and intermediate acuity testing, with an attached 40cm guide string to ensure consistent test distance for near. Investigators were provided with standardized grading scales for biomicroscopy measures.
Many earlier reports compared the clinical and visual benefits of Air Optix Aqua Multifocal lenses with other products and with monovision (Woods et al, 2009; Long and Giles, 2009; Rappon and Rothschild, 2009). In this multi-center, randomized clinical trial, significant objective and subjective clinical advantages were demonstrated for Air Optix Aqua Multifocal over Acuvue Oasys for Presbyopia. CLS
For references, please visit www.clspectrum.com/references.asp and click on document #205.