Presbyopia is an age-related vision condition in which the crystalline lens gradually loses its ability to change shape when acted upon by the ciliary muscle. Age-related changes in ocular structure and function, including alterations to the tear film,^1-4 result in impaired vision and decreased ocular comfort, particularly toward the end of the day.^5-7 Presbyopia typically becomes evident by age 40 to 45 years and is manifested by the inability to define objects or letters at near distance. It is the most common age-related refractive error worldwide, occurring in more than 1 billion persons, and uncorrected presbyopia accounts for an estimated $25 billion in lost productivity.^8,9 Presbyopia can be corrected by the use of single-vision or bifocal spectacles, progressive addition lenses, or monovision or multifocal contact lenses.

Recent studies have indicated that presbyopic patients prefer contact lens correction when comfort and good vision can be attained,¹⁰ yet many presbyopic contact lens wearers discontinue use, primarily due to discomfort and poor vision.^11-12 Studies have also shown that proper fit of multifocal contact lenses is important for good distance and near vision.¹³

Delefilcon A daily disposable multifocals feature a silicone-rich core (33% water) and a hydrophilic surface (> 80% water). Delefilcon A multifocal lenses have been shown to maintain a low coefficient of friction over time, resulting in a high level of lubricity.^14,15 A lower coefficient of friction has been found to correlate with greater comfort in contact lens wearers,^16-18 and delefilcon A lenses have been associated with greater end-of-day comfort, longer wear time, and reduced feelings of dryness compared with other silicone hydrogel lenses.^19,20

As older contact lens wearers who have symptoms of discomfort are at risk to discontinue lens use,⁷ it is of interest to determine the comfort level with delefilcon A multifocal lenses of presbyopic adults who have experienced discomfort with their current multifocal lenses. Because contact lens fit is essential for good vision, it is also important to establish clinicians’ perceived ability to fit delefilcon A multifocal lenses.¹³ This study compared objective and subjective measures of comfort, dryness, vision, and successful fit among symptomatic presbyopic wearers of multifocal lenses who wore daily disposable delefilcon A and their habitual multifocal lenses for 14 ± 3 days.

METHODS

The study was performed in accordance with the principles of the Declaration of Helsinki and the International Conference on Harmonization (ICH) E6 Good Clinical Practice (GCP) consolidated guidelines and other regulations as applicable. Voluntary written informed consent was obtained from each subject.

Subjects Eligible subjects were aged 40 to 65 years. They were current daily wearers of soft multifocal contact lenses (for at least six months) who had symptoms of end-of-day contact lens discomfort, as determined by responses to questions on the prescreening eligibility questionnaire. The questionnaire consisted of three questions, on which subjects could provide five responses (strongly disagree, disagree, undecided, agree, and strongly agree). Eligible subjects disagreed or strongly disagreed with the statement “My contacts are comfortable all day long” and agreed or strongly agreed with the statements “During the day, I take my contacts out earlier than I like because my eyes feel dry,” and “Late in the day, my eyes become dry, but I continue to wear my contacts.”

Eligible subjects had to have a near spectacle add of +0.50D to +2.50D and best-corrected visual acuity (VA) ≥ 20/30 (≥ 0.2 logarithmic minimum angle of resolution [logMAR]) in each eye at distance and had to be willing to wear each study lens for at least six hours per day for a minimum of five days per week for two weeks. Subjects were excluded if they had a structural or medical contraindication to contact lens wear; if biomicroscopy findings on slit lamp examination at screening were Grade ≥ 3; had undergone prior refractive surgery; had a history of herpetic keratitis, ocular surgery, or irregular cornea; or had pathologic dry eye precluding contact lens wear.

Study Design This was a prospective, randomized, observer-masked, active-controlled, crossover study of four weeks’ duration conducted on volunteers at 11 sites in the United States. Enrolled subjects were randomized 1:1 to wear their habitual multifocal lenses or delefilcon A daily disposable multifocals (Dailies Total1 Multifocal [Alcon Laboratories, Inc.]). Randomization was stratified by habitual lens modality (daily disposable and non-daily disposable). The randomization scheme was generated and maintained by the sponsor and blocked to ensure balance of study lens sequence allocation within investigational sites and strata (daily disposable or non-daily disposable). The study subjects were not masked to lens identification, whereas the investigators and the study teams performing the assessments were masked. Study subjects were instructed to not reveal this information to the investigators or staff members performing assessments.

Delefilcon A multifocals were fit by the site investigator and dispensed by unmasked clinical staff to maintain investigator masking. Subjects wore the assigned lenses bilaterally for 14 ± 3 days for ≥ six hours per day on a daily wear modality (Period 1). Subjects randomized to continue wearing their habitual contact lenses, all of which were frequently replaced, continued to use their habitual care solutions. Subjects were subsequently crossed over to alternate contact lenses for 14 ± 3 days (Period 2). All subjects wore and assessed both types of lenses. There were four study visits: Visit 1 for screening and fitting, Visit 2 to dispense lenses for Period 1, Visit 3 at the end of Period 1 and to dispense lenses for Period 2, and Visit 4 at the end of Period 2. Study parameters were assessed at each visit. Subjects were instructed to not use eye drops (artificial tears or rewetting drops) on the day of their visits.

Efficacy Parameters Efficacy endpoints were measured at Visits 3 and 4, after 14 ± 3 days of wear of delefilcon A or habitual multifocal lenses. Discomfort symptomatology was assessed by the abbreviated Contact Lens Dry Eye Questionnaire-8 (CLDEQ-8), measured at baseline and at Visits 3 and 4; scores ranged from 0 to 37, with lower scores indicating less dryness. Average daily wear time and average comfortable daily wear time were measured at baseline and at Visits 3 and 4; comfort throughout the day and at the end of the day was measured on a scale of 1 (poor) to 10 (excellent); reduced feelings of end-of-day dryness and dryness during digital device use were measured on a scale of 1 to 10; and frequency of end-of-day dryness symptoms were measured on a five-point scale from “never” to “constantly.” Subject preference—based on comfort, vision, feeling of dryness, and overall—was assessed on a five-point scale ranging from “Strongly prefer delefilcon A MF CLs” to “Strongly prefer habitual multifocal contact lenses” at Visit 4 after subjects wore both lenses for 14 ± 3 days each. Investigators reported the number of delefilcon A multifocals lenses needed to achieve a final, successful fit as well as their ease of fit on a scale of 1 (difficult) to 10 (easy).

Vision was tested using logarithmic VA charts and reported as logMAR binocular high-contrast/high-illumination (HC/HI) VA at near (40cm), intermediate (80cm), and far (4m) distance, measured when lenses were dispensed (Visits 2 and 3) and after 14 ± 3 days of wear (Visits 3 and 4).

Safety Parameters Investigators monitored adverse events at each visit, with event intensity rated as mild, moderate, or severe. Both investigators and the sponsor assessed the relationship of adverse events to the device or study procedure. Biomicroscopy parameters were assessed by slit lamp exam at each study visit; each parameter was graded on a five-point scale. Device deficiencies, rated by investigators, included failure to meet product specifications, cloudy lens, lens surface/edge defect, torn lens, suspected contamination, and lack of performance.

Statistical Analysis and Sample Size Justification Efficacy was evaluated in the full analysis set, consisting of all randomized subjects exposed to any study lens; and safety was evaluated in the safety analysis set, consisting of all subjects/eyes exposed to any study lenses, except for lenses used for optimization and fitting.

Continuous variables were reported as number of observations, mean, standard deviation (SD), minimum, and maximum; and categorical variables were reported as numbers and percentages. Because of the crossover design, demographic and selected baseline data are presented by lens sequence group and overall. For VA, a mixed-effect repeated measures model was fitted, including terms for lens, period, sequence group, visit (dispense, Day 14), lens-by-visit interaction, and habitual lens modality (daily disposable or non-daily disposable) as fixed effects and subject as a random effect. Differences between delefilcon A and habitual multifocal contact lenses and their corresponding one-sided 95% upper confidence limits (UCLs) were computed. Non-inferiority in binocular intermediate VA was defined as UCL < 0.05 on Day 14. For the efficacy endpoint (CLDEQ-8), a mixed-effect repeated measures model was fitted, including terms for lens, period, sequence group, baseline CLDEQ-8, and habitual lens modality as fixed effects and subject as a random effect. A mixed-effect repeated measures analysis was performed for comfortable wear time, with baseline comfortable wear time, lens, period, sequence, and habitual lens modality as fixed effects. Similar mixed-effect repeated measures models were used to analyze dryness and end-of-day comfort, with exploratory variables other than baseline adjustment summarized descriptively by lens at each collection visit, including relevant confidence intervals.

A sequential gatekeeping strategy was implemented to control testing of multiple efficacy endpoints. Overall, Type I error was controlled at one-sided 0.05 by sequentially testing each endpoint in a predefined order, such that an endpoint was tested only if the null hypothesis for the preceding endpoint was rejected. The predefined testing order was as follows: non-inferiority of the primary endpoint, superiority of the secondary endpoint, and superiority of the key exploratory endpoints (comfortable wear time, end-of-day dryness, dryness during digital device use, and end-of-day comfort).

Sample size calculation for the pre-specified endpoint of CLDEQ-8 was based on published data.²¹ Assuming a SD for paired differences of 10, 49 subjects per sequence provide 90% power to detect a difference of three. For the exploratory endpoints of comfortable wear time, dryness, and comfort, 62 subjects per sequence provide 88% to 98% power to detect a difference of one unit.

RESULTS

Subjects Of the 170 enrolled subjects, two were screening failures; the remaining 168 were randomized to lens sequence. Two subjects were randomized in error but not exposed, with 166 subjects being randomized and exposed. One subject withdrew from the study following randomization and exposure to habitual multifocal lenses but prior to exposure to delefilcon A multifocal lenses for failing to meet all inclusion criteria. Of the 168 randomized subjects, 166 were exposed to study lenses and comprised the full analysis set, and 165 completed the study. Their mean ± SD age was 52.0 ± 5.1 years; 77% were women, and 91% were white (Table 1). The demographic characteristics of the two groups were similar.

Table 2 lists the multifocal lenses habitually worn by study subjects. Of the 166 subjects, 55 (33.1%) habitually wore daily disposable multifocal lenses, and 111 (66.9%) habitually wore non-daily disposable multifocal lenses.

Safety Twelve ocular adverse events were reported during the study, five during delefilcon A multifocal lens wear and seven during habitual multifocal lens wear. The five ocular adverse events during wear of delefilcon A lenses included reduced VA in two eyes as well as ocular discomfort, hordeolum, and tension headache in one eye each. The seven ocular adverse events during wear of habitual lenses included dry eye in six eyes and ocular discomfort in one. All ocular adverse events were mild and resolved by the end of the study, and no subjects discontinued study participation due to an adverse event.

No subjects experienced biomicroscopy findings greater than Grade 2 at baseline or on day 14 of lens wear. Five device deficiencies were reported by four subjects using delefilcon A multifocals: fit issues (two instances), a feeling of the lens being inside out (with poor close vision), a suspected edge defect, and discomfort during lens application. No device deficiencies were reported for habitual lenses.

Daily Wear Time Mean daily wear time at baseline was similar in subjects randomized initially to delefilcon A (13.2 ± 2.4 hours) and habitual (13.3 ± 2.8 hours) multifocals. Mean daily wear time was also similar after wearing delefilcon A (13.6 ± 2.4 hours) and habitual (13.6 ± 2.3 hours) lenses for 14 ± 3 days. Comfortable wear time was similar in the two groups at baseline (Figure 1) but was significantly longer after wearing delefilcon A compared to habitual multifocal lenses for 14 days (12.8 ± 3.0 hours/day, versus 11.1 ± 3.7 hours/day, P < 0.0001).

Subjective Comfort Ratings Mean subjective scores for comfort during the day and for end-of-day comfort after 14 days of wear were significantly higher (indicating better end-of-day comfort) for delefilcon A than for habitual multifocal lenses (P < 0.0001) (Figure 2A). Mean scores for reduced feelings of end-of-day dryness and dryness during digital device use were also significantly higher (indicating less dryness) for delefilcon A than for habitual lenses (P < 0.0001 each). None of these scores differed significantly between habitual wearers of daily disposable and non-daily disposable multifocals (Table 3).

Mean CLDEQ-8 scores at baseline were similar in subjects randomized initially to delefilcon A and habitual multifocal lenses (Figure 2B). Mean CLDEQ-8 scores, however, were significantly (P < 0.0001) lower after wearing delefilcon A compared to habitual lenses worn for 14 days, indicating a greater improvement in dryness symptoms after wearing delefilcon A. Scores at baseline and after wearing lenses for 14 days did not differ significantly between habitual wearers of daily disposable and non-daily disposable lenses (Table 4).

More than 72% of subjects reported never or rarely feeling end-of-day dryness over 14 days of wearing delefilcon A lenses, compared with only 32% of subjects while wearing habitual lenses (Figure 3). These percentages did not differ significantly between habitual wearers of daily disposable and non-daily disposable lenses. Moreover, about 27% of these symptomatic subjects never felt end-of-day dryness while wearing delefilcon A multifocals.

Subject Preferences Subjects preferred delefilcon A multifocal lenses almost four times more than they preferred their habitual multifocal lenses, based on multiple comfort measures including overall comfort, end-of-day comfort, feeling as comfortable at the end as at the beginning of the day, and end-of-day dryness (Figure 4).

Visual Acuity At contact lens dispensing during both study periods, mean intermediate (80cm) binocular HC/HI VA was similar in subjects randomized first to delefilcon A (–0.07 ± 0.10 logMAR) and habitual (–0.09 ± 0.10 logMAR) multifocal contact lenses. After 14 ± 3 days of wear during both study periods, VA remained similar for delefilcon A (–0.07 ± 0.10 logMAR) and habitual (–0.09 ± 0.10 logMAR) lenses. Based on the 95% upper confidence level of the least squares mean (LSM) difference, which was 0.03, and a non-inferiority margin of 0.05, delefilcon A were non-inferior to habitual multifocals after two weeks of wear.

Mean near (40cm) and far (4m) binocular HC/HI visual acuities were also similar in the two groups. At dispensing during both study periods, mean near VA was 0.13 ± 0.134 logMAR in subjects initially dispensed delefilcon A and 0.11 ± 0.134 logMAR in subjects initially dispensed habitual multifocal contact lenses. After 14 ± 3 days during both study periods, mean near VA was 0.15 ± 0.150 in subjects who wore delefilcon A and 0.11 ± 0.153 logMAR in subjects who wore habitual multifocal lenses.

At dispensing during both study periods, mean distance VA was –0.09 ± 0.072 logMAR in subjects initially dispensed delefilcon A and –0.10 ± 0.084 logMAR in subjects initially dispensed habitual multifocals. After 14 ± 3 days during both study periods, mean distance VA was –0.10 ± 0.069 in subjects who wore delefilcon A and –0.09 ± 0.074 logMAR in subjects who wore habitual lenses.

Success and Ease of Fit of Delefilcon A Multifocal Lenses Of the 334 eyes, 235 (70.4%) were successfully fit with the first delefilcon A multifocal lens, 90 eyes (26.9%) required two lenses, eight (2.4%) required three lenses, and one eye (0.3%) required four lenses for a successful fit. A successful fit was achieved with a mean 1.3 ± 0.5 lenses per eye and 2.7 ± 1.0 lenses per subject. On a scale of 1 (difficult) to 10 (easy), investigators rated ease of fit of delefilcon A multifocal lenses as ≥ 7 for 163 of 167 (98%) subjects, with a mean rating of 9.2 ± 1.0.

DISCUSSION

In this study, delefilcon A multifocal contact lenses were superior on multiple measures of comfort, including feelings of end-of-day comfort, length of average comfortable wear time, and lens comfort symptomology, measured by scores on the CLDEQ-8 questionnaire.

Delefilcon A multifocals also showed improvements in dryness symptoms. Feelings of dryness at end-of-day and during digital device use were significantly reduced after wearing delefilcon A compared to habitual multifocals, with 72% of subjects wearing delefilcon A lenses rarely or never experiencing end-of-day dryness. Based on multiple measures of comfort and dryness, subjects preferred delefilcon A to their habitual multifocals in a 4-to-1 ratio.

Investigators were usually able to fit delefilcon A multifocal lenses with the first lens (70% of eyes) or sometimes with two lenses, with investigator mean ease-of-fit rating being > 9 of 10. VA was similar for delefilcon A and habitual multifocals, both at baseline and after two weeks of wear. Similarly, previous studies reported that delefilcon A multifocal lenses were associated with greater comfort, reduced feelings of dryness, and longer wear time than were other lenses.^19,20 Because discomfort and dryness have been associated with contact lens wear^5-7 and have been reported to increase with age,¹ it was encouraging that symptomatic lens wearers in this study experienced improved comfort with delefilcon A multifocal lenses.

Additionally, VA at near, intermediate, and distance while wearing delefilcon A multifocals was non-inferior to that with habitual lenses, which should prevent potential discontinuation due to poor vision.¹³ Both the increased comfort and similar VA observed with delefilcon A multifocals in subjects experiencing discomfort may enable presbyopes to continue wear of multifocal lenses.

Few adverse events were associated with these lens types, with these adverse events being generally mild and resolving by study end. No subject discontinued study participation due to an adverse event. Five device deficiencies were reported for the delefilcon A contact lenses that appeared primarily related to fit.

This study had certain limitations. Subjects in the study were older adults (aged 40 to 65 years) and were symptomatic wearers of multifocal contact lenses, reducing generalizability to other populations, including subjects naïve to contact lens wear. In addition, subjects were not masked to lens use, as some were randomized to their habitual contact lenses. CLS

Portions of this report were previously presented at the annual meetings of the British Contact Lens Association, June 9 to 11, 2017 in Liverpool, UK; the American Optometric Association, June 21 to 25, 2017 in Washington, DC; and the American Academy of Optometry, Oct. 11 to 14, 2017 in Chicago.

This study was funded by Alcon Research, LLC. BelMed Professional Resources, Inc. provided editorial support, which was contracted and funded by Alcon.

REFERENCES

1. Gipson IK. Age-related changes and diseases of the ocular surface and cornea. Invest Ophthalmol Vis Sci. 2013 Dec 13;54:ORSF48-ORSF53.
2. Petrash JM. Aging and age-related diseases of the ocular lens and vitreous body. Invest Ophthalmol Vis Sci. 2013 Dec 13;54:ORSF54-ORSF59.
3. Craig JP, Willcox MD, Argüeso P, et al; members of the TFOS International Workshop on Contact Lens Discomfort. The TFOS International Workshop on Contact Lens Discomfort: report of the contact lens interactions with the tear film subcommittee. Invest Ophthalmol Vis Sci. 2013 Oct 18;54:TFOS123-TFOS156.
4. Jones L, Brennan NA, González-Méijome J, et al; members of the TFOS International Workshop on Contact Lens Discomfort. The TFOS International Workshop on Contact Lens Discomfort: report of the contact lens, materials, design and care subcommittee. Invest Ophthalmol Vis Sci. 2013 Oct 18;54:TFOS37-TFOS70.
5. Dumbleton K, Keir N, Moezzi A, Feng Y, Jones L, Fonn D. Objective and subjective responses in patients refitted to daily-wear silicone hydrogel contact lenses. Optom Vis Sci. 2006 Oct;83:758-768.
6. Dumbleton K, Woods C, Jones L, Fonn D, Sarwer DB. Patient and practitioner compliance with silicone hydrogel and daily disposable lens replacement in the United States. Eye Contact Lens. 2009 Jul;35:164-171.
7. Richdale K, Sinnott LT, Skadahl E, Nichols JJ. Frequency of and factors associated with contact lens dissatisfaction and discontinuation. Cornea. 2007 Feb;26:168-174.
8. Frick KD, Joy SM, Wilson DA, Naidoo KS, Holden BA. The global burden of potential productivity loss from uncorrected presbyopia. Ophthalmology. 2015 Aug;122:1706-1710.
9. Bourne RRA, Flaxman SR, Braithwaite T, et al; Vision Loss Expert Group. Magnitude, temporal trends, and projections of the global prevalence of blindness and distance and near vision impairment: a systematic review and meta-analysis. Lancet Glob Health. 2017 Sep;5:e888-e897.
10. Rueff EM, Bailey MD. Presbyopic and non-presbyopic contact lens opinions and vision correction preferences. Cont Lens Anterior Eye. 2017 Oct;40:323-328.
11. Rueff EM, Varghese RJ, Brack TM, Downard DE, Bailey MD. A survey of presbyopic contact lens wearers in a university setting. Optom Vis Sci. 2016 Aug;93:848-854.
12. Sulley A, Young G, Hunt C. Factors in the success of new contact lens wearers. Cont Lens Anterior Eye. 2017 Feb;40:15-24.
13. Novillo-Diaz E, Villa-Collar C, Narvaez-Pena M, Martin JLR. Fitting success for three multifocal designs: multicentre randomised trial. Cont Lens Anterior Eye. 2018 Jun;41:258-262.
14. Peterson RC, Wolffsohn JS, Nick J, Winterton L, Lally J. Clinical performance of daily disposable soft contact lenses using sustained release technology. Cont Lens Anterior Eye. 2006 Jul;29:127-134.
15. Maissa C, Nelson J, DeCenzo-Verbeten T, Kramer D, Martin A. Evaluation of the lubricity of DAILIES TOTAL1 contact lenses after wear. Optom Vis Sci. 2014;91:E-abstract 145195.
16. Stapleton F, Tan J. Impact of contact lens material, design, and fitting on discomfort. Eye Contact Lens. 2017 Jan;43:32-39.
17. Kern J, Rappon J, Bauman E, Vaughn B. Relationship between contact lens coefficient of friction and subjective lens comfort. Contact Lens Anterior Eye. 2013 Dec;36 Suppl 2:e26 (abstract).
18. Coles C, Brennan N. Coefficient of friction and soft contact lens comfort. Optom Vis Sci. 2012;89:E-abstract 129603.
19. Varikooty J, Keir N, Richter D, Jones LW, Woods C, Fonn D. Comfort response of three silicone hydrogel daily disposable contact lenses. Optom Vis Sci. 2013;90 Sep:945-953.
20. Insua Pereira E, Lira M. Comfort, ocular dryness, and equilibrium water content changes of daily disposable contact lenses. Eye Contact Lens. 2018 Nov;44 Suppl 2:S233-S240.
21. Chalmers RL, Begley CG, Moody K, Hickson-Curran SB. Contact Lens Dry Eye Questionnaire-8 (CLDEQ-8) and opinion of contact lens performance. Optom Vis Sci. 2012 Oct; 89:1435-1442.