Tear film dynamics of a new soft contact lens

To present the objective metrics from a study that evaluated the clinical performance of a senofilcon A contact lens, both with and without a new manufacturing technique.


INTRODUC TION
Tear film stability is the hallmark for optimum ocular surface health and rendering high-quality, clear vision. [1][2][3] The tear film not only prevents infection and inflammation but also heals injuries, clears debris and especially prevents dryness and discomfort. 4 Therefore, tear film stability becomes pertinent in individuals who wear contact lenses considering that dryness, red eyes, discomfort and vision problems are the most common reasons for discontinuation of contact lens wear. 5 Contact lenses have a multitude of effects on the eye. 5 They can destabilise the tear film, isolate the mucin layer behind the lens and disrupt the lipid layer, 6 thus adversely impacting the biocompatibility. 7 Once worn, the contact lens splits the tear film into a pre-lens and post-lens film and evokes some changes in the ocular surface. 6 In addition, the tear volume and the tear film thickness are reduced (tear meniscus volume from 1.5 to 1 μL and tear film thickness from about 7 to 1-2 μm), [8][9][10] while the osmolarity is increased. 11

O R I G I N A L A R T I C L E Tear film dynamics of a new soft contact lens John Buch
| Donald Riederer | Charles Scales | Jie Xu Furthermore, the non-invasive tear break-up time may be reduced from 15 to 30 s before insertion to <10 s after wearing the contact lenses. 12 Besides these, factors such as evaporation from the lens surface also contribute to thinning or quicker break-up of the tear film. An altered water gradient (more moisture inside the lens than on the lens surface) due to evaporation leads to contact lens dehydration and might damage the epithelial cells. 5,13 These changes have a notable impact on vision as nonuniform tear film thinning and exposure of the uneven epithelial surface causes light to scatter as well as wavefront aberrations where the tear film breaks. 14 This causes visual disturbances and poor performance of the contact lens, especially under conditions such as low humidity, high temperature and varying contrast and luminescence. More importantly, both blink frequency and blink completeness have a notable impact on tear film optical quality dynamics. Thus, maintaining appropriate balance among these components as well as the dynamics between tear production, evaporation, absorption and drainage is crucial for proper vision, comfort and ocular health. 15 Apart from these intrinsic factors, the contact lens material and design may cause alterations in the lipid layer and aqueous phase of the pre-lens tear film, which influence the ocular health and quality of vision. 15 Therefore, current research in this area focuses on developing contact lenses that work with the tear film rather than against it, maintain tear film homeostasis and optimise wearer comfort while providing high-quality vision. 16 In such an endeavour, a senofilcon A contact lens was developed using a new manufacturing method, which involved double-sided curing. This curing method is believed to optimise the wetting agent distribution, polyvinylpyrrolidone (PVP), throughout the lens matrix and at the surface. The hydrophilic and lipophilic properties of PVP are known to improve the wettability of the lens 17,18 and are often used in eyedrops indicated for dry eyes. 19 It has also been shown to decrease the rate of evaporation at the lens surface. 20 Therefore, this study hypothesized that improvements from this curing process would alter tear film stability.
Here, we present the objective results from a clinical study that evaluated the performance of a senofilcon A contact lens both with (test) and without (control) the enhanced curing method. The control lens is marketed under the brand name ACUVUE® OASYS 1-Day (acuvue.com). The test lens was recently launched under the brand name ACUVUE® OASYS Max 1-Day (acuvue.com).

Study design
This was a single-site, five-visit, controlled, randomised, subject-masked, 2 lenses × 2 wearing periods crossover study conducted from 15 May 2021 to 30 August 2021.
Healthy adults (18-39 years) who were habitual wearers of spherical silicone hydrogel contact lenses were included. The investigation comprised a 2-week lens-dispensing period with bilateral wear, daily disposable and weekly follow-up visits.

Participants
All participants were between 18 and 39 years of age. They were habitual (≥6 h/day for a minimum of 5 days/week during the past 30 days) spherical silicone hydrogel soft contact lens wearers in each eye in a daily reusable or daily disposable wear modality (i.e., no extended wear modality). They had to have a vertex-corrected distance spherical equivalent refractive error between −1.00 and −6.00 DS (inclusive), vertex-corrected distance cylindrical refraction ≤1.00 D and best corrected, monocular, distance visual acuity of 6/7.5 or better in each eye.
Participants were excluded if they were using any medication(s), had any ocular or systemic allergies or diseases and/or any Grade 3 or greater slit lamp findings as per the US Food and Drug Administration (FDA) scale that could interfere with contact lens wear. 21 Habitual medications taken by successful wearers were generally considered acceptable. Participants were excluded if they had undergone any previous, or planned (during the study) ocular or interocular surgery, were currently wearing lenses in a monovision, multi-focal, toric or extended wear modality, had participated in a contact lens or lens care product clinical trial within 14 days prior to study enrolment, had a history of binocular vision abnormality or strabismus or had any infectious disease or contagious immunosuppressive diseases by self-report. Pregnant (by self-report) and lactating women were excluded. All participants were provided an IRB-informed consent form to sign and received a fully executed copy of the form.

Key points
• This study evaluated the clinical performance of a senofilcon A contact lens manufactured with a new methodology (test lens) and the marketed ACUVUE® OASYS 1-Day (control lens). • The High-definition (HD) Analyzer™ was used to objectively measure the vision break-up time, modulation transfer function cutoff, Strehl ratio, potential visual acuity for 100% contrast and objective scatter index. • Results revealed that the odds of having a vision break-up time greater than 10 s among participants wearing the test lens were about 1.6 times those for the control lens.

Study contact lenses and measurements
Lens assignment (Test/Control, or Control/Test) was generated using randomly permuted block randomisation in SAS version 9.0 (SAS Institute; sas.com). The powers for the test and control contact lenses were initially determined by subjective refraction. A spherical over-refraction was used to optimise the lens power until a 0.00 D over-refraction was achieved in both eyes. The lenses were dispensed as daily disposable for approximately 2 weeks where subjects were asked to wear them for at least 5 days/week and 6 h/ day. At the first follow-up visit, a sphero-cylindrical overrefraction was performed. For eyes displaying residual astigmatism between 0.00 and 0.50 D, pupil size was measured three times under mesopic conditions (Neuroptics VIP-300; neuro ptics.com). Eyes displaying an average mesopic pupil size ≥4 mm were then evaluated with the HD Analyzer (Keeler; keele rusa.com). 22 Iris colour was recorded using the scale described previously. 23 The irides were characterised by lightness (light, medium and dark) and hue (grey, blue, green, hazel and brown). The ability of an optical system to form a quality image is fundamental to optical designers and is the basis for several international standards. 24 The HD Analyzer™ was used to measure objectively the lens-on-eye optical system quality resulting from the two contact lenses. The following measurements were assessed at the follow-up visit: (1) vision break-up time (VBUT): the open-eye time before a vision deficit is predicted, (2) modulation transfer function (MTF) cutoff: the highest spatial frequency resolved by the eye, (3) Strehl ratio (SR): the MTF of the system divided by the MTF of a diffraction-limited (optimal) system, (4) potential visual acuity (PVA) for 100% contrast: predicted visual acuity based on the MTF and (5) objective scatter index (OSI), or more commonly termed the point spread function. During measurement acquisition, subjects were asked to blink a couple of times and then refrain from blinking. VBUT was measured over several seconds. The remaining metrics were measured within the first second after blinking. All HD Analyzer measurements were acquired five times for both the right and left eyes.

HD Analyzer
The HD Analyzer™ provides an objective and reliable clinical evaluation of the optical quality of the eye based on the double-pass technique. 25 It works on the principle of refraction. An isolated light source is produced by a 780 nm laser beam, the image of which is formed on the retina. When reflected from the retina, the light crosses the ocular media twice. The size and shape of the reflected light source are analysed by the system for optical quality to determine the higher-order aberrations and scattered light. The system is easy to use and is helpful in refractive surgery, to detect and classify cataract and evaluate the degradation of tear film over time. 22,26 Vision break-up time is the elapsed period from 0 s to the time at which the participant's vision quality index has dropped below a defined threshold. Essentially, it is the time needed for the point spread function to deteriorate, whereupon vision is predicted to be impacted. It is measured every 0.5 s. The MTF of an optical system is the function that allows evaluation of the degree of detail that the system can distinguish, or the relationship between the contrast of the object and the image. With the eye being an optical system, the MTF indicates the decrease in contrast of the retinal image with respect to the real scene. The SR is a quantitative measure of eye quality (value between 0 and 1) and can be calculated as the MTF quotient of the eye and the MTF of a diffraction-limited system. Therefore, the higher the value, the greater the optical quality. PVA is assessed from the MTF. The visual acuity imposed by the optics of the eye is estimated for different contrasts (PVA predicted 100%). The OSI allows objective evaluation of intraocular scattering and is calculated from the amount of light that is on the outside of the patient's double-pass image, relative to the amount of light in its central part. Thus, the higher the OSI value, the greater the level of intraocular scattering. 27 OSI is akin to the more familiar term point spread function.
Any observation graded as three or four on the biomicroscopy scale 28 provided by the US FDA was designated as an ocular adverse event (AE). This study was performed in accordance with ISO 14155:2020 standards for Good Clinical Practice and the ethical principles of the Declaration of Helsinki. This study was approved by Sterling IRB (Sterlingirb.com; No: 8794).

Statistical analysis
Statistical analyses were performed using the Statistical Analysis System (SAS) software Version 9.4 (SAS Institute; sas.com). The objective metrics were analysed on the intent-to-treat population (ITT, defined as all randomised participants regardless of actual treatment and regardless of withdrawal from the study or deviation from protocol). Each endpoint was analysed separately using the (generalised) linear mixed effects model, which included an intercept random effect for subjects and the unstructured covariance structure to address the correlation of the residual errors from the within-subject repeated measures. The models were adjusted for the subject's age and gender. The VBUT values from the HD Analyzer™ were converted into a binary variable (0 = VBUT ≤ 10 s and 1 = VBUT > 10 s) for the analysis, given that a VBUT value >10 s was not available due to the setup of the instrument. The generalised linear mixed model with a binary distribution and the logit link function was used to analyse the dichotomised VBUT data and the probability of '1' (VBUT > 10 s) was modelled. The OSI was analysed using the generalised linear mixed model with a lognormal distribution to account for skewed data. The estimated least squares means (LSMs) of the log-transformed observations were transformed back to the original scale using the exponential function. Estimates of the median OSI for each lens and the ratio of median OSI (test over control) on the original scale were derived via the backtransformation. The linear mixed effects model with a normal distribution was used for other endpoint analyses (PVA 100%, MTF cutoff and SR). Statistical inference was made based on the estimated two-sided 95% confidence interval (CI) constructed for the odds ratio (VBUT), ratio of medians (OSI) and LSM difference (PVA 100%, MTF cutoff and SR).

R ESULTS
Of the 50 participants enrolled in the study, 47 (94.0%) were randomised to one of the two possible lens wear sequences (test/control or control/test, ITT population), and they have dispensed at least one study lens (safety population), while three (6.0%) participants were enrolled but did not receive the study lenses (Table 1). Overall, 42 (84.0%) participants completed the investigation while five (10.0%) discontinued the study. A total of 41 (82.0%) participants completed the experiment without any major protocol deviation (per protocol population [PP]). Five participants (two in period 1 [one lost to follow-up and one due to COVID-19-related issues] and three participants in period 2 [all due to AEs]) discontinued the study (Figure 1).

Objective metrics
The overall results are summarised in Figure 2.

Vision break-up time
With respect to VBUT, the test lens was just significantly better than the control lens (p = 0.046). The lower limit of the 95% CI constructed for the odds ratio was above 1.0.
The estimated odds ratio suggests that participants wearing the test lens were more likely (~1.6 times) to have VBUT > 10 s versus the control lens.

Modulation transfer function
The test lens was just significantly better than the control lens with respect to MTF (p = 0.049). The estimated difference between the test and control lenses was ≈2.2. The lower limit of the 95% CI for the LSM difference (test -control) was above zero.

Strehl ratio
No significant difference between the lenses was observed for the SR (p = 0.09). The lower limit of the 95% CI for the LSM difference (test -control) was below zero, but the estimated mean difference trended in favour of the test lens.

Potential visual acuity
No significant difference was observed between the lenses (p = 0.05). The lower limit of the 95% CI for the LSM difference (test -control) was below zero, but the estimated mean difference trended in favour of the test lens.

Objective scatter index
No significant difference was observed between the lenses (p = 0.23). The upper limit of the 95% CI for the estimated ratio of median OSI (test over control) was above 1.0, but the estimated ratio trended in favour of the test lens.
Overall, the test lens was significantly better than the control lens for VBUT and MTF cutoff, but not for the SR, PVA or OSI ( Figure 2).

Adverse events
No serious adverse events were reported. A total of eight AEs (three ocular and five non-ocular) were reported by six participants (Table 3). Of the reported AEs, only one was considered to be possibly related to the study (control lens).

Population Test/control lens Control/test lens Not treated Total
Total participants enrolled 24 23 3 50 Per

DISCUSSION
The test and control lenses were evaluated for objective metrics (VBUT, MTF cutoff, SR, PVA for 100% contrast and OSI) using the HD Analyzer™ at the 1-week follow-up visit. The data showed that the test lens was statistically superior to the control lens with respect to the VBUT and MTF cutoff. A non-significant trend in favour of the test lens based on the three other metrics (SR, PVA and OSI) was also observed. Vision break-up time is a key parameter when a contact lens user needs to maintain focus for longer durations without losing image quality, which is especially pertinent in the current digital age. 29 The time spent viewing digital devices has increased considerably during the recent COVID-19 pandemic. 30 These visual demands may lead to digital eye strain, characterised by dry and red eyes, itching, foreign body sensation, tearing, blurred vision and headache. 31 The prevalence of digital eye strain has increased from 5% to 65% in the pre-COVID-19 times to 80%-94% in the COVID-19 era. 31 Additionally, digital device use is associated with up to a 60% decreased rate of blinking, compared with normal conversational rates. 32 Coupled with increased digital device time, the decreased blink rate can lead to the development of dry eye symptoms and discomfort, particularly at the end of the day. 32 The test lens was superior to the control for achieving a VBUT of 10 s, which may imply that it could offer good quality vision for a longer duration. The results also indicated that the odds of having a VBUT > 10 s were about 1.6 times greater while wearing the test lenses. This might also help to extend the tear film break-up time. These benefits may be useful to individuals who spend a long time viewing digital devices, improving visual clarity and comfort and which might lead to increased satisfaction and use of the lens.
Another important parameter from the lens wearers' perspective is the MTF cutoff, which evaluates the degree of detail that the eye can distinguish, or the difference between the contrast of the real scene and the contrast of the ocular image. The MTF cutoff exhibits a positive correlation with vision, that Completed is the higher the MTF cutoff, the better is the vision, especially peripheral vision. 33 Factors adversely impacting the MTF include ocular dryness and shorter tear break-up time. 29 The test lens was superior to the control lens, and hence seems to provide better vision by addressing these two key issues. The MTF combines the effect of all aberrations while transferring contrast, while excluding the sensitivity and limits of neural processing of the visual system and phase errors, which influence visual quality. 34 Hence, combining it with the SR may give a better indicator of vision quality. As expected, there was a trend towards a better SR and PVA with the test versus the control lens since MTF was superior with the test lens. A better SR at 1-week post-fitting indicates better optical quality and reduced aberrations, as defined quantitatively. Similarly, a better PVA at 1-week post-fitting for the test lens suggests that participants might achieve further improved vision with the test lens. The SR is predictive of subjective best focus and correlates well with the change in visual performance. 34 However, the clinical significance of these metrics is not completely understood due to the lack of historical and comparative data. Furthermore, there are no similar studies providing either a direct or indirect comparison of the results.
The OSI is indicative of low-contrast parameters and decreases with age, thereby hampering vision. 34 It is effectively a measure of the point spread function measured here 1 s following a blink. No significant difference between the two lenses was observed with respect to this index.
A natural question is if the VBUT measurement was significantly different between the two lenses, then why did the OSI also not show significant effects? It should be noted that VBUT is ultimately based on a series of OSI measurements over time (every 0.5 s). Comparisons between VBUT and the OSI measurement are therefore valid within the first second after the blink. Plotting the OSI measurements during the VBUT assessment shows a general separation between the test and control lens (Figure 3). Note that the test lens appears to have a consistently smaller OSI than the control lens.
A stable tear film is essential to form a smooth refractive surface for vision and is responsible for ocular surface comfort and health, as well as mechanical, environmental and immunological protection. 35 Therefore, apart from the objective metrics, other factors such as tear production, contact lens material and pervaporation may also influence the tear film equilibrium.
The PVP matrix in the contact lens closely mimics the properties of mucin and improves comfort when the lens interacts with the tear film. 36 This is particularly important in the pre-lens tear film where the eye's natural mucin is replaced by a contact lens. The presence of PVP has also been associated with a reduced rate of pervaporation, 37 and hence is a likely driver of improved tear film dynamics. Pervaporation is the evaporation of water from the ocular environment through the contact lens by the combined processes of permeation and evaporation. An in vitro investigation regarding the influence of lens material on pervaporation rate showed that lenses containing PVP had the lowest pervaporation rates and were particularly resistant to evaporative water loss at low humidity. 38 These results indicate that the contact lens material and tear production may interact to determine water loss and lens comfort. 38 Evaporation increases with age as the tear film gradually becomes less stable, possibly due to significant changes in the tear lipid layer. 38 Therefore, the test lens examined here may help to provide a more stable tear film, particularly with extended use of digital devices and in older lens wearers, given that tear film stability naturally decreases by ~50% by 50 years of age. 38,39 Both the test and control lenses examined here were made of senofilcon A, a lens material that contains PVP, which helps reduce discomfort and dryness and increases oxygen delivery to the cornea when compared with a hydrogel lens. 40 A significant distinction between the test and control lenses occurred during manufacturing. Both lenses were polymerised with light. The manufacturing process of the control lens utilised an established methodology whereby the lens is formed/polymerised by exposure to light from one side, whereas the test lens employed a new manufacturing process that formed/polymerized the lens through exposure to light from both sides. The double-sided curing is believed to enable a more optimal distribution of PVP throughout the lens, which helps promote increased tear-film stability. Studies have shown that senofilcon A lenses offer better lubrication and wettability and reduce post-lens tear film disruption, lid sensation while blinking and corneal swelling associated with overnight wear when compared with hydrogel lenses. 41,42 Overall, contact lenses often adversely impact tear film stability, which is the primary cause of dry eye disease. 43 The contact lenses compartmentalise the tear film and induce subsequent changes in the ocular surface, which warrants research to optimise lens properties. The main areas of interest are increased wettability and lubricity of the contact lens that enhances the quality of vision and comfort for the wearer. 44 This study suggests that the test lens examined here may provide greater comfort with respect to vision and wearability.  One of the strengths of the present study was the use of an HD Analyzer™ to assess vision quality objectively. This is a better measure of clinical visual performance than visual acuity, as it measures visual capacity in real situations, whereas visual acuity is a quantitative measure obtained under controlled conditions. 45 However, vision quality is multifactorial and determined using parameters such as OSI, VBUT, point spread function etc. 46,47

CONCLUSION
This study presents the objective metrics of a test lens produced using a new manufacturing method. The test lens was statistically superior to the control lens for VBUT and the MTF cutoff. Furthermore, it demonstrated an increased probability of having a VBUT > 10 s. Future studies should be designed to evaluate the efficacy and long-term use of this lens in a larger population.

AC K N O W L E D G E M E N T S
Medical writing assistance for this manuscript was provided by Dr Shridevi Venkataramani and Dr Payal Bhardwaj (both employed by Tata Consultancy Services, India) under the direction of the authors.

FU N D I N G I N FO R M AT I O N
Funding for this study was provided by Johnson & Johnson Vision Care, Jacksonville, Florida.