Chan V, Drolle E, Phan CM, Hui A, Shi C, Subbaraman L, Wu J, Jones L. Evaluating the activity of lysozyme deposited on contemporary reusable silicone hydrogel contact lenses using an in vitro eye model The Association for Research in Vision and Ophthalmology, New Orleans, LA, USA, 2023 [ Show Abstract ][ PDF ]

Purpose: To evaluate lysozyme activity (LA) on five contemporary reusable silicone hydrogel contact lens (CL)materials over their proposed wear period using an advanced in vitro blink model.

Methods: Five CL materials (lotrafilcon B, samfilcon A, comfilcon A, senofilcon A, and serafilcon A) were cycled daily for 16h on an eye model, followed by 8h of soaking in OPTI-FREE PureMoist, to mimic a typical wear cycle. An artificial tear solution containing physiologically representative proteins and lipids was delivered to the model at a rate of 1.2-2.1μl/min. The model includes an artificial eyelid that blinks at a rate of 6blinks/min, which was kept at room temperature and humidity above 50%. Serafilcon A and senofilcon A were tested over 14 days, whereas the other CLs were evaluated for 30 days. At specified time intervals, including after 1, 7, 14 and 30 days, CLs were removed from the model and lysozyme extracted using a solvent containing acetonitrile and trifluoroacetic acid. The LA from the extracts were then evaluated using a micrococcal absorbance assay.

Results: Overall, LA decreased over time, reaching non-detectable levels by day 30 (p<0.05). Serafilcon A (13.9 ± 7.8μg/lens), and samfilcon A (9.6 ± 2.3μg/lens), had the highest LA after 1 day, followed by comfilcon A (4.7 ± 1.8μg/lens), lotrafilcon B (3.3 ± 1.6μg/lens), and senofilcon A (2.2 ± 3.7μg/lens). By day 7, LA for the weekly replacement lens, serafilcon A, decreased to 0.5 ± 0.6μg/lens. By day 14, LA for the biweekly replacement lens, senofilcon A, decreased to 0.6 ± 0.7μg/lens. Lotrafilcon B, samfilcon A, and comfilcon A, all monthly replacement lenses, decreased in activity by day 30 (0.1 ± 0.2μg/lens, 0.5 ± 0.7μg/lens, 0.0 ±0.0μg/lens respectively).

Conclusions: Deposition of biologically active lysozyme has been proposed to be an important factor for biocompatible CL wear. A decline in activity over time as the deposited protein becomes denatured may impact overall CL performance and has been linked to reduced comfort. LA decreases over time and reaches near zero for all lens types by the end of their proposed wearing period, confirming that they should be replaced within their specified replacement intervals. Compared to simple in vitro vial models, using an advanced blink model for CL deposition testing aims to provide more physiologically relevant results prior to clinical testing.

Garg P, Wulff D, Phan CM, Jones L. Evaluation of a biodegradable bioink for the fabrication of ophthalmic devices using 3D printing The Association for Research in Vision and Ophthalmology, New Orleans, LA, USA, April, 2023 [ Show Abstract ][ PDF ]

Purpose: To develop a degradable bioink for fabricating ophthalmic devices using 3D printing.

Methods: The bioink formulation consisted of 10% gelatin methacrylate (GelMA), 0.6% lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP), and 5% yellow dye as a light absorbing agent to improve print resolution. The bioink was used to 3D print square sheets (7x7x1 mm) using a commercial masked-stereolithography (mSLA) 3D printer at 95% humidity and 37°C temperature. The degradation of printed sheets was evaluated with different concentrations (0,25,50,100 μg/ml) of matrix metalloproteinase (MMP9) enzyme 37°C. MMP9s are naturally found in the tear film and elevated in various diseased states such as in corneal wounds and dry eye disease. The weights of the sheets were measured at t = 0,4,6,8,12,16,24 hrs. Another set of cubes (1x1x1 cm) was autoclaved and kept sealed in storage at different temperatures (4°C, 25°C, and 37°C) in phosphate buffered saline (PBS) and their weight was measured on day 10. An attempt was made to fabricate a contact lens using this bioink.

Results: Samples that were exposed to MMP9 enzymes showed a time-dependent degradation with increasing enzyme concentration. The samples incubated with 100 and 50 μg/ml of MMP9 were completely degraded by the end of 12 and 16 hrs, respectively. At the end of 24 hrs, the samples incubated at 25 μg/ml enzyme showed 72.8% degradation whereas the control samples did not show any signs of degradation. Interestingly, samples that were autoclaved and kept in storage also did not show any signs of degradation at all temperatures. A 3D-printed CL with overall diameter 14mm and thickness 1mm was printed without any support structures within 1 hour.

Conclusion: This study showed GelMA-based bioink can be used to fabricate biodegradable devices such as contact lenses. The biomaterials degrade in the presence of MMP-9 and future work will work on tuning the degradation kinetics of these materials, as well as incorporating ocular drugs.

Garg P, Wulff D, Phan CM, Jones L. Fabrication of a degradable ocular drug delivery system using 3D printing CBB 2023 Conference: Waterloo for Health, Technology and Society, March, 2023 [ PDF ]

Guthrie S, Chow T, Luensmann D, Woods J, Lumb E, Orsborn G. Short term visual performance of two myopia control soft contact lenses British Contact Lens Association Clinical Conference & Exhibition, Manchester, Jun 9-11, 2023 [ Show Abstract ]

PURPOSE: To gain insights into the short-term visual performance of two myopia control contact lenses which employ different optical designs.

METHODS: Children aged 8 to 15 years, with no history of contact lens wear or recent myopia control intervention, participated in a non-dispensing, single visit, double masked trial where the study lenses were fit and worn contralaterally in randomised eyes. The myopia control study lenses were senofilcon A (AA1D, Johnson & Johnson Vision) and omafilcon A (M1D, CooperVision). After participants had worn the lenses for 1 hour, they rated their subjective experience with vision using a 0-100 scale (100 is best) and distance visual acuity (LogMAR (VA)) was measured. Lens preference was determined at the end of the wear period using a 5-point Likert scale and reasons for preference were provided.

RESULTS: Twenty-six participants completed the study (9F:17M; mean age 11.6 ± 2.1 years). Mean refraction was OD Sph -1.96 ± 0.93D (-0.25 to -3.50D), Cyl -0.34 ± 0.35D (0.00 to -1.00D) and OS Sph -1.77 ± 0.97D (-0.25 to -3.50D), Cyl -0.38 ± 0.38D (0.00 to -1.00D). Subjective ratings of distance vision at 1 hour were better (Wilcoxon matched pairs, p<0.01) with M1D (88 ± 14) versus AA1D (79 ± 18). Distance VA was also significantly better (Wilcoxon matched pairs, p<0.01) with M1D (0.02 ± 0.04 logMAR) over AA1D (0.09 ± 0.08 logMAR). When asked to provide an overall lens preference after 1 hour of wear, more participants preferred M1D than AA1D, and vision was reported as the main reason for their preference (M1D:14 vs AA1D:6, No preference:6; p=0.17).

CONCLUSIONS: When worn contralaterally for 1 hour, the different optical designs of M1D and AA1D performed significantly differently. M1D resulted in better distance vision ratings and visual acuity, and both of these differences would also be considered clinically relevant.

Guthrie S, Woods J, Luensmann D, Chow T, Lumb C, Orsborn G. Subjective Vision Experience in Soft Myopia Control Contact Lenses by Age American Academy of Optometry, New Orleans, October 12, 2023 [ Show Abstract ]

PURPOSE: To compare the short-term vision experience of preteens (PT) and teens (T) with two myopia control (MC) contact lenses of different optical designs: senofilcon A, with a noncoaxial ring-focus design (AA1D, Johnson & Johnson Vision) and omafilcon A, with a dual-focus design (M1D, CooperVision, Inc.).

METHOD: Children aged 8-15 years who had no prior history of contact lens wear or recent MC intervention were recruited for a single-visit, double-masked trial with study lenses randomly fit and worn contralaterally. Participants were separated into two age groups: PT: 8-12 years and T:13-15 years. After wearing the lenses for 1 hour, participants rated their subjective visual experience on a 0-100 scale (where 100 indicated the best experience), and distance visual acuity was measured using LogMAR (VA). At the end of the wear period, lens preference was determined using a 5-point Likert scale, and participants provided reasons for their preference.

RESULTS: Twenty-six participants completed the study (9F:17M; mean age 11.6 ± 2.1 years), 16 PT and 10 T. Mean refraction was OD Sph -1.96 ± 0.93D (-0.25 to -3.50D), Cyl -0.34 ± 0.35D (0.00 to -1.00D) and OS Sph -1.77 ± 0.97D (-0.25 to -3.50D), Cyl -0.38 ± 0.38D (0.00 to -1.00D). When participants rated their subjective experience with vision at 1 hour, both age groups reported better distance vision with M1D compared to AA1D (PT:M1D: 90 ± 15, AA1D: 82 ± 17, p<0.01; T:M1D: 85 ± 13, AA1D: 73 ± 18, p=0.02). Distance visual acuity (VA) was also better with M1D over AA1D in both groups, with the difference in the PT group being statistically significant (PT:M1D: 0.03 ± 0.04, AA1D: 0.09 ± 0.08, p<0.01; T:M1D: 0.02 ± 0.04, AA1D: 0.08 ± 0.09, p=0.07). For near VA, M1D performed better than AA1D in PT (PT:M1D: 0.07 ± 0.08, AA1D: 0.12 ± 0.08, p<0.05; T:M1D: 0.05 ± 0.05, AA1D: 0.06 ± 0.06, p=0.29). When asked to provide an overall lens preference after 1 hour of wear, more PT preferred M1D than AA1D (M1D:8 vs AA1D:4, No preference:4) and more T preferred M1D than AA1D (M1D:6 vs AA1D:2, No preference:2), with both groups reporting vision as the main reason for their preference.

CONCLUSION: When worn contralaterally for 1 hour, the different optical designs of M1D and AA1D performed significantly differently. The preteen and teen groups responded similarly, with M1D preferred by both groups for better distance vision. In addition, while teens had an equivalent vision experience to the preteens, they were overall more likely to rate that experience lower than preteens, indicating a potential difference in subjective experience between the groups and a more critical assessment of vision in teenagers.

Ho B, Phan CM, Ramasamy M, Hui A, Jones L. PDMS microfluidic devices fabricated from commercial 3D printers support growth of viable HCECs and enable cell biological assays for low-cost high-throughput screening The Association for Research in Vision and Ophthalmology, New Orleans, LA, USA, April, 2023 [ Show Abstract ]

Purpose: To integrate human corneal epithelial cells (HCECs) into a PDMS microfluidic chip fabricated from a novel 3D printing method to perform cell biological assays.
Introduction: The advent of microfluidic devices has enabled tight control over the physical and chemical cellular environment in vitro, while allowing for large-scale imaging and biochemical reactions at single-cell resolution. These devices are capable of miniaturizing assays to the microliter and nanoliter range, thereby increasing assay throughput with high sensitivity, a feature that is highly advantageous in high-throughput cell-based screens. Polydimethylsiloxane (PDMS) has been widely used in microfluidics devices due to its optical clarity and non-toxicity to cells, among other desirable features. However, the fabrication of PDMS devices traditionally requires specialized facilities and instruments. Additionally, PDMS itself is highly hydrophobic and does not support mammalian cellular viability and growth.

Methods: PDMS devices were cured in 3D-printed moulds generated using the FormLabs stereolithography (SLA) printer (FormLabs 3B+, FormLabs, Somerville, MA). These devices were sterilized by autoclaving, and coated with 0.01% polydopamine (PDA) and 20μg/mL collagen. HCECs were seeded onto the device, and allowed to grow for 18-36 hours in DMEM/F12 media at 37oC. HCECs were imaged by light microscopy, and viability was assessed by alamarBlue assays.

Results: Here, we present a novel and simple method of generating PDMS microfluidic devices suitable for mammalian cell biology assays using commercial 3D printing. We show that PDMS devices coated with polydopamine (PDA) support the growth of human corneal epithelial cells (HCECs) that are metabolically active (~60-90% viability) and are comparable to HCECs cultured in standard tissue culture plastic consumables. Finally, HCECs cultured in our devices are capable of growth with fluid flow rates of up to 1mm/s.

Conclusion: Our study shows that PDMS devices manufactured through the aid of a novel 3D printing pipeline support the growth of HCECs. We aim to utilize these microfluidic devices as a tool to screen different compounds and formulations while assessing cellular viability and acquiring high resolution microscopic and fluorescence images of HCECs.

Hui A. Commercialized Ocular Drug Delivery Devices XXV Biennial Meeting of the International Society for Eye Research, Feb 21, 2023 [ Show Abstract ]

The goal of creating a sustained drug delivery device for the anterior or posterior segment has been approached from numerous avenues, from inserts to contact lenses and punctal plugs. The utility of a device which can sustain drug release allows for the potential to increase patient compliance as well as improve clinical outcomes, as agents are able to be maintained at appropriate concentrations for desired periods with less administration. This presentation will discuss drug releasing devices for the eye which have reached commercialization. The indications for these devices, their reported effectiveness and known adverse reactions will be discussed. The experience on the use of the devices after they have been released on to the market will also be discussed, as well as their current clinical usage in contemporary eye care management.

Hui A, Heynen M, Chan V, Mirzapour P, Enstone D, Saad M, George M, Ngo W, Jones L. The impact of RGP care solutions on ISO measured lens parameters and the protein deposition on RGP lenses when managed with a hydrogen peroxide care solution Global Specialty Lens Symposium, Las Vegas, Jan 20, 2023 [ PDF ]

Jin Y, Jones L, Gorbet M. Investigation of the Circadian Recruitment of Tear Neutrophils to the Ocular Surface and Their Phenotypes  The Association for Research in Vision and Ophthalmology, New Orleans, LA, USA, April, 2023 [ Show Abstract ]

Purpose: Hundreds of thousands of leukocytes (with approximately 60% of the population being polymorphonuclear neutrophils (PMNs)) can be collected from the ocular surface immediately on waking, while only a few are harvested during the daytime. To better understand their role in ocular surface homeostasis and inflammation, this study aimed to investigate potential factors contributing to the circadian infiltration of tear PMNs and changes in phenotype across different time points in a 24-hour cycle.

Methods: Tear leukocytes were collected from 30 participants using a gentle eyewash after 2-hr and 7-hr of sleep at night, after 2-hr sleep during the day, and towards the end of the day (around 5 pm). Cell count and morphology were determined using a Moxi Z cell counter and May-Grunwald stain, respectively. Cells were stimulated by fMLP. Changes in the degranulation (lactoferrin, CD66b, CD63) and cell aging state (CD184) of PMNs were measured via flow cytometry. Neutrophil extracellular traps (NETs) were also identified by flow cytometry and microscopy following staining with myeloperoxidase, citrullinated histones, and CD15.

Results: Significantly more cells were collected from the nighttime compared to the daytime (p<0.001). There was a positive correlation between IL-8 concentrations and PMN numbers, but not with C5a, suggesting that the recruitment of tear PMNs to the ocular surface may be driven mainly by IL-8. 2hr-sleep-derived tear PMNs were less degranulated than 7hr-sleep-derived tear PMNs (p<0.03) and possessed a larger functional activation potential in response to stimulus (p<0.03). Furthermore, 7hr-sleep-derived tear PMNs exhibited hyper-segmented nuclei and were prone to aggregation, when compared to 2hr-night-derived tear PMNs, suggesting an aged and activated phenotype. A significantly increased number of NETs were present in 7hr-night-derived tear samples (p<0.05).

Conclusions: The diurnal-nocturnal recruitment pattern of tear PMNs may be driven by the increase in IL-8 in nighttime tears. Higher levels of degranulation and NETs indicate that tear PMNs become more activated on the ocular surface during prolonged eye closure at night. This PMN inflammatory response must then be balanced by other anti-inflammatory processes to prevent ocular surface damage.

Jones D, Guthrie S, Woods J, Nguyen M, Chamberlain P, Hammond D. . Young Adult Acceptance of Dual Focus Myopia Control Soft Contact Lenses British Contact Lens Association Clinical Conference & Exhibition, Manchester, Jun 10, 2023 [ Show Abstract ]

Purpose: Myopia can continue to progress during early adulthood and previously observed acceptance of dual focus contact lenses in adolescents does not verify that progressing young adult myopes will similarly accept potential minor vision compromises when achieving the desired myopia control effect. This study assessed acceptance of dual focus myopia control contact lenses by myopic young adults.

Methods: Habitual single vision (SV) contact lens wearers (age 17-25) were dispensed MiSight 1 day (M1d, omafilcon A, CooperVision, Inc.) for 3 months. The Quality of Vision (QoV) questionnaire (McAlinden, 2010) was performed at baseline, 2 weeks, 1, 2 & 3 months. Frequency, severity and bothersome scores were summed for each vision symptom (e.g. glare) to give a combined metric (Best:0/Worse: 9). Non-parametric repeated measure ANOVA with Wilcoxon post-hoc analysis was used to determine how visual experience in M1d changed over the duration of the study and compared to SV at baseline.

Results: 27/29 of participants completed the study (23F:4M; age 22.5±1.7; SERE -3.55D±1.55D). Subjects self-reported that M1d was worn at least 6 days per week and this wear pattern was sustained over three months, averaging >12h per day (2w: 12.5±1.9h, 1M: 12.6±2.0h, 3M: 12.2±1.7h). Perception of starbursts, hazy vision, blurred vision, distortion, and fluctuating vision were not significantly different in M1d than SV. While glare, haloes, focusing difficulties, depth perception and double vision summed symptom scores at all timepoints were significantly increased compared to SV (range between 2-4 points higher, p<=0.002), 70% of subjects responded that they were likely to continue M1d wear given the likely myopia control benefits.

Conclusion: Full day wear of MiSight 1 day soft contact lenses was well tolerated in young myopic adults with mild increases in a limited number of vision symptoms that had no impact on wear time.

Jones D, Luensmann D, Alton K. The prevalence of refractive error in children in a Canadian rural, First Nation Community 4th World Congress of Optometry O=MEGA23, Melbourne, Sep 8, 2023

Jones L. Osmolarity: Gold Standard for Dry Eye Disease Determination or Random Number Generator? XXV Biennial Meeting of the International Society for Eye Research, Feb 23, 2023 [ Show Abstract ]

The potential impact of osmolarity on dry eye symptoms dates back to the early 1970’s. The concept that tear film instability leads to hyperosmolarity and that this is a key factor in the development of dry eye disease (DED) is described in the 2017 TFOS Reports. Both aqueous deficient and evaporative DED can lead to tear hyperosmolarity, which stimulates ocular surface inflammation through increased expression and production of proinflammatory cytokines and chemokines, resulting in corneal epithelial cell death by apoptosis. Ocular surface disease and tear hyperosmolarity have also been associated with goblet cell loss, which can lead to altered mucin expression and tear film instability, further exacerbating inflammatory processes. These changes may stimulate sensory nerve fibers innervating the ocular surface, generating sensations of ocular discomfort. Although osmolarity has gained fairly widespread acceptance as a DED diagnostic, findings suggest that tear osmolarity measurements do not possess the very high sensitivity and specificity claimed by some studies and it may have limited value in the diagnosis of DED. A key factor in determining the relationship between DED and osmolarity relates to the ability to measure osmolarity, a process that is not without its challenges. The low volume of tears on the ocular surface necessitate using techniques that can estimate osmolarity using micolitre or nanolitre volumes of fluid. Clinical assessment methods typically occur through estimation of the osmolarity of the inferior tear meniscus. However, calculations using fluorescence assessments and hyperosmolar drops suggest that hyperosmolar levels in the tear film overlying the ocular surface may transiently spike during tear instability to levels far greater than that determined in the inferior tear meniscus, resulting in corneal inflammation and triggering sensory neurons. This may explain the relative disconnect between DED symptoms and osmolarity measurements.
Additonally, variability in results obtained between instruments, within-visit measures, differences between eyes and the impact
of treatments on osmolarity values over time require further examination.
In addition to DED, this review will examine other factors that may impact osmolarity values, including contact lens wear, cataract
and refractive surgery and systemic drugs. Finally, the osmolarity of ocular lubricants and contact lens blister packs and their
clinical relevance will be discussed.

Jones L, Craig J, Hinds M, Alster Y, Bosworth C, Ng A.. Sign and Symptom Improvement Rates Among MGD Patients Following 6 Months of Treatment With AZR MD 001 American Academy of Optometry, New Orleans, October 12, 2023 [ Show Abstract ]

Purpose: AZR MD 001, a topical ophthalmic ointment consisting of selenium sulfide as an active ingredient (either 0.5% or 1.0% concentration), was investigated in a Phase 2 clinical trial as a new treatment for meibomian gland dysfunction (MGD). Treatments for MGD seek to demonstrate strong efficacy, restore gland function, and improve patient symptoms. The aim of this study was to determine the responder rates for signs and symptoms in patients with MGD following 6 months of treatment with AZR MD 001.

Methods: For this multicenter, double-masked, vehicle-controlled, parallel-group trial (NCT03652051), randomized patients (1:1:1) received AZR MD 001 (0.5% [n=82] or 1.0% [n=83]) or vehicle (n=80) twice weekly before bed for 6 months. Eligible patients were ≥18 years of age, exhibited meibomian gland obstruction (Meibomian Gland Secretion [MGS] score ≤12 for 15 lower lid glands), and were required to discontinue topical prescription ocular surface treatments for ≥2 weeks and topical ophthalmic preparations (including artificial tear substitutes). Predefined responder criteria, based on literature thresholds, were: Meibomian Glands Yielding Liquid Secretion (MGYLS) change from baseline ≥5, MGS score >12, and Ocular Surface Disease Index (OSDI) score <13. Analyses included all data through month 6.

Results: AZR MD 001 showed a higher percentage of patients with a clinically meaningful improvement of ≥5 more glands yielding meibum compared with vehicle (MGYLS: 60%, p<0.0001 for AZR MD 001 0.5%; 43%, p=0.0218 for AZR MD 001 1.0%; 22% for vehicle). Significantly more patients randomized to AZR MD 001 demonstrated normal meibum (MGS >12) as early as 14 days (20%, p=0.0380 for AZR MD 001 0.5%; 19%, p=0.0949 for AZR MD 001 1.0%; 7.6% for vehicle). Patients continued to demonstrate normal meibum at month 6 (74%, p=0.0017 for AZR MD 001 0.5%; 63%, p=0.1273 for AZR MD 001 1.0%; 48% for vehicle). By month 6, significantly more patients treated with AZR MD 001 were asymptomatic for disease (OSDI <13: 48%, p=0.0333 for AZR MD 001 0.5%; 50%, p=0.0205 for AZR MD 001 1.0%; 30% for vehicle).

Conclusion: Over 6 months, a statistically significant proportion of patients applying AZR MD 001 demonstrated a clinically meaningful response, with normalization of their meibomian gland function and the achievement of asymptomatic status for disease.

Luensmann D, Guthrie S, Woods J, Voltz K, Vega J.. Software Guided Orthokeratology Fitting Success American Academy of Optometry, New Orleans, October 12, 2023 [ Show Abstract ]

PURPOSE: To evaluate the ease of fit and success rate of the recommended orthokeratology lens parameters as determined by the Visavyä software (CooperVision Inc.).

METHOD: This four-site prospective study recruited participants aged 6-35 years and fit them bilaterally with Paragon CRT® or Paragon CRT Dual Axis® orthokeratology lenses (CooperVision Inc.), worn every night for 1 month. Four different topographers were used in the study: Medmont E300, Oculus Keratograph 5, Oculus Pentacam or Topcon CA-800. Topography data were uploaded into the software and together with subjective refraction and white-to-white corneal diameter data, the software calculated the recommended lens parameters for the first trial lens. If fit and/or vision was not acceptable, lens modifications were permitted at the dispense visit, after the first night or after one week of wear. Best-corrected visual acuity was determined at baseline and unaided acuity was measured after one month of overnight lens wear.

RESULTS: 54 participants (33F:21M), mean age 17.5±7.4 years [7 to 35 years] were included in the analysis. An additional 8 participants were successfully screened and dispensed but exited the study early for lens related and other reasons, they are not included in the analysis. The mean subjective refraction (OU) of all completed participants was Sph -2.60±1.30DS [-5.75 to 0.00] and Cyl -0.50±0.47DC [-1.75 to 0.00]. The software recommended either CRT or CRT Dual Axis lenses depending on the corneal toricity: • Medmont: 13 CRT, 17 Dual Axis • Oculus Keratograph 5: 10 CRT, 28 Dual Axis • Oculus Pentacam: 11 CRT, 9 Dual Axis • Topcon CA-800: 13 CRT, 7 Dual Axis Only four eyes (<4%) involving 3 different participants required a lens parameter change from the initial lens recommendation by the fitting software (all CRT Dual Axis) and involved two different topographers. For the cohort, the best-corrected visual acuity (logMAR) prior to lens wear was -0.07±0.11 (-0.30 to 0.14) and unaided vision after 1 month of lens wear was -0.03 ± 0.15 (-0.30 to +0.38) (p<0.01). Remaining refraction after 1 month was Sph –0.04 ± 0.34 DS. (-1.25 to +0.75). The 1-month unaided vision by lens type was: • CRT: -0.07 ± 0.12 (-0.30 to 0.14) • CRT Dual Axis: -0.01 ± 0.16 (-0.30 to 0.38) There were no significant or serious ocular adverse events in this study.

CONCLUSION: The Visavy™ software successfully integrated data from four different topographers and provided a >96% first fit success rate for Paragon CRT® and Paragon CRT Dual Axis®. This predictable outcome makes the Visavy™ software a valuable tool for eye care professionals when fitting these lenses to minimize chair time and optimize wearer satisfaction.

Luensmann D, Guthrie S, Woods J, Voltz K, Vega J.. Orthokeratology fitting success using a new software British Contact Lens Association Clinical Conference & Exhibition, Manchester, Jun 9-11, 2023 [ Show Abstract ]

PURPOSE:
To determine vision outcome after orthokeratology (Ortho-K) lens wear when using the new Visavy software (CooperVision Specialty EyeCare) to determine the recommended lens parameters.

METHODS:
This multisite (3) prospective study recruited participants aged 6-35 years and fit them with Paragon CRT or Paragon CRT Dual Axis Ortho-K lenses (CooperVision Specialty EyeCare), worn every night for 1 month. Topography images (Oculus Keratograph 5, Medmont E300, or Topcon CA-800) were uploaded in the software and together with entries for subjective refraction and white-to-white corneal diameter, the software provided the recommended lens parameters. If fit and/or vision was not acceptable, lens modifications were permitted at the dispense visit, after the first night or after one week of wear. Best-corrected visual acuity was determined at baseline and unaided after one day, one week and one month of Ortho-K wear. Subjective comfort was collected after the first lens application and after one month (0-10 scale, 10=very comfortable).

RESULTS:
Thirty participants (19F:11M), mean age 13.6±5.9 years [7 to 35 years] were included in the analysis. The mean refraction of all 60 eyes was Sph -2.98±1.27DS and Cyl -0.54±0.43DC. Best-corrected visual acuity (logMAR) prior to lens wear was -0.01±0.04 and unaided vision was +0.30±0.33 after the first night, +0.05±0.13 after 1 week and +0.06±0.10 after 1 month of Ortho-K lens wear. Remaining subjective refraction after 1 month was Sph –0.37±0.82DS. Only two eyes (<3%) required a lens parameter change after the initial lens recommendation by the fitting software. Comfort ratings were significantly better after 1 month (7.8±1.6) compared to the dispense visit (5.6±2.2)(p<0.01). There were no ocular adverse events in this study.

CONCLUSIONS:
The software provided a 97% first fit success rate for Paragon CRT and Paragon CRT Dual Axis. This predictable outcome makes the Visavy software a valuable tool for ECPs when fitting Ortho-K lenses.

Luensmann D, Schulze M, Guthrie S, Woods J, Jones L. Evaluating the change in symptoms when symptomatic daily disposable lens wearers are refit with delefilcon A Optometry's Meeting ePosters Virtual Event, Jun 13, 2023

Luensmann D, Schulze M, Guthrie S, Woods J, Jones L. Early lens handling experience of neophyte wearers fitted contralaterally with a hydrogel and a silicone hydrogel daily disposable contact lens Optometry's Meeting ePosters Virtual Event, Jun 13, 2023

Luensmann D, Tucker AW, Voltz K, Guthrie S, Woods J, Vega J. Orthokeratology Lens Fit Success Using a New Software Global Specialty Lens Symposium, Las Vegas, Jan 20, 2023 [ Show Abstract ][ PDF ]

Purpose: To determine orthokeratology (Ortho-K) lens parameters in as few steps possible is beneficial for the eye care professionals (ECPs) and patient and this study investigated how the new Visavy software can help to inform the initial lens parameters.

Methods: This prospective study recruited participants aged 6-35 years and fit them with Paragon CRT or Paragon CRT Dual Axis Ortho-K lenses (CooperVision Specialty EyeCare), worn every night for 1 month. Topography images (Oculus Keratograph 5) were uploaded in the software and together with additional entries for subjective refraction and white-to-white corneal diameter, the software populated the initial lens parameters. Lens modifications for fit and/or vision were permitted at any of the following three timepoints: the dispense visit, after the first night or after one week of wear. Visual acuity (LogMAR) was determined with subjective refraction at baseline and unaided after one month of Ortho-K wear. Subjective comfort was collected after the first lens application and after one month (0-10 scale, 10=very comfortable). Subjective vision clarity was collected via home ratings just after lens application on the first night and after one month (0-10 scale, 10=Sharp, clear/ very good vision).

Rresults: Sixteen participants (12F:4M), mean age 11.3±3.2 years [7 to 18 years] were included in the analysis. The mean refraction of all 32 eyes was Sph -2.80±1.38DS [-1.00 to -5.75DS] and Cyl -0.56±0.46DC [0.00 to -1.25DC]. Best-corrected visual acuity prior to lens insertion was 0.00±0.01 logMAR and unaided vision after 1 month was +0.09±0.11 logMAR. Remaining correction after 1 month was Sph -0.12±0.46DS [+0.75 to -1.25DS]. Almost all lens designs predicted by the software were considered acceptable (fit and vision) by the investigator with just one lens requiring a modification after the first night due to corneal staining. Comfort ratings were significantly better after 1 month (7.8 ± 1.4) compared to the dispense visit (5.2 ± 2.2)(p<0.01). Vision clarity ratings were also better after 1 month (8.4 ± 1.5) compared to after the first night (7.0 ± 3.2)(p=0.02).

Conclusions: The Visavy software could help determine acceptable lens parameters for the Paragon CRT or Paragon CRT dual axis Ortho-K lenses in 97% of eyes (31 of 32 eyes). This high initial success rate has the potential to reduce chair time and assist ECPs to confidentially fit these lenses to their patients.

Ng A, Tan J, Read S, Alster Y, Bosworth C, Jones L. AZR-MD-001 Improved Tear Film Stability and Symptoms of Meibomian Gland Dysfunction in a 6-Month Study American Academy of Optometry, New Orleans, October 12, 2023 [ Show Abstract ]

Purpose: Abnormalities of the tear film and subsequent ocular surface disease symptoms can be caused by meibomian gland dysfunction (MGD). In a Phase
2 clinical trial, AZR-MD-001 topical ointment (selenium sulfide, 0.5% or 1.0% concentration) was investigated as a new treatment for MGD.
Changes in tear film stability, meibomian gland secretion and ocular surface symptoms were monitored in adults with signs and symptoms of
MGD.

Methods: For this multicenter, double-masked, vehicle-controlled, parallel-group trial (NCT03652051), 245 adults were randomized to receive treatment
(AZR-MD-001 0.5% [n=82] or AZR-MD-001 1.0% [n=83]) or vehicle (n=80) twice a week before bed. Eligible patients were ≥18 years old, had a
Meibomian Gland Secretion (MGS) score ≤12 in both eyes, and an Ocular Surface Disease Index (OSDI) score from 13 to 33, and TBUT <10
seconds. Prespecified co-primary endpoints were change from baseline in Meibomian Glands Yielding Liquid Secretion (MGYLS) and OSDI score at
month 3. Tear film stability was considered improved if tear breakup time (TBUT; with 2% fluorescein sodium) increased by more than 2 seconds
from month 3 onward. Patients were defined as asymptomatic if their OSDI score was <13. Statistical differences from baseline were calculated
for visit days 14, 45 (1.5 months), 90 (3 months), 135 (4.5 months), and 180 (6 months). Co-primary endpoints were evaluated using a
hierarchical approach that controlled for family-wise Type I error, using an ANCOVA model. Responder endpoints were evaluated via Cochran-
Mantel-Haenszel test using Wilson-Hilferty transformation.

Results: AZR-MD-001 0.5% achieved statistically significant improvements vs vehicle for both co-primary endpoints, MGYLS (p=0.0004) and OSDI score
(p=0.0438), at month 3, which continued through to month 6 (MGYLS: p=0.0002; OSDI: p=0.0135). Tear film stability (TBUT) significantly
increased from baseline in both treatment groups compared with vehicle at month 3 (AZR-MD-001 0.5% mean change=2.2 s, p<0.0001 vs
vehicle; AZR-MD-001 1.0%=1.5 s, p=0.0187 vs vehicle; vehicle=0.5 s), with increases generally sustained at month 6 but no longer significant vs
vehicle (0.5%=2.3 s; 1.0%=1.3 s; vehicle=1.6 s; p>0.05 vs vehicle for both concentrations). Many patients treated with AZR-MD-001 were
considered asymptomatic for disease (OSDI <13) at month 3 (0.5%=47%, p=0.0199 vs vehicle; 1.0%=38%, p>0.05 vs vehicle; vehicle=28%),
which was sustained for the 0.5% concentration and improved for 1.0% concentration at month 6 (0.5%=48%, p=0.0333 vs vehicle; 1.0%=50%
p=0.0205 vs vehicle; vehicle=30%).

Conclusion: Compared to vehicle, AZR-MD-001 significantly improved meibomian gland secretions and tear film stability, which resulted in clinically significant
improvements in ocular symptoms after 6 months of treatment.

Phan C-M, Chan V, Walther H, Pereira da Mota A, Lorenzo CA, Jones L. Developing a High-throughput in vitro Eye Model for Evaluating Ocular Drug Delivery with Contact Lenses XXV Biennial Meeting of the International Society for Eye Research, Feb 21, 2023 [ Show Abstract ]

Purpose: To develop a high-throughput in vitro eye model for evaluating ocular drug delivery with contact lenses (CLs).
Method: The eye model was designed using CAD software and manufactured using a combination of fabrication methods, including moulding, CNC machining, laser cutting, and 3D printing. The model consists of an eyeball, an upper and lower eyelid, and a collection tray to collect flow-through fluid. The portion of the upper eyelid that comes into contact with the eyeball is moulded with a highly wettable and durable polyvinyl alcohol hydrogel. The centre of the eyeball is designed with a 300 µm thick, 15 mm diameter cut-out that allows for a contact lens to be mounted. Simulated tear fluids can be delivered through an inlet located on the upper eyelid using a pump. During each blink cycle, the eyelid slides and flexes across the eyeball to create an artificial tear film layer. The blink distance, speed and rate are actuated using a motor controlled by an Arduino board and software. The release of a red dye from two CLs (etafilcon A and senofilcon A) and the release of two drugs (resveratrol and pravastatin sodium) from drug-loaded CLs were evaluated using the model and compared to the traditional vial testing method. Phosphate buffered saline (PBS) was used as the simulated tear fluid and infused into the model at 5 µL/min, at a blink rate of 1 blink/10 s.
Results: The fluid flows from the inlet, spreads across the eye, accumulates in the lower eyelid and then flows into the collection tray via gravity. During this process, approximately 25% of the fluid originally injected into the model was lost due to evaporation, nonspecific absorption, and residual dead volume. Overall, the release of the dye and drugs from the CLs was higher in a vial compared with the eye model. Interestingly, the drug release profiles from the drug-loaded CLs on the eye model were similar to in vivo results previously collected from a rabbit study, although the total amount of drugs released was significantly less. 9 or 24 CLs can be tested with one syringe or peristaltic pump, respectively.
Conclusion: The current eye model developed from this study could be used to measure the release of ophthalmic drugs or comfort agents from CLs in a high-throughput manner. However, further work is required to fine-tune the parameters of the model, such as the composition of the tear fluid, blink rate, tear flow rates, and temperature, to better simulate in vivo conditions.

Phan CM, Ramasamy M, Ho B, Hui A, Jones L. Fabrication of a microfluidic chip using 3D printing for evaluating ocular cytotoxicity The Association for Research in Vision and Ophthalmology, New Orleans, LA, USA, April, 2023 [ Show Abstract ][ PDF ]

Purpose: To develop a PDMS (polydimethyl siloxane) microfluidic chip to evaluate ocular cytotoxicity with ophthalmic formulations and materials.

Methods: The microfluidic chip was designed using CAD software (FreeCAD), and the moulds of the chips were printed using (1) a stereolithography (SLA) and (2) digital light processing (DLP) 3D printer. The printed moulds were washed with isopropyl alcohol (IPA), UV-cured for 1-hour at 60oC, followed by heating in an oven at 120oC for 2 hours to remove any unreacted polymers. The surface of the chips was smoothed with sandpaper with increasing grit, followed by an application of nail polish. The moulds were then cast with PDMS, a gas-permeable and clear polymer commonly used for the fabrication of microfluidic chips. The moulds and chips were imaged using SEM (scanning electron microscopy). The light transmittance of the chips was also measured. The PDMS top half of the chip was adhered to a microscope slide using medical-grade double-sided tape. For a pilot study, the PDMS chips were sterilized via autoclaving, coated with 0.1% polydopamine to improve their surface wettability, and then seeded with immortalized human corneal epithelial cells (HCEC). After 2 days of incubation in a nutrient media broth (no flow), cell adhesion and growth were evaluated using light microscopy.

Results: Both 3D printers were able to print moulds with high resolution, with channel dimensions as low as 50 µm, and with faster print times for the DLP printer. SEM images revealed that moulds that were both sanded and had a nail coating were significantly smoother than the original 3D-printed moulds. The chips cast from the polished moulds were transparent, with >85% transmittance from 450-700 nm, and could be used to image cells through a microscope. The microfluidic chips were able to handle flow rates up to 1 mL/min for 24 hours without any signs of leakage. HCEC cells were able to adhere and grow on the coated PDMS microfluidic chip after 2 days.

Conclusion: This study showed that SLA and DLP printers could be used to fabricate PDMS microfluidic chips as a low-cost rapid prototyping approach. The fabricated chips were clear and could be used to incorporate HCEC cells. Future work will examine the viability of cells under different flow rates and shear stress conditions on these chips.

Ramasamy M, Ho B, Phan CM, Jones L. Fabrication of a microfluidic chip for ophthalmic drug delivery studies using 3D printing The Association for Research in Vision and Ophthalmology, New Orleans, LA, USA, April, 2023 [ Show Abstract ]

Purpose: To develop a microfluidic chip for testing the release of ocular drugs from soft contact lenses using 3D printing.

Methods: The microfluidic chips were designed using CAD (computer-aided design) software consisting of a top and bottom portion. The top portion comprised of inlet, outlet, and channels for fluid flow. The lower portion contained a dome-shaped mount to mount a contact lens. The chips were printed using clear resin on a commercial stereolithography (SLA) 3D-printer. The printed chips were washed in isopropyl alcohol (IPA) for 30 minutes, air dried and UV cured for 30 minutes. The top and bottom portions of the chip were fused by applying a thin layer of resin, followed by UV-curing for 10 minutes. In another design iteration, moulds for the chips were 3D printed and casted with polydimethylsiloxane (PDMS). The two halves of the PDMS chips were fused using double-sided adhesive tape. In a preliminary study, two commercial contact lenses, etafilcon A and senofilcon A, were soaked in 2 ml of red food dye for 2 hours. The release of the dye was measured using the PDMS chip with phosphate-buffered saline at a flow rate of 1.5 L/min over 24 hours via absorbance at 520 nm. The dye extraction from both lenses was
performed by incubating the dye-soaked lenses in 1:1 acetonitrile/water solution for 24 hours with gentle shaking.

Results: Both the chip and moulds were printed in less than 5 hours, with a minimum resolution of 50 μm. The resulting resin and PDMS chips can also be sterilized by autoclaving. The top and bottom parts of the chips were completely sealed such that no leakage was detected at a flow rate of up to 100 μL/min for 24 hours. The release kinetics of the dye was linear throughout the 24 h period for both lens types under the current parameters. The total amount of dye released after 24 h was higher for etafilcon A (26.26 mg/lens) than senofilcon A (18.41 mg/lens), which corresponded to approximately 83.1% and 40.01% release, respectively. Both the lens types were still visibly red after 24 hours. The output of the microfluidic chip could be used as an input for subsequent analyses.

Conclusions: This study showed a cost- and time-efficient approach to fabricate a microfluidic chip for evaluating drug release from contact lenses. Future work will examine the release profile of various ocular drugs from contact lenses using different flow conditions.

Woods J, Guthrie S, Luensmann D, Vega J, Orsborn G. Task-based Evaluations of Two Daily Disposable Soft Multifocal Lenses American Academy of Optometry, New Orleans, October 12, 2023 [ Show Abstract ]

Purpose: Drop-outs from contact lens (CL) wear remains problematic across the entire sector, however for presbyopes it has been reported to be higher
and largely related to comfort and vision problems. Many practitioners use daily disposable (DD) CLs to improve comfort, therefore it is of high
interest to evaluate two recently launched DD multifocal (MF) CLs with a particular emphasis on evaluating subjective comfort and situational or
task-related vision performance: stenfilcon A (stenA) DDMF (CooperVision, Inc.) and senofilcon A (senoA) DDMF (Johnson & Johnson Vision).

Methods: Habitual MFCL wearers were recruited for this randomized, subject masked, cross-over study. After a successful screening both lenses were fit
following manufacturers’ fitting guides. Lens 1 was dispensed and optimized 3-8 days later, prior to entering a 2-week optimized lens wear period,
after which Likert ratings were completed for comfort, vision and everyday tasks. Then, Lens 2 was dispensed and the same power optimization
and data collection schedule were followed. Likert ratings used 4-point forced choice, with strongly or slightly agree considered positive responses
and strongly or slightly disagree considered negative responses.

Results: 54 subjects, 43F/11M, completed the study with demographic means [range]: age 53yrs [42-75]; OD: sphere -1.72D [+4.00 to -5.50], cyl -0.29D [0.00 to -0.75] near addition +1.94D [+1.00 to +2.50]. At the end of each optimized lens wear period, Likert data showed no differences between lenses (p>0.05). Each lens showed statistically higher counts of positive versus negative responses for each statement (all p<0.05). Percentage of positive responses were:
• These CLs feel good on my eyes: stenA 93%; senoA 89%
• These CLs gave me all day comfort: stenA 87%; senoA 87%
• These CLs give me crisp clear vision at all distances: stenA 81%; senoA 69%
• These CLs give me crisp clear vision in different lighting conditions: stenA 89%; senoA 74%
• These CLs give me crisp clear vision even in dim/dark light conditions: stenA 80%; senoA 69%
• These CLs give me crisp clear vision when driving: stenA 90%; senoA 81%
• These CLs give me crisp clear vision when using a laptop: stenA 88%; senoA 92%
• These CLs give me crisp clear vision when reading text on my phone: stenA 91%; senoA 85%
• These CLs give me crisp clear vision when reading up close: stenA 83%; senoA 80%
• These CLs give me reliable vision: stenA 93%; senoA 87%
• I do not experience halos and starbursts in my vision: stenA 94%; senoA 94%

Conclusion
The high percentage of positive responses to these task specific reports of lens performance suggests that both lenses largely met or exceeded the needs of these subjects for those tasks. It seems plausible to assume that if a MFCL is reported as comfortable and it also performs well in frequent everyday vision tasks and situations, then it is likely to help minimise future drop-out.

Woods J, Guthrie S, Luensmann D, Vega J, Orsborn G. Investigation of Ease of Fit to a Different Daily Disposable Multifocal Soft Lens American Academy of Optometry, New Orleans, October 12, 2023 [ Show Abstract ]

PURPOSE: Eye care professionals (ECPs) regularly need to decide whether to switch their multifocal contact lens (MFCL) patients to new products. Common reasons for switching are visual or comfort performance, prescription availability, new optical designs, or lens material benefits. This study evaluated the visual and comfort impacts of switching habitual MFCL wearers from somofilcon-A MF 2 add design (somA) into stenfilcon-A MF 3 add system (stenA) (both 1-day, CooperVision, Inc.) and collected information about the ease of fit.

METHOD: In this crossover, subject-masked study, subjects were first fit and dispensed with somA; power adjustments were permitted at the fit visit and also 1-week later. Optimal lens powers were worn for 2 weeks. After this adaptation period to optimized somA MFCLs, subjects were refit with stenA MFCLs which were worn and optimized following the same schedule. Fitting guides were followed for both. Subjects used diaries on days 6 and 13 to report whether stenA performance exceeded or met their needs (positive response) or whether they failed to meet their needs (negative response). Likert ratings were collected at the end of the stenA wear period.

RESULTS: Sixty participants (mean age 52.6±6.9; 50F:10M) completed. Mean OD refraction: sph -1.97D [-5.00D to +2.75D], cyl -0.50D [0.00 to -0.75], near addition: +1.95D [+1.00D to +2.50D]. All achieved successful fit with both MFCLs. 78% subjects achieved optimal fit with the first pair of trial stenA, the remaining 22% required just one adjustment. Lenses were worn on average >13hrs/day, ≥5 days/week. Diary responses showed stenA resulted in statistically more positive responses vs negative responses for various comfort and vision criteria (all p<0.01): • Comfort on lens application: Day 6 & 13: 98% & 100% positive responses • Comfort at time of removal: Day 6 & 13: 90% & 95% • Dryness at time of removal: Day 6 & 13: 90% & 92% • Vision stability throughout the day: Day 6 & 13: 93% & 95% • Overall speed & ability to change focus between distances: Day 6 & 13: 95% & 92% Through Likert questions, statistically more subjects agreed than disagreed with the following statements: • I could see clearly right away with these [stenA] contact lenses, and it was easy to adapt (p<0.01) • My vision improved when I switched from somA to stenA (p<0.01) • The transition from somA to stenA was easy (p<0.01)

CONCLUSION: Success was high with the first trial lens pair for stenA 3 add system lenses. Subjects reported the transition to be easy, resulting in clear vision straight away and through the wear period most reported that comfort and vision experiences met or exceeded their needs. These results should reassure ECPs when considering refitting their presbyopic patients from somA 2 add to stenA 3 add system; these subjects reported transitioning was easy and performance improvements were recognized within 2-weeks.

Wulff D, Phan C-M, Jones L. Development of a 3D-printed hydrogel eye model for evaluating ocular drug delivery The Association for Research in Vision and Ophthalmology, New Orleans, LA, USA, April, 2023 [ Show Abstract ][ PDF ]

Purpose: To 3D-print a soft hydrogel eye model using a novel bioink for evaluating ocular drug delivery.

Methods: The eye model was designed using CAD software. It includes several key components made from a hydrogel, including an upper and lower eyelid, a frontal surface to mimic the cornea and sclera, and an internal chamber to mimic the interior of the eye. The components were designed to fit with an existing blink model that was developed previously in our laboratory that allows for automated blinking and tear collection. The eyeball and the lower eyelid were 3D bioprinted using a modified commercial mSLA printer (Photon Mono X, AnyCubic, Shenzhen, China). Various bioinks were tested, consisting of 5-15% gelatin methacryloyl, 1-5% polyvinyl alcohol, 5-30% polyethylene glycol diacrylate, 0.4-0.6% lithium phenyl-2,4,6-trimethylbenzoylphosphinate, and 2-3% of a yellow food-grade dye in phosphate buffer solution. Different formulations were evaluated to create prints that were desirable in terms of print quality, stiffness, and flexibility. Printing was undertaken at 40˚C to ensure the ink remained a liquid and at 90% humidity to protect the parts and ink from desiccation.

Results: Both the eye and the lower eyelid were successfully printed in high resolution using 100 µm layer heights without any support structures within 3 hours. The prints are hydrophilic with a 60-80% water content, are soft and flexible, and are fabricated with biocompatible biomaterials. Both components were able to be incorporated into an in vitro blink model which will allow for improved testing that more closely mimics a human ocular system, in particular, drug absorption through the cornea. A port on the eye allows for the sampling of fluid from the interior eye model for testing the diffusion of drugs to the posterior chamber when released by topical ophthalmic formulations or anterior segment devices such as contact lenses.

Conclusion: This study demonstrated that a modified mSLA 3D printer can be used to fabricate soft, hydrophilic ocular model components using a novel biocompatible bioink.