Fadel D, Wong S, Luensmann D, Guthrie S, Seo J, Woods J, Voltz K, Vega J. The use of Scleral Lenses to Manage Dry Eye Symptoms in Habitual Soft Lens Wearers Global Specialty Lens Symposium, Las Vegas, Jan 20, 2024 [ Show Abstract ]

PURPOSE: To determine if scleral lenses (SLs) with and without Hydra-PEG coating can improve ocular comfort and reduce dryness in symptomatic soft lens wearers.

METHODS: This prospective, randomized, double masked, 1-month bilateral cross over, daily wear study recruited symptomatic soft lens wearers who presented with healthy eyes and a CLDEQ-8 score ≥12 with their habitual contact lens (hab-CL). Eligible participants were fit with SLs (Onefit MED, CooperVision, Inc.) and wore these with and without HydraPEG coating (coated (C-SL) / uncoated (U-SL)) in a randomized order for 1 month per pair. Participants completed a CLDEQ-8 and rated comfort, vision clarity, dryness and handling after each 1-month wear period using a 0-10 scale (10=best) and these data were compared between study SLs and to their hab-CL.

RESULTS: Twenty participants (16F:4M), mean age 29.3±12.4 years [18-64 years] completed the study. The mean refraction of the right eye was Sph -4.69±3.42DS [-15.25 to -0.50DS] and Cyl -0.84±0.79DC [0.00 to -2.75DC]. At 1 month, the CLDEQ-8 score improved with both study SLs in comparison to hab-CL (p0.05) and both were rated better compared to hab-CL (p0.05). At study exit, 9 of the 20 participants requested the SL details to be shared with their eye care professional because they wanted to continue wearing these SLs in future.

CONCLUSIONS: Switching symptomatic soft lens wearers into scleral lenses improved comfort and reduced dryness symptoms after 1 month of wear, with little reduction in ease of lens handling. Subjective ratings were similar with uncoated and HydraPEG coated scleral lenses, with the latter providing slightly better visual clarity.

Garg P, Shokrollahi P, Phan CM, Jones L. 3D printing of PVA loaded ocular inserts for ocular drug delivery The Association for Research in Vision and Ophthalmology, Seattle, WA, May 9, 2024 [ Show Abstract ][ PDF ]

Purpose: To develop ocular inserts comprised of polyvinyl alcohol (PVA) and gelatin methacrylate (GelMA), using 3D printing technology.

Methods: Inserts were synthesized using a bioink formulation consisting of 10% (w/v) GelMA, 5% (w/v) and 7.5% (w/v) PVA, 0.6% (w/v) lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP), and 5% (v/v) yellow dye as a light absorbing agent to improve print resolution. They had a 4mm diameter, 1mm thickness and were fabricated using a commercial masked-stereolithography (mSLA) 3D printer at 95% humidity and 37°C temperature. Morphology of the inserts was investigated by freeze-drying samples and imaging them using a scanning electron microscope (SEM). Release of PVA over 5 hours was studied by incubating at 35°C in PBS in an incubator shaker at 50rpm. The hydrogel samples were freeze dried and their equilibrium swelling was studied in PBS using gravimetric method.

Results: The PVA-loaded ocular inserts were 3D printed within 30 minutes. SEM images showed that 7.5% PVA loaded inserts had more uniform pore size distribution compared to the gels with no PVA. Approximately 37% of PVA was released within the first 2 hrs from the inserts containing PVA, and the release continued up to approximately 4 hrs before reaching a plateau. The release kinetics can be attributed primarily due to passive diffusion. The swelling curves of these hydrogels suggest that they reach equilibrium swelling within 24hr. From the slope of the swelling curve in the first hour, it can be inferred that swelling happens at a slower rate for GelMA/PVA compared to GelMA alone. This slower swelling rate helps to control the release and supports a sustained release of PVA from the combination.

Conclusions: This study showed that a GelMA-PVA based bioink can be used to 3D print ocular inserts that can release PVA for up to 4 hours. Future work will focus on designing 3D scaffolds to increase the release duration of PVA from these gels.

Ho B, Phan CM, Garg P, Shokrollahi P, Jones L. A screening platform for simultaneous evaluation of biodegradation and therapeutic release from an ocular hydrogel and its effect on human corneal epithelial cells The Association for Research in Vision and Ophthalmology, Seattle, WA, May 7, 2024 [ Show Abstract ][ PDF ]

Purpose: To integrate human corneal epithelial cells (HCECs) into a millifluidic screening platform that quantifies biodegradation and release of an entrapped therapeutic from an ocular hydrogel.

Introduction: Biodegradable hydrogels are novel drug delivery methods designed to release entrapped drugs or therapeutics as the gel degrades in situ. The primary challenge in developing biodegradable hydrogels for drug delivery lies in accurately measuring their degradation over time, while simultaneously being able to evaluate the drug release kinetics, which is typically a cumbersome procedure. To properly evaluate the biodegradation of a hydrogel, it is also essential to simulate key factors of the target tissue environment. In the context of the eye, this includes ocular temperature, tear flow, and low tear volume. Recent advances in organ-on-a-chip technologies have made it possible to emulate the human corneal environment. This will allow more accurate measurements of hydrogel degradation rates, subsequent drug or therapeutic release, and ultimately the overall effect on human corneal epithelial cells.

Methods: Gelatin Methacrylate (GelMA) ocular inserts with polyvinyl alcohol (PVA) (10% GelMA 7.5% PVA) were placed inside a custom-designed millifluidic device. Ocular inserts were degraded with up to 200 μg/mL of matrix metallipeptidase 9 (MMP9) for 24 hours at 37oC in PBS. Biodegradation of the ocular insert was quantified using a computational image analysis pipeline. The eluates containing the degradation products were collected to measure PVA released using a spectrophotometric assay, and its toxicity on human corneal epithelial cells (HCECs) was determined by alamarBlueTM assays.

Results: There was significant biodegradation of the GelMA-PVA inserts with increasing concentration of MMP9 in the millifluidic device, which was accurately quantified using a custom computational analysis. Degradation products in the eluate were collected, and there was a ~2-fold increase of PVA released in samples treated with MMP9 compared to the control. The same eluates were non-toxic to HCECs, and interestingly protected HCECs from hyperosmotic conditions mimicking dry eye disease.

Jabeen A, Luensmann D, Woods J, Hill J, Jones L. Short-term effect of DOT spectacle lenses on choroidal thickness in emmetropic children The Association for Research in Vision and Ophthalmology, Seattle, WA, May 9, 2024 [ Show Abstract ][ PDF ]

Purpose: To investigate regional changes in choroidal thickness (ChT) following short-term wear of Diffusion Optics Technology™ (DOT) spectacle lenses, designed to control myopia by lowering retinal contrast.

Method: Emmetropic children (SER +1.00 to -0.75 D) aged 8 to 14 years wore plano DOT spectacle lenses without central apertures and +3.00D spectacle lenses in a two-visit, prospective, randomized, subject-masked crossover study. High-resolution OCT (Triton DRI-OCT, Topcon) evaluated central, parafoveal (3 mm from the fovea) and perifoveal (6 mm from the fovea) ChT after 0, 30 and 60 minutes of viewing a high contrast video at each visit.

Results: A total of 30 participants (17F, 13M) with a mean (± SD) age of 10.9 (1.7) years completed the study. After 30 minutes of spectacle lens wear, a significant increase in ChT was observed with DOT spectacle lenses compared to +3.00D spectacle lenses in 4 of the 9 macula regions evaluated (p<0.05 for all). DOT spectacles showed a significant ChT thickening in the central (+7.69 ± 4.19 μm), parafoveal regions at nasal (+9.01 ± 2.77 μm) and temporal (+6.20 ± 5.46 μm) and inferior perifoveal (+9.79 ± 2.31 μm) compared to myopic defocus with +3.00D lenses. After 60 minutes, ChT remained higher only in the inferior parafoveal region (+3.96 ± 8.33 μm, p=0.03), while all other regions returned to baseline levels.

Conclusion: After short-term DOT spectacle lens wear, emmetropic children experienced macula ChT thickening, similar or greater than the response observed with +3.00D spectacle lens wear. These results indicate the choroid is able to respond to contrast reduction. Further research is required to investigate the long-term impact of contrast modulation on ChT.

Jones L. New materials and emerging techniques Minisymposium: Contact lens is not a piece of plastic: Back to the future. The Association for Research in Vision and Ophthalmology, Seattle, WA, May 8, 2024 [ Show Abstract ]

Recent advancement and diversification in contact lenses are remarkable. Today, contact lenses are not merely correcting tools for refractive errors, but can be used as therapeutic modalities for various diseases. With new materials and technologies entering the market, several options, such as lenses with internal wetting agents and silicone hydrogel lenses, have become available for wearers seeking relief from contact lens discomfort. Custom-made contact lenses can address irregular astigmatism and improve the vision in eyes with irregular corneas. Myopia has become increasingly prevalent worldwide over the past century. Contact lenses such as orthokeratology lenses or multifocal soft contact lenses are commonly used for myopia control. Numerous studies and clinical experience show that we can prescribe interventions that significantly slow the rate of myopia progression. Contact lenses can be used as biosensors and medication depots. Intraocular pressure monitoring is essential in the diagnosis and management of glaucoma patients. Currently, continuous ocular monitoring contact lens sensor is available in clinical use, which helps clinicians personalize glaucoma treatment according to the patient’s intraocular pressure profiles. Drug-eluting contact lenses can be used for ocular drug delivery with widespread therapeutic applications. Future development of both types of lenses are of great interest. This symposium will cover some of the hottest topics in contact lenses today. Attendees will learn about exciting new lens technologies and how these lenses can help their patients.

Jones L, Schallhorn J, Stapleton F, Alster Y, Bosworth C. AZR-MD-001 Opens Meibomian Glands, Improves Meibum and Tear Quality Resulting in Increased Wear Time and Desired Lens Use in Patients With CLD The Association for Research in Vision and Ophthalmology, Seattle, WA, May 6, 2024 [ Show Abstract ][ PDF ]

Purpose: Contact lens discomfort (CLD) is a common problem for practitioners and wearers. Individuals with CLD experience episodic or persistent ocular discomfort symptoms related to lens wear, including visual disturbances, decreased wear time, or discontinuation overall. AZR MD 001 (AZR) is an ophthalmic keratolytic, keratostatic, and lipogenic ointment containing selenium sulfide, developed to improve signs and symptoms of MGD. This study evaluated if biweekly AZR can open meibomian glands and improve comfortable wear time, allowing patients with CLD who continue to challenge their ocular surface, tear film, and meibomian glands with contact lens use, to wear their contact lenses as desired.

Methods: Adults with CLD and evidence of meibomian gland obstruction (n=67) were randomized (1:1) to AZR 0.5% (n=34) or vehicle (n=33) applied twice weekly at bedtime for 3 months in a Phase 2, multi-center, single-masked parallel-group study (NCT05548491). Key efficacy endpoints evaluated were the change from baseline (CFB) at month 3 compared to vehicle in meibomian gland secretion score (MGS), Tear film stability (TBUT) post lens removal, and total and comfortable wear time.

Results: At month 3, AZR 0.5% significantly improved signs (MGS; TBUT) and lens wear time vs vehicle. Mean [SE] CFB in MGS was 13.8 [0.67] vs vehicle 3.8 [0.68], p<0.0001; TBUT was +3.31 s [0.70] vs vehicle 0.65 s [0.72], p<0.0001; and total comfortable wear time was +192 min [38.07] vs vehicle +2.9 min [38.01], p<0.0001. Significantly more patients, who were unable to comfortably wear contact lenses as desired at baseline, were able to wear them as long as desired by month 3 (42.5% vs vehicle 6.2%, p=0.0015). Improvements over vehicle were first seen on Day 14 in MGS (Mean [SE] CFB 3.2 [0.97] vs vehicle 0.8 [0.91], p<0.0007) and at Month 1 for comfortable wear time +41.6 minutes [24.04] vs vehicle -14.2 minutes [24.04], p=0.0111. All treatment-emergent adverse events (TEAEs) (47/47, 100%) in the 0.5% group were mild to moderate. There were no discontinuations due to a TEAE.

Conclusion: AZR MD 001 significantly improved the meibum and tear film quality, resulting in improved wear time in patients with CLD compared to vehicle starting as early as 8 doses of treatment. AZR demonstrated efficacy, safety, and tolerability, with no major adverse events observed.

NG AY, Jones L, Woods J, Basuthkar S, Keir N. Diurnal changes in corneal dendritic cell density and morphology in symptomatic and asymptomatic contact lens wearers The Association for Research in Vision and Ophthalmology, Seattle, WA, May 6, 2024 [ Show Abstract ][ PDF ]

Purpose: To explore corneal dendritic cell (DC) density and morphology in soft contact lens (CL) wearers using in vivo confocal microscopy (IVCM) after different wear times, imaging with and without CLs in situ.

Methods: This was a prospective study involving hydrogel and silicone hydrogel CL wearers (17F, 3M; 29.5±10.5 years): 10 symptomatic (S-CL) and 10 asymptomatic (A-CL), by Young’s criterion and comfortable wear time. Eligible participants attended a baseline day (no CL wear, IVCM conducted in the morning (AM) and 8 hours later (PM), three separate CL wearing days (IVCM after 1, 4 or 8 hours [randomized] with CLs removed immediately before imaging and topical anesthesia), and a day where CLs were worn all day (IVCM after 1, 4 and 8 hours of CL wear, with CLs in situ during imaging and no anesthesia). At least five non-overlapping sequence scans were taken at the central and inferior cornea with the Heidelberg Retina Tomograph III with Rostock Cornea Module. Up to five images per location were analyzed with automated DC counting software. A linear mixed model was applied for all statistical analyses.

Results: At the central cornea, DC density was greater in the AM/1 hour compared to PM/8 hours (p<0.001), and for the A-CL group compared to the S-CL group (p=0.041). There was no effect of imaging with CLs in situ on DC density; DC density with and without CLs in situ strongly correlated across all time points at both corneal locations (r=0.694 to 0.843, all p≤0.01). For cell morphology, immature dendritic cells were the dominant cell type in both groups at both locations (S-CL ≥77%, A-CL ≥78%). Mature cells made up 8-15% of all DCs. The A-CL group had 5% more mature cells than the S-CL group at the inferior cornea only (p=0.034). At both locations, 5% more mature cells were observed on lens wearing days (central p=0.043, inferior p=0.027). Time of imaging was not a significant effect on the proportion of immature or mature cells at either location.

Conclusions: This study shows subtle differences in DC density and morphology between symptomatic and asymptomatic CL wearers and over the course of the day in different corneal regions. The clinical significance of these results requires further investigation. This study supports the imaging of DCs with CLs in situ, which could simplify monitoring these cells during CL wear.

Shukla M, Jones L, Hui A.. Poly (vinyl alcohol) elution from commercial contact lenses . Controlled Release Society Annual Meeting and Expo, Bologna, Italy, Jul 10, 2024 [ Show Abstract ]

Introduction: Contact lenses (CL) are a common form of refractive error correction, with approximately 140 million contact lens wearers across the world and 40 million in the US. Unfortunately, wearing contact lenses can cause discomfort and dryness, with almost half of all wearers experiencing these type of symptoms during use. (2) (1) Polyvinyl alcohol (PVA) is a lubricant which is effective against CL discomfort when used as an eye drop.(3) The purpose of this study was to investigate PVA elution from commercial contact lenses for a one-day wear modality. This study hypothesizes that by incorporating freezing as part of PVA loading into contact lenses, hydrogen bonding of PVA to lens materials will be enhanced, enabling the formation of a surface layer on contact lenses and increased PVA elution.

Methods: Commercial contact lenses (1-Day Acuvue® Moist® (etafilcon A, Johnson and Jonson), Acuvue® Oasys (senofilcon A, Johnson and Johnson), and DAILIES® AquaComfort PLUS® (nelfilcon A, Alcon)) were soaked in 2.5% w/v high molecular weight (avg. - 166 kDa) PVA solutions at 37°C for 48 hours. This was followed by 1 hour at either room temperature or freezing at -80°C. Total PVA release from lenses was determined in a vial containing 2 mL PBS on an orbital shaker at 50 RPM for 24 h. PVA was quantified using UV at 630 nm. All experiments were performed with n=6.

Results: A significant (p0.05) change in the amount of PVA released after freezing. Etafilcon A lenses released 17.03 ± 3.03 μg and 20.21 ± 2.51 μg (p>0.05), and senofilcon A showed 20.33 ± 6.60 μg and 24.14 ± 2.58 μg (p>0.05) at room temperature and after freezing at -80°C for one hour, respectively. However, nelfilcon A did not show significant (p>0.05) effect after 5 free-thaw cycles.

Conclusions/Implications: The findings suggest that the freezing technique has potential applications in enhancing the release of PVA from nelfilcon A contact lenses, which contains PVA internally. This provides insights into optimizing contact lens design for improved comfort by utilizing PVA release. The impact of freezing on nelfilcon A lenses releasing PVA indicates a promising potential avenue for enhancing the release of other comfort agents. Learning Objective 1: Understand the impact of freezing on enhancing the release of PVA from different contact lenses

Wong S, Fadel D, Seo J, Luensmann D, Guthrie S, Woods J, Voltz K, Vega J. Dry eye management with scleral lenses in non-lens wearers NCC, Veldhoven, Netherlands, Mar 10, 2024 [ Show Abstract ]

PURPOSE: To assess the benefits of scleral lenses (SLs) with and without Hydra-PEG in non-lens wearers with dry eye symptoms.

METHODS: This prospective, randomised, double-masked, 1-month bilateral cross-over study recruited symptomatic non-wearers with healthy eyes and an OSDI score ≥13. Participants were fitted with SLs (hexafocon A, Onefit MED, CooperVision, Inc.) with and without Hydra-PEG coating (Tangible Science) (coated (C-SL)/uncoated (U-SL)) for 1-month daily wear per pair. LogMAR visual acuity was measured, and participants rated overall satisfaction with ocular comfort, dryness and vision clarity using a 0-10 scale (10=best) at baseline (BL) and after each 1-month wear period with the two SLs.

RESULTS: In total, 22 participants were eligible and 18 completed the study (18F:0M, mean age 34.9±13.4 years [20-66], OSDI score 39.8±18.0 [14-80], reason for discontinuation: n=3 handling, n=1 comfort). Mean refraction of the right eye was -3.28±1.13DS [-12.00 to +1.00] and -1.11±0.90DC [0.00 to -3.25]. At 1-month, satisfaction with ocular comfort and dryness was similar between study SLs (p>0.05), and both were rated better than BL (p0.05) (BL: 7.6±19, C-SL: 7.8±2.3, U-SL: 7.8±2.9), which was confirmed by LogMAR visual acuity with no clinically relevant differences noted (BL: -0.14±0.07, C-SL: -0.17±0.07, U-SL: -0.18±0.08). At study exit, 44% asked to share their SL details with their eye care professional to continue wear in the future.

CONCLUSIONS: Symptomatic non-lens wearers were successfully fit with SLs, which improved ocular comfort and reduced dryness after 1 month of wear. Although no difference was noted between Hydra-PEG-coated and uncoated lenses, participants with a wide range of dryness symptoms benefited from SL wear and almost every second participant indicated an interested to continue SL wear.

Woods J, Guthrie S, Luensmann D, Vega J, Orsborn G. Evaluating the Success of Habitual Multifocal Soft Lens Wearers when Refit with a Progressive Multifocal Lens System NCC, Veldhoven, Netherlands, Mar 11, 2024 [ Show Abstract ]

PURPOSE: To evaluate the ease and predictability of fit and success when switching habitual, multifocal (MF) wearers from a somofilcon A (som-A) multifocal 2-Add system to a som-A 3-Add system.

METHODS: Presbyopic habitual MF wearers were recruited to a crossover, daily wear, subject-masked study. At first, participants were fit and dispensed bilaterally with som-A 2-Add (CooperVision) lenses and power optimizations were permitted at the fitting visit and the 1-week visit. The optimal lens powers were worn for 2-weeks. Next, som-A 3-Add (CooperVision) was fit and worn following the same visit schedule. Visual acuity and subjective ratings (0–10 scale;10=best) were collected after each lens wear period and preference ratings were completed at study exit (5-point Likert).

RESULTS: Fifty-eight participants (mean age 53.5±6.2 years, 46F:12M) completed the study. Mean refraction OD: Sph -1.11±2.44D [-4.75D to +3.50D], Cyl -0.27±0.25D [-0.75D to 0.00D], near addition +2.05±0.36D [+1.25D to +2.50D]. There was no difference between lenses for satisfaction with comfort (p=0.76), vision quality (p=0.78), or overall satisfaction (p=0.94). The only statistical difference among preferences related to vision clarity for near tasks, where som-A 3-Add was preferred (p=0.03). After 2-weeks, LogMAR acuity was significantly better with som-A 3-Add for distance vision (p<0.01) and near vision (p=0.02), but not different for intermediate vision (p=0.10). When strictly following the fitting guides, som-A 2-Add was successful with the first pair of lenses in 59% of participants, whereas som-A 3-Add was successful with the first pair in 80% of participants (p=0.03).

CONCLUSIONS: The performance of som-A 3-Add either matched or exceeded that of som-A 2-Add based on visual acuity, participant ratings and participant preferences. The 3-Add lens system had a higher rate of success with the first lens pair than the 2-Add system. Results indicate that switching som-A 2-Add wearers to the updated som-A 3-Add lens system was successful and well accepted.

Woods J, Richards J, Guthrie S, Kollbaum P. Can Optical Modelling Predict Clinical Vision Outcomes of Myopia Control Contact Lenses? NCC, Veldhoven, Netherlands, Mar 11, 2024 [ Show Abstract ]

PURPOSE: To understand if optical metrology and computational modelling can predict the clinical visual performance of two myopia control contact lenses which employ different optical designs: non-coaxial senofilcon A (NC) (Acuvue Abiliti 1-Day, Johnson & Johnson Vision) and dual-focus omafilcon A (DF) (MiSight 1 day, CooperVision).

METHODS: For clinical assessments, children aged 8-15 years with no history of contact lens wear or recent myopia control intervention completed a randomised, non-dispensing, contralateral double-masked trial. After 1-hour of wear, participants rated their lens preference (Likert) and subjective vision (0-100 scale, 100=best), then distance visual acuity (VA) was measured.
For optical metrology and modeling, wavefront errors were measured with an aberrometer (Optocraft GmbH). Custom software was used to compute point spread functions, image quality and simulated retinal images for 3-6mm pupils by combining the lens optics with the optics of a model young eye, assuming centred and decentred lens positions.

RESULTS: Twenty-six participants completed the clinical study: 17M; mean age 11.6yrs [8-15yrs]; mean OD refraction: -1.96DS [-0.25 to -3.50DS], -0.34DC [0.00 to -1.00DC]. Ratings of distance vision at 1-hour were better with DF (88±14) versus NC (79±18), p<0.01. Distance logMAR VA was better with DF (0.02±0.04) versus NC (0.09±0.08), p<0.01. A higher number of participants indicated overall preference for DF, with vision the most common reason (DF:14 vs NC:6, p=0.17).
Optical modelling of well-centred lenses showed reduction in image quality for both lenses as the pupil increased. Lens decentration degraded image quality for both designs, but more for the NC design. Differences in add power zone geometry and NC optics may account for these differences.

CONCLUSIONS: Both optical modelling and clinical subjective results support better image quality with the dual-focus design. These results suggest that optical modelling techniques may be valuable in evaluating and comparing myopia control lens designs prior to on-eye testing.