Peer-reviewed Articles

Please use the year list below to look at past peer-reviewed articles.

2021

Bai,Y., Ngo,W., Khanal,S., Nichols,K. K., Nichols,J. J. Human precorneal tear film and lipid layer dynamics in meibomian gland dysfunction Ocular Surface 2021;Online ahead of print [ Show Abstract ]

Purpose: To evaluate the precorneal tear film (PCTF) and lipid layer (TFLL) thicknesses and thinning rates in meibomian gland dysfunction (MGD) using a combined ultra-high-resolution optical coherence tomography (OCT) and thickness dependent fringe (TDF) interferometry system.

Methods: Based on the Tear Film and Ocular Surface Society (TFOS) International Workshop on Meibomian Gland Dysfunction diagnostic algorithm, the Ocular Surface Disease Index (OSDI) and meibum grade score (MGS) were used to classify subjects into four groups: Normal (OSDI<13 and MGS<10), MGD (OSDI≥13 and MGS≥10), Asymptomatic MGD (OSDI<13 and MGS≥10), and Mixed (OSDI≥13 and MGS<10). The OCT/TDF system was used to capture PCTF and TFLL thicknesses and thinning rates. Kruskal-Wallis was used to compare median PCTF and TFLL thicknesses and thinning rates.

Results: There were 190 subjects categorized into four groups: Normal (n = 63), MGD (n = 51), Asymptomatic MGD (n = 29), and Mixed (n = 47). The PCTF was significantly thinner in the Mixed group (3.3 [1.2]) than in the Normal (p < 0.001), MGD (p < 0.001) and Asymptomatic MGD (p = 0.009) groups. Relative to the Normal (4.5 [4.5] μm/min) and Mixed (5.0 [2.0] μm/min) groups, the rate of PCTF thinning was faster in the MGD (8.1 [3.0] μm/min, both p < 0.001) and Asymptomatic MGD (6.9 [3.1] μm/min, p = 0.009 and p = 0.04, respectively) groups. The correlation between PCTF thinning rate and TFLL thickness was ρ = −0.46, p < 0.001.

Conclusions: Symptomatic and asymptomatic MGD shows rapid PCTF thinning rates (evaporation), while the PCTF thickness was reduced in mixed disease. Thicker lipid layers were associated with slower PCTF thinning.

Chan,V. W. Y., Phan,C-M., Ngo,W., Jones,L. Lysozyme Deposition on Contact Lenses in an In Vitro Blink-Simulation Eye Model Versus a Static Vial Deposition Model Eye & Contact Lens 2021;Online ahead of print [ Show Abstract ]

Purpose:
To evaluate active lysozyme deposition on daily disposable (DD) contact lenses (CL) using a novel in vitro blink model.

Methods:
Three conventional hydrogel DD CL materials (etafilcon A, omafilcon A, nelfilcon A) and three silicone hydrogel DD CL materials (delefilcon A, senofilcon A, somofilcon A) were tested. The device blink rate was set to 6 blinks/min with a tear flow rate of 1 μL/min using an artificial tear solution (ATS) containing lysozyme and other typical tear film components. After incubation at 2, 4, or 8 hr, lenses were removed, and lysozyme activity was measured. A separate experiment was conducted with lenses incubated in a static vial containing 480 μL of ATS.

Results:
Etafilcon A deposited significantly higher amounts of active lysozyme (402±102 μg/lens) than other lens materials after 8 hr (P<0.0001). Etafilcon A had a higher amount of active lysozyme using the blink model compared with the static vial (P=0.0435), whereas somofilcon A (P=0.0076) and senofilcon A (P=0.0019) had a higher amount of lysozyme activity in the vial compared with the blink model.

Conclusion:
The blink model can be tuned to provide quantitative data that closely mimics ex vivo studies and can be used to model deposition of lysozyme on CL materials.

Craig,J.P., Muntz,A., Wang,M.T.M., Luensmann,D., Tan,J., Travé-Huarte,S., Xue,A.L., Jones,L.W., Willcox,M.D.P., Wolffsohn,J.S. Developing evidence-based guidance for the treatment of dry eye disease with artificial tear supplements: A six-month multicentre, double-masked randomised controlled trial Ocular Surface 2021;20(April):62-69 [ Show Abstract ]

Purpose
To assess the six-month therapeutic profiles of lipid and non-lipid-based artificial tear supplements in managing dry eye disease (DED).

Methods
Ninety-nine participants fulfilling the TFOS DEWS II diagnostic criteria for DED (64% females; mean ± SD age, 44 ± 16 years) were enrolled in a prospective, multicentre, double-masked, parallel group, randomised controlled trial. Participants instilled lipid-based nanoemulsion drops or non-lipid-based aqueous drops for six months, at least four times daily. Symptomology, tear film and ocular surface characteristics were assessed at Days 0, 30, 60, 90, 120, 150 and 180.

Results
Sustained reductions in OSDI, DEQ-5, and SANDE symptom scores from baseline were observed from Day 30 onwards in both groups (all p < 0.05) and decreased superior lid wiper epitheliopathy grades from Day 60 onwards (all p ≤ 0.01). Improvements in non-invasive tear film breakup time, and sodium fluorescein and lissamine green staining scores followed from Day 120 onwards in both groups (all p < 0.05). Tear lipid layer grades increased from Day 90 onwards only with the lipid-based drops, and with significantly greater improvement in those with suboptimal lipid layer thickness at baseline (grade ≤3; p = 0.02). By Day 180, 19% of participants no longer fulfilled the diagnostic criteria for DED.

Conclusions
Over a six-month treatment period, improvements in dry eye symptomology preceded tear film and ocular surface changes with regular use of both lipid and non-lipid-based artificial tear supplements. Both formulations addressed most mild-to-moderate forms of aqueous deficient and evaporative DED, while evaporative cases benefitted preferentially from lipid-based supplementation. This represents a first step towards mapping DED therapeutic strategies according to disease subtype and severity.

Downie,L. E., Bandlitz,S., Bergmanson,J. P. G., Craig,J. P., Dutta,D., Maldonado-Codina,C., Ngo,W., Sowjanya Siddireddy,J., Wolffsohn,J. S. CLEAR - Anatomy and physiology of the anterior eye Contact Lens Anterior Eye 2021;44(2):132-156 [ Show Abstract ]

A key element of contact lens practice involves clinical evaluation of anterior eye health, including the cornea and limbus, conjunctiva and sclera, eyelids and eyelashes, lacrimal system and tear film. This report reviews the fundamental anatomy and physiology of these structures, including the vascular supply, venous drainage, lymphatic drainage, sensory innervation, physiology and function. This is the foundation for considering the potential interactions with, and effects of, contact lens wear on the anterior eye. This information is not consistently published as academic research and this report provides a synthesis from all available sources. With respect to terminology, the report aims to promote the consistent use of nomenclature in the field, and generally adopts anatomical terms recommended by the Federative Committee for Anatomical Terminology. Techniques for the examination of the ocular surface are also discussed.

Efron,N., Morgan,P. B., Jones,L. W., Morgan,G. A., Nichols,J. A Global optometrist top 200 research ranking Clinical and Experimental Optometry 2021;Online ahead of print [ Show Abstract ]

Clinical relevance: Clinical optometric practice is underpinned by a rigorous research base, the
primary evidence for which is publications in refereed scientific journals. Leading optometrists who
publish this work should be identified and celebrated.
Background: This work aims to derive publication metrics of the leading optometric researchers
worldwide.
Methods: An extensive global search was conducted to discover leading optometric researchers; 480
names were identified. A custom-designed bibliographic search tool was developed to interrogate
the Scopus database (Elsevier) and extract publication metrics using the unique Scopus Author
Identifier number for each optometrist. On 13 January 2021, the full list was reduced to 200
optometrists (the ‘Top 200’) ranked by h-index – the ‘Global Optometrist Top 200 Research
Ranking’. The output from the custom tool automatically updates every 24 hours and is available at
www.optomrankings.com.
Results: The Top 200 have h-indices ranging from 20 to 67 and have published between 28 and 440
papers. Sixty one (30.5%) are women. Konrad Pesudovs has the highest h-index (67) and citations
(51,193). The most prolific author is Robert Hess (442 papers). David Piñero is publishing at the
fastest rate (17.6 papers per year). The Top 200 work in 13 nations, of whom 172 (86.0%) work in
four nations: USA – 76 (38.0%), Australia – 43 (21.5%), UK – 41 (20.5%) and Canada – 16 (8.0%). Of
the 72 institutions represented, the University of California, Berkeley, USA is home to the most Top
200 optometrists (17) and has the highest combined h-index of Top 200 optometrists (132).
Conclusions: The optometric profession is supported by a robust research base, prosecuted by
a large international cohort of optometric researchers who publish extensively on a broad range of
ophthalmic issues and whose work is highly cited. The 200 most impactful optometrists in the world
are identified

Efron,N., Morgan,P. B., Jones,L. W., Nichols,J. A 21st century citation analysis of the field of contact lenses Clinical and Experimental Optometry 2021;Online ahead of print [ Show Abstract ]

Clinical relevance: The scientific foundations for clinical contact lens practice are rooted in the ophthalmic literature. This analysis of contact lens papers celebrates contemporary research achievements in the contact lens field.

Background: This work aims to assemble contact lens-related publication metrics so as to identify the most impactful papers published so far this century, as well the top countries, authors, institutions and journals.

Methods: A search was undertaken of the titles of papers on the Scopus database to identify contact lens-related articles published this century. The ten most highly cited papers were determined from the total list of 4,164 papers found. Rank-order lists by count were assembled for the ‘top 25ʹ in each of four categories: authors, institutions, countries and journals. A 20-year subject-specific contact lens h-index (hCL-20-index) was derived for each author, institution, country and journal to serve as a measure of impact in the field. The top 10 constituents (of the top 25) of each category were ranked by hCL-20-index and tabulated for consideration.

Results: The most highly cited paper this century is entitled ‘Soft contact lens polymers: An evolution’, by Nicholson and Vogt. Lyndon Jones is the most impactful author, with a hCL-20-index of 32. The University of New South Wales (Australia) produces the most impactful contact lens-related papers, and the United States is the most highly-ranked country. Optometry and Vision Science is the most impactful journal in the contact lens field.

Conclusions: Contact lens materials and lens-associated keratitis are topics of high interest in the contemporary contact lens literature, with an emerging interest in orthokeratology for myopia control and glucose monitoring. Impactful 21st century authors, institutions, countries and journals are identified. Optometry is revealed as the leading profession in relation to the publication of impactful contact lens-related papers.

Efron,N., Morgan,P. B., Jones,L. W., Nichols,J. A Bibliometric analysis of the refractive error field Clinical and Experimental Optometry 2021;Online ahead of print [ Show Abstract ]

Research into the epidemiology, aetiology, and optics of ametropia is a fundamental cornerstone of the correction and management of refractive errors by eye care practitioners. At present, much of this work is driven by the clinical concern that myopia is a common cause of vision loss, with uncorrected myopia the leading cause of vision impairment globally. Holden et al. predict that by 2050, about 50% of the population of the world will be myopic.
The aetiology of myopia continues to be hotly debated, centring around the relative impact of nature (genetics) versus nurture (environment). Research aimed at optimising optical (spectacles and contact lenses) and surgical (laser refractive techniques) modes of correcting refractive error continues unabated, and novel approaches for arresting the progression of myopia, using ophthalmic lenses, contact lenses (including orthokeratology), pharmacological approaches, or lifestyle modification, are also under active investigation. As is the case in all fields of investigation, the foundation of these various lines of refractive error research is rooted in the ophthalmic literature. Modern bibliographic search tools enable targeted interrogation of this vast literature to facilitate identification of the research foundations that underpin our understanding of refractive error. This Viewpoint uses
these bibliographic search tools and employs a subjectspecific measure of impact to identify key papers, authors, institutions, countries, and journals in the field of refractive error research.

Heynen,M., Ng,A., Martell,E., Subbaraman,L. N., Jones,L. Activity of Deposited Lysozyme on Contemporary Soft Contact Lenses Exposed to Differing Lens Care Systems Clinical Ophthalmology 2021;15(April):1727-1733 [ Show Abstract ]

Purpose: The amount of protein deposition on soft contact lenses and to what extent the proteins are denatured may have an impact on comfortable wearing times of contact lenses. The purpose of this study was to evaluate the effects of two lens care systems on total protein and the quantity and activity of lysozyme deposited on worn senofilcon A, silicone hydrogel contact lenses.

Participants and Methods: Thirty symptomatic soft contact lens wearers were enrolled into a 4-week prospective, randomized, bilateral eye, daily-wear, crossover, double-masked study. Participants were fitted with biweekly senofilcon A lenses and were assigned either a polyquaternium-1 and myristamidopropyl dimethylamine-containing system (OPTI-FREE RepleniSH) or a peroxide-based system (CLEAR CARE). After each wear period, proteins were extracted from the lenses and analyzed for total protein, total lysozyme quantity and activity.

Results: The use of either the peroxide-based system or the polyquaternium-1 and myristamidopropyl dimethylamine-containing system resulted in no difference (P> 0.05) to the amount of total protein deposited on the lenses (6.7 ± 2.8 micrograms/lens versus 7.3 ± 2.8 micrograms/lens, respectively) or to the amount of denatured lysozyme deposits (0.8 ± 0.7 versus 0.9 ± 0.7 micrograms/lens), respectively. The total amount of lysozyme deposited on the lenses was significantly lower when using the peroxide-based system (1.3 ± 0.9 micrograms/lens) compared to the polyquaternium-1 and myristamidopropyl dimethylamine-containing system (1.7 ± 1.0 micrograms/lens) (P=0.02).

Conclusion: The inactivation of lysozyme deposited on senofilcon A lenses when disinfected with the peroxide-based or the polyquaternium-1 and myristamidopropyl dimethylamine-containing systems were neither statistically nor clinically significant and the overall amounts of denatured lysozyme recovered from the lenses were low (< 1 microgram/lens).

Jones,L., Hui,A., Phan,C-M., Read,M. L., Azar,D., Buch,J., Ciolino,J. B., Naroo,S. A., Pall,B., Romond,K., Saknaridurg,P., Schnider,C. M., Terry,L., Willcox,M. CLEAR - Contact lens technologies of the future Contact Lens Anterior Eye 2021;44(2):398-430 [ Show Abstract ]

Contact lenses in the future will likely have functions other than correction of refractive error. Lenses designed to control the development of myopia are already commercially available. Contact lenses as drug delivery devices and powered through advancements in nanotechnology will open up further opportunities for unique uses of contact lenses.

This review examines the use, or potential use, of contact lenses aside from their role to correct refractive error. Contact lenses can be used to detect systemic and ocular surface diseases, treat and manage various ocular conditions and as devices that can correct presbyopia, control the development of myopia or be used for augmented vision. There is also discussion of new developments in contact lens packaging and storage cases.

The use of contact lenses as devices to detect systemic disease has mostly focussed on detecting changes to glucose levels in tears for monitoring diabetic control. Glucose can be detected using changes in colour, fluorescence or generation of electric signals by embedded sensors such as boronic acid, concanavalin A or glucose oxidase. Contact lenses that have gained regulatory approval can measure changes in intraocular pressure to monitor glaucoma by measuring small changes in corneal shape. Challenges include integrating sensors into contact lenses and detecting the signals generated. Various techniques are used to optimise uptake and release of the drugs to the ocular surface to treat diseases such as dry eye, glaucoma, infection and allergy. Contact lenses that either mechanically or electronically change their shape are being investigated for the management of presbyopia. Contact lenses that slow the development of myopia are based upon incorporating concentric rings of plus power, peripheral optical zone(s) with add power or non-monotonic variations in power. Various forms of these lenses have shown a reduction in myopia in clinical trials and are available in various markets.

Mirzapour,P., McCanna,D. J., Jones,L. In vitro analysis of the interaction of tear film inflammatory markers with contemporary contact lens materials Contact Lens Anterior Eye 2021;Online ahead of print [ Show Abstract ]

Purpose
Several clinical studies have suggested that reusable silicone hydrogel contact lens materials exhibit a two-times increased rate of corneal infiltrative events compared to reusable hydrogels. One potential factor contributing to this complication relates to the differential uptake of tear film-based pro-inflammatory cytokines. The purpose of this study was to use an in vitro assay to investigate whether four pro-inflammatory cytokines differed in their uptake onto six contemporary contact lens materials.

Methods
Conventional hydrogel (etafilcon A, omafilcon A) and silicone hydrogel (balafilcon A, comfilcon A, senofilcon A, somofilcon A) contact lens materials were soaked in solutions containing pro-inflammatory cytokines IL-1β, IL-6, IL-8 and TNF-α. Samples of the soaking solutions were collected over various time points and analyzed using the Meso Scale Discovery system, which served as a measurement of cytokine uptake onto the contact lens materials.

Results
Both conventional hydrogels (etafilcon A, omafilcon A) and two of the four silicone hydrogels tested (balafilcon A, comfilcon A), exhibited some uptake of IL-1β, IL-8 or TNF-α (p < 0.05). Senofilcon A and somofilcon A did not exhibit uptake of any of these cytokines (p > 0.05). There was no uptake of IL-6 onto any of the contact lens materials investigated (p > 0.05).

Conclusion
The contact lens materials tested did not exhibit any uptake of IL-6 and furthermore, did not exhibit more than 10 ± 3 % to 25 ± 12 % uptake of IL-1β, IL-8 or TNF-α. Numerous factors could contribute to the reported increase in corneal infiltrative events with reusable silicone hydrogel materials, however, based on these results, it appears that uptake of these four cytokines are unlikely to contribute to this finding.

Morgan,P. B., Murphy,P. J., Gifford,K. L., Gifford,P., Golebiowski,B., Johnson,L., Makrynioti,D., Moezzi,A. M., Moody, K., Navascues-Cornago,M., Schweizer,H., Swiderska,K., Young,G., Willcox,M. CLEAR - Effect of contact lens materials and designs on the anatomy and physiology of the eye Contact Lens Anterior Eye 2021;44(2):192-219 [ Show Abstract ]

This paper outlines changes to the ocular surface caused by contact lenses and their degree of clinical significance. Substantial research and development to improve oxygen permeability of rigid and soft contact lenses has meant that in many countries the issues caused by hypoxia to the ocular surface have largely been negated. The ability of contact lenses to change the axial growth characteristics of the globe is being utilised to help reduce the myopia pandemic and several studies and meta-analyses have shown that wearing orthokeratology lenses or soft multifocal contact lenses can reduce axial length growth (and hence myopia).

However, effects on blinking, ptosis, the function of Meibomian glands, fluorescein and lissamine green staining of the conjunctiva and cornea, production of lid-parallel conjunctival folds and lid wiper epitheliopathy have received less research attention. Contact lens wear produces a subclinical inflammatory response manifested by increases in the number of dendritiform cells in the conjunctiva, cornea and limbus. Papillary conjunctivitis is also a complication of all types of contact lenses. Changes to wear schedule (daily disposable from overnight wear) or lens materials (hydrogel from SiHy) can reduce papillary conjunctivitis, but the effect of such changes on dendritic cell migration needs further study. These changes may be associated with decreased comfort but confirmatory studies are needed. Contact lenses can affect the sensitivity of the ocular surface to mechanical stimulation, but whether these changes affect comfort requires further investigation.

In conclusion, there have been changes to lens materials, design and wear schedules over the past 20+ years that have improved their safety and seen the development of lenses that can reduce the myopia development. However, several changes to the ocular surface still occur and warrant further research effort in order to optimise the lens wearing experience.

Nichols,J. J., Morgan,P. M., Jones,L. W., Efron,N 21st century bibliometric analysis of the field of dry eye disease Clinical and Experimental Optometry 2021;Online ahead of print [ Show Abstract ]

In 2012, the lead author of this paper (JJN) conducted a citation analysis of dry eye research to identify the leading papers, authors, institutions, countries and journals in the field. That analysis was essentially an historical overview of publications on this topic extending back over the past century. Because a strong and growing foundation of scientific literature is a fundamental component of evidenced-based clinical care of patients, the current work was conducted to update the research community on trends in the 21st century dry eye literature, and to compare this new literature with the prior analysis in the context of events or trends in the dry eye field.

Omali,N. B., Subbaraman,L. N., Heynen,M., Lada,M., Canavan,K., Fadli,Z., Ngo,W., Jones,L. Lipid deposition on contact lenses in symptomatic and asymptomatic contact lens wearers Cont Lens Anterior Eye 2021;44(1):56-61 [ Show Abstract ]

Purpose
Lipid deposition on contact lenses (CL) has traditionally been believed to reduce comfort during CL wear. The purpose of this study was to quantify lipid deposition on CL in a group of symptomatic and asymptomatic adapted CL wearers.

Methods
This was a single-masked, randomized clinical trial. Only confirmed symptomatic (comfortable lens wear time (CWT) < 8 h and a noticeable reduction in comfort over the course of the day) and asymptomatic (CWT > 10 h and minimal reduction in comfort over the course of the day) participants were recruited to participate in the study. Participants wore senofilcon A lenses in combination with a polyquaternium-based care solution (OPTI-FREE Replenish). Worn CL samples were collected on Day 14. Deposited lipid amounts from the lenses (including cholesteryl ester, cholesterol and triolein) were quantified using a liquid chromatography-mass spectrometry technique.

Results
Lipid deposition was significantly higher in CL extracts of asymptomatic wearers compared to the symptomatic wearers for all lipid types quantified, including cholesteryl ester (2.1 ± 0.6 vs 1.6 ± 0.5 log μg/lens), cholesterol (1.5 ± 0.3 vs 1.1 ± 0.3 log μg/lens) and triolein (0.3 ± 0.2 vs 0.1 ± 0.1 log μg/lens) (all p < 0.002). The amount of cholesteryl ester deposited was greatest (p = 0.0001), followed by cholesterol, then triolein, for both the asymptomatic and symptomatic groups (both p = 0.0001).

Conclusion
This study demonstrated that the asymptomatic group deposited a significantly greater amount of lipid on their CL. Although lipid levels measured are considered low to trigger any observable clinical deposition, they may influence other clinical outcomes, particularly comfort.

Phan,C. M., Shukla,M., Walther,H. Heynen,M., Suh,D., Jones,L Development of an In Vitro Blink Model for Ophthalmic Drug Delivery Pharmaceutics 2021;13(Article 300):1-10 [ Show Abstract ]

Purpose: The purpose of this study was to develop an advanced in vitro blink model that
can be used to examine the release of a wide variety of components (for example, topical ophthalmic
drugs, comfort-inducing agents) from soft contact lenses. Methods: The model was designed using
computer-aided design software and printed using a stereolithography 3D printer. The eyelid and
eyeball were synthesized from polyvinyl alcohol and silicone material, respectively. Simulated
tear fluid was infused through tubing attached to the eyelid using a syringe pump. With each
blink cycle, the eyelid slides and flexes across the eyeball to create an artificial tear film layer. The
flow-through fluid was collected using a specialized trough. Two contact lenses, etafilcon A and
senofilcon A, were incubated in 2 mL of a water-soluble red dye for 24 h and then placed on the eye
model (n = 3). The release of the dye was measured over 24 h using a tear flow rate of 5 µL/min.
Results: Approximately 25% of the fluid that flowed over the eye model was lost due to evaporation,
nonspecific absorption, and residual dead volume. Senofilcon A absorbed more dye (47.6 ± 2.7 µL)
than etafilcon A (22.3 ± 2.0 µL). For etafilcon A, the release of the dye followed a burst-plateau
profile in the vial but was sustained in the eye model. For senofilcon A, the release of the dye was
sustained in both the vial and the eye model, though more dye was released in the vial (p < 0.05).
Overall, the release of the dye from the contact lenses was higher in the vial compared with the eye
model (p < 0.05). Conclusion: The blink model developed in this study could be used to measure
the release of topical ophthalmic drugs or comfort agents from contact lenses. Simulation of a blink
mechanism, an artificial tear film, and nonspecific absorption in an eye model may provide better
results than a simple, static vial incubation model.

Phan,C. M., Qiao,H., Yee,A., Jones,L. Deposition of Fluorescently Tagged Lysozyme on Contact Lenses in a Physiological Blink Model Eye & Contact Lens 2021;47(2):127-133 [ Show Abstract ]

PURPOSE: To visualize the deposition of fluorescein isothiocyanate (FITC) lysozyme on daily disposable contact lenses (CLs) using a novel blink model.

METHODS: Three daily disposable conventional hydrogel CLs (etafilcon A, omafilcon A, and nelfilcon A) and three silicone hydrogel CLs (delefilcon A, senofilcon A, and somofilcon A) were evaluated in the study. The CLs were mounted onto a novel blink model and exposed to an artificial tear solution containing FITC lysozyme for 2 and 10 hr. The flow rate and blink speed were set to 1 μL/min and 6 blinks/min, respectively. After the incubation period, a 5-mm-diameter disc was punched out from the center of the lens and mounted on a microscope slide. The slides were imaged using the Zeiss 510 Meta confocal laser scanning microscope, which scanned the lens from the front to the back surface at 5-μm increments.

RESULTS: There was an increase in deposition of FITC lysozyme for all lens types with increasing incubation time (P<0.05), with the exception of somofilcon A, which did not show statistical significance between 2 and 10 hr (P>0.05). The conventional hydrogel CLs deposited higher amounts of FITC lysozyme than the silicone hydrogel CLs (P<0.001), with etafilcon A depositing the highest at all time points (P<0.05). Interestingly, at the 2-hr incubation time, most CLs showed a higher amount of deposition at the front surface than the back surface of the lens. In particular, etafilcon A showed preferred deposition at the front surface at all time points.

CONCLUSION: The results suggest that there is differential deposition at the front surface of the CL, which is exposed to the prelens tear film, compared with the back surface of the CL, which is exposed to the postlens tear film. Therefore, it may be beneficial to design CL materials with differing surface properties for the front and back surfaces of the CL to enhance interactions with the tear film and ocular surface.

Schulze,M., Ng,A. Y., Yang,M., Panjwani,F., Srinivasan,S., Jones,L., Senchyna,M. Bulbar redness and dry eye disease: comparison of a validated subjective grading scale and an objective automated method Optometry & Vision Science 2021;98(2):113-120 [ Show Abstract ]

SIGNIFICANCE
In this study, assessments of conjunctival redness were performed to evaluate whether patients with or without dry eye disease (DED) could be discriminated based on this measure. Our findings suggest that subjectively grading redness by quadrant, as opposed to automated en face measurements, may be more suitable for this purpose.

PURPOSE
This study aimed to quantify bulbar redness using the validated bulbar redness (VBR) grading scale and an automated objective method (Oculus Keratograph 5M; K5M) in participants with DED and non-DED controls.

METHODS
Participants with DED (Ocular Surface Disease Index score ≥20 and Oxford scale corneal staining ≥2) and controls (Ocular Surface Disease Index score ≤10 and corneal staining ≤1) attended two study visits. In part 1A of visit 1, baseline bulbar redness was graded with the VBR scale in each conjunctival quadrant of both eyes, followed by automated measurements of temporal and nasal redness with the K5M. This was immediately followed by part 1B, during which a topical vasoconstrictor was instilled into both eyes. Redness assessments were repeated 5 and 30 minutes after instillation with both instruments. Participants returned 14 days later for visit 2, where the same assessments as for visit 1A were repeated.

RESULTS
Seventy-four participants (50 DED and 24 controls) completed the study. There were statistically significant differences in redness between the DED and control groups when assessed with the VBR scale (14/16 comparisons; all, P < .05), whereas no significant differences in K5M-derived redness between the DED and non-DED groups were found at any location or time point. Both subjective and objective instruments detected statistically significant reductions in redness 5 and 30 minutes after instillation of the vasoconstrictor (all, P < .01).

CONCLUSIONS
Although both subjective and objective instruments were sensitive to detecting changes in redness induced by vasoconstriction, statistically significant differences in redness between DED and control groups were only found using the VBR scale.

Stapleton,F., Bakkar,M., Carnt,N., Chalmers,R., Kumar Vijay,A., Marasini,S., Ng,A. Y., Tam,J., Wagner,H., Woods,C., Wolffsohn,J. S. CLEAR - Contact lens complications Contact Lens Anterior Eye 2021;44(2):330-367 [ Show Abstract ]

Contact lens-related complications are common, affecting around one third of wearers, although most are mild and easily managed. Contact lenses have well-defined anatomical and physiological effects on the ocular surface and can result in other consequences due to the presence of a biologically active material. A contact lens interacts with the tear film, ocular surface, skin, endogenous and environmental microorganisms, components of care solutions and other antigens which may result in disease specific to contact lens wear, such as metabolic or hypersensitivity disorders. Contact lens wear may also modify the epidemiology or pathophysiology of recognised conditions, such as papillary conjunctivitis or microbial keratitis. Wearers may also present with intercurrent disease, meaning concomitant or pre-existing conditions unrelated to contact lens wear, such as allergic eye disease or blepharitis, which may complicate the diagnosis and management of contact lens-related disease.

Complications can be grouped into corneal infection (microbial keratitis), corneal inflammation (sterile keratitis), metabolic conditions (epithelial: microcysts, vacuoles, bullae, tight lens syndrome, epithelial oedema; stromal: superficial and deep neovascularisation, stromal oedema [striae/folds], endothelial: blebs, polymegethism/ pleomorphism), mechanical (corneal abrasion, corneal erosion, lens binding, warpage/refractive error changes; superior epithelial arcuate lesion, mucin balls, conjunctival epithelial flaps, ptosis, discomfort), toxic and allergic disorders (papillary conjunctivitis, solution-induced corneal staining, incomplete neutralisation of peroxide, Limbal Stem Cell Deficiency), tear resurfacing disorders/dry eye (contact lens-induced dry eye, Meibomian gland dysfunction, lid wiper epitheliopathy, lid parallel conjunctival folds, inferior closure stain, 3 and 9 o'clock stain, dellen, dimple veil) or contact lens discomfort. This report summarises the best available evidence for the classification, epidemiology, pathophysiology, management and prevention of contact lens-related complications in addition to presenting strategies for optimising contact lens wear.

Vincent,S. J., Cho,P., Yin Chan,K., Fadel,D., Ghorbani-Mojarrad,N., González-Méijome,J. M., Johnson,L., Michaud,L., Simard,P., Jones,L. CLEAR - Orthokeratology Contact Lens Anterior Eye 2021;44(2):240-269 [ Show Abstract ]

Orthokeratology (ortho-k) is the process of deliberately reshaping the anterior cornea by utilising specialty contact lenses to temporarily and reversibly reduce refractive error after lens removal. Modern ortho-k utilises reverse geometry lens designs, made with highly oxygen permeable rigid materials, worn overnight to reshape the anterior cornea and provide temporary correction of refractive error. More recently, ortho-k has been extensively used to slow the progression of myopia in children.

This report reviews the practice of ortho-k, including its history, mechanisms of refractive and ocular changes, current use in the correction of myopia, astigmatism, hyperopia, and presbyopia, and standard of care. Suitable candidates for ortho-k are described, along with the fitting process, factors impacting success, and the potential options for using newer lens designs. Ocular changes associated with ortho-k, such as alterations in corneal thickness, development of microcysts, pigmented arcs, and fibrillary lines are reviewed. The safety of ortho-k is extensively reviewed, along with an overview of non-compliant behaviours and appropriate disinfection regimens. Finally, the role of ortho-k in myopia management for children is discussed in terms of efficacy, safety, and potential mechanisms of myopia control, including the impact of factors such as initial fitting age, baseline refractive error, the role of peripheral defocus, higher order aberrations, pupil size, and treatment zone size.

Walther,H., Lorentz,H., Heynen,M., Kay,L., Jones,L. W. The Impact of Incubation Conditions on in Vitro Phosphatidylcholine
Deposition on Contact Lens Materials
Optometry & Vision Science 2021;Online ahead of print [ Show Abstract ]

SIGNIFICANCE: Previous in vitro measurements of contact lenses commonly investigate the impact of nonpolar
tear film lipids (i.e., sterols). Polar lipids, however, are equally important stabilizing components of the tear film.
This research explores and presents further knowledge about various aspects of polar lipid uptake that may impact
contact lens performance.

PURPOSE: This study evaluated the impact of incubation time, lipid concentration, and replenishment of an artificial
tear solution (ATS) on the uptake of phosphatidylcholine (PC) onto conventional hydrogel (CH) and silicone
hydrogel (SH) contact lens materials.

METHODS: Four SHs and two CH lens materials (n = 4) were soaked in a complex ATS containing radioactive
14C-PC as a probe molecule. Phosphatidylcholine uptake was monitored at various incubation time points (1, 3,
7, 14, and 28 days), with different ATS lipid concentrations (0.5, 1, 2) and with and without regular replenishment
of the ATS. Phosphatidylcholine was extracted from the lenses, processed, and counted by a β counter,
and accumulated PC (μg/lens) was extrapolated from standard lipid calibration curves.

RESULTS: All materials exhibited increasing PC deposition over time. Conventional hydrogel materials showed significantly lower PC uptake rates (P < .001) than any of the SH materials. Increasing lipid concentration in the ATS
resulted in increased PC binding onto the contact lens materials (P < .001). Replenishing the ATS every other day,
however, impacted the PC deposition differently, showing increased binding (P < .001) on CHs and reduced PC
deposition for SH materials (P < .001).

CONCLUSIONS: Length of incubation, lipid concentration in the ATS, and renewal of the incubation solution all
influenced the amount of PC that sorbed onto various lens materials and therefore need to be considered when
conducting future in vitro deposition studies.

Willcox,M., Keir,N., Maseedupallu,V., Masoudi,S., McDermott,A., Mobeen,R., Purslow,C., Santodomingo-Rubio,J., Tavazzi,S., Zeri,F., Jones,L. W. CLEAR - Contact lens wettability, cleaning, disinfection and interactions with tears Contact Lens Anterior Eye 2021;44(2):157-191 [ Show Abstract ]

Contact lens materials have undergone significant changes over the past 20 years, particularly with respect to the introduction of silicone hydrogel materials. Whilst this development addressed hypoxic issues, other important areas relating to contact lens success, notably comfort, require further research.

Contact lens wettability remains a crucially important part of biocompatibility. Contact lenses can be made more wettable by incorporation of surfactants into blister packs, internal wetting agents, surface treatments or care solutions. However, there remains no clear association between contact lens wettability and comfort, making it challenging to determine the potential for these approaches to be of significant clinical benefit. Most contact lenses are used on a daily wear, reusable basis, which requires them to be disinfected when not worn. The ideal disinfecting solution would also improve comfort during wear. However, balancing these requirements with other factors, including biocompatibility, remains a challenge. Soft lens materials invariably take up and subsequently release certain components of disinfecting solutions onto the ocular surface. This may affect tear film stability and the normal ocular microbiome, and further research is needed in this area to determine whether this has any affect on comfort. Finally, contact lens materials sorb components of the tear film, and these interactions are complex and may change the biochemistry of the tear film, which in turn may affect their comfort.

In conclusion, the interaction between lens materials, tear film and disinfection solution plays an important role in the biocompatibility of lenses. However, the exact role and whether this can be altered to improve biocompatibility and comfort during wear remains debatable. This report summarises the best available evidence to examine this complex relationship and the opportunities for practitioners to enhance in-eye comfort of contemporary lenses, along with providing suggestions for areas of study that may provide further information on this topic.

Wolffsohn,J. S., Dumbleton,K., Huntjens,B., Kandel,H., Koh,S., Kunnen,C. M. E., Nagra,M., Pult,H., Sulley,A. L., Vianya-Estopa,M., Walsh,K., Wong,S., Stapleton,F. CLEAR - Evidence-based contact lens practice Contact Lens Anterior Eye 2021;44(2):368-397 [ Show Abstract ]

Evidence-based contact lens -->practice involves finding, appraising and applying research findings as the basis for patient management decisions. These decisions should be informed by the strength of the research study designs that address the question, as well as by the experience of the practitioner and the preferences and environment of the patient. This reports reviews and summarises the published research evidence that is available to inform soft and rigid contact lens history and symptoms taking, anterior eye health examination (including the optimised use of ophthalmic dyes, grading scales, imaging techniques and lid eversion), considerations for contact lens selection (including the ocular surface measurements required to select the most appropriate lens parameter, lens modality and material selection), evaluation of lens fit, prescribing (teaching self-application and removal, adaptation, care regimen and cleaning instructions, as well as -->minimising risks of lens wear through encouraging compliance) and an aftercare routine.

Wolffsohn,J. S., Morgan,P. B., Barnett,M., Downie,L. E., Jacobs,D. S. Jones,L. W., Richdale, K., Stapleton,F., Vincent,S. J., Willcox,M. Contact Lens Evidence-Based Academic Reports (CLEAR) Contact Lens Anterior Eye 2021;44(2):129-131 [ Show Abstract ]

Since contact lenses were invented in 1887, innovations have included advances in optical design, material, care systems, wear modality, lens size, lens shape and applications. Over 19,000 peer reviewed academic papers on the contact lenses have been published. The Contact Lens Evidence-based Academic Reports (CLEAR) follow the exemplary work of organisations such as the Tear Film and Ocular Surface Society dry eye, meibomian gland disease, contact lens discomfort and dry eye II workshops and the International Myopia Institute white papers on myopia control, in collating and appraising the academic literature in an ocular field of interest. CLEAR represent the work of nearly 100 multidisciplinary experts in the field, who set out to critically review, synthesise and summarise the research evidence on contact lenses to date; this serves to inform both clinical practice, manufacturing innovation and future research directions.

Woods,J., Jones,D., Jones,L., Jones,S., Hunt,C., Chamberlain,P., McNally,J Ocular health of children wearing daily disposable contact lenses over a 6-year period Contact Lens Anterior Eye 2021;Online ahead of print [ Show Abstract ]

Purpose
To report on the ocular health and safety of children fit with soft hydrogel daily-disposable contact lenses, and followed for 6-years in a double-masked clinical trial investigating the performance of a dual-focus contact lens designed to control myopia progression.

Methods
Children aged 8−12 years, naïve to contact lens wear, were enrolled across four international sites. During years 1–3, children were randomised to either MiSight® 1 day or Proclear® 1 day (both omafilcon A, CooperVision, Inc.). The lenses were identical in material and geometry except for the front optical zone design. At the end of year-3, all those wearing Proclear 1 day were switched to MiSight 1 day, therefore all wore MiSight 1 day in years 4−6. Subjects agreed to wear the lenses at least 10-hours/day, 6-days/week. After dispensing, study visits were at 1-week, 1-month, 6-months and every 6-months until 6-years. At each visit, ocular measurements and subjective responses were recorded. Biomicroscopy used 0–4 grading scales; grade 0 represented no findings.

Results
144 children were enrolled: 69F:75M; mean age 10.1 years; mean cycloplegic spherical-equivalent refraction -2.11D; ethnicities included 34 East-Asian, 12 West-Asian, and 79 Caucasian. 92 completed the 6-years. Only three subjects discontinued due to an ocular adverse event (AE). No contact lens related AEs were classified as serious. The incidence rate of infiltrative AEs was 0.61% (6.1/1000 wearing-years; 95%CI: 0.24%–1.57%). The most common biomicroscopy findings were limbal, bulbar and tarsal hyperaemia and tarsal roughness. 99% of all biomicroscopy findings were grade-1 or lower. After 6-years of lens wear, ocular health by biomicroscopy was similar to pre-lens wear.

Conclusions
Across the 6-years, there were no contact lens related serious AEs and biomicroscopy showed no significant changes. Results suggest that children this age can successfully wear daily-disposable hydrogel contact lenses with minimal impact on ocular physiology.

Xu,M., Sivak,J. G., McCanna,D. J. Neutralization of the eye and skin irritant benzalkonium chloride using UVC radiation Cutaneous and Ocular Toxicology 2021;Online ahead of print [ Show Abstract ]

Benzalkonium chloride (BAK) is a widely used disinfectant and preservative which is effective against a wide range of viruses (e.g. SARS-CoV and SARS-CoV-2), bacteria and fungi. However, it is toxic to the eye and skin. This study investigated the neutralization of BAK using ultraviolet C (UVC) radiation as an effort to reduce BAK toxicity potential.

Methods
BAK solutions were irradiated with a germicidal UVC lamp at various doses. Human corneal epithelial cells (HCEC) were then exposed to the UVC-irradiated BAK solutions for 5 minutes. After exposure, the cultures were assessed for metabolic activity using PrestoBlue; for cell viability using confocal microscopy with viability dyes; and for tight junction proteins using immunofluorescence staining for zonula occludens (ZO)-1.

Results
UVC radiation reduced BAK toxicity on cell metabolic activity in a dose-dependent manner. When the solution depth of BAK was 1.7 mm, the UVC doses needed to completely neutralize the toxicity of BAK 0.005% and 0.01% were 2.093 J/cm2 and 8.374 J/cm2, respectively. The cultures treated with UVC-neutralized BAK showed similar cell metabolic activity and cell viability to those treated with phosphate buffered saline (PBS) (p = 0.806 ∼ 1.000). The expression of ZO-1 was greatly disturbed by untreated BAK; in contrast, ZO-1 proteins were well maintained after exposure to UVC-neutralized BAK.

Conclusions
Our study demonstrates that the cell toxicity of BAK can be neutralized by UVC radiation, which provides a unique way of detoxifying BAK residues. This finding may be of great value in utilizing the antimicrobial efficacy of BAK (e.g. fighting against SARS-CoV-2) while minimizing its potential hazards to human health and the environment.

Yamasaki,K., Mizuno,Y., Kitamura,Y., McCanna,D. J., Ngo,W., Jones,L. W. The efficacy of povidone-iodine, hydrogen peroxide and a chemical multipurpose contact lens care system against Pseudomonas aeruginosa on various lens case surfaces Cont Lens Anterior Eye 2021;44(1):18-23 [ Show Abstract ]

Purpose
To determine the antimicrobial efficacy of a povidone-iodine system (PVP-I; cleadew, OPHTECS Corporation, Kobe, Japan), a peroxide system (AOSEPT Plus with HydraGlyde, Alcon, Fort Worth, TX), and a chemical multipurpose system (renu fresh, Bausch & Lomb, Rochester, NY) on contact lens case surfaces that are both in contact and not in contact with the solutions during lens disinfection.

Methods
The surfaces of the inner walls, underside of the lid, and lens holder (if applicable) of the cases were inoculated with P. aeruginosa ATCC 27853. The cases were disinfected with the solutions as per their manufacturer instructions. After disinfection, the inoculated surfaces were swabbed and the amount of surviving P. aeruginosa was determined. Following this experiment, separate cases were inoculated and disinfected as before. This time the cases were agitated after recommended disinfection time and the amount of P. aeruginosa in the disinfecting solution was quantified immediately, and again after resting for 7 days. Experiments were conducted in triplicate (n = 3).

Results
Units are expressed in log CFU. All three solutions significantly reduced P. aeruginosa on direct-contact surfaces (all p < 0.039). On non-contact surfaces, the reduction of P. aeruginosa in the PVP-I system (pre-disinfection: 6.8 ± 0.5, post-disinfection: 1.0 ± 0.0; p < 0.001) was significant, but not for the hydrogen peroxide system (pre-disinfection: 6.3 ± 0.6, post: 5.5 ± 0.5; p = 0.194) and the chemical multipurpose system (pre-disinfection: 6.6 ± 0.1, post-disinfection: 5.6 ± 0.8; p = 0.336). After 7 days post-disinfection, no P. aeruginosa regrowth was observed in the PVP-I system (Day 1: 1.0 ± 0.0, Day 7: 1.0 ± 0.0; p = 1) and the chemical multipurpose system (Day 1: 4.2 ± 0.2, Day 7: 1.8 ± 0.9; p = 0.012), however regrowth was observed in the hydrogen peroxide system (Day 1: 3.4 ± 0.6, Day 7: 6.1 ± 0.4; p = 0.003).

Conclusion
The PVP-I system was more effective against P. aeruginosa on non-contact surfaces than the hydrogen peroxide system or the chemical multipurpose system and is capable of inhibiting regrowth of P. aeruginosa for at least 7 days post-disinfection.

Yee,A., Walsh,K., Schulze,M., Jones,L The impact of patient behaviour and care system compliance on reusable soft contact lens complications Contact Lens Anterior Eye 2021;Online ahead of print [ Show Abstract ]

Reusable soft daily wear contact lenses (CLs) remain popular and were fit to just over half of all wearers in the most recent international CL prescribing survey. Unlike daily disposable CLs, reusables require cleaning and disinfecting after every use, along with storage in a CL case. These additional requirements add a number of steps to the daily wear and care routine, increasing the opportunities for CL wearers to exhibit non-compliant behaviour. The impact of non-compliance ranges from poor lens comfort through to potentially sight- threatening infective keratitis. The coronavirus pandemic has refocused the profession on the importance of hand hygiene in particular, and the need for promoting safe CL wear in general. This review summarises typical non-compliant behaviour related to reusable CLs, and examines strategies and opportunities to better support wearers. Patient education has a central role in encouraging compliant behaviour, although patient recall of information is low, and personal belief systems may result in continuation of non-compliant behaviour despite awareness of the risks. CL care solutions are required for the daily disinfection of lenses, however misuse of multipurpose solutions (MPS) and hydrogen peroxide (H2O2)-based care systems can challenge their ability to be fully efficacious. Standard efficacy testing is reviewed, with consideration of how well current protocols model real-world use of CL solutions. Although some recommendations are in place for the inclusion of additional variables such as lens cases, CL materials, organic soil and efficacy against Acanthamoeba, opportunity still exists to reevaluate global standards to ensure consistency of testing in all markets. Finally, potential future innovations are discussed which may further support increased safety in reusable lens wear through novel antimicrobial additions to both CL materials and cases