Abdi,B., Mofidfar,M., Hassanpout,F., Cilingir,E. K., Kalajahi,S., Milani,P. K., Ghanbarzadeh,M., Fadel,D., Barnett,M., Ta,C. N., Leblanc,R. M., Chauhan,A., Abbasi,F. Therapeutic contact lenses for the treatment of corneal and ocular surface diseases: Advances in extended and targeted drug delivery International Journal of Pharmaceutics 2023;638(May):122740 [ Show Abstract ]

The eye is one of the most important organs in the human body providing critical information on the environment. Many corneal diseases can lead to vision loss affecting the lives of people around the world. Ophthalmic drug delivery has always been a major challenge in the medical sciences. Since traditional methods are less efficient (∼5%) at delivering drugs to ocular tissues, contact lenses have generated growing interest in ocular drug delivery due to their potential to enhance drug bioavailability in ocular tissues. The main techniques used to achieve sustained release are discussed in this review, including soaking in drug solutions, incorporating drug into multilayered contact lenses, use of vitamin E barriers, molecular imprinting, nanoparticles, micelles and liposomes. The most clinically relevant results on different eye pathologies are presented. In addition, this review summarizes the benefits of contact lenses over eye drops, strategies for incorporating drugs into lenses to achieve sustained release, results of in vitro and in vivo studies, and recent advances in the commercialization of therapeutic contact lenses for allergic conjunctivitis.

Akbari,E., Imani,R., Shokrollahi,P., Keshel,S. H. Corneal sustained delivery of hyaluronic acid from nanofiber-containing ring-implanted contact lens Journal of Biomaterials Application 2023;37(6):992-1006 [ Show Abstract ]

Dry eye syndrome, as a persist corneal epithelial defect (PED), is an inconvenient ocular disorder that is generally treated by high-dosage, conventional eye drops. Addressing low efficacy and rather restricted bioavailability of the conventional eye drops, drug-eluting contact lenses (CLs) are widely used as alternatives in ophthalmic drug delivery applications. In the present study, a nanofiber-containing ring implant poly (vinyl alcohol) (PVA) hydrogel is designed as a carrier for hyaluronic acid (HA) delivery. hyaluronic acid is physically encapsulated in a nanofiber-containing ring-shaped hydrogel with a 2 mm width that is implanted in the final CLs hydrogel. The designed CL has 59% porosity, 275% swelling ratio and undergoes no weight loss at physiological conditions in14 days. In-vitro release studies were performed on the CLs with and without nanofibers. The results showed that nanofiber incorporation in the designed CL was highly influential in decreasing burst release and supported sustained release of HA over 14 days. In addition, nanofiber incorporation in the designed system strengthened the lens, and the young modulus of the PVA hydrogel increased from 6 to 10 kPa. Cell viability study also revealed no cell cytotoxicity and cell attachment. Overall, the study demonstrated the effective role of nanofibers in the physical strengthening of the CL. Also, the designed system holds promise as a potential candidate for HA delivery over an extended period for treating dry eye syndrome.

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;21(July):250-256 [ 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.

Bajgrowicz,M., Phan,C. -M, Subbaraman,L. N., Jones,L. Release of ciprofloxacin and moxifloxacin from daily disposable contact lenses from an in vitro eye model Investigative Ophthalmology and Visual Science 2015;56(4):2234-2242 [ Show Abstract ]

Purpose. To analyze the release of two fluoroquinolones, ciprofloxacin and moxifloxacin, from conventional hydrogel (CH) and silicone hydrogel (SH) daily disposable contact lenses (CLs), comparing release from a fixed-volume vial and a novel in vitro eye model. Methods. Four CH CLs (nelfilcon A, omafilcon A, etafilcon A, ocufilcon B) and three SH CLs (somofilcon A, narafilcon A, delefilcon A) were used. The lenses were incubated in drug solutions for 24 hours. After the incubation period, the lenses were placed in two release conditions: (1) a vial containing 4.8 mL PBS for 24 hours and (2) an in vitro eye model with a flow rate at 4.8 mL over 24 hours. Results. Release in the vial for both drugs was rapid, reaching a plateau between 15 minutes and 2 hours for all lenses. In contrast, under physiological flow conditions, a constant and slow release was observed over 24 hours. The amounts of ciprofloxacin released from the lenses ranged between 49.6 ±0.7 and 62.8 ± 0.3 µg per lens in the vial, and between 35.0 ± 7.0 and 109.0 ± 5.0 µg per lens in the eye model. Moxifloxacin release ranged from 24.0 ± 4.0 to 226.0 ± 2.0 µg per lens for the vial, and between 13.0 ± 2.0 and 151.0 ± 10.0 µg per lens in the eye model. In both systems and for both drugs, HEMA-based CLs released more drugs than other materials. Conclusions. The parameters of the release system, in particular the volume and flow rate, have a significant influence on measured release profiles. Under physiological flow, release profiles are significantly slower and constant when compared with release in a vial. © 2015, The Association for Research in Vision and Ophthalmology, Inc.

Barton,J. J. S., Rizzo,M., Nawrot,M., Simpson,T. Optical blur and the perception of global coherent motion in random dot cinematograms Vision research 1996;36(19):3051-3059 [ Show Abstract ]

We evaluated the effect of +3.25 dioptres of optical blur on the discrimination of motion direction in random dot cinematograms. Dot displacement between frames varied from 2.1 to 63' of visual angle while the temporal interval was held constant. Optical blur worsened discrimination in three normal subjects at displacements below 16', but improved discrimination at displacements of 21' or more. In a second experiment, two subjects viewed equivalent velocity stimuli constructed with different combinations of temporal interval and spatial displacement. Results showed that the effect of blur was specific to displacement and not velocity. Furthermore, varying the dot density of the display showed that the effect of blur correlated with dot displacement and not the probability of dot mismatches. Since optical blur attenuates high spatial frequencies, this suggests that high spatial frequencies are important for motion perception when dot displacements are less than 16' to 21', but reduce motion perception at larger dot displacements. The use of random dot cinematograms in populations must take into account stimulus displacement and optical causes of reduced spatial acuity.

Barton,J. J. S., Simpson,T., Kiriakopoulos,E., Stewart,C., Crawley,A., Guthrie,B., Wood,M., Mikulis,D. Functional MRI of lateral occipitotemporal cortex during pursuit and motion perception Annals of Neurology 1996;40(3):387-398 [ Show Abstract ]

We performed functional imaging with a conventional 1.5-T magnetic resonance scanner in 9 normal subjects. We used a gradient-echo technique to examine changes in signal between periods when subjects viewed a stationary black-and-white grating, a moving grating, and when they followed a moving spot. We located image pixels with significant differences between the viewing conditions. In 7 subjects, these occurred in the lateral occipitotemporal cortex, a region previously identified as a putative human homologue of the motion-sensitive middle temporal area (MT, or V5) of monkeys. Signal intensity was greater during pursuit of the moving dot than during viewing of the moving grating with the eyes still, despite the fact that the moving grating generated more retinal image motion. In contrast, signal intensity in striate cortex was least during pursuit of the moving dot. These findings suggest that the lateral occipitotemporal cortex has extraretinal signals during pursuit. Such signals may include attentional input, corollary eye movement information, or even a pursuit command. Extraretinal signals suggest that the lateral occipitotemporal cortex may contain a human homologue not only of MT but also of other components of the monkey V5 complex, such as the medial superior temporal area.

Begley,C. G., Chalmers,R. L., Abetz,L., Venkataraman,K., Mertzanis,P., Caffery,B. A., Snyder,C., Edrington,T., Nelson,D., Simpson,T. The relationship between habitual patient-reported symptoms and clinical signs among patients with dry eye of varying severity Investigative Ophthalmology and Visual Science 2003;44(11):4753-4761 [ Show Abstract ]

PURPOSE. To investigate symptom profiles and clinical signs in subjects with dry eye and normal subjects in a cross-sectional multicenter study. METHODS. Subjects aged 35 to 65 were recruited according to dry eye diagnostic codes and telephone interview and completed the Dry Eye Questionnaire 2001, among others, and underwent dry eye clinical tests. RESULTS. Subjects (122) included 28 control subjects (C), 73 with non-Sjögren's keratoconjunctivitis sicca (non-SS KCS) and 21 with Sjögren's syndrome (SS). Subjects with SS or non-SS KCS reported discomfort and dryness most frequently and that many symptoms worsened over the day and were quite bothersome. Groups were significantly different in corneal fluorescein staining, conjunctival lissamine green staining, Schirmer 1 tear test, and tear break-up time (TBUT; X2 and Kruskal-Wallis, P 0.0001). CONCLUSIONS. Subjects with SS or non-SS KCS reported frequent and intense ocular surface symptoms in the evening, some of which correlated moderately with clinical test results. The global clinician grade of dry eye correlated more highly with patient symptoms than did clinical signs, suggesting that patient symptoms influence dry eye diagnosis and grading of dry eye more than clinical test results.

Begley,C. G., Chalmers,R. L., Mitchell,G. L., Nichols,K. K., Caffery,B., Simpson,T., DuToit,R., Portello,J., Davis,L. Characterization of ocular surface symptoms from optometric practices in North America Cornea 2001;20(6):610-618 [ Show Abstract ]

Purpose. This study characterized ocular symptoms typical of dry eye in an unselected optometric clinical population in the United States and Canada. Methods. Self-administered dry eye questionnaires, one for non-contact lens wearers (dry eye questionnaire) and one for contact lens wearers (contact lens dry eye questionnaire), were completed at six clinical sites in North America. Both questionnaires included categoric scales to measure the prevalence, frequency, diurnal severity, and intrusiveness of nine ocular surface symptoms. The questionnaires also asked how much these ocular symptoms affected daily activities and contained questions about computer use, medications, and allergies. The examining doctors, who were masked to questionnaire responses, recorded a nondirected dry eye diagnosis for each patient, based on their own diagnostic criteria. Results. The dry eye questionnaires were completed by 1,054 patients. The most common ocular symptom was discomfort, with 64% of non-contact lens wearers and 79% of contact lens wearers reporting the symptom at least infrequently. There was a diurnal increase in the intensity of many symptoms, with symptoms such as discomfort, dryness, and visual changes reported to be more intense in the evening. The 22% percent of non-contact lens wearers and 15% of contact lens wearers diagnosed with dry eye (most in the mild to moderate categories) reported symptoms at a greater frequency than those not diagnosed with dry eye. Conclusions. Our results show that symptoms of ocular irritation and visual disturbances were relatively common in this unselected clinical population. The intensity of many ocular symptoms increased late in the day, which suggested that environmental factors played a role in the etiology of the symptoms.

Begley,C. G., Himebaugh,N., Renner,D., Liu,H., Chalmers,R., Simpson,T., Varikooty,J. Tear breakup dynamics: A technique for quantifying tear film instability Optometry and Vision Science 2006;83(1):15-21 [ Show Abstract ]

PURPOSE: The purpose of this study was to develop a novel, quantitative measurement of tear film breakup dynamics (TBUD) to study the phenomenon of tear breakup in dry eye and control subjects and its impact on dry eye symptoms. METHODS: Ten control and 10 dry eye subjects completed the Dry Eye (DEQ) and other questionnaires. After the instillation of sodium fluorescein, subjects kept the tested eye open for as long as possible, similar to a staring contest, while tear film breakup was videotaped (S-TBUD). The maximum blink interval (MBI) and tear breakup time (TBUT) were measured from digital movies by a masked observer. Individual frames of movies were converted to gray-scale images, maps of relative tear film fluorescence were generated, and the total area of tear breakup (AB) of the exposed cornea was quantified. RESULTS: On average, dry eye subjects demonstrated a higher AB and shorter TBUT and MBI, but only the AB was significantly different (p = 0.023). Subjects most often used the descriptors stinging and burning to describe their sensations during staring trials. The AB showed a high correlation between eyes and with some DEQ symptom measures. CONCLUSIONS: These methods allow objective quantification and tracking of the phenomenon of tear breakup. Our results suggest that tear breakup stresses the corneal surface, resulting in stimulation of underlying nociceptors. The tear film of dry eye subjects was less stable than controls. They had a larger AB measured from the last video frame before MBI (i.e., just before blinking) than did controls. This perhaps reflects adaptation to the repeated stress of tear instability in dry eye.

Berntsen,D. A., Hickson-Curran,S. B., Jones,L. W., Mathew,J. H., Maldonado-Codina,C., Morgan,P. B., Schulze,M. M., Nichols,J. J. Subjective comfort and physiology with modern contact lens care products Optometry and Vision Science 2016;93(8):809-819 [ Show Abstract ]

Purpose. To compare subjective comfort and ocular physiology with three multipurpose solutions (MPSs) to that of a peroxide-based system with three different soft contact lens materials. Methods. Habitual soft contact lens wearers (n = 236) were enrolled at three sites and completed a washout period with no contact lens solution for =4 days. Subjects were randomly assigned to one of three lens types: etafilcon A, galyfilcon A, or senofilcon A. A new lens of the assigned type was worn for 10 to 14 days each while using one of four care solutions, in random order (A - polyaminopropyl biguanide + polyquaternium, B - POLYQUAD + Aldox, C - alexidine + polyquaternium-1, and D - hydrogen peroxide) with a washout period (=4 days) between each solution. After each care solution, biomicroscopy was performed and subjective comfort was assessed using the Contact Lens User Experience (CLUE) questionnaire and other instruments including comfortable wear time (CWT). Linear mixed models were used for analysis. Comfort and biomicroscopy signs with each MPS were compared to that of the peroxide solution. Results. Subjective CLUE Comfort score across all lens types with each MPS was not significantly different than with the peroxide solution (p = 0.98). There were no differences in CWT between each MPS and the peroxide solution for any lens type (range of differences: -0.8 to 0.8 h; all p = 0.13). Six MPS/material combinations had no clinically meaningful change in corneal staining versus peroxide (<0.5 units); three combinations could increase staining by up to 0.57 units. Staining was <grade 1 for all combinations. Conclusions. Comparable levels of comfort were found between the latest generation of MPSs compared to peroxide disinfection. Three MPS/material combinations tested could result in increased corneal staining of up to 0.57 units versus a peroxide solution. Overall, these data suggest the care systems investigated are generally appropriate for usewith the contact lenses tested. © Copyright 2016 American Academy of Optometry.

Bitton,E., Elder,M., Srinivasan,S., Luensmann,D., Jones,L. Dry Eye Disease in University-based Clinics in Canada: A Retrospective Chart Review Optometry & Vision Science 2020;97(11):944-953 [ Show Abstract ]

SIGNIFICANCE
Dry eye disease (DED) imposes a substantial burden on patients, which can lead to significant economic consequences for society. We provide insights into the DED patient population and DED diagnostic/management practices in Canada, which to date have been inadequately addressed in the literature.

PURPOSE
The purpose of this study was to describe DED patient demographic/clinical characteristics alongside DED diagnosis/management in university-based optometry clinics in Canada.

METHODS
This was a retrospective chart review of nonconcurrent non-Sjögren patients with DED at two university-based optometry clinics in Montreal and Waterloo. Waterloo charts with a diagnosis of DED and all charts from the Montreal dry eye clinic were considered for inclusion.

RESULTS
Overall, 200 charts were reviewed. Most patients were female (Montreal, 76%; Waterloo, 72%), and the mean age was 57.2 ± 14.9 years at Montreal and 52.6 ± 20.1 years at Waterloo. Patients commonly reported multiple health conditions (e.g., allergies [Montreal, 44%; Waterloo, 36%]), and high use of systemic nonocular medications was observed (Montreal, 76%; Waterloo, 62%). Clinical signs and symptoms of DED were recorded more often in Montreal patients than in Waterloo patients (e.g., dryness symptoms, 100 vs. 72%; tear breakup time, 100 vs. 60%). Warm compresses (Montreal, 63%; Waterloo, 83%) and artificial tears (Montreal, 94%; Waterloo, 96%) were the most frequently recommended nonmedical treatment and ocular lubricant, respectively. Topical steroids were the most frequently prescribed medications (Montreal, 22%; Waterloo, 21%), with typically three to four different interventions recommended per patient at each clinic. No relationship was found between symptoms and clinical signs or recommended interventions.

CONCLUSIONS
This retrospective chart review provided the demographics, clinical characteristics, diagnosis, and management options for DED patients in Canadian university-based optometry clinics. The more comprehensive assessments conducted at Montreal may be beneficial to better monitor the progression of DED and to determine treatment effects over time.

Bitton,E., Jones,D., Wittich,W. Financial Inequities in Optometric Education in Canada: A Comparison of Two Optometry Programs Optometry and Vision Science 2023;Online ahead of print [ Show Abstract ]

Significance: The advancing age of the population will require increased access to eyecare services to manage eye diseases and vision correction. Optometric education requires a sound financial plan to manage student debt. This study evaluates the financial inequalities of optometric programs in Canada, and how this may impact the provision of eyecare professionals.

Purpose: The objective of this study was to compare the financial inequities in Optometric education in Canada from the 2020 graduating class.

Methods: A cross-sectional study assessed monetary variables related to the study of optometry in Canada, including academic and personal expenses, and overall debt and expenses related to the COVID-19 lockdown for the 2020 graduating class.

Results: 108 optometry students from the 2020 graduating classes of the University of Montreal and the University of Waterloo responded, with 68 (53 F:15 M, age 25.66, SD = 2.01) completing the study. Waterloo students spent more years in university (P < .001); had higher academic fees (P <.001); spent more on travelling to their family residence (P =.007) and received more provincial (P = .002) and federal (P <.001) loans than Montreal students. Overall debt prior to optometry was similar amongst students but differed (P <.001) at the end of their program, with Waterloo students having a higher debt burden.

Conclusions: There is a financial inequity in optometric education in Canada depending on the chosen program. Cumulative optometry student debt for the 2020 graduating class in Canada ranges from $CAN 0 to 189,000 with an average of $CAN 65,800 and a median of $CAN 50,000. The results of this study can assist financial, government agencies and future optometry students to better understand the financial burdens and establish a financial plan to study optometry in Canada, to respond to the growing eyecare needs of the public.

Bitton,E., Jones,L., Simpson,T., Woods,C. Influence of the blink interval on tear meniscus height in soft contact lens and nonlens wearers Eye and Contact Lens 2010;36(3):156-163 [ Show Abstract ]

Purpose: Tear meniscus height (TMH) is an indirect measurement of tear film volume. This study investigated the temporal changes in the TMH during the blink interval in the morning (8-9 am) and at the end of the day (5-6 pm) in both soft contact lens (CL) and nonlens wearers (NLW). Methods: Fifty participants (25 CL; 25 NLW) were evaluated for their subjective symptoms, TMH, noninvasive break up time, and bulbar hyperemia at the am and pm visits on the same day. The TMH was measured at set intervals between 2 and 15 sec during the blink interval, using an optical coherence tomographer. Results: The NLW group revealed no changes in a variety of symptoms during the day, whereas the CL group reported an increase in dryness (P=0.03) and grittiness (P=0.02) over the day. For both groups, the TMH and calculated tear meniscus volume revealed lower values immediately after the blink and increased progressively afterwards, mainly due to reflex tearing. The am tear meniscus volume values tended to be higher than the pm values for both groups, but this was not significant (NLW P=0.13; CL P=0.82). Noninvasive break up time deteriorated during the day for both groups but was only significant for the CL group (P=0.002), whereas bulbar hyperemia revealed no statistically significant change for either group. Conclusions: Reflex tearing may play a substantial role in the TMH differences observed over the blink interval. Standardization of the time when a TMH measurement is performed will be valuable in comparing tear film clinical studies. Copyright © Contact Lens Association of Ophthalmologists, Inc.

Bitton,E., Keech,A., Jones,L., Simpson,T. Subjective and objective variation of the tear film pre- and post-sleep Optometry and Vision Science 2008;85(8):740-749 [ Show Abstract ]

PURPOSE: To date, few studies have correlated the overnight effects of the preocular tear film (POTF) with subjective symptoms. This study investigates the POTF volume and stability, bulbar hyperemia (BH), tear ferning (TF) and the participant's subjective symptoms, pre- and post-sleep. METHODS: Thirty subjects were recruited, consisting of two evenly distributed groups who were symptomatic of dry eye (DE) and those that were asymptomatic dry eye, determined using the McMonnies questionnaire. Subjects were evaluated at 10 p.m. (baseline), on waking at 7 a.m., and then hourly until 10 a.m. At each visit, tear meniscus height (TMH), various subjective factors, BH and POTF stability by non-invasive break-up time (NIBUT) were assessed. Tear collection was performed at 10 p.m, 7 and 10 a.m. for TF analysis. RESULTS: With the exception of burning, all other symptoms (comfort, dryness, clarity of vision, and grittiness) revealed an overnight change (p < 0.05) within each group, but not between the two groups (p > 0.05). Both the tear meniscus height and BH were elevated upon waking and differed significantly between test times for each group (p < 0.05), but not between groups (p > 0.05). NIBUT was lower for the DE group (p < 0.001). The non-dry eye (NDE) group did not significantly alter over time (p > 0.05), but the DE group did (p = 0.004), with a longer NIBUT in the morning. TF demonstrated a degraded pattern upon waking for both groups (p < 0.05). Most of the changes returned to baseline within an hour after waking. CONCLUSIONS: The properties of the POTF undergo a change during extended periods of eye closure and the human POTF is different upon waking to that present immediately before sleep. Most of the parameters determined rapidly revert to baseline levels once the POTF is allowed to refresh.

Bitton,E., Keech,A., Simpson,T., Jones,L. Variability of the analysis of the tear meniscus height by optical coherence tomography Optometry and Vision Science 2007;84(9):E903-E908 [ Show Abstract ]

PURPOSE. Tear meniscus height (TMH) is an established parameter indicative of tear film volume and has recently been determined using an optical coherence tomographer (OCT). The purpose of this study was to evaluate the inter and intra observer variability in TMH assessment using OCT. METHODS. Ten subjects (6 M, 4 F; aged 32.5 ± 6.4 years) had 10 consecutive scans taken of their inferior central tear meniscus (5 scans originating at 90° and 5 origination at 270°) using the OCT2 (Humphrey-Zeiss). Images were analyzed by two observers using custom software on three separate occasions. Following a training session among observers, the images were reevaluated to assess differences in variability. Data were analyzed for differences within and across examiners, for the effect of examiner training and between scan directions. RESULTS. The mean TMH and tear volume collapsed across subjects were between 0.24 and 0.25 mm and 25 to 27 nL/mm, respectively. No difference was noted within observers. An interobserver mean volume difference (p = 0.044) was present but was eliminated post training (p = 0.167). Variability was less with scans originating at 90°. CONCLUSIONS. The values of the TMH and tear volume are similar to those reported in the literature. Due to the interobserver differences observed, a training session between examiners may prove to be valuable, especially in a large or multicenter study. © 2007 American Academy of Optometry.

Bitton,E., Ngo,W., Dupont,P. Eyelid hygiene products: A scoping review Cont Lens Anterior Eye 2019;42(6):591-597

Blackie,C. A., Coleman,C. A., Nichols,K. K., Jones,L., Chen,P. Q., Melton,R., Kading,D. L., O’Dell,L. E., Srinivasan,S. A single vectored thermal pulsation treatment for meibomian gland dysfunction increases mean comfortable contact lens wearing time by approximately 4 hours per day Clinical Ophthalmology 2018;12:169-183 [ Show Abstract ]

Purpose: To evaluate the effect of a single vectored thermal pulsation (VTP) treatment in contact lens wearers with meibomian gland dysfunction (MGD) and dry eye symptoms. Methods: The prospective, nonsignificant risk, open-label, randomized, multi-center clinical trial included 55 soft contact lens (SCL) wearers with MGD and evaporative dry eye. Subjects were randomized to the single VTP treatment group or an untreated control. The controls received a crossover VTP treatment at 3 months (crossover treatment group). Primary effectiveness measures were meibomian gland secretion (MGS) score and Standard Patient Evaluation of Eye Dryness (SPEED) that were evaluated at baseline, at 1 and 3 months post-VTP treatment, and at 1 month post-VTP treatment in the crossover treatment group. Exploratory variables included fluorescein tear break-up time (TBUT), lid wiper epitheliopathy (LWE), lid parallel conjunctival folds (LIPCOF), ocular surface staining, frequency of over-the-counter (OTC) drop use, and hours of comfortable contact lens wear. Results: At 3 months, the treatment group showed significantly greater mean change from baseline in MGS (12.4±9.1 vs 1.4±6.4, p˂0.0001), SPEED (−8.4±4.7 vs −0.7±4.4, p˂0.0001) and significantly greater improvement in exploratory variables (TBUT, LWE, and frequency of OTC drop use) relative to the controls. Mean comfortable contact lens wearing time increased by 4.0±3.9 hours at 1 month. This was sustained for 3 months with no change in the control group. The crossover treatment group demonstrated similar results to the treatment group at 1 month post-VTP. Conclusion: In SCL wearers with MGD, a single VTP treatment significantly improved mean meibomian gland function and significantly reduced dry eye signs and symptoms compared to an untreated control. The treatment increased mean comfortable lens wearing time by 4 hours (approximately doubling the pretreatment findings). This was sustained for up to 3 months post-treatment on average.

Boone,A., Heynen,M., Joyce,E., Jones,L. Ex vivo protein deposition on bi-weekly silicone hydrogel contact lenses Optometry and Vision Science 2010;87(2):146

Boone,A., Heynen,M., Joyce,E., Varikooty,J., Jones,L. Ex vivo protein deposition on bi-weekly silicone hydrogel contact lenses Optometry and Vision Science 2009;86(11):1241-1249 [ Show Abstract ]

Purpose. This study investigated the protein deposition that occurs on daily wear silicone hydrogel (SH) lenses, after 2 weeks of wear. Methods. A total of 40 subjects were divided into equal groups, based on their habitual SH contact lens [CIBA Vision O2OPTIX (O2); Johnson & Johnson ACUVUE ADVANCE with HYDRACLEAR (ADV); Bausch & Lomb PureVision (PV); CIBA Vision Night & Day (ND)]. A randomized, double-masked, cross-over study was conducted in which subjects wore either their habitual SH material or Johnson & Johnson ACUVUE OASYS with HYDRACLEAR PLUS (OAS) for 2 weeks. At the end of the 2-week period, lenses were collected for analysis of total protein, total lysozyme, and percent denatured lysozyme. Results. Total protein was greatest for PV (33 ± 6 μg/lens), with other lenses depositing 0.05). Total lysozyme was also greatest for the PV lens (11 ± 3 μg/lens), with other lenses depositing 0.05). Total lysozyme was also greatest for the PV lens (11 ± 3 μg/lens), with other lenses depositing 0.05). Total lysozyme was also greatest for the PV lens (11 ± 3 μg/lens), with other lenses depositing 0.05). The percentage of lysozyme that was denatured was greatest for ND (90 ± 8%) and lowest for PV (23 ± 10%). The lysozyme extracted from ND and O2 lenses was significantly more denatured than that extracted from the other lens materials (p 0.05) or between ADV, OAS, and PV (p > 0.05). The amount of denatured lysozyme/lens was <3 μg/lens for all materials. Lysozyme as a percentage of the total protein deposited ranged from 32 (PV) to 6% (O2). Conclusions. This study confirms that all SH lenses deposit low levels of protein, and that the amount and percentage of denatured lysozyme can vary, depending on the overall surface charge of the material and absence or type of surface treatment. © 2009 American Academy of Optometry.

Boone,A., Hui,A., Jones,L. Uptake and release of dexamethasone phosphate from silicone hydrogel and FDA group I, II, and IV hydrogel contact lenses Eye and Contact Lens 2009;35(5):260-267 [ Show Abstract ]

OBJECTIVES: To investigate the uptake and release kinetics of the synthetic glucocorticoid anti-inflammatory drug dexamethasone into various conventional and silicone hydrogel contact lens materials. METHODS: Three conventional and six silicone hydrogel lenses were used in this study. A 0.1% dexamethasone solution was formulated and used to dope the various contact lens materials. The uptake and release of the drug was measured using a UV-visible light spectrophotometer at various time points during a period of 24 hr for each phase. RESULTS: Statistical analysis showed that all lenses took up a significant amount of dexamethasone. Alphafilcon A and lotrafilcon A showed the greatest uptake of dexamethasone, at 118 +/- 10 microg/lens and 102 +/- 11 microg/lens, respectively, and galyfilcon took up the least amount of drug at 34 +/- 6 microg/lens. The release of the drug from the lens materials was also statistically significant. The majority of the lenses released between 20 and 30 microg/lens, except for alphafilcon A and lotrafilcon A, which released a statistically different amount of drug when compared with the other lens materials. Alphafilcon A released 65 +/- 1.3 microg/lens, whereas lotrafilcon A slowly released only 11 +/- 0.2 microg/lens. CONCLUSIONS: Although most of the lenses released enough drug to have anti-inflammatory action, none of the materials released drug for a long enough period of time to be clinically useful as a drug delivery device.

Bose,S., Phan,C.-M., Rizwan,M., Tse,J. W., Yim,E., Jones,L. Fabrication and Characterization of an Enzyme-Triggered, Therapeutic-Releasing Hydrogel Bandage Contact Lens Material Pharmaceutics 2024;16(1):Article 26 [ Show Abstract ]

Purpose: The purpose of this study was to develop an enzyme-triggered, therapeutic-releasing bandage contact lens material using a unique gelatin methacrylate formulation (GelMA+).

Methods: Two GelMA+ formulations, 20% w/v, and 30% w/v concentrations, were prepared through UV polymerization. The physical properties of the material, including porosity, tensile strain, and swelling ratio, were characterized. The enzymatic degradation of the material was assessed in the presence of matrix metalloproteinase-9 (MMP-9) at concentrations ranging from 0 to 300 µg/mL. Cell viability, cell growth, and cytotoxicity on the GelMA+ gels were evaluated using the AlamarBlueTM assay and the LIVE/DEADTM Viability/Cytotoxicity kit staining with immortalized human corneal epithelial cells over 5 days. For drug release analysis, the 30% w/v gels were loaded with 3 µg of bovine lactoferrin (BLF) as a model drug, and its release was examined over 5 days under various MMP-9 concentrations.

Results: The 30% w/v GelMA+ demonstrated higher crosslinking density, increased tensile strength, smaller pore size, and lower swelling ratio (p < 0.05). In contrast, the 20% w/v GelMA+ degraded at a significantly faster rate (p < 0.001), reaching almost complete degradation within 48 h in the presence of 300 µg/mL of MMP-9. No signs of cytotoxic effects were observed in the live/dead staining assay for either concentration after 5 days. However, the 30% w/v GelMA+ exhibited significantly higher cell viability (p < 0.05). The 30% w/v GelMA+ demonstrated sustained release of the BLF over 5 days. The release rate of BLF increased significantly with higher concentrations of MMP-9 (p < 0.001), corresponding to the degradation rate of the gels.

Discussion: The release of BLF from GelMA+ gels was driven by a combination of diffusion and degradation of the material by MMP-9 enzymes. This work demonstrated that a GelMA+-based material that releases a therapeutic agent can be triggered by enzymes found in the tear fluid.

Bzovey,B., Ngo,W. Eyelid Warming Devices: Safety, Efficacy, and Place in Therapy Clinical Optometry 2022;14133-147 [ Show Abstract ]

Meibomian gland dysfunction (MGD) is characterized by the obstruction and/or inflammation of the meibomian glands that result in decreased and altered meibum secretion. This results in deficiencies in the tear film lipid layer which contributes to increased evaporation and destabilization of the tear film. One of the mainstay therapies for MGD is medical devices that apply heat and/or pressure to the eyelids and promote the liquification and outflow of meibum into the tear film. Over the past two decades, there have been a surge of interest in diagnosing and managing MGD. As a result, numerous medical devices have been developed and each have their own unique approach to treating MGD. This narrative review was conducted to summarize the current state of knowledge on eyelid warming devices, specifically warm eye coverings, devices that direct heat and/or pressure to the eyelids, moisture chamber goggles, and light-based therapy. This review summarized 58 human clinical studies and found that most eyelid warming devices were efficacious in improving signs and symptoms in a wide range of MGD severities and were generally safe to use.

Caffery,B. E., Joyce,E., Heynen,M. L., Ritter,R., Jones,L. A., Senchyna,M. Quantification of conjunctival TNF-a in aqueous-deficient dry eye Optometry and Vision Science 2014;91(2):156-162 [ Show Abstract ]

PURPOSE: This study aimed to quantify and compare conjunctival epithelial tumor necrosis factor (NF) a mRNA expression in Sjögren syndrome (SS), non-Sjögren syndrome aqueous-deficient dry eye (non-SS DE), and non-dry eye (NDE) control subjects. METHODS: A total of 76 subjects were recruited for this study: 25 SS (confirmed via American-European Consensus Criteria 2002), 25 non-SS DE (confirmed by symptoms and Schirmer scores = 10 mm), and 26 NDE. Superior and temporal bulbar conjunctival epithelial cells were collected via impression cytology. Epithelial RNA was extracted, and TNF-a mRNA expression was quantified by real-time quantitative polymerase chain reaction. RESULTS: The expression of TNF-a mRNA was found to be significantly higher in the SS group (2.48 ± 1.79) compared to both non-SS DE (0.95 ± 1.18; p < 0.05) and NDE (0.84 ± 0.51; p < 0.05) groups. No difference in TNF-a mRNA expression was found between the non-SS DE and NDE groups (p = 0.67). CONCLUSIONS: These results demonstrate that SS-associated aqueous-deficient dry eye is associated with a significant upregulation of conjunctival epithelial TNF-a mRNA relative to both non-SS DE and control groups. The degree to which TNF-a mRNA is upregulated in SS may contribute to the severe ocular surface damage observed in these patients. Copyright © 2014 American Academy of Optometry.

Caffery,B., Dogru,M., Jones,L. W., Lin,M. C., Nichols,J. J., Papas,E., Pucker,A., Pult,H., Willcox,M. D. P. Contact lens comfort Optometry and Vision Science 2016;93(8):790-792

Caffery,B., Heynen,M. L., Joyce,E., Jones,L., Robert III,R., Senchyna,M. MUC1 expression in Sjogren's syndrome, KCS, and control subjects Molecular Vision 2010;161720-1727 [ Show Abstract ]

Purpose: To quantify and compare human mucin 1 (MUC1) protein and mRNA expression in tears and conjunctival epithelial cells collected from Sjogren's syndrome (SS), non-Sjogren's keratoconjunctivitus sicca (KCS) and non-dry eyed (NDE) control subjects. Methods: Seventy-six subjects were recruited for this study: 25 SS (confirmed via American-European Consensus Criteria 2002), 25 KCS (confirmed by symptoms and Schirmer scores ≤10 mm) and 26 NDE. Tears were collected using an eyewash technique. Impression cytology was used to gather protein and mRNA from conjunctival epithelial cells. Soluble and membrane bound MUC1 were quantified via western blotting and MUC1 mRNA was quantified by real time qPCR. Results: The SS group demonstrated significantly higher concentrations of soluble MUC1 (0.12±0.11 [SS]; 0.013±0.02 [KCS; p=0.001]; 0.0023±0.0024 [NDE; p<0.001]) and MUC1 mRNA (3.18±1.44 [SS]; 1.79±1.18 [KCS; p<0.05]; 1.60±0.74 [NDE; p<0.05]) compared to both KCS and NDE groups. Soluble MUC1 expression was also higher in the KCS group compared to the NDE group (p=0.02), where as MUC1 mRNA expression was similar in both KCS and NDE groups. Membrane bound MUC1 expression differed only between the SS and NDE groups (0.005±-0.003 [SS]; 0.003±0.002 [NDE; p=0.002]). Conclusions: These results demonstrate that SS subjects express greater quantities of MUC1 protein and mRNA compared to both KCS and control subjects. Increased soluble MUC1 expression was also found in KCS subjects compared to controls. Membrane bound MUC1 was present in higher concentration in SS versus NDE only. These significant changes in MUC1 expression may represent compensatory or protective responses to chronic insult to the ocular surface. © 2010 Molecular Vision.