Optometry and Vision Science

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Ocular Effects of Scleral Lens Wear on Dry Eye Patients
(University of Waterloo, 2024-11-14) Otchere, Heinz
Purpose: Dry eye disease (DED) is among the most complex ocular surface diseases to treat. Complaints of ocular discomfort and dryness are common in DED patients and in contact lens wearers. The use of SL to restore the integrity of the ocular surface in a more severe DED has become increasingly accepted among eye care practitioners. However, little is known about this treatment regimen and its impact on ocular surface in mild to moderate DED. Also, the potential impact of coated SL designs incorporating Hydra-PEG (polyethylene glycol) technology on ocular surface health has not yet been fully investigated. This thesis aimed to address this gap in knowledge and determine whether SL (uncoated or Hydra-PEG) could be used as a viable option for patients who are experiencing milder forms of DED. Over the course of the study, participants were asked to complete DE questionnaires; lens settling and vision, corneal thickness, osmolarity and matrix metalloproteinase 9 (MMP-9) in the pre-corneal tear film were investigated. The study also examined the relationship between the respective parameters and compared the two lens pairs. Methods and Materials: The study was a prospective, double-masked, randomized, dispensing, crossover clinical trial involving five visits, where 20 subjects with mild to moderate dry eye disease (DED) were enrolled. Eligibility of the participants was confirmed following the Tear Film and Ocular Society (TFOS) Diagnostic Report in the first visit: presence of symptoms using the Ocular Surface Disease Index (OSDI) and Standardized Patient Evaluation of Eye Dryness (SPEED) questionnaires (OSDI ≥ 13, SPEED ≥ 4), plus osmolarity values (> 308 mOsmol/L in either eye or interocular difference of > 8 mOsmol/L) and or a positive MMP-9 result (using InflammaDry® test kit) or both. The second visit involved randomization and dispensing of customized hydra-PEG coated or uncoated SL, where each pair of lenses were worn on a daily wear basis for four weeks. Prior to dispensing the lenses, high contrast (HCVA) and low contrast acuities (LCVA) were recorded. The central corneal clearance (CCC) was measured with VisanteTM OCT to determine lens settling over time. Two standard clinical questionnaires (contact lens impact on quality of life (CLIQ) and contact lens dry eye questionnaire 8 (CLDEQ-8)) and an internally developed wearing habit and subjective rating questionnaire were provided to subjects and completed. The third visit (after 4 weeks) involved follow-up of the first randomized SL, where the lenses were evaluated, and clinical measurements repeated. A wash-out period of at least 48 hours was allowed before dispensing (visit 4) and follow-up (visit 5) of the other pair of SL, using the same procedures, measurement protocols and visit schedule. The SL used in the study were Zen™ RC (Alden Optical, Bausch & Lomb, Lancaster, NY, USA) available in only two diameters (14.80 and 15.40 mm), with a central thickness of 250 µm. Results: Eighteen females and two males, mean age 29.10 ± 7.48 years, participated in the study. The overall OSDI and SPEED scores were 36.45 ± 17.08 and 12.50 ± 4.03 respectively. There was no significant difference in the CLIQ and CLDEQ-8 scores between uncoated and coated SL. In terms of wearing habit and subjective ratings, no statistically significant differences were observed in any of the parameters (wear time, dryness, burning, vision, and comfort). This suggests that the use of hydra-PEG coated SL did not show greater performance compared to the uncoated SL. The central corneal clearance (CCC) at the dispensing visit was 260 ± 40 (range: 200 - 300 µm) for both lens pairs. This significantly reduced to 190 ± 40 µm (lens settling: 70 ± 42 µm) for the uncoated SL and 200 ± 30 µm (lens settling: 70 ± 43 µm) for the coated SL at the follow-up visits, (all, p < 0.001). Comparing the CCC for the two lens pairs at the follow-up visits, no significant difference was observed, thus, the lens pairs settled at similar rates. In terms of HCVA and LCVA between the two lens pairs at both the dispensing and follow-up visits, there were no significant differences between them. Also, no significant correlations were found comparing the CCC with HCVA and LCVA of each lens pair at both visits. The CCT at the baseline and follow-up visits were: baseline: 560.55 ± 32.28 µm, post wear of uncoated SL: 557.65 ± 32.10 µm, and post wear of coated SL: 560.50 ± 34.02 µm. There were no significant differences for either lens type for central corneal thickness (CCT) at the baseline and follow-up visits (all, p > 0.05). Also, no significant correlations between CCC and CCT were observed at baseline or follow-up visits. These results demonstrated there were minimal corneal hypoxic effects when these SL were worn on a daily wear basis. For osmolarity measures, there was a statistically significant difference between the baseline and follow-up visit for the coated lenses (311.00 ± 14.86 vs 302.85 ± 7.96 mOsmol/L; p = 0.04). While this is statistically significant, the clinical relevance of this small difference remains questionable. Comparing the two lens pairs, no significant difference was found at all visits. The inflammaDry® test results indicated that 80 % of the participants tested positive for elevated MMP-9 at the baseline visit. There was a reduction in MMP-9 positive test results following the SL wear, however, there were no significant differences between the baseline and follow-up visits for each lens pair. Comparing the two lens pairs, no significant difference was observed. For either lens, no correlation was observed between osmolarity and MMP-9 test results. Conclusion: There is a potential for using SL to manage symptoms in subjects suffering from mild to moderate DED, as the overall wearing habit and subjective ratings showed > 70 % of lens tolerance among the study cohort. SL wear over the month of wear in this cohort induced little change to the cornea or conjunctival tissue. Furthermore, SL may appear to marginally reduce tear film osmolarity, however, further studies are needed to confirm this result and its impact on subjective dryness. The clinical phenomenon of lens settling needs further investigation, especially on its impact on conjunctival morphology. In this cohort of subjects of mild to moderate DED, the hydra-PEG coating technology did not show superior performance over the uncoated lens for any of the factors assessed. Keywords: dry eye disease. scleral contact lens, hydra-PEG, osmolarity, inflammadry, cornea
Extended Release of Ciprofloxacin from Commercial Silicone-Hydrogel and Conventional-Hydrogel Contact Lenses containing Vitamin E Diffusion Barriers
(University of Waterloo, 2024-08-13) Al Atrach, Mehdi
Abstract Purpose: Contact Lenses (CLs) are ophthalmic devices globally used by more than 140 million people to correct vision problems. To overcome the drawbacks of eye drops, drug-delivering CLs have been given much attention because they increase the bioavailability of ocular drugs, resulting in increasing efficacy and reducing potential side effects. These systems typically have a burst and rapid release. To address these concerns, this study aims to develop a contact lens-based ocular drug delivery system using vitamin E as a diffusion barrier to extend the release duration of ciprofloxacin. Methods: The purpose of the first experiment in the thesis (Chapter 3) was to develop and evaluate drug delivery contact lenses: Four commercial silicone hydrogel lenses (senofilcon A, lotrafilcon B, comfilcon A, and samfilcon A) and one conventional hydrogel lens (etafilcon A) were soaked for 24 hours in various concentrations of vitamin E dissolved in ethanol (0.0125 - 0.2 g/mL). The amount of vitamin E loaded was calculated by measuring the dry lens weight before and after vitamin E loading. The lenses were loaded with ciprofloxacin for 24 hours. The amount of ciprofloxacin loaded was determined using an extraction protocol. The drug release was evaluated in phosphate-buffered saline solution in an amber glass vial, at 37°C with shaking. The amount of ciprofloxacin released was measured using a UV-VIS spectrophotometer at 270 nm. The second experimental chapter (Chapter 4) aimed to evaluate the effect of ciprofloxacin loading duration on the uptake and release profiles of senofilcon A. This was done by applying the same method described in Chapter 3, except ciprofloxacin loading durations for senofilcon A were 24 hours and 7 days. Results: The data showed that there was a decrease in ciprofloxacin loading with increasing amounts of vitamin E loaded into the silicone hydrogel lenses. For each lens type, there was an optimal amount of vitamin E loaded that extended the release duration of the drug from 1 hour (without vitamin E) to as long as 16 hours. Senofilcon A with 0.025 g/mL vitamin E loaded exhibited the longest-sustained release for all lens types, achieving 16 hours of release. In contrast, vitamin E loaded into etafilcon A had no effect on the amount of drug loaded or the release duration. The data obtained in Chapter 4 showed no significant difference in the uptake and release profiles among the different loading durations (24 hours and 7 days), except in lenses with 0.025 and 0.05 g/mL vitamin E concentrations, which absorbed and released more drugs in the 7-day loading duration experiment. In addition, senofilcon A longest release duration (16 hours) achieved in chapter 3 did not further increase in chapter 4 after increasing the drug loading duration to 7 days. Conclusion: Vitamin E can be used as a diffusion barrier with commercial silicone hydrogel lenses to provide sustained release of ciprofloxacin. The results suggest that vitamin E may form blockages in channels within a silicone hydrogel lens material, thereby forcing a longer path for drugs to diffuse into and out of the lens material. There is an optimal amount of vitamin E that needs to be loaded to extend the release duration, and this is lens material dependent. Additionally, increasing the drug loading duration to 7 days was not enough to increase the drug-loaded amount, and subsequently the release duration specifically for senofilcon A loaded with 0.2 g/ml vitamin E concentration.
Colour Vision Deficiencies in the Digital Age: A Survey of User Experiences with Digital Displays
(University of Waterloo, 2024-07-09) Mazur, Sandra
Introduction: Approximately 90% of dichromats and 67% of anomalous trichromats experience difficulty performing colour-related tasks daily (Steward & Cole, 1989). As technology becomes more prevalent, examining whether this condition impacts their use of digital displays is increasingly essential. Limited studies analyze the relationship between colour vision deficiencies (CVD) and digital displays. Mashige (2019) found that 63.2% of schoolchildren with CVD reported challenges when “working with computers,” suggesting that this condition may have some effect. Purpose: The purpose of this study is to examine the impact that congenital red-green CVD has on an individual’s interaction with digital displays in different areas of their daily life, such as “school,” “work/volunteering,” “gaming and eSports,” “driving/motorized vehicle,” and “travelling.” Materials and Method: An online survey was administered to people with CVD from Canada and the United States of America (USA). In addition to collecting demographic information and awareness of their CVD, information regarding difficulties carrying out colour-related tasks was collected. Because several software and filter options may improve performance on colour-related tasks, we asked whether they tried any and to rate their effectiveness. Results: A total of 381 individuals with CVD (280 males) completed the survey. Nearly 100% reported some difficulty with one of the tasks in most areas of life, individually, except for travelling (54.1%). For most tasks, there were no significant differences in the rankings based on sex and/or age group. Still, some tasks showed significant differences based on severity, primarily between mild and severe defects. Some examples included “colour-coded diagrams” at school, work/volunteering, and recreation/hobbies; “editing photos or other coloured images” at school, recreation/hobbies, and social media; and “reading coloured letters on various backgrounds” in gaming/eSports, online shopping/banking, and in-person shopping/banking. Nearly 65% of respondents reported making changes or implementing modifications to their displays, but there were 35% who did not. The most popular aid was “trial-and-error adjustments” of the colour and brightness of the display. Of the individuals who tried an aid, approximately 90% reported a modification to be at least a little effective, less than 3% reported at least one aid as ineffective, and only 25% rated the modifications as highly effective. There was no significant difference based on sex, age group, or severity for most modifications, except for passive aids (“coloured filters”) where youth found them more effective than adults. “Desktops/laptops,” “cell phones,” and “tablets” were the displays that people with CVD most frequently encountered difficulty and modified. The displays showed significant association with age group for some areas of life (work/volunteering, recreation/hobbies, gaming & eSports, and online shopping/banking) and modifications. This was probably due to the greater use of displays or differences in content, with youth having more problems with tablets and adults more with cell phones. Conclusion: Most respondents encountered some difficulty with at least one task, indicating that CVD had some effect on their ability to use digital displays. Although most respondents have tried some modifications to their displays, some respondents reported that at least one modification was ineffective and only 25% found an aid to be highly effective. Software developers should focus on making aids more accommodating and customizable to individual preferences.
New method to improve the diagnostic utility of OCTA images in retinal disease
(University of Waterloo, 2024-05-23) BHARDWAJ, RISHAV
Purpose: Diagnosing medical images necessitates years of experience to ensure accurate diagnoses. However, the current workforce available for this task falls significantly short compared to the volume of images requiring assessment. This places a considerable burden on the medical system during diagnosis. Additionally, medical images often contain artifacts, further complicating and prolonging the diagnostic process. This thesis serves as a solution to expedite diagnosis by enhancing the image quality of Optical Coherence Tomography Angiography (OCTA) images, thereby alleviating the strain on the system. Aims: 1. Method 1 (Chapter 2): Removal of motion artifacts from OCTA images. It is one of the toughest artifacts to be removed from an image. 2. Method 2 (Chapter 3): Super-Resolution of OCTA image. Increasing the dimensions of the image and enhancing the quality to make diagnosis process efficient. Conclusion: This work allows the removal of motion artifacts from the OCTA image and then enhance the quality of the image using super-resolution. In chapter 4 we show that the scatterplots were used to compare the correlations of the most commonly used parameters, Foveal Avascular Zone (FAZ) area, perimeter, and circularity index, between before and after super-resolution at ×2 and ×3 magnification. A p-value < 0.05 was considered significant for all statistical tests. Thus, making the diagnosis process simpler and better for medical practitioners.
Advancements in ThermOcular image processing algorithms for precise ocular surface temperature analysis
(University of Waterloo, 2024-05-22) shahsavari, mohammad navid
In recent advancements in the field of Ocular Surface Temperature (OST) measurement, this thesis presents significant enhancements to the ThermOcular system, primarily focusing on its application in real-world clinical and diagnostic settings. The ThermOcular system, initially developed for precise OST measurement using infrared thermography, serves as a pivotal tool in measuring and tracking the OST in different components of the ocular surface. Recognizing the potential and limitations of the existing system, this work aims to introduce improvements that significantly elevate its diagnostic accuracy, user-independence, and overall applicability in clinical environments. In this thesis, a comprehensive strategy to refine the ThermOcular system is introduced, highlighting the simplification of the control point selection for clinicians using an innovative eye tag integration. This development is aimed at enhancing the registration process’s efficiency by reducing the need for manual input and the associated error margin prevalent in the prior methodology. Alongside, the thesis describes an enhancement of image segmentation accuracy, using state-of-the-art machine learning models trained on a comprehensive dataset prepared for this purpose. These models enable more precise classification of ocular components, crucial for accurate OST measurement. The thesis also addresses the challenge of artifacts due to the presence of eyelashes in thermal images and the effect of blinks on tracked OST, which previously compromised measurement accuracy. By developing and implementing algorithms for artifact detection and elimination, the thesis ensures that these common issues no longer compromise the reliability of OST assessments. This not only enhances measurement precision, but also contributes to the system’s robustness against varied conditions. In conclusion, the thesis encapsulates a significant advance in the domain of ocular health diagnostics using the ThermOcular system. By focusing on automation, accuracy, and artifact mitigation, this work contributes to the development of a more reliable, efficient, and clinically applicable system for OST measurement. The advancements highlighted in this thesis not only underscore the potential of infrared thermography in ocular diagnostics, but also pave the way for future research in this evolving field.
The Effect of Freezing on the Elution of PVA from Contact Lenses
(University of Waterloo, 2024-04-30) Shukla, Manish
Contact lenses are widely used, with over 140 million wearers globally. Wearing contact lenses can cause symptoms of discomfort and dryness, which affect nearly half of all wearers. To address this concern, this thesis explores the release of polyvinyl alcohol (PVA) from contact lenses, aiming to improve comfort through controlled elution. PVA forms a protective film when placed on the ocular surface and serves to reduce ocular discomfort. This research specifically studies the impact of freezing on PVA interaction with various contact lens materials and its subsequent release kinetics. This thesis hypothesizes that freezing enhances the hydrogen bonding of PVA to lens materials, enabling the formation of a surface layer on contact lenses and increasing PVA elution. To investigate this hypothesis, commercial lenses (Acuvue® Oasys – senofilcon A, DAILIES® AquaComfort PLUS® - nelfilcon A, 1-Day Acuvue® Moist® - etafilcon A) were soaked in 2.5% w/v high molecular weight PVA solutions at 37°C for 48 hours, followed by 1 hour at either room temperature or freezing at -80°C. The results demonstrate a significant (p<0.05) increase in the cumulative PVA release from nelfilcon A lenses after 24 hours following freezing at -80°C for one hour, with 55.07 ± 2.46 μg of high molecular weight PVA released in comparison to lenses kept at room temperature which showed 46.16 ± 6.94 μg of PVA release. In contrast to nelfilcon A, etafilcon A and senofilcon A did not show a significant (p>0.05) change in the amount of PVA released after freezing. Etafilcon A lenses released 17.03 ± 3.03 μg and 20.21 ± 2.51 μg (p>0.05), and senofilcon A showed 20.33 ± 6.60 μg and 24.14 ± 2.58 μg (p>0.05) at room temperature and after freezing at -80°C for one hour, respectively, suggesting that freezing enhances these iv effects only for nelfilcon A lenses. To further explore the impact of PVA with lenses, experiments with synthesized lenses (pHEMA and PVA loaded pHEMA) were performed, which demonstrated that the presence of PVA inside the lens significantly (p<0.05) impacts subsequent PVA loading and release and the freezing effect. The cumulative release of PVA over 24 hours from pHEMA lenses were 32.64 ± 5.48 μg and 36.25 ± 6.11 μg (p>0.05), at room temperature and after freezing at -80°C for one hour, respectively. PVA loaded pHEMA lenses, in contrast, showed a significant (p<0.05) increase in the cumulative PVA release over 24 hours after freezing, rising from 42.88 ± 4.96 μg to 47.39 ± 6.26 μg after one hour at -80°C. The study emphasizes the importance of PVA incorporation within contact lenses to observe a substantial impact on release after soaking or freezing. The findings suggest that the freezing technique has potential applications in enhancing the release of comfort agents such as PVA from contact lenses, especially those containing PVA internally. In conclusion, this research provides insights into optimizing contact lens design for improved comfort by utilizing PVA release. The demonstrated impact of freezing on nelfilcon A lenses indicates a promising avenue for enhancing the release of comfort agents.
Exploration of the Underlying Visual Perceptual and Cognitive Mechanisms of Dynamic Visual Acuity
(University of Waterloo, 2024-01-25) Hudecki, Heather
Purpose: Dynamic visual acuity (dynamic VA) is a complex, perceptual ability of the visual system that involves determining fine details of objects as they move across one’s field of view (1–4). Over the years, there has been increasing interest in dynamic VA because of its apparent relevance to everyday life, and its ability to account for motion, which static VA is unable to do. Dynamic VA has a crucial role in a variety of real-world situations and daily tasks that involve functioning in a dynamic environment, such as driving, piloting, crossing a busy intersection, and many ball sports (5–8). In addition, dynamic VA is an essential element involved in one’s ability to adapt to moving and changing environments (1). Although various research has been performed, dynamic VA as a visual function is not very well understood. This study was designed to investigate the potential underlying neurophysiological mechanisms that may be associated with dynamic VA. Methods: This study was an observational analysis of visual and cognitive function data collected from 130 participants. Participants were members of the University of Waterloo Department of Psychology Research Experiences Group (i.e., SONA), the University of Waterloo undergraduate and graduate community, the University of Waterloo Optometry Program, and the Kitchener-Waterloo Community. Five visual function tasks were studied including static visual acuity (static VA), horizontal and random dynamic VA, global motion (GM), global form (GF), and local motion (LM), along with two cognitive tasks, multiple object tracking (MOT) and the Stroop task. Static VA was measured first at each study visit to confirm participant eligibility, followed by horizontal and random motion dynamic VA (randomized order). After dynamic VA, the remaining visual and cognitive function tasks were measured in a randomized order. Static VA (LogMAR) was tested with an Early Treatment Diabetic Retinopathy Study (ETDRS) chart. Binocular dynamic VA (LogMAR; moV&, V&mp Vision Suite) was assessed using tumbling E optotypes moving in a horizontal (left to right) or unpredictable random motion. GM perception, and LM perception were assessed using random dot kinematograms (RDKs), GF perception was tested using Glass patterns, Stroop was assessed using word stimuli, and MOT was tested using randomly moving ball stimuli. Experimental effects, including the effects of participant age, participant gender, and testing order were examined for each task independently using one-way independent measures ANOVAs (age and visual function task order), and two-sample t-tests (gender and dynamic VA task order). Tukey post-hoc test was used to further evaluate any significant order effects found with the one-way independent measures ANOVAs. Correlation plots, matrices, and tables including Pearson correlation coefficients were calculated to examine the relationships between dynamic VA performance and the visual function tasks. Backwards stepwise regression analyses were conducted to determine which visual or cognitive function tasks were most predictive of dynamic VA performance. The correlation and regression analyses were performed separately for horizontal and random dynamic VA. Results: Highly significant correlations were found between horizontal dynamic VA and random dynamic VA (r = 0.49, p = 4.84e-9), static VA (r = 0.48, p = 6.35e-9), and LM (r = 0.32, p = 2.47e-4); a weak, significant correlation also noted with GM (r = 0.23, p =9.16e-3). Highly significant correlations with random dynamic VA were found with static VA (r = 0.46, p = 4.39e-8) and horizontal dynamic VA (r = 0.49, p = 4.84e-9); weak, significant correlations were found with LM (r =0.16, p = 6.43e-2), and GF (r = 0.15, p = 9.89e-2). Statistically significant predictors for horizontal dynamic VA were static VA (p = 6.09e-4), LM (p = 3.96e-2), and random dynamic VA (p = 1.20e-4) . GM (p = 0.139) was not a significant predictor of horizontal dynamic VA but still had a trend towards a positive relationship with the task. Static VA (p = 7.85e-4) and horizontal dynamic VA (p = 8.14e-5) were the only statically significant predictors of random dynamic VA, but there were also trends towards positive relationships between random dynamic VA and LM (p = 8.70e-2), and GF (p = 0.135). Additional analyses determined there to be no age or gender effects on any of the visual function tasks. A statistically significant order effect was present for GF (F(2, 127) = [4.92], p = 1.02e-3), but no other tasks. Conclusion: Horizontal dynamic VA appears to be most closely related to random dynamic VA, static VA, GM, and LM, suggesting the dorsal stream and V1 pathway may be the underlying neurophysiological pathways associated with processing horizontal dynamic VA. This is in comparison to random dynamic VA, which was most closely connected with horizontal dynamic VA, static VA, GF, and LM, suggesting the neuro pathways involved with random dynamic VA could be the ventral stream and V1 pathway. Further research is required to confirm and validate such neurophysiological mechanisms are associated with both horizontal and random dynamic VA.
Investigating the enhancement of visual cortex plasticity through non-invasive brain stimulation
(University of Waterloo, 2024-01-02) Chen, Xiaoxin
Purpose: (1) To investigate the effects of various non-invasive brain stimulation (NIBS) modalities, including high-frequency transcranial random noise stimulation (hf-tRNS), anodal transcranial direct current stimulation (a-tDCS), and repetitive transcranial magnetic stimulation (rTMS), on short-term ocular dominance plasticity in adults with normal vision; (2) To probe the neural mechanisms underlying short-term ocular dominance plasticity using NIBS techniques; (3) To explore the state-dependency of NIBS within the visual cortex; (4) To evaluate the efficacy of a novel ocular dominance test (the letter-polarity test) as a tool of measuring ocular dominance shifts following monocular deprivation (MD). Methods: Three studies using hf-tRNS, a-tDCS and rTMS were conducted. NIBS was delivered to V1 during MD. The primary outcome was ocular dominance shift, measured through two ocular dominance tests, a traditional binocular rivalry test and the letter-polarity test, before and after the interventions. Secondary outcomes included mixed percept durations and alternation rates as provided by the binocular rivalry test. The reliability of the letter-polarity test was evaluated in comparison to the binocular rivalry test through a comprehensive set of analyses. Results: (1) In three studies, short-term ocular dominance plasticity was observed as a shift in ocular dominance towards the deprived eye. (2) No significant effects of NIBS were observed on the primary and secondary outcome measures. (3) By comparing the effect of 120-minute MD and 30-minute MD, we observed a significantly smaller magnitude of ocular dominance shifts with 30-minute MD. (4) The reliability of the letter-polarity test was similar to that of the binocular rivalry test. Conclusions: These experiments suggest that the neural mechanisms underlying short-term ocular dominance plasticity in adults with normal vision may be more complex than a simple reduction in cortical inhibition. It may be necessary to reconsider the cortical site responsible for this plasticity and the neuromodulatory effects of NIBS on visual cortex activity. Our null findings of NIBS effects may also be explained by a different cortical activation state induced by MD. These findings provide valuable reference points for future studies investigating the enhancement of visual cortex plasticity.
Fabrication of microfluidic chip using 3D printing for ocular cell studies
(University of Waterloo, 2023-09-25) Ramasamy, Megala
Purpose: This thesis aimed to create a polydimethylsiloxane (PDMS) microfluidic chip utilizing low-cost commercial 3D printers and to integrate human corneal epithelial cells (HCEC) into the fabricated chip. Methods: The purpose of the first experimental chapter (Chapter 3) of this thesis was to develop PDMS devices from 3D printed moulds of two commercially available 3D printers: the Formlabs Form 3B+, which employs Stereolithography (SLA) technology, and the AnyCubic D2 DLP, which utilizes Digital Light Processing (DLP) technology. The fabrication of PDMS from 3D printed moulds can be achieved by introducing three simple post-processing steps: heating, sanding, and nail polish coating. A biomaterial coating was applied to the surfaces of the PDMS devices to render their surfaces hydrophilic. The second experimental chapter (Chapter 4) centred on incorporating HCEC into the PDMS device fabricated using the method described in Chapter 3. Results: Both 3D printers could generate optically clear PDMS devices with smaller channel dimensions of 100 µm, with faster print times and higher accuracy for the DLP 3D printer. Heating the 3D printed moulds produced fully cured PDMS chips with perfect channel edges. The sanding and nail polish coating of the mould produced optically transparent and smooth PDMS devices. Coating the PDMS surface with polydopamine (PDA) improved its surface wettability from 110° to 75°. On the PDA and collagen-coated device, HCEC exhibited significantly better growth than on the untreated PDMS device. HCEC cultured on these PDA/collagen-coated PDMS devices demonstrated 80% cell viability compared to conventional tissue culture plates. Conclusion: This study demonstrated that SLA and DLP printers can be used to produce PDMS microfluidic chips quickly and affordably. Notably, the DLP printer offered better accuracy and faster printing time than the SLA printer. The fabricated PDMS chips were transparent and capable of incorporating HCEC.
Advancing Hyperacuity for Vision Screening
(University of Waterloo, 2023-09-22) Mohammed, Abdul Rasheed
Introduction: The human visual system is extremely sensitive to certain spatial visual tasks. It can detect the subtle misalignment of closer objects to a degree of 2-5 arcseconds, which is smaller than the foveal cone diameter or spacing. This ability is referred to as hyperacuity, and one such visual task is the Vernier task, which involves misalignment detection of Vernier lines or dots. It is also called Vernier acuity and has a significant diagnostic value for screening various eye abnormalities. However, due to methodological and technical limitations, its utility was restricted to laboratory applications due to concerns over test reliability and testing time. I hypothesized that applying advanced psychophysical procedures, techniques, and modern technological interventions might improve the Vernier acuity testing standards for clinical consideration. Therefore, I attempted to address the challenges noticed in the literature by advancing the methodology and technicality to improve the Vernier acuity test efficiency for clinical application. Aims: ⸰ Experiment 1 (Chapter-2): To develop a software application and assess the Vernier acuity program performance, measurements, and stimuli characteristics. ⸰ Experiment 2 (Chapter-3): To enhance the Vernier acuity program efficiency, assess program performance and reliability for technical validation. ⸰ Experiment 3 (Chapter-4): To modify the Vernier acuity program for the visual field quantification (Hyperacuity perimetry) and assess reliability for technical validation. ⸰ Experiment 4 (Chapter-5): To develop a software application for the visual distortions quantification (Metamorphopsia) using Vernier acuity-based bisectional program and assess reliability for technical validation. Methods: This study was performed through two pilot studies: the first pilot study had five adult volunteers with the best corrected visual acuity of 20/20 vision in the right eye (tested right eye only) and included all the experiments from Chapter 2, whereas the second pilot study was carried out on 21 adult emmetrope (unaided 20/20 vision) volunteers (tested both eyes individually) and included all the experiments from Chapters-3, 4, and 5. I used PsychoPy3 to develop each software program. However, I employed two methods to provide the test results efficiently and reliably for clinical testing. I developed three software applications and could only perform technical validation because of the pandemic. ⸰ Experiment 1 (Chapter-2): I programmed a software program and employed a 3-Down, 1-Up adaptive staircase method and three alternative forced choices technique to quantify the Vernier acuity. The Vernier acuity was measured at seven vertical separations (gaps) to assess test performance. The initial testing was focused on determining test performance using stimuli shapes, followed by technical validation of the software application program and assessment of stimuli contrast for standardization. ⸰ Experiment 2 (Chapter-3): I adjusted the measurement parameters to improve test efficiency. I assessed the program performance from response accuracy, reaction time, and testing time, along with repeatability of measurements for technical validation of the Vernier acuity program. ⸰ Experiment 3 (Chapter-4): I modified the Vernier acuity program to quantify the hyperacuity perimetry in superior, inferior, nasal, and temporal visual fields. I assessed the repeatability of measurements for technical validation of this modified Vernier acuity program. ⸰ Experiment 4 (Chapter-5): I programmed a Vernier bisection program to quantify the metamorphopsia using a method of adjustment. The testing involved Vernier stimuli in two different orientations and referred to them as patterns (A and B), Pattern-A had a presentation of two vertical and horizontal line stimuli that are equally away from the center of the screen in either direction, whereas pattern B involved presentations of pattern-A at oblique angles to the screen center. Using both patterns, I measured the metamorphopsia in central 5 degrees and assessed the repeatability of the measurements and testing time for technical validation of the Vernier bisection program. Results: ⸰ Experiment 1 (Chapter-2): In the initial experiment, the line stimuli achieved comparable measurements to dot stimuli at most gap sizes except at 32 arcminutes of gap size. The test detected the lowest misalignment of 2 arcseconds at 2 arcminutes of gap size. The mean lowest acuity was below 8 arcseconds at 2 arcminutes, and the highest acuity was within an arcminute at 128 arcminutes. The negative contrast line stimuli were comparably precise to positive line stimuli at most gap sizes except at 16 arcminutes. ⸰ Experiment 2 (Chapter-3): The right eyes were repeatable at most of the gap sizes except for the 32 and 64 gap sizes, whereas the left eyes were repeatable at all gap sizes except 128. The right and left eye measurements were statistically the same at both visits. Since no difference was observed between the eyes, results from both eyes were compiled to assess the test performance and response accuracy. The Vernier acuity measured at 16, 8, 4, and 2 gap sizes were statistically repeatable, and the correlation was positive but weak. The response accuracy was estimated to be above 90% for mean correct responses, below 3% for mean incorrect responses, and about 5% for mean aligned responses through the gap sizes at both visits. The estimated reaction time was just below a second for mean correct responses, below 0.75 seconds for the mean incorrect responses, and about 2.5 seconds for the mean aligned responses. The test time was below 2 minutes at each gap size at both visits. ⸰ Experiment 3 (Chapter-4): The right eye hyperacuity perimetry results were repeatable in all four quadrants of 15 gap size, and the correlation was positive but weak in all quadrants except the superior visual field, where the correlation was negative and weak. Whereas for gap size 30, the results were repeatable in all quadrants except the inferior visual field, where the results were not repeatable. However, results from all the quadrants had a positive but weak correlation. The left eye hyperacuity perimetry results were repeatable in all quadrants of 15 gap size, except the nasal visual field, where the results were not repeatable. However, results from all the quadrants had a positive but weak correlation. For gap size 30, the results were repeatable in all four quadrants, and all quadrants had a positive but weak correlation. The results from both eyes showed no significant difference for a gap of 15 arcminutes. However, there was a substantial difference between the eyes only at the inferior field for a gap of 30 arcminutes. ⸰ Experiment 4 (Chapter-5): The right eye metamorphopsia results were repeatable in the central 5 degrees using a pattern A with a positive but weak correlation at all degrees except 5 and 1 degrees, where the correlation was negative and weak. Similarly, the results were repeatable in the central 5 degrees using a pattern B except for 5 degrees, and the correlation was positive but weak at all degrees except 3 and 2 degrees, where there was a negative and weak correlation. On the other hand, the left eye results were repeatable in the central 5 degrees using a pattern A with positive and moderate to strong correlations at all degrees. Similarly, the results were repeatable in the central 5 degrees using a pattern B except for 4 degrees, and the correlation was positive and moderate to strong at all degrees. There was no difference between the eyes for individual patterns at both visits. Conclusions: ⸰ Experiment 1 (Chapter-2): The developed software application program measured the Vernier acuity precisely using 3-down, 1-up, an adaptive staircase method, and the 3AFC technique. In addition, I standardized stimuli for shape and contrast to measure the Vernier acuity. The calculated results are precise and consistent with the previously reported data. Therefore, motivating to advance the test further for Vernier acuity testing. While performing the test, some areas for improvement were identified. By adjusting the necessary parameters, the test's efficiency can be enhanced. I plan to make those adjustments in the following pilot testing and perform technical validation. ⸰ Experiment 2 (Chapter-3): I adjusted the necessary parameters to improve the efficiency of the Vernier acuity testing. The results showed that the program is efficient, robust, and repeatable. The mean Vernier acuity measured at seven different gap sizes was consistent with previously reported data and comparable with pilot study 1 results. This cohort’s Vernier acuity measured at smaller gap sizes was highly dependable. The measurements were significantly repeatable at most gap sizes but were poorly dependable. Therefore, this program may need further modifications to achieve better reliable results for clinical testing. ⸰ Experiment 3 (Chapter-4): I modified the Vernier acuity program to quantify the Vernier acuity in eccentric 5 degrees of the macula (para-foveal area). The right eye results were repeatable for 15 arc minutes of gap size, whereas the left eye results were repeatable for the 30 arc minutes of gap size. However, both eyes had poor reliability at most of the gap sizes except the superior field of gap 30, where the reliability was moderate. This inconsistency between the eyes could be due to distinct reasons and therefore needs further investigations to address the underlying cause. ⸰ Experiment 4 (Chapter-5): I programmed a software application to quantify the metamorphopsia using a method of adjustment. The right eye results were repeatable at most gap sizes for both patterns. However, the measurements were poorly dependable at most gap sizes of both patterns. Similarly, the left eye results were repeatable at most gap sizes for both patterns. However, the measurements were poorly dependable at most gap sizes of both patterns, except at 3 degrees of pattern A and 5 and 2 degrees of pattern B, where the reliability was moderate. Further modifications in the program may provide better reliability for clinical testing.
Optometry Outreach in Indigenous Communities in British Columbia, Saskatchewan, and Manitoba
(University of Waterloo, 2023-08-31) Warren, Adrianna
Introduction: Inuit, Métis, and First Nations, the three main Indigenous groups within Canada, face disproportionate barriers to access for primary eye and vision care. Optometrists visit rural and remote Indigenous communities to provide outreach care to areas without a local optometrist; however, the approach is fragmented and not well represented. The purpose of this project is to assess the current state of outreach optometry within Indigenous communities by surveying optometrists who provide outreach care. Methods: In collaboration with the provincial optometry regulatory bodies, eligible participants were identified as optometrists who travel outside of their primary clinics to provide care within non-urban Indigenous communities. A questionnaire was developed through iterative stakeholder review for phase I of the study. The online questionnaire captured the delivery of care across one year (2022). The process of planning logistics, distances travelled, patient care provided and associated expenses were queried. A Semi-structured interview guide was developed for phase II of the study. One-on-one interviews expanded on questionnaire themes, providing insight into individual experiences. Data was collated through descriptive statistics and thematic coding for case and cross-case analysis. Results: The overall response rate was 50% (18/36) for the questionnaire and 30.5% (11/36) for the interview. Total questionnaire responses represent 96 outreach visits, 312.5 optometry clinic days, and 8,386 patient encounters across 64 communities in the three provinces. Optometrists coordinate with health center employees and school contacts to plan outreach visits, travelling primarily north to some of the most remote areas within each province. Overall Euclidean distances between participants primary clinic locations and communities visited ranged from 65 to 1405 kilometers (kms) (median: 438 kms). Costs per clinic day were highly variable ($174.44 - $3,800, mean: $765 per clinic day). Challenges reported were related to logistics, economic burden, and organizational challenges. Complementary enablers were identified, and recommendations are provided. Conclusions: This study is the first to provide visibility to the current state of outreach optometry care to Indigenous communities in British Columbia, Saskatchewan, and Manitoba. The process of planning outreach visits was variable for individual optometrists and between provinces. High variability in reported costs associated with outreach visits requires additional investigation. Multi-stakeholder collaboration to support optometry outreach programming would encourage outreach participation and improve services towards reducing eye and vision health inequity experienced by non-urban Indigenous populations. Acknowledgements: Project supported by Anonymous Philanthropic Foundation, Canadian Institute for Health Research Canadian Graduate Scholarship, and Canadian Optometric Education Trust Fund. No conflicts to declare.
The Phenotype of Tear Neutrophils and Their Role in Ocular Homeostasis and Inflammation
(University of Waterloo, 2023-07-31) Jin, Yutong
Introduction: Neutrophils (polymorphonuclear neutrophils, PMNs) are part of the innate immune system with potent killing mechanisms against pathogens. Although the anterior segment of the eye has a unique characteristic, immune privilege, a significant influx of PMNs has been detected after a prolonged eye closure at night, such as sleep. However, the functions and roles of tear PMNs in ocular homeostasis and complications remain largely unknown. The overall objectives of this thesis were to examine and compare the phenotype and functions of tear PMNs from healthy participants and participants with ocular allergy. Methods: Participants used a gentle eye wash method to collect tear PMNs from the ocular surface by washing their eyes with sterile phosphate buffer saline (PBS). • Study 1: Tear PMNs were either isolated from the eyewash by using the MACS-Column or EasySep cell separation system or reconcentrated by centrifugation. Stimulated (phorbol-12myristate-13-acetate (PMA), lipopolysaccharides (LPS) or N-Formylmethionyl-leucylphenylalanine (fMLP)) and unstimulated ROS production by both isolated and non-isolated tear PMNs were measured using luminol-enhanced chemiluminescence for 60 min. • Study 2: Tear PMNs were incubated with different medium conditions, Hank’s Balanced Salt Solution (HBSS) only, HBSS with lactoferrin, lysozyme, mucin, albumin, and IgG (ATS), and ATS without lactoferrin and lysozyme (MAI). Unstimulated or PMA-stimulated ROS production by tear PMNs was measured using luminol-enhanced chemiluminescence and flow cytometry with DCFH-DA. • Study 3: Tear leukocytes were collected at four different time points, after 2-hr and 7-hr of sleep at night, after 2-hr sleep during the day, and towards the end of the day (around 5 pm). After stimulation with fMLP, changes in the degranulation (lactoferrin, CD66b, CD63) and cell aging state (CD184) of tear PMNs were measured via flow cytometry. Neutrophil extracellular traps (NETs) were quantified by flow cytometry and visualized by microscopy following staining with myeloperoxidase, citrullinated histones, and CD15. • Study 4: Tear PMNs were collected from participants suffering from ocular allergy on two consecutive days, after a full night of sleep in the morning on Day 1 and at the end of the day, i.e., around 4:30 pm, on Day 2. Tear PMNs were either activated with fMLP or left unstimulated, followed by staining with antibodies against degranulation markers (CD66b and CD63), adhesion markers (CD11b and CD54), eosinophil marker (CD193), aging markers (CD184 and CD62L), as well as with the fluorescent probe DCFH-DA. The intensity of fluorescence was measured via flow cytometry. Results: • Study 1: Tear PMNs have a high level of constitutive/spontaneous ROS production even in the absence of any stimulus. However, tear PMNs failed to appropriately respond to LPS and fMLP, although they were able to produce ROS in response to PMA. Higher ROS generation was observed in isolated tear PMNs which may be caused by priming from the magnetic bead cell separation system. • Study 2: The presence of tear proteins significantly reduced the unstimulated and PMAstimulated ROS production by tear PMNs in HBSS and ATS. However, the findings on ROS production by PMA-stimulated PMNs incubated in MAI were different between the flow cytometry and chemiluminescence, suggesting that lactoferrin and lysozyme may have a greater impact on extracellular ROS production. • Study 3: Significantly more cells were collected from the nighttime compared to the daytime. 2hr EC night tear PMNs were less degranulated than 7hr EC night tear PMNs and possessed a higher activation ratio in response to fMLP. Furthermore, 7hr EC night tear PMNs exhibited hypersegmented nuclei and were prone to aggregation, when compared to 2hr EC night tear PMNs, suggesting an aged and activated phenotype. A significantly increased number of NETs were present in 7hr nocturnal closed-eye tear samples. • Study 4: There were significantly more tear PMNs collected from individuals with ocular allergy compared to healthy participants upon awakening. Tear PMNs from ocular allergy participants exhibited a less activated phenotype but a higher activation potential in response to fMLP compared to healthy participants, which was correlated with their younger maturation state. However, no significant difference in the production of ROS by tear PMNs between these two groups was observed. Conclusion: Tear PMNs become more aged and activated with increasing eye closure time at night, which can potentially aid in ocular surface surveillance. The presence of tear proteins may limit the ROS release by tear PMNs, thereby protecting the ocular environment from potential damage. However, in individuals suffering from ocular allergy, tear PMNs may be constantly recruited to the ocular surface, contributing to symptoms of ocular allergy and development of ocular complications associated with inflammation. This thesis identified some of the functionalities and potential roles of tear PMNs in maintaining ocular homeostasis and regulating inflammation. While further investigation is needed to comprehensively characterize the underlying mechanisms of tear PMNs involved in ocular inflammation, the current results may support the development of new therapeutical strategies to reduce ocular surface inflammation.
Fabrication of an enzyme responsive biomaterial for the treatment of recurrent corneal erosion
(University of Waterloo, 2023-04-11) Bose, Susmita
Purpose: Recurrent corneal erosion (RCE) arising from the loss of superficial corneal epithelial cells causes tremendous ocular pain affecting one’s productivity and quality of life. RCE was traditionally treated with eye lubricants and patching (to stop blinking). Soft bandage contact lenses (BCLs), which enable the use of vision during the healing process, have become more widely used in recent years. Because BCLs do not yet contain the therapeutic components necessary for ocular surface repair, they do not outperform ocular lubricants in terms of effectiveness or recovery time. This is a problem. Multiple studies have shown elevated levels of matrix metalloproteinase (MMP) enzymes, particularly MMP-9 and MMP-2, in RCE. The purpose of this thesis was to develop an enzyme-triggered therapeutic release platform using a unique gelatin methacrylate formulation (GelMA+) and bovine lactoferrin (BLF), a potential corneal wound healing therapeutic. Method: Two different formulations of GelMA+ gels were synthesized: 20% w/v and 30% w/v GelMA+ gels. To determine the effect of polymer concentration on the physical characteristics and cytotoxicity of the gels, physical characterization, including mechanical strength, swelling behaviour, pore size, optical clarity, degradation profile in the enzyme MMP-9 and MMP-8, were evaluated. To evaluate whether GelMA+ is suitable to be a biomaterial, cytotoxicity assays (alamarBlue and live/dead assay) were performed on both the GelMA+ formulations. These physical and biological characterization of GelMA+ gels helped to choose the specific GelMA+ formulation for studying the in vitro release profile of BLF from the GelMA+ matrix. To assess the efficacy and therapeutic window of BLF for corneal epithelial cells wound healing, a scratch induced assay model was used. Results: GelMA showed a tunable profile suitable for the diffusion- and enzyme-mediated controlled release of therapeutics above the molecular weight region of 70 kDa. Owing to the high polymer concentration as opposed to 20% w/v GelMA+, the 30% w/v GelMA+ had a higher crosslinking density, tensile strength, smaller pore size, and lower swelling ratio than the 20% w/v GelMA+ (p<0.05). The degradation rate of the 20% w/v gel was much faster (p<0.001), degrading almost completely after 48 hours at 300 µg/mL of MMP-9 whereas 30% w/v GelMA+ gels took almost 6 days to achieve around 95% degradation in the same MMP-9 concentration. After 5 days, no cytotoxicity was detected in the live/dead staining for either formulation, but the 30% w/v GelMA+ showed significantly higher cell viability (p<0.05). In the BLF release study, no burst release of BLF was observed for the 30% w/v gel, and the therapeutic release was sustained over 5 days. The rate of release from the gel significantly increased with increasing concentrations of MMP-9 (p<0.001) and correlated to the rate of degradation of the gels. BLF at 10 mg/mL induced complete wound closure in four days, and 7.5 mg/mL completely closed the wound in six days, suggesting that BLF might be an excellent therapeutic option for corneal abnormalities brought on by mechanical injury. A concentration of 7.5mg/mL or 10 mg/mL BLF would be an appropriate therapeutic window to be released from 30% w/v GelMA+ for treating RCE within a week. Conclusion: The results showed that the degradation of GelMA+ can be tuned by modifying the crosslinking density or exposure to different concentrations of MMP-9. The release of BLF from 30% w/v GelMA+ is driven by a combination of diffusion and degradation of the material by MMP-9 enzymes. Hence the therapeutic releasing enzyme responsive GelMA+ as a BCL can be potential future treatment for RCE. Future work will focus on optimizing the materials to deliver other therapeutic agents at physiologically relevant concentrations of MMP enzymes found in the tear fluid.
Understanding concussion in para athletes with vision impairment
(University of Waterloo, 2023-02-15) Teodoro, Juliette
Sports-related concussions occur in para sport as they do in able-bodied sport. There is evidence to suggest athletes with vision impairment (VI) may be more likely to sustain concussion injuries compared to athletes with other impairment types. However, there is limited understanding of best practices in concussion assessment and management for athletes with VI. Symptoms intrinsic to pre-existing conditions in para athletes are also commonly seen in athletes suffering from a concussion, which makes the assessment and management of concussion more challenging in the para athlete population. Perspectives and experiences of VI para sport athletes and coaches with concussion are also poorly understood. The purpose of this project was to understand how concussions are currently assessed and managed in elite para athletes with vision impairment, to move toward establishing clinical practice guidelines and critical research priorities in concussion management for elite athletes with VI. The secondary objective of this thesis was to understand the perspectives, experiences, and knowledge of elite athletes with VI and coaches concerning concussion in VI para sport. A two-round Delphi study was conducted to solicit the opinions of healthcare professionals, researchers, and administrators in VI para sport concerning concussion assessment and management practices. Eight out of the nine interested participants completed the first-round survey; seven of those completed the second-round survey. Five out of eight participants were sports medicine physicians, and the remaining three participants had a background in physical therapy. Experts identified that VI athletes may exhibit different observable signs of concussion (e.g., lack of blank look, balance issues at baseline, etc.) compared to able-bodied athletes. Experts unanimously agreed that pre-season baseline testing is necessary for para athletes with VI. While most experts (86%) agreed the SCAT5 currently represents the most effective assessment tool available for the evaluation of suspected concussion, one expert disagreed and explained that the SCAT5 is too complex for regular sideline use. Some experts suggested prescribing a longer period of initial rest or doubling the time between return-to-sport steps for athletes with VI. Experts came to a unanimous consensus that there is a lack of after-care in VI para sport in addition to the lack of on-site specially trained medical support. Elite para athletes with VI and coaches were invited to participate in a single-round survey study. The survey questions covered the following topics: Demographics; Concussion incidence, recognition, response, assessment, and management; Return-to-sport; and Education. Analysis consisted of categorizing written responses and analyzing response frequencies. A total of 8 participants (athletes (n = 4); coaches (n = 4)) from elite VI para sport took part. Athletes were found to have less awareness of medics at sidelines, assessment tools, how decisions are made to investigate for concussion, and the need for concussion assessments than coaches. Athletes were also more likely to not report incidents with reasons for not reporting including “don’t think it’s serious”, “time and money”, and “misdiagnosis because of underlying conditions”. Coaches are not considering athlete involvement in return-to-play decisions. Athletes and coaches agreed that it is important for medical professionals to have concussion education but differ on the need for education of athletes and guides. Athletes reported having little and poor quality concussion education. Future investment in the provision of specially trained on-site medical support is needed to ensure the safety and well-being of VI para athletes. Education strategies should prioritize informing para athletes of the potential long-term consequences of concussion, so they understand the significance of failing to report concussion symptoms and of neglecting concussion injury protocol.
Diabetic retinopathy grading with respect to the segmented lesions
(University of Waterloo, 2022-05-19) Kheradfallah, Hoda
One of the leading causes of irreversible vision loss is Diabetic Retinopathy (DR). The International Clinical Diabetic Retinopathy scale (ICDRS) provides grading criteria for DR. Deep Convolutional Neural Networks (DCNNs) have high performance in DR grading in terms of classification evaluation metrics; however, these metrics are not sufficient for evaluation. The eXplainable Artificial Intelligence (XAI) methodology provides insight into the decisions made by networks by producing sparce, generic heat maps highlighting the most critical DR features. XAI also could not satisfy clinical criteria due to the lack of explanation on the number and types of lesions. Hence, we propose a computational tool box that provides lesion-based explanation according to grading system criteria for determining severity levels. According to ICDRS, DR has 10 major lesions and 4 severity levels. Experienced clinicians annotated 143 DR fundus images and we developed a toolbox containing 9 lesion-specified segmentation networks. Networks should detect lesions with high annotation resolution and then compute DR severity grade according to ICDRS. The network that was employed in this study is the optimized version of Holistically Nested Edge Detection Network (HEDNet). Using this model, the lesions such as hard exudates (Ex), cotton wool spots (CWS), neovascularization(NV), intraretinal haemorrhages (IHE) and vitreous preretinal haemorrhages (VPHE) were properly detected but the prediction of lesions such as venous beading (VB), microaneurysms (MA), intraretinal microvascular abnormalities (IRMA) and fibrous proliferation (FP) had lower mAPs. Consequently, this will affect the value of grading which uses the segmented masks of all contributing lesions.
Effects of ML-7 on the Actomyosin Networks of the Avian Crystalline Lens
(University of Waterloo, 2022-04-29) Suko, Adeline
Assemblies of contractile proteins such as actin, myosin and myosin light chain kinase (MLCK) are found on the posterior surface of the lens fibre cells. The mechanical properties of chicken lenses, as well as their focal lengths, were found to be affected by the disruption of the network using inhibitors such as 1-(5-Iodonaphthalene-1sulfonyl)-1H-hexahydro-1,4-diazepine hydrochloride (ML-7). The purpose of this study is to determine if ML-7, a MLCK inhibitor influences actomyosin organization in the chicken lens, which may have lead to the reported changes in stiffness and focal lengths. The Nearest Neighbour Distance (NND) values will be used to test the following hypotheses: ML-7-treated lenses have further NNDs compared to their vehicle counterparts, and that the NNDs of the 100μM-treated lenses would be lower than the lenses treated with lower concentrations (1μM and 10μM) of ML-7. Eyes of 7-day old white leghorn chickens (gallus gallus domesticus) were obtained. The anterior segment of one eye is treated with 1μM, 10μM, or 100μM of ML-7, and the other, with vehicle. The lenses were stained for actin and myosin. The NNDs for actin-actin, actin-myosin, myosin-actin and myosin-myosin were determined from confocal images of the networks to quantify the network distribution. Myosin-myosin NNDs of 10μM-treated lenses showed significantly lower values compared to 100μM-treated lenses. However, it is uncertain whether the significant change observed was indeed due to ML-7 activity or due to variation between birds. Additionally, only myosin-actin NNDs showed a significant reduction in treated lenses. These results suggest that actomyosin interactions affected by ML-7 may have been too subtle to detect, or compensation by other kinases occurred. Thus, this study was unable to determine if the stiffness and focal length changes in ML-7-treated lenses observed in previous studies were related to changes that ML-7 imparts on the actomyosin networks.
A differential role for the posterior cerebellum in the adaptive control of convergence eye movements
(Elsevier, 2020-02) Erkelens, Ian M.; Bobier, William R.; Macmillan, Alicia C.; Maione, Nicole L.; Calderon, Claudia Martin; Patterson, Heidi; Thompson, Benjamin
Introduction The vergence oculomotor system possesses two robust adaptive mechanisms; a fast “dynamic” and a slow “tonic” system that are both vital for single, clear and comfortable binocular vision. The neural substrates underlying these vergence adaptive mechanisms in humans is unclear. Methods We investigated the role of the posterior cerebellum in convergence adaptation using inhibitory continuous theta-burst repetitive transcranial magnetic stimulation (cTBS) within a double-blind, sham controlled design while eye movements were recorded at 250hz via infrared oculography. Results In a preliminary experiment we validated our stimulation protocols by reproducing results from previous work on saccadic adaptation during the classic double-step adaptive shortening paradigm. Following this, across a series of three separate experiments we observed a clear dissociation in the effect of cTBS on convergence adaptation. Dynamic adaptation was substantially reduced while tonic adaptation was unaffected. Baseline dynamic fusional vergence response were also unaffected by stimulation. Conclusions These results indicate a differential role for the posterior cerebellum in the adaptive control of convergence eye movements and provide initial evidence that repetitive transcranial magnetic stimulation is a viable tool to investigate the neurophysiology of vergence control. The results are discussed in the context of the current models of implicit motor adaptation of vergence and their application to clinical populations and technology design in virtual and augmented head mounted display architectures. Significance statement The cerebellum plays a critical role in the adaptive control of motor systems. Vergence eye movements shift our gaze in depth allowing us to see in 3D and exhibit two distinct adaptive mechanisms that are engaged under a range of conditions including reading, wearing head-mounted displays and using a new spectacle prescription. It is unclear what role the cerebellum plays in these adaptive mechanisms. To answer this, we temporarily disrupted the function of the posterior cerebellum using non-invasive brain stimulation and report impairment of only one adaptive mechanism, providing evidence for neural compartmentalization. The results have implications for vergence control models and applications to comfort and experience studies in head-mounted displays and the rehabilitation of clinical populations exhibiting vergence dysfunctions.
Impact of contact lens wear on epithelial alterations in keratoconus
(Elsevier, 2021-03) Sorbara, Luigina; Lopez, Jose Carlos Lopez; Gorbet, Maud; Bizheva, Kostadinka; Lamarca, Jose Mateu; Pastor, José-Carlos; López, Miguel José Maldonado; Hileeto, Denise
Purpose The purpose of this study was to characterize the central epithelial thickness (CET) of penetrating keratoplasty corneal specimens obtained from patients with keratoconus (KC) and correlate the histological patterns with their clinical history.Methods Ex vivo histological imaging was performed to measure CET and total corneal thickness (TCT) in 56 patients with KC. Microscopic slides from penetrating keratoplasty corneal specimens, stained with hematoxylin and eosin were evaluated using bright field microscopy. CET and TCT were measured, and morphological features were studied. Clinical history regarding duration of KC prior to surgery and length of and tolerance to contact lens wear were compared and analyzed. Results The microscopic slides of all patients available for follow up (n = 48) were analyzed and CET and TCT were measured. The histological evaluation revealed 3 distinctive epithelial patterns. Pattern 1 with central hypertrophic and hydropic changes (n = 19) measured 70.89 ± 25.88 μm in CET and 308.63 ± 100.74 μm in TCT; Pattern 2 (n = 14) had not changed, similar to normal epithelium CET and TCT measuring 36.5 ± 7.02 μm and 260.14 ± 87.93 μm respectively. Pattern 3 (n = 15) demonstrated thinner central epithelium characterized by atrophy and focal hydropic changes measuring 19.93 ± 4.60 μm and 268.00 ± 79.39 μm in CET and TCT respectively (all p < 0.0001). The presence of Pattern 2 characterized by similar to normal CET was correlated with the duration of the condition (R = 0.600, p = 0.030). There was a significant difference in the length of CL wear comparing those with patterns 1 and 2 versus 3 (least no. of CL years) (p = 0.05 and p = 0.33 respectivelly). Conclusions Patients with advanced disease have various central corneal epithelial changes detected with histology. Although each central epithelial pattern type was distinctive comparing the 3 patterns, there was no correlation with years of CL wear but only with the duration of the condition.
The Optometric Management of Concussion
(University of Waterloo, 2022-01-31) Yeboah, Anne Marie
Traumatic brain injury is a major public health problem that affects millions of people annually and hundreds of people experience brain injury daily. Many of these individuals develop visual symptoms. Optometrists play a prominent role in the management of patients with concussion-associated vision deficits and persistent concussion symptoms. At present, there is no accepted optometric standard of care for individuals with concussion. Patients receiving optometric concussion related care would benefit from a standardized evidence-based concussion management process. The purpose of this project was to determine the current assessment methods and prescribing practices of optometrists seeing individuals with persistent concussion-associated vision deficits in private practice and at a university academic optometry clinic. Study 1: A retrospective review examined the frequency of visual assessments and management strategies at an academic university optometry clinic. A total of 238 patient files were examined. Of the 238 patient files, 119 individuals had persistent concussion symptoms (concussed group) and 119 individuals did not have concussion (non-concussed cohort). The frequency of visual assessments (ocular structure and visual function) and management strategies were determined. A chi square test was used to compare the frequency of assessments and management strategies between cohorts. In the concussed group, an emphasis on visual function and management strategies, for example assessments of vergence, saccades, pursuits and stereopsis were observed in comparison to the reference group. In non-concussed individuals, ocular structure assessments (e.g., posterior segment, anterior segment and confrontation visual field) were more prevalent than in the concussed cohort. It is important to note that ocular structure assessments did not include assessments conducted by the referring optometrists. Diagnostic drugs, for example tropicamide and anesthetics, were used more commonly in the non-concussed group, while cycloplegia was more prevalent in the concussed group. Study 2: A 6-question online survey was distributed to optometric provincial and national regulators and associations in Canada. Questions pertaining to visual assessments, prescribed medications and supplements, advice about daily living activity, appointment duration and appointment follow-up were asked. Analysis consisted of binning and determining the frequency of responses. Of the 199 responses received, 142 were completed and analysis was only conducted from these responses. A total of 128 optometrists managed concussion and 13 optometrists did not. The top reasons for optometrists who did not manage concussion was referral and no training. Ocular structure assessments were more prevalent than visual function and management strategies of concussion. Optometrists most frequently recommended Omega 3 (54%) and oral supplements (38%). The majority of optometrist’s (64%) advice on daily living activity was to limit physical and cognitive activity, the second most common suggestion was to rest (12%). The majority of optometrists, 57%, employed 30 to 60-minute assessments and over one-fifth conducted follow-up appointments within 2-months. Conclusion: This project informs optometrists on the state of concussion management in Canadian private practice and at a university academic optometry clinic. Findings can be used to aid in the development of standardized strategies for the optometric management of concussion and related regulatory decisions. This can lead to reductions in persistent post-concussive symptoms, improved patient outcomes, and overall improved quality of life.
A System for Ocular Surface Temperature Measurement Using Infrared Thermography
(University of Waterloo, 2022-01-20) Zare Bidaki, Ehsan
Background: Ocular surface temperature (OST) is affected by changes in the physiology of the eye caused by normal homeostasis, environmental changes, or systemic and local disease. OST can help a physician to diagnose eye disease with improved accuracy and provide useful information for eye research. OST is assessed non-invasively using a thermal (infrared radiation (IR)) camera. Current methods of OST measurement are restricted in their ability to analyze individual pixel data across the area of measurement due to being unable to localize and track the cornea accurately during a period of measurement. They are also unable to detect eye blinks and are dependent on manual management of the data collection. Purpose: This thesis presents a novel hardware design, as well as several novel algorithms, for control of the hardware and for image processing of the captured data stream as part of a novel system to measure and track OST from the cornea automatically over any period of time. Methods/Results: The system uses an IR camera and a visible light camera to capture thermal and visible videos, respectively, from the eye surface. The videos are captured synchronously using designed hardware and an implemented algorithm (data acquisition). The frames for the two video sequences are then registered together (video registration) using two sets of control points. The points are manually selected on the first pair of timestamped thermal and visible frames, and then tracked over the subsequent frames using the Lucas–Kanade optical flow algorithm (point tracking). A mean square error of 5.43±2.01 pixels (equal to 5.43 * 0.09 mm) was reported for salient point tracking for the thermal video and 6.81±2.32 pixels (equal to 6.81 * 0.09 mm) for the visible video. The mean square error for the registration was 5.03 ±1.82, which is approximately 0.45 mm. The corneal area was segmented in the visible images and localized on the images using semantic segmentation method (corneal segmentation). A mean Intersection over Union (IoU) of 94.6% was found, representing the accuracy in identifying corneal pixels in the tracked corneal segmentation, was achieved. Using video registration, the corneal segmentation in the visible image was mapped to the thermal image. OST data extraction from the segmented corneal area in the thermal image was then possible. Conclusion: A system for measuring and tracking eye surface temperature over time was developed. The system captures thermal and visible image sequences synchronously from the eye surface of corresponding thermal and visible images taken at the same time. The system is able to localise the cornea on both visible and thermal images. The system is able to report temperature profiles of the cornea over the period of measurement. Experimental results shows that the whole system can work as a tool for measuring and tracking OST over time.

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