Optometry and Vision Sciences - Research Publications

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    Test Reliability and Compliance to a Twelve-Month Visual Field Telemedicine Study in Glaucoma Patients
    Prea, SM ; Vingrys, AJ ; Kong, GYX (MDPI, 2022-08)
    Background: Our primary aim is to quantify test reliability and compliance of glaucoma patients to a weekly visual field telemedicine (VFTM) schedule. A secondary aim is to determine concordance of the VFTM results to in-clinic outcomes. Methods: Participants with stable glaucoma in one eye were recruited for a 12 month VFTM trial using the Melbourne Rapid Fields (MRF-home, MRFh) iPad application. Participants attended routine 6 month clinical reviews and were tasked with weekly home monitoring with the MRFh over this period. We determined compliance to weekly VFTM (7 + 1 days) and test reliability (false positives (FPs) and fixation loss (FL) <33%). A secondary aim considered concordance to in-clinic measures of visual field (MRF-clinic (MRFc) and the Humphrey Field Analyzer (HFA)) in active participants (≥10 home examinations and 5 reliable HFA examinations). The linear trend in the MRFh mean deviation (MD) was compared to the HFA guided progression analysis (GPA) using Bland−Altman methods. Data are shown as the mean ± standard deviation. Results: Forty-seven participants with a mean age of 64 ± 14.6 years were recruited for the trial. The VFTM uptake was 85% and compliance to weekly home monitoring was 75% in the presence of weekly text reminders in the analysed group (n = 20). The analysed group was composed of test subjects with five reliable in-clinic HFA examinations (GPA analysis available) and who submitted a minimum of 10 MRFh examinations from home. Of the 757 home examinations returned, approximately two-thirds were reliable, which was significantly lower than the test reliability of the HFA in-clinic (MRFh: 65% vs. HFA: 85%, p < 0.001). The HFA-GPA analysis gave little bias from the MRFh slope (bias: 0.05 dB/yr, p > 0.05). Two eyes were found to have clinical progression during the 12 month period, and both were detected by VFTM. Conclusions: VFTM over 12 months returned good compliance (75%) to weekly testing with good concordance to in-clinic assays. VFTM is a viable option for monitoring patients with glaucoma for visual field progression in between clinical visits.
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    Screening for Glaucomatous Visual Field Defects in Rural Australia with an iPad.
    Chia, MA ; Trang, E ; Agar, A ; Vingrys, AJ ; Hepschke, J ; Kong, GY ; Turner, AW (Jaypee Brothers Medical Publishing, 2021)
    AIM AND OBJECTIVE: Developing improved methods for early detection of visual field defects is pivotal to reducing glaucoma-related vision loss. The Melbourne Rapid Fields screening module (MRF-S) is an iPad-based test, which allows suprathreshold screening with zone-based analysis to rapidly assess the risk of manifest glaucoma. The versatility of MRF-S has potential utility in rural areas and during infectious pandemics. This study evaluates the utility of MRF-S for detecting field defects in non-metropolitan settings. MATERIALS AND METHODS: This was a prospective, multicenter, cross-sectional validation study. Two hundred and fifty-two eyes of 142 participants were recruited from rural sites through two outreach eye services in Australia. Participants were tested using MRF-S and compared with a reference standard; either Zeiss Humphrey Field Analyzer or Haag-Streit Octopus performed at the same visit. Standardized questionnaires were used to assess user acceptability. Major outcome measures were the area under the curve (AUC) for detecting mild and moderate field defects defined by the reference tests, along with corresponding performance characteristics (sensitivity, specificity). RESULTS: The mean test duration for MRF-S was 1.88 minutes compared with 5.92 minutes for reference tests. The AUCs for mild and moderate field defects were 0.81 [95% confidence interval (CI): 0.75-0.87] and 0.87 (95% CI: 0.83-0.92), respectively, indicating very good diagnostic accuracy. Using a risk criterion of 55%, MRF-S identified moderate field defects with a sensitivity and specificity of 88.4 and 81.0%, respectively. CONCLUSION AND CLINICAL SIGNIFICANCE: The MRF-S iPad module can identify patients with mild and moderate field defects while delivering favorable user acceptability and short test duration. This has potential application within rural locations and amidst infectious pandemics. HOW TO CITE THIS ARTICLE: Chia MA, Trang E, Agar A, et al. Screening for Glaucomatous Visual Field Defects in Rural Australia with an iPad. J Curr Glaucoma Pract 2021;15(3):125-131.
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    Vision and Visuomotor Performance Following Acute Ischemic Stroke.
    Wijesundera, C ; Crewther, SG ; Wijeratne, T ; Vingrys, AJ (Frontiers Media SA, 2022)
    BACKGROUND: As measurable sensory and motor deficits are key to the diagnosis of stroke, we investigated the value of objective tablet based vision and visuomotor capacity assessment in acute mild-moderate ischemic stroke (AIS) patients. METHODS: Sixty AIS patients (65 ± 14 years, 33 males) without pre-existing visual/neurological disorders and acuity better than 6/12 were tested at their bedside during the first week post-stroke and were compared to 40 controls (64 ± 11 years, 15 males). Visual field sensitivity, quantified as mean deviation (dB) and visual acuity (with and without luminance noise), were tested on MRFn (Melbourne Rapid Field-Neural) iPad application. Visuomotor capacity was assessed with the Lee-Ryan Eye-Hand Coordination (EHC) iPad application using a capacitive stylus for iPad held in the preferred hand.Time to trace 3 shapes and displacement errors (deviations of >3.5 mm from the shape) were recorded. Diagnostic capacity was considered with Receiver Operating Characteristics. Vision test outcomes were correlated with National Institutes of Health Stroke Scale (NIHSS) score at the admission. RESULTS: Of the 60 AIS patients, 58 grasped the iPad stylus in their preferred right hand even though 31 had left hemisphere lesions. Forty-one patients (68%) with better than 6/12 visual acuity (19 right, 19 left hemisphere and 3 multi-territorial lesions) returned significantly abnormal visual fields. The stroke group took significantly longer (AIS: 93.4 ± 60.1 s; Controls: 33.1 ± 11.5 s, p < 0.01) to complete EHC tracing and made larger displacements (AIS: 16,388 ± 36,367 mm; Controls: 2,620 ± 1,359 mm, p < 0.01) although both control and stroke groups made similar numbers of errors. EHC time was not significantly different between participants with R (n = 26, 84.3 ± 55.3 s) and L (n = 31, 101.3 ± 64.7 s) hemisphere lesions. NIHSS scores and EHC measures showed low correlations (Spearman R: -0.15, L: 0.17). ROC analysis of EHC and vision tests found high diagnostic specificity and sensitivity for a fail at EHC time, or visual field, or Acuity-in-noise (sensivity: 93%, specificity: 83%) that shows little relationship to NIHSS scores. CONCLUSIONS: EHC time and vision test outcomes provide an easy and rapid bedside measure that complements existing clinical assessments in AIS. The low correlation between visual function, NIHSS scores and lesion site offers an expanded clinical view of changes following stroke.
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    Scaling the size of perimetric stimuli reduces variability and returns constant thresholds across the visual field
    Bedggood, P ; Prea, SM ; Kong, YXG ; Vingrys, AJ (ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2020-10)
    The conventional stimulus for standard automated perimetry is fixed in size, giving elevated contrast thresholds and reduced test reliability in the periphery. Here, we test the hypothesis that appropriate scaling of the size of perimetric stimuli will return fixed thresholds and reduced variability across the visual field. We derived frequency-of-seeing (FOS) curves in five healthy subjects at central (3 degrees) and peripheral (27 degrees) locations with a method of constant stimuli (MOCS) using a desktop LCD display. FOS curves for a Goldmann III (GIII) stimulus were compared with those for size scaled spots. To consider clinical translation, we tested a further five healthy subjects (22-24 years) with the Melbourne Rapid Fields (MRF) tablet perimeter at several locations spanning 1 degree to 25 degrees from fixation, deriving FOS curves (MOCS) and also conducting repeated adaptive clinical thresholding to assess intra- and interobserver variability. We found that GIII contrast thresholds were significantly elevated in the periphery compared with the parafovea, with concomitant reduction of FOS slope. Using appropriately size scaled spots, threshold and slope differences between these locations were significantly reduced. FOS data collected with the tablet perimeter confirmed that size scaling confers broad equivalence of the shape of the FOS curve across the visual field. Repeated adaptive thresholding with size scaled stimuli gave relatively constant intra-observer variability across the visual field, which compares favorably with published normative data obtained with the GIII stimulus. The reduced variability will improve signal-to-noise ratio for correct classification of normal visual field test results, whereas the lower contrast thresholds yield greater dynamic range, which should improve the ability to reliably monitor moderate defects.
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    The Short-Term Compliance and Concordance to in Clinic Testing for Tablet-Based Home Monitoring in Age-Related Macular Degeneration
    Prea, SM ; Kong, GYX ; Guymer, RH ; Sharangan, P ; Baglin, EK ; Vingrys, AJ (ELSEVIER SCIENCE INC, 2022-03)
    PURPOSE: The aim of this study was to determine the short-term compliance with regular home monitoring of macular retinal sensitivity (RS) in intermediate age-related macular degeneration (iAMD). Home-based outcomes were compared with in-clinic outcomes determined using (1) the same tablet device under supervision, and (2) the Macular Integrity Assessment (MaIA) microperimeter. DESIGN: Single-center longitudinal compliance and reliability study. METHODS: A total of 73 participants with iAMD were trained to perform macular field testing with the Melbourne Rapid Fields-macular (MRF-m) iPad application. Volunteers were asked to return 6 weekly tests from home, guided by audio instructions. We determined compliance with weekly testing and surveyed for factors that limited compliance. Test reliability (false positive, false negative) and RS were compared to in-clinic assays (MaIA). Data are given as mean ± SD or as median [quartile 1-3 range]. Group comparisons were achieved with bootstrap to define the 95% confidence limits. RESULTS: A total of 59 participants submitted 6 home examinations with a median intertest interval of 8.0 [7.0-17] days. Compliance with weekly testing (7 days ±24 hours) was 55%. The main barrier to compliance was information technology (IT) logistic reasons. Of 694 home examinations submitted, 96% were reliable (false-positive results <25%). The mean RS returned by the tablet was significantly higher (+3.2 dB, P < .05) compared to the MaIA. CONCLUSIONS: Home monitoring produces reliable results that differ from in-clinic tests because of test design. This should not affect self-monitoring once an at-home baseline is established, but these differences will affect comparisons with in-clinic outcomes. Reasonable compliance with weekly testing was achieved. Improved IT support might lead to better compliance.
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    Uptake, Persistence, and Performance of Weekly Home Monitoring of Visual Field in a Large Cohort of Patients With Glaucoma
    Prea, SM ; Kong, GYX ; Guymer, RH ; Vingrys, AJ (ELSEVIER SCIENCE INC, 2021-03)
    PURPOSE: This study examines the short-term uptake, compliance, and performance of a tablet device used for home monitoring of visual field (VF-Home) by glaucoma patients. DESIGN: Single-center, observational, longitudinal, compliance study. METHODS: Participants who were glaucoma suspects or had stable glaucoma in at least one eye were recruited during a regular clinic review. Baseline in-clinic visual field (VF) was recorded with the Humphrey Field Analyser (HFA, SITA standard) and repeated at 6 months. Participants were tasked with performing 6 VF examinations from home, at weekly intervals, using a loaned iPad tablet. Uptake was defined as returning at least 1 test from home. Reliability and global indices from VF-Home were compared to in-clinic outcomes. Data are shown as either mean ± [standard deviation] or median [quartile 1-3 range], and group comparisons were achieved with bootstrap. RESULTS: We recruited 186 eyes of 101 participants. VF-Home uptake was excellent, with 88% of participants successfully completing ≥1 home examination and 69% completing all 6 examinations. The median duration between tests was 7.0 [7.0-8.0] days. Barriers to uptake and compliance involved information technology (IT) logistical reasons, lack of motivation, or competing life demands. VF-Home gave greater fixation loss but a similar level of False Positives (FP) as the HFA. A high correlation was found for the mean defect between in-clinic and at-home outcomes (R = 0.85). CONCLUSIONS: VF-Home can return a high level of short-term compliance and results comparable to those found by in-clinic testing. IT logistical reasons and lack of motivation are barriers to uptake and compliance.
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    Safety and Efficacy of a Preservative-Free Artificial Tear Containing Carboxymethylcellulose and Hyaluronic Acid for Dry Eye Disease: A Randomized, Controlled, Multicenter 3-Month Study
    Aragona, P ; Benitez-del-Castillo, JM ; Coroneo, MT ; Mukherji, S ; Tan, J ; Vandewalle, E ; Vingrys, A ; Liu, H ; Carlisle-Wilcox, C ; Vehige, J ; Simmons, PA (DOVE MEDICAL PRESS LTD, 2020)
    PURPOSE: To compare the efficacy and safety of an artificial tear combining the polymers carboxymethylcellulose (CMC) and hyaluronic acid (HA), to a formulation of CMC alone in subjects with dry eye. METHODS: A preservative-free artificial tear (CMC-HA) was compared with an existing artificial tear (CMC). Subjects with mild-to-severe signs and symptoms of dry eye were enrolled in this double-masked, randomized, multicenter trial, and dosed at least twice daily for 90 days, with follow-up visits at Days 7, 30, 60, and 90. Ocular Surface Disease Index (OSDI) was the primary outcome measure. Secondary outcome measures were tear break-up time (TBUT), ocular surface staining, Schirmer test with anesthesia, and visual analog scale (VAS) scores of dry eye symptom severity and formulation acceptability. Safety measures included adverse events, biomicroscopy, and visual acuity. RESULTS: A total of 460 subjects were enrolled across 45 sites (38 in Europe; 7 in Australia), of whom 454 were randomized to receive treatment. The per-protocol (PP) population consisted of 394 subjects, 364 (92.4%) of whom completed the study. In the PP population, the mean ± SD change from baseline in OSDI score at the primary timepoint, Day 90, was -16.9±17.5 for CMC-HA and -16.0±16.1 for CMC. CMC-HA was non-inferior to CMC based upon a confidence interval method. Both treatments significantly improved (P<0.001) OSDI, symptom VAS scores, TBUT, and ocular surface staining from baseline at all follow-up visits, with minimal differences between groups. Greater reduction of overall ocular pain/discomfort was reported in subjects using CMC-HA versus CMC (P=0.048). Approximately 10% of subjects in each group reported treatment-related adverse events of generally mild to moderate severity. CONCLUSION: The new CMC-HA formulation was effective and well tolerated, and demonstrates a greater potential for symptom relief compared with CMC. These data support implementation of this formula for the management of dry eye patients.
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    Acquired Visual Deficits Independent of Lesion Site in Acute Stroke
    Wijesundera, C ; Vingrys, AJ ; Wijeratne, T ; Crewther, SG (FRONTIERS MEDIA SA, 2020-07-17)
    Most clinical diagnoses of stroke are based on the persistence of symptoms relating to consciousness, language, visual-field loss, extraocular movement, neglect (visual), motor strength, and sensory loss following acute cerebral infarction. Yet despite the fact that most motor actions and cognition are driven by vision, functional vision per se is seldom tested rigorously during hospitalization. Hence we set out to determine the effects of acute stroke on functional vision, using an iPad application (Melbourne Rapid Field-Neural) that can be used to assess vision (visual acuity and visual field sensitivity) at the bedside or in the emergency ward in about 6 min per eye. Our convenience sample comprised 60 (29-88 years, 65 ± 14 years, 33 males) of 160 sequentially presenting first episode, acute (<7 days) ischemic stroke patients at Sunshine Hospital, Melbourne. One hundred patients were excluded due to existing eye disease, inadequate radiological confirmation, inability to comply with English directions or too ill to participate. Stroke cases were compared with 37 (29-85 years, 64 ± 12 years,14 males) similar-aged controls using a Mann-Whitney U-test. A significant loss in visual field sensitivity was measured in 68% of stroke cases (41/60, Mean Deviation: Stroke: -5.39 ± 6.26 dB, Control: 0.30 ± 0.60 dB, MWU = 246, p < 0.0001). Surprisingly, 44% (18/41) of these patients were unaware of their field loss. Although high contrast visual acuity was unaffected in most (55/60) patients, visual acuity-in-noise was reduced in 62% (37/60, Stroke: mean 6/12-2, log MAR 0.34 ± 0.21 vs. Control: mean 6/7·5-2, log MAR 0.14 ± 0.10; MWU = 470, p < 0.0001). Visual field defects were associated with all occipital, parietal and posterior cerebellar artery strokes while 9/15 middle cerebral artery lesions and 11 lesions in other brain regions were also associated with visual field defects. Our findings demonstrate that ~2/3 of acute first episode ischemic stroke patients experience acquired vision deficits, often unrelated to the confirmed lesion site. Our results also imply that visual dysfunction may be associated with a more generalized cerebral dysfunction while highlighting the need for bedside testing of vision for every stroke patient and demonstrating the translational clinical value of the "Melbourne Rapid Field- Neural" iPad application. Clinical Trial: http://www.ANZCTR.org.au/ACTRN12618001111268.aspx.
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    Retinal Functional and Structural Changes in the 5xFAD Mouse Model of Alzheimer's Disease
    Lim, JKH ; Li, Q-X ; He, Z ; Vingrys, AJ ; Chinnery, HR ; Mullen, J ; Bui, BV ; Nguyen, CTO (FRONTIERS MEDIA SA, 2020-08-13)
    Alzheimer's disease is characterized by the aberrant deposition of protein in the brain and is the leading cause of dementia worldwide. Increasingly, there have been reports of the presence of these protein hallmarks in the retina. In this study, we assayed the retina of 5xFAD mice, a transgenic model of amyloid deposition known to exhibit dementia-like symptoms with age. Using OCT, we found that the retinal nerve fiber layer was thinner in 5xFAD at 6, 12, and 17 months of age compared with wild-type littermates, but the inner plexiform layer was thicker at 6 months old. Retinal function showed reduced ganglion cell responses to light in 5xFAD at 6, 12, and 17 months of age. This functional loss was observed in the outer retina at 17 months of age but not in younger mice. We showed using immunohistochemistry and ELISA that soluble and insoluble amyloid was present in the retina and brain at all ages. In conclusion, we report that amyloid is present in brain and retina of 5xFAD mice and that the pattern of neuronal dysfunction occurs in the inner retina at the early ages and progresses to encompass the outer retina with age. This implies that the inner retina is more sensitive to amyloid changes in early disease and that the outer retina is also affected with disease progression.