Optometry and Vision Sciences - Research Publications
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ItemScaling the size of perimetric stimuli reduces variability and returns constant thresholds across the visual field(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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ItemSafety and Efficacy of a Preservative-Free Artificial Tear Containing Carboxymethylcellulose and Hyaluronic Acid for Dry Eye Disease: A Randomized, Controlled, Multicenter 3-Month Study(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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ItemAcquired Visual Deficits Independent of Lesion Site in Acute Stroke(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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ItemRetinal Functional and Structural Changes in the 5xFAD Mouse Model of Alzheimer's Disease(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.