Optometry and Vision Sciences - Research Publications

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    Oscillopsia and the Influence of Stress and Motivation in Fusion Maldevelopment Nystagmus Syndrome
    Cham, KM ; Anderson, AJ ; Abel, LA (ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2013-03-01)
    PURPOSE: We examined factors influencing perceptual stability in observers with fusion maldevelopment nystagmus syndrome (FMNS). In addition, we also investigated the effect of visual demand, task-related physiologic stress, and motivation on the nystagmus waveform. METHODS: Perception of oscillopsia during daily activities was assessed via a questionnaire. Perception of oscillopsia in the laboratory was assessed using central and peripheral (10°) light emitting diodes (LEDs) in front of a background display of random, fixed-contrast shapes. Task-induced stress was achieved via a time restricted acuity task with or without concurrent mental arithmetic challenge, and motivation varied using a reward-penalty paradigm. The experiments have been previously described elsewhere. RESULTS: Six out of nine subjects reported experiencing oscillopsia in certain daily activities. in the laboratory, the percentages of trials with perceptions of motion of the led and background were as follows: neither, 60% to 70%; background only, 20% to 30%; both, 5% to 15%, and LED only, 5% to 15%. Over all trials, six of nine experienced oscillopsia for both the low- and high-contrast image respectively (i.e., three subjects never experienced oscillopsia). The background was frequently seen moving for both images regardless of contrast and/or condition. Trials with and without oscillopsia did not differ when comparing foveation. In the second experiment, task-related physiologic stress and motivation were reflected in an increase in heart rate; nystagmus waveform intensity increased and foveation decreased. The magnitude of changes in heart rate was uncorrelated with changes in waveform parameters for all experiments, however. CONCLUSIONS: Preliminary results suggest that the FMNS group does perceive spatially inhomogeneous oscillopsia, similar to infantile nystagmus syndrome (INS), in certain visual environments. In investigating the effect of stress and motivation on FMNS, a new, if tentative, finding suggests that task-induced stress and/or motivation may have a negative impact on the nystagmus. Taken together, our findings provide an insight into the particular environments and tasks that are likely to present particular challenges to persons with FMNS.
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    Hypertensive retinopathy: comparing the Keith-Wagener-Barker to a simplified classification
    Downie, LE ; Hodgson, LAB ; D'Sylva, C ; McIntosh, RL ; Rogers, SL ; Connell, P ; Wong, TY (LIPPINCOTT WILLIAMS & WILKINS, 2013-05-01)
    PURPOSE: This study assessed the interobserver and intraobserver grading reliability of the Keith-Wagener-Barker (KWB) system to the proposed Mitchell-Wong 'simplified' three-grade classification for hypertensive retinopathy. METHODS: Digital retinal images of normal and hypertensive human fundii (n = 50 per group) were randomly graded by an optometrist and an ophthalmologist using the two systems. Interobserver agreement was compared to a 'gold standard' research grader. Intraobserver agreement was assessed through a repeat grading after 6 months. Cohen's kappa coefficients were used to assess the degree of agreement. RESULTS: Both clinicians demonstrated a good level of agreement with the KWB and simplified classification compared with a 'gold standard' grader; there was no significant difference in the level of agreement for either of the two classification methods for either observer. The simplified classification was found to be equally as efficacious as the KWB system with respect to interobserver and intraobserver agreement for both practitioners. CONCLUSION: These findings indicate that the simplified classification of hypertensive retinopathy is both reliable and repeatable. The advantage of the simplified method over the KWB system in correlating retinal microvascular signs to incident cardiovascular risk supports its adoption in clinical practice.
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    How Useful Is Population Data for Informing Visual Field Progression Rate Estimation?
    Anderson, AJ ; Johnson, CA (ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2013-03-01)
    PURPOSE: Bayesian estimators allow the frequency of visual field progression rates in the population (the prior distribution) to constrain rate estimates for individuals. We examined the benefits of a prior distribution accounting for one of progression's major risk factors--whether intraocular pressure is treated--to gauge the maximum benefit expected from developing priors for other glaucoma risk factors. METHODS: Our prior distribution was derived from published data from either treated (matched-prior condition) or untreated (unmatched-prior condition) glaucoma patients. We simulated MD values (6-monthly) with true underlying progression rates drawn from the same distribution as the prior for the matched-prior condition. We estimated rates through linear regression, and determined the likelihood of obtaining this estimate as a function of a range of true underlying progression rates (the likelihood function). The maximum likelihood estimate of rate was the most likely value of the posterior distribution (the product of the prior distribution and likelihood function). RESULTS: For short (4) visual field series, the matched-prior condition, unmatched-prior condition, and linear regression gave median errors (estimated minus true rate) of 0.02, 0.20, and 0.00 dB/y, respectively. Positive predictive values for determining rapidly progressing (<-1 dB/y) rates were 0.46, 0.42, and 0.38, with negative predictive values of 0.93, 0.94, and 0.95. For more extended series the magnitude of the differences between techniques decreased, although the order was unchanged. CONCLUSIONS: Performance shifts in bayesian estimators of visual field progression are modest even when prior distributions do not reflect large risk factors, such as IOP treatment.
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    Susceptibility of Streptozotocin-Induced Diabetic Rat Retinal Function and Ocular Blood Flow to Acute Intraocular Pressure Challenge
    Wong, VHY ; Vingrys, AJ ; Jobling, AI ; Bui, BV (ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2013-03-01)
    PURPOSE: To consider the hypothesis that streptozotocin (STZ)-induced hyperglycemia renders rat retinal function and ocular blood flow more susceptible to acute IOP challenge. METHODS: Retinal function (electroretinogram [ERG]) was measured during acute IOP challenge (10100 mm Hg, increments of 5 mm Hg, 3 minutes per step, vitreal cannulation) in adult Long-Evans rats (6 weeks old; citrate: n = 6, STZ: n = 10) 4 weeks after citrate buffer or STZ (65 mg/kg, blood glucose >15 mM) injection. At each IOP, dim and bright flash (-4.56, -1.72 log cd x s x m(-2)) ERG responses were recorded to measure inner retinal and ON-bipolar cell function, respectively. Ocular blood flow (laser Doppler flowmetry; citrate: n = 6, STZ: n = 10) was also measured during acute IOP challenge. Retinas were isolated for quantitative PCR analysis of nitric oxide synthase mRNA expression (endothelial, eNos; inducible, iNos; neuronal, nNos). RESULTS: STZ-induced diabetes increased the susceptibility of inner retinal (IOP at 50% response, 60.1, CI: 57.0-62.0 mm Hg versus citrate: 67.5, CI: 62.1-72.4 mm Hg) and ON-bipolar cell function (STZ: 60.3, CI: 58.0-62.8 mm Hg versus citrate: 65.1, CI: 61.9-68.6 mm Hg) and ocular blood flow (43.9, CI: 40.8-46.8 versus citrate: 53.4, CI: 50.7-56.1 mm Hg) to IOP challenge. Citrate eyes showed elevated eNos mRNA (+49.7%) after IOP stress, an effect not found in STZ-diabetic eyes (-5.7%, P < 0.03). No difference was observed for iNos or nNos (P > 0.05) following IOP elevation. CONCLUSIONS: STZ-induced diabetes increased functional susceptibility during acute IOP challenge. This functional vulnerability is associated with a reduced capacity for diabetic eyes to upregulate eNos expression and to autoregulate blood flow in response to stress.
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    Increased Susceptibility to Injury in Older Eyes
    Charng, J ; Nguyen, CTO ; Vingrys, AJ ; Jobling, AI ; Bui, BV (LIPPINCOTT WILLIAMS & WILKINS, 2013-03-01)
    PURPOSE: To determine whether there is an age-dependent susceptibility in retinal function in response to repeated anterior chamber cannulation with or without intraocular pressure (IOP) elevation. METHODS: Baseline electroretinograms were measured in 3- and 18-month-old Sprague-Dawley rats (n = 16 each group). Following baseline assessment, eyes were randomly assigned to undergo a 60-min anterior chamber cannulation with IOP either left at baseline (sham, 15 mm Hg) or elevated to 60 mm Hg. This was repeated three additional times, with each episode separated by 1 week. At weeks 1 to 3, dark-adapted retinal function was assessed immediately before cannulation, with final functional assessment at week 4. RESULTS: Both sham and IOP elevated eyes of older rats showed retinal dysfunction, which became more pronounced with the number of repeated insults. This effect was largest for responses arising from the inner retina. Repeated insult in younger eyes did not produce a change in amplitude but an increase in the sensitivity to light of photoreceptoral and bipolar cell components of the electroretinogram. CONCLUSIONS: Repeated trauma, not IOP, produces permanent retinal dysfunction in older eyes. Younger eyes appear to be able to withstand this type of injury by upregulating sensitivity of outer and middle retinal responses to maintain normal inner retinal function.
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    Glial and neuronal dysfunction in streptozotocin-induced diabetic rats.
    Wong, VHY ; Vingrys, AJ ; Bui, BV (Springer Science and Business Media LLC, 2011-06)
    Neuronal dysfunction has been noted very soon after the induction of diabetes by streptozotocin injection in rats. It is not clear from anatomical evidence whether glial cell dysfunction accompanies the well-documented neuronal deficit. Here, we isolate the Müller cell driven slow-P3 component of the full-field electroretinogram and show that it is attenuated at 4 weeks following the onset of streptozotocin-hyperglycaemia. We also found a concurrent reduction in the sensitivity of the phototransduction cascade, as well as in the components of the electroretinogram known to indicate retinal ganglion cell and amacrine cell integrity. Our data support the idea that neuronal and Müller cell dysfunction occurs at the same time in streptozotocin-induced hyperglycaemia.
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    Short-Term Stability in Refractive Status Despite Large Fluctuations in Glucose Levels in Diabetes Mellitus Type 1 and 2
    Huntjens, B ; Charman, WN ; Workman, H ; Hosking, SL ; O'Donnell, C ; Bui, BV (PUBLIC LIBRARY SCIENCE, 2012-12-28)
    PURPOSE: This work investigates how short-term changes in blood glucose concentration affect the refractive components of the diabetic eye in patients with long-term Type 1 and Type 2 diabetes. METHODS: Blood glucose concentration, refractive error components (mean spherical equivalent MSE, J0, J45), central corneal thickness (CCT), anterior chamber depth (ACD), crystalline lens thickness (LT), axial length (AL) and ocular aberrations were monitored at two-hourly intervals over a 12-hour period in: 20 T1DM patients (mean age ± SD) 38±14 years, baseline HbA1c 8.6±1.9%; 21 T2DM patients (mean age ± SD) 56±11 years, HbA1c 7.5±1.8%; and in 20 control subjects (mean age ± SD) 49±23 years, HbA1c 5.5±0.5%. The refractive and biometric results were compared with the corresponding changes in blood glucose concentration. RESULTS: Blood glucose concentration at different times was found to vary significantly within (p<0.0005) and between groups (p<0.0005). However, the refractive error components and ocular aberrations were not found to alter significantly over the day in either the diabetic patients or the control subjects (p>0.05). Minor changes of marginal statistical or optical significance were observed in some biometric parameters. Similarly there were some marginally significant differences between the baseline biometric parameters of well-controlled and poorly-controlled diabetic subjects. CONCLUSION: This work suggests that normal, short-term fluctuations (of up to about 6 mM/l on a timescale of a few hours) in the blood glucose levels of diabetics are not usually associated with acute changes in refractive error or ocular wavefront aberrations. It is therefore possible that factors other than refractive error fluctuations are sometimes responsible for the transient visual problems often reported by diabetic patients.
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    Is primary open angle glaucoma part of a generalised sensory neurodegeneration? A review of the evidence
    O'HARE, FLEUR ; RANCE, GARY ; MCKENDRICK, ALLISON ; CROWSTON, JONATHAN ( 2012)
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    Intrinsic physiological properties of rat retinal ganglion cells with a comparative analysis
    Wong, RCS ; Cloherty, SL ; Ibbotson, MR ; O'Brien, BJ (AMER PHYSIOLOGICAL SOC, 2012-10-01)
    Mammalian retina contains 15-20 different retinal ganglion cell (RGC) types, each of which is responsible for encoding different aspects of the visual scene. The encoding is defined by a combination of RGC synaptic inputs, the neurotransmitter systems used, and their intrinsic physiological properties. Each cell's intrinsic properties are defined by its morphology and membrane characteristics, including the complement and localization of the ion channels expressed. In this study, we examined the hypothesis that the intrinsic properties of individual RGC types are conserved among mammalian species. To do so, we measured the intrinsic properties of 16 morphologically defined rat RGC types and compared these data with cat RGC types. Our data demonstrate that in the rat different morphologically defined RGC types have distinct patterns of intrinsic properties. Variation in these properties across cell types was comparable to that found for cat RGC types. When presumed morphological homologs in rat and cat retina were compared directly, some RGC types had very similar properties. The rat A2 cell exhibited patterns of intrinsic properties nearly identical to the cat alpha cell. In contrast, rat D2 cells (ON-OFF directionally selective) had a very different pattern of intrinsic properties than the cat iota cell. Our data suggest that the intrinsic properties of RGCs with similar morphology and suspected visual function may be subject to variation due to the behavioral needs of the species.
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    Investigation of Ocular Hemodynamics in Sturge-Weber Syndrome
    Conway, M ; Hosking, SL (LIPPINCOTT WILLIAMS & WILKINS, 2012-06-01)
    PURPOSE: Sturge-Weber syndrome (SWS) is a condition often associated with facial cutaneous angioma, vascular malformations in the brain, and ocular anomalies such as glaucoma. Reduced cerebral blood flow and ischemia have been well documented. Less is known about ocular blood flow despite the frequent associations between altered hemodynamics and the mechanisms underlying glaucomatous optic neuropathy. The aim of this research was to investigate retrobulbar hemodynamics in patients diagnosed with SWS. METHODS: The sample comprised 16 patients diagnosed with SWS and 16 age- and gender-matched normal control subjects. Four patients were diagnosed with both SWS and primary open-angle glaucoma (mean age 34.3 years; SD 26.9 years), three patients with both SWS and closed-angle glaucoma (mean age 23.3 years; SD 18.0 years), and nine patients with SWS and no glaucoma (mean age 17.2 years; SD 9.1 years). Systemic blood pressure and intraocular pressure were measured to determine the mean arterial pressure and ocular perfusion pressure. All patients and subjects underwent ultrasonography of the ophthalmic artery, central retinal artery, and short posterior ciliary arteries. RESULTS: No significant difference between groups for mean arterial pressure or ocular perfusion pressure (p > 0.05) was recorded. Participants diagnosed with SWS and primary open-angle glaucoma showed significantly reduced end-diastolic velocity (mean 0.036 m/s; SD 0.005 m/s) in their central retinal artery (p = 0.016) when compared against their age-matched normal controls (mean 0.054 m/s; SD 0.010 m/s). Participants diagnosed with SWS and no glaucoma also showed significantly reduced end-diastolic velocity (mean 0.038 m/s; SD 0.015 m/s) in their central retinal artery (p = 0.046) when compared against their age-matched normal controls (mean 0.054 m/s; SD 0.014 m/s). CONCLUSIONS: Retrobulbar hemodynamics appear to be altered in participants diagnosed with SWS irrespective of their diagnosis of glaucoma. Further research is needed to ascertain whether there are any long-term consequences of such changes to ocular physiology.