Anatomy and Neuroscience - Research Publications

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    Equating spatial summation in visual field testing reveals greater loss in optic nerve disease
    Kalloniatis, M ; Khuu, SK (WILEY, 2016-07-01)
    PURPOSE: To test the hypothesis that visual field assessment in ocular disease measured with target stimuli within or close to complete spatial summation results in larger threshold elevation compared to when measured with the standard Goldmann III target size. The hypothesis predicts a greater loss will be identified in ocular disease. Additionally, we sought to develop a theoretical framework that would allow comparisons of thresholds with disease progression when using different Goldmann targets. METHODS: The Humphrey Field Analyser (HFA) 30-2 grid was used in 13 patients with early/established optic nerve disease using the current Goldmann III target size or a combination of the three smallest stimuli (target size I, II and III). We used data from control subjects at each of the visual field locations for the different target sizes to establish the number of failed points (events) for the patients with optic nerve disease, as well as global indices for mean deviation (MD) and pattern standard deviation (PSD). RESULTS: The 30-2 visual field testing using alternate target size stimuli showed that all 13 patients displayed more defects (events) compared to the standard Goldmann III target size. The median increase for events was seven additional failed points: (range 1-26). The global indices also increased when the new testing approach was used (MD -3.47 to -6.25 dB and PSD 4.32 to 6.63 dB). Spatial summation mapping showed an increase in critical area (Ac) in disease and overall increase in thresholds when smaller target stimuli were used. CONCLUSIONS: When compared to the current Goldmann III paradigm, the use of alternate sized targets within the 30-2 testing protocol revealed a greater loss in patients with optic nerve disease for both event analysis and global indices (MD and PSD). We therefore provide evidence in a clinical setting that target size is important in visual field testing.
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    Peripheral retinal findings in populations with macular disease are similar to healthy eyes
    Nivison-Smith, L ; Milston, R ; Chiang, J ; Ly, A ; Assaad, N ; Kalloniatis, M (WILEY, 2018-11-01)
    PURPOSE: Recent evidence suggests several macular diseases are associated with peripheral retinal changes. This study investigated the number, type and management consequences of peripheral retinal findings detected in patients attending a referral only, eye-care clinic, the Centre for Eye Health(CFEH) with macular disease. METHODS: Records of 537 patients attending CFEH for a macular assessment were included in the study. Subjects were classified as having age-related macular degeneration (AMD), epiretinal membrane (ERM), central serous chorioretinopathy (CSCR), inherited macular dystrophy or no macular disease. Data extracted included reason for referral, macular findings, peripheral findings (based on examination by ultra-widefield scanning laser ophthalmoscopy), diagnosis and management. RESULTS: After age-matching, the number of peripheral findings in subjects with AMD, ERM or CSCR was not significant different to normal subjects. The most common finding for all cohorts were non-specific, degenerative changes such as drusen or pigmentation (61-72%) except inherited macular dystrophy subjects who had mostly vascular findings (30%; p < 0.05). Subjects with AMD and ERM with peripheral findings were significantly more likely to be reviewed or referred to an ophthalmologist than discharged back to their community eye care provider compared to subjects without findings. However only 8% of subjects had altered management based specifically on peripheral findings suggesting the macular findings in most subjects dictated their management. For those with a change, it was significant (upgrade to referral to an ophthalmologist). Peripheral findings also flagged 5% of subjects with vascular findings for referral to their general practitioner (GP). CONCLUSIONS: Overall, the percentage and distribution of peripheral retinal findings in some macular diseases was similar to normal subjects. However, subjects with peripheral findings appeared to have significant differences in management. Considering some common findings, such as peripheral drusen may be relevant to AMD pathogenesis and therefore affect management of this disease, assessment of the peripheral retina should not be overlooked when the clinical focus is on the posterior pole.
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    Neutralizing Peripheral Refraction Eliminates Refractive Scotomata in Tilted Disc Syndrome
    Phu, J ; Wang, H ; Miao, S ; Zhou, L ; Khuu, SK ; Kalloniatis, M (LIPPINCOTT WILLIAMS & WILKINS, 2018-10-01)
    SIGNIFICANCE: We demonstrate that the visual field defects in patients with tilted disc syndrome can be reduced or eliminated by neutralizing the peripheral scotoma in the area of posterior retinal bowing, which may allow differentiation between a congenital anomaly and acquired pathology. PURPOSE: Tilted disc syndrome is a congenital and unchanging condition that may present with visual field defects mimicking loss seen in neurological diseases, such as transsynaptic retrograde degeneration. Our purpose was to systematically investigate the ability of a neutralized peripheral refraction to eliminate refractive visual field defects seen in tilted disc syndrome. This was compared with the same technique performed on patients with neurological deficits. METHODS: The Humphrey Field Analyzer was used to measure sensitivities across the 30-2 test grid in 14 patients with tilted disc syndrome using four refractive corrections: habitual near correction and with an additional -1.00, -2.00 or -3.00 D negative lens added as correction lenses. Peripheral refractive errors along the horizontal meridian were determined using peripheral retinoscopy and thus allowed calculation of residual peripheral refraction with different levels of refractive correction. Visual field defects were assessed qualitatively and quantitatively using sensitivities and probability scores in both patient groups. RESULTS: A smaller residual refractive error after the application of negative addition lenses correlated with improvement in visual field defects in terms of sensitivity and probability scores in patients with tilted disc syndrome. Patients with established neurological deficits (retrograde degeneration) showed improvement in sensitivities but not in probability scores. CONCLUSIONS: Neutralizing the refractive error at the region of posterior retinal bowing due to tilted disc syndrome reduces the apparent visual field defect. This may be a useful and rapid test to help differentiate between tilted disc syndrome and other pathological causes of visual field defects such as neurological deficits.
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    Advanced imaging for the diagnosis of age-related macular degeneration: a case vignettes study
    Ly, A ; Nivison-Smith, L ; Zangerl, B ; Assaad, N ; Kalloniatis, M (TAYLOR & FRANCIS LTD, 2018-03-01)
    BACKGROUND: The aim of this study is to evaluate the diagnosis, staging, imaging and management preferences, and the effect of advanced imaging among practising optometrists in age-related macular degeneration (AMD). METHODS: Up to 20 case vignettes (computer-based case simulations) were completed online in a computer laboratory in random order by 81 practising optometrists of Australia. Each case presented findings from a randomly selected patient seen previously at the Centre for Eye Health for a macular assessment in the following order: case history, preliminary tests and colour fundus photography. Participants were prompted to provide their diagnosis, management and imaging preference. One additional imaging result (either modified fundus photographs and infrared images, fundus autofluorescence, or optical coherence tomography [OCT]) was then provided and the questions repeated. Finally, all imaging results were provided and the questions repeated a third time. RESULTS: A total of 1,436 responses were analysed. The presence of macular pathology in AMD was accurately detected in 94 per cent of instances. The overall diagnostic accuracy of AMD was 61 per cent using colour fundus photography. This improved by one per cent using one additional imaging modality and a further four per cent using all imaging. Across all responses, a greater improvement in the diagnostic accuracy of AMD occurred following the presentation of OCT findings (versus other modalities). OCT was the most preferred imaging modality for AMD, while multimodal imaging was of greatest benefit in cases more often misdiagnosed using colour fundus photography alone. Overall, the cohort also displayed a tendency to underestimate disease severity. CONCLUSION: Despite reports that imaging technologies improve the stratification of AMD, our findings suggest that this effect may be small when applied among practising optometrists without additional or specific training.
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    The advantages of intermediate-tier, inter-optometric referral of low risk pigmented lesions
    Ly, A ; Nivison-Smith, L ; Hennessy, M ; Kalloniatis, M (WILEY, 2017-11-01)
    PURPOSE: Pigmented ocular lesions are commonly encountered by eye-care professionals, and range from benign to sight or life-threatening. After identifying a lesion, the primary care professional must establish the likely diagnosis and decide either to reassure, to monitor or to refer. The increasing use of ocular imaging technologies has contributed to an increase in the detection rate of pigmented lesions and a higher number of referrals, which may challenge existing pathways of health-care delivery. Specialist services may be over-burdened by referring all patients with pigmented lesions for an opinion, while inter-optometric referrals are underutilised. The aim of this study was to describe the referral patterns of pigmented lesions to an optometry led intermediate-tier collaborative care clinic. METHODS: We performed a retrospective review of patient records using the list of patients examined at Centre for Eye Health (CFEH) for an initial or follow up pigmented lesion assessment between the 1/7/2013 and the 30/6/2016. Analysis was performed on: patient demographic characteristics, the referrer's tentative diagnosis, CFEH diagnosis and recommended management plan. RESULTS: Across 182 patient records, the primary lesion prompting referral was usually located in the posterior segment: choroidal naevus (105/182, 58%), congenital hypertrophy of the retinal pigment epithelium (CHRPE; 11/182, 6%), chorioretinal scarring (10/182, 5%) or not specified (52/182, 29%). Referrals described a specific request for ocular imaging in 25 instances (14%). The number of cases with a non-specific diagnosis was reduced after intermediate-tier care assessment (from 29% to 10%), while the number of diagnoses with less common conditions rose (from 2% to 21%). There was a 2% false positive referral rate to intermediate-tier care and a first visit discharge rate of 35%. A minority required on-referral to an ophthalmologist (22/182, 12%), either for unrelated incidental ocular findings, or suspicious choroidal naevi. Conditions most amenable to optometric follow up included: 1) chorioretinal scarring, 2) choroidal naevus, and 3) CHRPE. CONCLUSIONS: Intermediate-tier optometric eye-care in pigmented lesions (following opportunistic primary care screening) has the potential to reduce the number of cases with non-specific diagnoses and to increase those with less common diagnoses. The majority of cases seen under this intermediate-tier model required only ongoing optometric surveillance.
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    Pattern Recognition Analysis of Age-Related Retinal Ganglion Cell Signatures in the Human Eye
    Yoshioka, N ; Zangerl, B ; Nivison-Smith, L ; Khuu, SK ; Jones, BW ; Pfeiffer, RL ; Marc, RE ; Kalloniatis, M (ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2017-07-01)
    PURPOSE: To characterize macular ganglion cell layer (GCL) changes with age and provide a framework to assess changes in ocular disease. This study used data clustering to analyze macular GCL patterns from optical coherence tomography (OCT) in a large cohort of subjects without ocular disease. METHODS: Single eyes of 201 patients evaluated at the Centre for Eye Health (Sydney, Australia) were retrospectively enrolled (age range, 20-85); 8 × 8 grid locations obtained from Spectralis OCT macular scans were analyzed with unsupervised classification into statistically separable classes sharing common GCL thickness and change with age. The resulting classes and gridwise data were fitted with linear and segmented linear regression curves. Additionally, normalized data were analyzed to determine regression as a percentage. Accuracy of each model was examined through comparison of predicted 50-year-old equivalent macular GCL thickness for the entire cohort to a true 50-year-old reference cohort. RESULTS: Pattern recognition clustered GCL thickness across the macula into five to eight spatially concentric classes. F-test demonstrated segmented linear regression to be the most appropriate model for macular GCL change. The pattern recognition-derived and normalized model revealed less difference between the predicted macular GCL thickness and the reference cohort (average ± SD 0.19 ± 0.92 and -0.30 ± 0.61 μm) than a gridwise model (average ± SD 0.62 ± 1.43 μm). CONCLUSIONS: Pattern recognition successfully identified statistically separable macular areas that undergo a segmented linear reduction with age. This regression model better predicted macular GCL thickness. The various unique spatial patterns revealed by pattern recognition combined with core GCL thickness data provide a framework to analyze GCL loss in ocular disease.
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    Determining Spatial Summation and Its Effect on Contrast Sensitivity across the Central 20 Degrees of Visual Field
    Choi, AYJ ; Nivison-Smith, L ; Khuu, SK ; Kalloniatis, M ; Barnes, S (PUBLIC LIBRARY SCIENCE, 2016-07-06)
    PURPOSE: Recent studies propose that the use of target stimuli within or close to complete spatial summation reveal larger threshold elevation in ocular disease. The Humphrey Visual Field Analyzer (HFA) is used to assess visual function yet the spatial summation characteristics are unexplored for the central macular region. We therefore wanted to establish the relationship between contrast sensitivity and stimulus size (spatial summation) within the central 20° visual field using the high sampling density of the 10-2 test grid. METHODS: Thresholds were measured for one eye from 37 normal subjects using the HFA 10-2 test grid with all five Goldmann (G) targets (GI to GV). Subject data were converted to 50-year-old equivalent using published and calculated location-specific decade correction factors. Spatial summation curves were fitted for all data at all locations. The size of Ricco's critical area (Ac) within which complete spatial summation operates (k = 1), and the slope of partial summation (k < 1: to characterize partial summation), was established. RESULTS: The 50-year-old age normative data were determined for all Goldmann stimulus sizes for the 10-2 HFA test grid and showed a marked change in contrast sensitivity for small test stimuli (e.g. GI) and little change in larger test stimuli (e.g. GV). Both the Ac and k values did not vary with age allowing for the application of the age correction factors. Ac and k values increased with eccentricity with GI remaining within complete spatial summation and GII was close or within complete spatial summation. GIII or larger test sizes were always outside complete spatial summation operating within various levels of partial summation. CONCLUSIONS: The developed normative data now allows comparisons of data sets with high sampling density using the 10-2 grid irrespective of subject age. Test size is important when assessing ocular disease yet only GI or GII stimuli operate close to or within complete spatial summation in the macula. Current visual field testing protocols employ GIII which is always outside complete spatial summation and operates under various values of partial summation: GIII may not be the most suitable test size to assess ocular disease affecting the macula.
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    Collaborative care of non-urgent macular disease: a study of inter-optometric referrals
    Ly, A ; Nivison-Smith, L ; Hennessy, MP ; Kalloniatis, M (WILEY, 2016-11-01)
    PURPOSE: Diseases involving the macula and posterior pole are leading causes of visual impairment and blindness worldwide and may require prompt ophthalmological care. However, access to eye-care and timely patient management may be limited due to inefficient and inappropriate referrals between primary eye-care providers and ophthalmology. Optometrists with a special interest in macular disease may be useful as a community aid to better stratify and recommend best-practice management plans for suitable patients. This study assesses such a notion by appraising the optometric referral patterns of patients with suspected macular disease to an intermediate-tier optometric imaging clinic. METHODS: We performed a retrospective review of patient records and referrals using patients examined at Centre for Eye Health (CFEH) for an initial or follow up macular assessment between the 1/7/2013 and 30/6/2014 (n = 291). The following data were analysed: patient demographic characteristics, primary reason for referral, diagnosed/suspected condition, CFEH diagnosis and recommended management plan. RESULTS: The number of referrals stipulating a diagnosis, confirmed after evaluation at CFEH was 121 of 291 (42%). After evaluation at CFEH, the number of cases without a specific diagnosis was approximately halved (reduced from 47% to 23%), while the number of cases with no apparent defect or normal aging changes rose from 1% to 15%. Overall diagnostic congruency for specified macular conditions was high (58-94%); cases were seldom (30/291, 10%) found to have a completely different macular condition. 244 of 291 (84%) patients seen at CFEH were recommended ongoing optometric care: either with the referring optometrist or through recall to CFEH. Referral to an ophthalmologist was recommended in 47 instances (16%). CONCLUSIONS: More widespread adoption of intermediate-tier optometric eye-care referral pathways in macular disease (following opportunistic primary care screening) has the potential to reduce the number of cases with non-specific diagnoses and to increase those with a diagnosis of normal aging changes or no apparent disease. The majority of cases seen under this intermediate-tier model required ongoing optometric care only and did not require face-to-face consultation with an ophthalmologist.
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    The Effect of Attentional Cueing and Spatial Uncertainty in Visual Field Testing
    Phu, J ; Kalloniatis, M ; Khuu, SK ; Thompson, B (PUBLIC LIBRARY SCIENCE, 2016-03-03)
    PURPOSE: To determine the effect of reducing spatial uncertainty by attentional cueing on contrast sensitivity at a range of spatial locations and with different stimulus sizes. METHODS: Six observers underwent perimetric testing with the Humphrey Visual Field Analyzer (HFA) full threshold paradigm, and the output thresholds were compared to conditions where stimulus location was verbally cued to the observer. We varied the number of points cued, the eccentric and spatial location, and stimulus size (Goldmann size I, III and V). Subsequently, four observers underwent laboratory-based psychophysical testing on a custom computer program using Method of Constant Stimuli to determine the frequency-of-seeing (FOS) curves with similar variables. RESULTS: We found that attentional cueing increased contrast sensitivity when measured using the HFA. We report a difference of approximately 2 dB with size I at peripheral and mid-peripheral testing locations. For size III, cueing had a greater effect for points presented in the periphery than in the mid-periphery. There was an exponential decay of the effect of cueing with increasing number of elements cued. Cueing a size V stimulus led to no change. FOS curves generated from laboratory-based psychophysical testing confirmed an increase in contrast detection sensitivity under the same conditions. We found that the FOS curve steepened when spatial uncertainty was reduced. CONCLUSION: We show that attentional cueing increases contrast sensitivity when using a size I or size III test stimulus on the HFA when up to 8 points are cued but not when a size V stimulus is cued. We show that this cueing also alters the slope of the FOS curve. This suggests that at least 8 points should be used to minimise potential attentional factors that may affect measurement of contrast sensitivity in the visual field.
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    Retinal Amino Acid Neurochemistry of the Southern Hemisphere Lamprey, Geotria australis
    Nivison-Smith, L ; Collin, SP ; Zhu, Y ; Ready, S ; Acosta, ML ; Hunt, DM ; Potter, IC ; Kalloniatis, M ; Barnes, S (PUBLIC LIBRARY SCIENCE, 2013-03-13)
    Lampreys are one of the two surviving groups of the agnathan (jawless) stages in vertebrate evolution and are thus ideal candidates for elucidating the evolution of visual systems. This study investigated the retinal amino acid neurochemistry of the southern hemisphere lamprey Geotria australis during the downstream migration of the young, recently-metamorphosed juveniles to the sea and during the upstream migration of the fully-grown and sexually-maturing adults to their spawning areas. Glutamate and taurine were distributed throughout the retina, whilst GABA and glycine were confined to neurons of the inner retina matching patterns seen in most other vertebrates. Glutamine and aspartate immunoreactivity was closely matched to Müller cell morphology. Between the migratory phases, few differences were observed in the distribution of major neurotransmitters i.e. glutamate, GABA and glycine, but changes in amino acids associated with retinal metabolism i.e. glutamine and aspartate, were evident. Taurine immunoreactivity was mostly conserved between migrant stages, consistent with its role in primary cell functions such as osmoregulation. Further investigation of glutamate signalling using the probe agmatine (AGB) to map cation channel permeability revealed entry of AGB into photoreceptors and horizontal cells followed by accumulation in inner retinal neurons. Similarities in AGB profiles between upstream and downstream migrant of G. australis confirmed the conservation of glutamate neurotransmission. Finally, calcium binding proteins, calbindin and calretinin were localized to the inner retina whilst recoverin was localized to photoreceptors. Overall, conservation of major amino acid neurotransmitters and calcium-associated proteins in the lamprey retina confirms these elements as essential features of the vertebrate visual system. On the other hand, metabolic elements of the retina such as neurotransmitter precursor amino acids and Müller cells are more sensitive to environmental changes associated with migration.