ORCID Profile
0000-0002-5264-4639
Current Organisation
Deakin University
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Publisher: Elsevier BV
Date: 12-2019
DOI: 10.1016/J.AJO.2019.08.013
Abstract: To compare the visual fields results obtained using the Swedish interactive thresholding algorithm-Standard (SS) and the Swedish interactive thresholding algorithm-Faster (SFR) in normal subjects, glaucoma suspects, and patients with glaucoma and to quantify potential time-saving benefits of the SFR algorithm. Prospective, cross-sectional study. One randomly selected eye from 364 patients (77 normal subjects, 178 glaucoma suspects, and 109 patients with glaucoma) seen in a single institution underwent testing using both SS and SFR on the Humphrey Field Analyzer. Cumulative test time using each algorithm was compared after accounting for different rates of test reliability. Pointwise and cluster analysis was performed to determine whether there were systematic differences between algorithms. Using SFR had a greater rate of unreliable results (29.3%) compared with SS (7.7%, P < .0001). This was mainly because of high false positive rates and seeding point errors. However, modeled test times showed that using SFR could obtain a greater number of reliable results within a shorter period of time. SFR resulted in higher sensitivity values (on average 0.5 dB for patients with glaucoma) that was greater under conditions of field loss (<19 dB). Cluster analysis showed no systematic patterns of sensitivity differences between algorithms. After accounting for different rates of test reliability, SFR can result in significant time savings compared with SS. Clinicians should be cognizant of false positive rates and seeding point errors as common sources of error for SFR. Results between algorithms are not directly interchangeable, especially if there is a visual field deficit <19 dB.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2021
DOI: 10.1097/OPX.0000000000001751
Abstract: Assessment of treatment efficacy via comparison with a target IOP is fundamental in monitoring patients with open-angle glaucoma and ocular hypertension. This article highlights that diurnal IOP fluctuations obtained using self-tonometry may more accurately reflect IOP responses to therapy. This study aimed to investigate fluctuations in diurnal IOP measurements in patients with open-angle glaucoma and ocular hypertension treated with latanoprost 0.005% and timolol 0.25%. In this crossover treatment trial, 14 participants performed self-tonometry with iCare HOME 4 times daily for (1) 1 week using latanoprost, (2) 4 weeks using no medications, and (3) 2 weeks using timolol. Daily peak IOPs, IOP fluctuations, and mean IOPs from different treatments were compared on an in idual basis. Treatment efficacy between medications was assessed by comparing mean percentage IOP reductions with latanoprost and timolol across participants. In addition, effects of age, years since commencing latanoprost, sex, and diagnosis were investigated, and peak IOP times were compared with assess impacts on diurnal profiles. Between in iduals, IOP responses ranged from reductions in peak IOPs, IOP fluctuations, and mean IOPs on both medications to no change in any parameter and medication. IOP fluctuations showed greater mean percentage reductions than did peak and mean IOPs (χ 2 = 16.51, P = .002). There were significant associations between years since commencing latanoprost and peak and mean IOP responses on timolol ( r = 0.69, P = .007), and sex and relative reductions in IOP fluctuations on both medications ( P = .03). There were no differences in peak IOP times between treatment conditions. Despite variability in IOP responses to latanoprost and timolol, IOP fluctuation with self-tonometry was more consistent in evaluating target IOP, reflecting its importance in ascertaining true IOP response to topical therapies. These findings may impact clinical decision making based on target IOP criteria in patients on topical therapy.
Publisher: Elsevier BV
Date: 2020
DOI: 10.1016/J.AJO.2019.08.014
Abstract: To apply computational methods to model normal age-related changes in corneal parameters and to establish their association with demographic factors, thereby providing a framework for improved detection of subclinical corneal ectasia (SCE). Cross-sectional study. One hundred seventeen healthy participants were enrolled from Centre for Eye Health (Sydney, Australia). Corneal thickness (CT), front surface sagittal curvature (FSSC), and back surface sagittal curvature (BSSC) measurements were extracted from 57 corneal locations from 1 eye per participant using the Pentacam HR. Cluster analyses were performed to identify locations demonstrating similar variations with age. Age-related changes were modeled using polynomial regression with sliding window methods, and model accuracy was verified with Bland-Altman comparisons. Pearson correlations were applied to examine the impacts of demographic factors. Concentric cluster patterns were observed for CT and FSSC but not for BSSC. Sliding window analyses were best fit with quartic and cubic regression models for CT and FSSC/BSSC, respectively. CT and FSSC sliding window models had narrower 95% limits of agreement compared with decade-based models (0.015 mm vs 0.017 mm and 0.14 mm vs 0.27 mm, respectively), but were wider for BSSC than decade-based models (0.73 mm vs 0.54 mm). Significant correlations were observed between CT and astigmatism (P = .02-.049) and FSSC and BSSC and gender (P = <.001-.049). The developed models robustly described aging variations in CT and FSSC however, other mechanisms appear to contribute to variations in BSSC. These findings and the identified correlations provide a framework that can be applied to future model development and establishment of normal databases to facilitate SCE detection.
Publisher: Wiley
Date: 10-07-2007
DOI: 10.1111/J.1471-4159.2007.04766.X
Abstract: Light exposure induces retinal photoreceptor degeneration and retinal remodeling in both the normal rat retina and in animal models of retinal degeneration. Although cation entry is one of the triggers leading to apoptosis, it is unclear if this event occurs in isolation, or whether a number of pathways lead to photoreceptor apoptosis following light exposure. Following light exposure, we investigated the characteristics of cation entry, apoptotic markers [using terminal deoxynucleotidyl transferase (EC 2.7.7.31) dUTP nick-end labeling (TUNEL) labeling] and metabolic properties of retina from Sprague-Dawley (SD) rats and a rat model of retinitis pigmentosa [proline-23-histidine (P23H) rat]. Assessment of cation channel permeability using agmatine (AGB) labeling showed that excessive cation gating accompanied the series of anomalies that occur prior to photoreceptor loss. Increased AGB labeling in photoreceptors was seen in parallel with the appearance of apoptotic photoreceptors detected by TUNEL labeling with only a smaller proportion of cells colocalizing both markers. However, SD and P23H retinal photoreceptors differed in the amounts and colocalization of AGB gating and TUNEL labeling as a function of light exposure. Finally, reduced retinal lactate dehydrogenase levels were found in SD and P23H rat retinas after a 24-h light exposure period. Short-term (2 h) exposure of the P23H rat retina caused an increase in lactate dehydrogenase activity suggesting increased metabolic demand. These results suggest that energy availability may be exacerbated during the early stages of light exposure in susceptible retinas. Also, the concomitant observation of increased ion gating and TUNEL labeling suggest the existence of at least two possible mechanisms in light-damaged retinas in both SD and the P23H rat retina.
Publisher: Informa UK Limited
Date: 2009
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 1990
DOI: 10.1097/00006324-199001000-00009
Abstract: A retrospective survey of pediatric clinical files from the Kooyong Low Vision Clinic (LVC) showed that the major causes of low vision were congenital or inherited conditions and most children had 6/60 (20/200) or better distance acuities. A classroom evaluation of these children showed that overall, the clinically determined visual acuity corresponded with classroom performance. A high rate of use of prescribed low vision aids was found, and a reading evaluation on a standardized test showed poor performance with respect to reading speed and comprehension, but almost all the children had adequate reading accuracy. Considering the importance of reading in education, greater emphasis on reading evaluations in routine low vision examinations is recommended.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 10-2018
DOI: 10.1167/TVST.7.5.22
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 09-03-2020
DOI: 10.1167/IOVS.61.3.2
Publisher: Wiley
Date: 07-08-2014
DOI: 10.1111/OPO.12146
Abstract: Guidelines for the screening, prognosis, diagnosis, management and prevention of glaucoma were released by the Australian National Health and Medical Research Council in 2010. Comparable guidance has been made available by respective bodies in the USA and UK at a similar time. Key to successful translation of guidelines into clinical practice includes clinicians having the necessary skills to perform required tests. Optometrists in Australia and New Zealand were invited to participate in an online survey exploring these aspects. The results provide insights for improving glaucoma diagnosis and management by optometric primary eye care practitioners. An online questionnaire was developed to investigate glaucoma assessment of optometrists as a function of demographic details, educational background and experience. Key points to ascertain compliance with current guidelines were the availability of equipment, procedural confidence in techniques, and preferences in visual field tests. Chi square statistics was employed to support similarity to national averages and highlight differences between the two countries. Multivariate linear regression analysis identified variables significantly associated with in idual tests being available to optometrists and their confidence in applying them. Thirteen per cent of all Australian and 36% of the New Zealand optometrists responded to the survey in 2013, which reflected the demographics/geography of the practising populations. Techniques considered essential or preferred for glaucoma assessment were widely available in both countries with the exception of gonioscopy and pachymetry. After correcting for availability, regression models highlighted therapeutic endorsement and knowledge of glaucoma guidelines as the main variables to maintain high diagnostic confidence. Correlations to number of years in optometric practice mirrored a changed emphasis in teaching and technology over the past 10-15 years. Australian and New Zealand optometrists were well equipped to perform glaucoma assessments with the possible exception of gonioscopy. Advanced imaging modalities were not yet fully integrated into optometric practice, although optical coherence tomography has shown use by 23-32% of optometrists. A marked increase in use, availability and procedural confidence of gonioscopy and other techniques with therapeutically endorsed optometrists demonstrates the advantage and importance of additional training.
Publisher: Elsevier BV
Date: 08-2023
Publisher: Informa UK Limited
Date: 05-2016
DOI: 10.1111/CXO.12403
Publisher: Frontiers Media SA
Date: 07-03-2023
DOI: 10.3389/FNANA.2023.997722
Abstract: A hallmark of photoreceptor degenerations is progressive, aberrant remodeling of the surviving retinal neurons and glia following photoreceptor loss. The exact relationship between neurons and glia remodeling in this late stage of retinal degeneration, however, is unclear. This study assessed this by examining Müller cell dysfunction via glutamine synthetase immunoreactivity and its spatial association with retinal neuron subpopulations through various cell markers. Aged Rd1 mice retinae (P150 – P536, n = minimum 5 per age) and control heterozygous rd1 mice retinae (P536, n = 5) were isolated, fixed and cryosectioned. Fluorescent immunolabeling of glutamine synthetase was performed and retinal areas quantified as having low glutamine synthetase immunoreactivity if proportion of labeled pixels in an area was less than two standard deviations of the mean of the total retina. Other Müller cell markers such as Sox9 and Glial fibrillary acidic protein along with neuronal cell markers Calbindin, Calretinin, recoverin, Protein kinase C-α, Glutamic acid decarboxylase 67, and Islet-1 were then quantified within areas of low and normal synthetase immunoreactivity. Glutamine synthetase immunoreactivity was lost as a function of age in the rd1 mouse retina (P150 – P536). Immunoreactivity of other Müller cell markers, however, were unaffected suggesting Müller cells were still present in these low glutamine synthetase immunoreactive regions. Glutamine synthetase immunoreactivity loss affected specific neuronal populations: Type 2, Type 8 cone, and rod bipolar cells, as well as AII amacrine cells based on reduced recoverin, protein kinase Ca and parvalbumin immunoreactivity, respectively. The number of cell nuclei within regions of low glutamine synthetase immunoreactivity was also reduced suggesting possible neuronal loss rather than reduced cell marker immunoreactivity. These findings further support a strong interplay between glia-neuronal alterations in late-stage degeneration and highlight a need for future studies and consideration in intervention development.
Publisher: Informa UK Limited
Date: 11-2017
DOI: 10.1111/CXO.12528
Abstract: The use of advanced imaging in clinical practice is emerging and the use of this technology by optometrists in assessing patients with age-related macular degeneration is of interest. Therefore, this study explored contemporary, self-reported patterns of practice regarding age-related macular degeneration diagnosis and management using a cross-sectional survey of optometrists in Australia and New Zealand. Practising optometrists were surveyed on four key areas, namely, demographics, clinical skills and experience, assessment and management of age-related macular degeneration. Questions pertaining to self-rated competency, knowledge and attitudes used a five-point Likert scale. Completed responses were received from 127 and 87 practising optometrists in Australia and New Zealand, respectively. Advanced imaging showed greater variation in service delivery than traditional techniques (such as slitl funduscopy) and trended toward optical coherence tomography, which was routinely performed in age-related macular degeneration by 49 per cent of respondents. Optical coherence tomography was also associated with higher self-rated competency, knowledge and perceived relevance to practice than other modalities. Most respondents (93 per cent) indicated that they regularly applied patient symptoms, case history, visual function results and signs from traditional testing, when queried about their management of patients with age-related macular degeneration. Over half (63 per cent) also considered advanced imaging, while 31 per cent additionally considered all of these as well as the disease stage and clinical guidelines. Contrary to the evidence base, 68 and 34 per cent rated nutritional supplements as highly relevant or relevant in early age-related macular degeneration and normal aging changes, respectively. These results highlight the emergence of multimodal and advanced imaging (especially optical coherence tomography) in the assessment of age-related macular degeneration by optometrists. Clinically significant variations in self-rated test competency and the understanding regarding nutritional supplements for different stages of age-related macular degeneration suggest that further work to up-skill optometrists may be required.
Publisher: Informa UK Limited
Date: 2017
DOI: 10.1111/CXO.12408
Abstract: The Heidelberg Retina Tomograph (HRT) is a commonly-used clinical instrument for glaucoma diagnosis however, the repeatability of the two most commonly used analysis tools, Moorfield regression analysis (MRA) and 'glaucoma probability score' (GPS) is not known and could have significant implications for patients at risk or suspected of developing glaucoma. Thus, the intra-visit repeatability of the HRT3 (an objective measure of instrument-induced variability) was investigated in a glaucoma suspect cohort. Two repeat 15° × 15° optic nerve head scans were taken from 164 eyes of 84 patients using the HRT (HRT3, software version 3) during a single visit. The variability of global and sectoral rim area, rim volume and GPS were analysed with and without image alignment using SPSS 22.0. Repeatability was evaluated as absolute difference between the two measurements. Repeatability of the global rim area, rim volume and GPS were high with and without image registration. Variability increased by a small, yet significant amount without image alignment (p < 0.001 to p = 0.002). This increase was more prominent for sectoral analysis with the exception of the rim area and volume in the temporal sector (p = 0.034 to p < 0.001). Increase in the variability of the GPS was also significant (p < 0.001). HRT3 demonstrated high short-term repeatability, which significantly improved with image registration for all global measurements. Sectoral analysis demonstrated higher repeatability with image registration for some of the sectors in rim area and volume analysis and all sectors for the GPS. Therefore, depending upon the assessed parameters, image registration may play a significant role in the interpretation of results in glaucoma suspects.
Publisher: Wiley
Date: 02-2000
DOI: 10.1002/(SICI)1097-4547(20000201)59:3<332::AID-JNR6>3.0.CO;2-2
Abstract: Stem cells from the adult forebrain of mice were stimulated to form clones in vitro using fibroblast growth factor-2 (FGF-2). At concentrations above 10 ng/ml of FGF-2, very few clones gave rise to neurons however, if FGF-2 was removed after 5 days, 20-30% of clones subsequently gave rise to neurons. The number of neuron-containing clones and the number of neurons per clone was significantly enhanced, if insulin-like growth factor (IGF)-1 or heparin were added subsequent to FGF-2 removal. The spontaneous production of neurons after FGF-2 removal was shown to be due to endogenous IGF-1, since antibodies to IGF-1 and an IGF-1 binding protein totally inhibited neuronal production. Similarly, these reagents also abrogated the neuron-promoting effects of heparin. Thus, it appears that endogenous IGF-1 may be a major regulator of stem cell differentiation into neurons. Furthermore, it was found that high levels of IGF-1 or insulin promoted the maturation and affected the neurotransmitter phenotype of the neurons generated.
Publisher: Cambridge University Press (CUP)
Date: 05-2001
DOI: 10.1017/S0952523801183082
Abstract: Glutamate and γ-aminobutyric acid (GABA) are two of the dominant neurotransmitters in the retina and brain. The production/degradation of glutamate and GABA involves an intricate interrelationship between neurons and glia, as well as aerobic and anaerobic metabolic pathways. The aim of this work was to develop an in vitro model of retinal ischemia/anoxia and determine the changes in cellular localization of glutamate and GABA and the time course for such changes. After anoxic/ischemic insult, glutamate and GABA rapidly accumulate within glia with GABA showing a quicker time course and larger magnitude change. The accumulation time constant for both glutamate and GABA under anoxic conditions was dependent upon glucose concentration: high glucose levels resulted in delayed glial amino acid loading. The differences in time constants between GABA and glutamate glial loading most likely reflect the multitude of glutamate degradation pathways compared to the single aerobically dependent GABA pathway. Oxygen availability and reduced glucose (hypoglycemia) lead to an almost immediate increase (within 1 min) of glutamate and GABA labelling within glia. In addition, altered labelling patterns were found under anoxic/ischemic conditions for amino acids involved in glutamate transamination reactions: aspartate, leucine, alanine, and ornithine. These changes are consistent with alterations of equilibria of enzymatic reactions involved in glutamate metabolism, and thus support a role for all four amino acids in glutamate metabolism within a variety of retinal neurons.
Publisher: Informa UK Limited
Date: 03-2014
DOI: 10.1111/CXO.12085
Abstract: Electrophysiological techniques allow clinical investigations to include a 'dissection' of the visual system. Using suitable electrophysiological techniques, the 'dissection' allows function to be ascribed to the different photoreceptors (rod and cone photoreceptors), retinal layers, retinal location or the visual pathway up to the visual cortex. Combined with advances in genetics, retinal biochemistry, visual fields and ocular imaging, it is now possible to obtain a better understanding of diseases affecting the retina and visual pathways. This paper reviews core electrophysiological principles that can complement other examination techniques, including advanced ocular imaging, and help the interpretation of other clinical data and thus, refine and guide clinical diagnosis.
Publisher: Informa UK Limited
Date: 11-2020
DOI: 10.1111/CXO.13054
Publisher: Wiley
Date: 08-10-1993
Abstract: Postembedding immunocytochemistry was used to determine the cellular localization of the amino acid neurotransmitters glutamate, aspartate, gamma-aminobutyric acid (GABA), and glycine in the avian retina. The through retinal pathway was glutamatergic, with all photoreceptors, bipolar cells, and ganglion cells being immunoreactive for glutamate. Bipolar cells displayed the highest level of glutamate immunoreactivity, with the cell bodies terminating just below the middle of the inner nuclear layer. All lateral elements, horizontal cells, amacrine cells, and interplexiform cells were immunoreactive for glycine or GABA. The GABAergic neurons consisted of two classes of horizontal cells and amacrine cells located in the lower part of the inner nuclear layer. GABA was also localized in displaced amacrine cells in the ganglion cell layer, and a population of ganglion cells that co-localize glutamate and GABA. Both the horizontal cells and GABAergic amacrine cells had high levels of glutamate immunoreactivity, which probably reflects a metabolic pool. At least two types of horizontal cells in the avian retina could be discriminated on the basis of the presence of aspartate immunoreactivity in the H2 horizontal cells. Glycine was contained in a subclass of amacrine cells, with their cell bodies located between the bipolar cells and GABAergic amacrine cells, two subclasses of bipolar cells, displaced amacrine cells in the ganglion cell layer, and ganglion cells that colocalize glutamate and glycine. Glycinergic amacrine cells had low levels of glutamate. We have also identified a new class of glycinergic interplexiform cell, with its stellate cell body located in the middle of the inner nuclear layer among the cell bodies of bipolar cells. Neurochemical signatures obtained by analyzing data from serial sections allowed the classification of subclasses of horizontal cells, bipolar cells, amacrine cells, and ganglion cells.
Publisher: Elsevier BV
Date: 09-2016
DOI: 10.1016/J.EXER.2015.10.019
Abstract: Retinitis Pigmentosa (RP) reflects a range of inherited retinal disorders which involve photoreceptor degeneration and retinal pigmented epithelium dysfunction. Despite the multitude of genetic mutations being associated with the RP phenotype, the clinical and functional manifestations of the disease remain the same: nyctalopia, visual field constriction (tunnel vision), photopsias and pigment proliferation. In this review, we describe the typical clinical phenotype of human RP and review the anatomical and functional remodelling which occurs in RP determined from studies in the rd/rd (rd1) mouse. We also review studies that report a slowing down or show an acceleration of retinal degeneration and finally we provide insights on the impact retinal remodelling may have in vision restoration strategies.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 04-09-2018
DOI: 10.1167/TVST.7.5.3
Publisher: Wiley
Date: 14-02-2023
DOI: 10.1111/OPO.13108
Abstract: The purpose of this study was to build an automated age‐related macular degeneration (AMD) colour fundus photography (CFP) recognition method that incorporates confounders (other ocular diseases) and normal age‐related changes by using drusen masks for spatial feature supervision. A range of clinical sources were used to acquire 7588 CFPs. Contrast limited adaptive histogram equalisation was used for pre‐processing. ResNet50 was used as the backbone network, and a spatial attention block was added to integrate prior knowledge of drusen features into the backbone. The evaluation metrics used were sensitivity, specificity and F1 score, which is the harmonic mean of precision and recall (sensitivity) and area under the receiver‐operating characteristic (AUC). Fivefold cross‐validation was performed, and the results compared with four other methods. Excellent discrimination results were obtained with the algorithm. On the public dataset ( n = 6565), the proposed method achieved a mean (SD) sensitivity of 0.54 (0.09), specificity of 0.99 (0.00), F1 score of 0.62 (0.06) and AUC of 0.92 (0.02). On the private dataset ( n = 1023), the proposed method achieved a sensitivity of 0.92 (0.02), specificity of 0.98 (0.01), F1 score of 0.92 (0.01) and AUC of 0.98 (0.01). The proposed drusen‐aware model outperformed baseline and other vessel feature‐based methods in F1 and AUC on the AMD/normal CFP classification task and achieved comparable results on datasets that included other diseases that often confound classification. The method also improved results when a five‐category grading protocol was used, thereby reflecting discriminative ability of the algorithm within a real‐life clinical setting.
Publisher: Wiley
Date: 06-10-2023
DOI: 10.1111/OPO.13229
Publisher: Wiley
Date: 20-02-2013
DOI: 10.1002/CNE.23284
Abstract: The rd1 mouse is a well-established animal model for human retinitis pigmentosa (RP). We used electroretinography (ERG) to evaluate retinal function and postembedding immunocytochemistry to determine the changes in cellular amino acid expression in the normal (C57Bl6) and degenerating mouse retina (rd1), as a function of age during development and the onset of degeneration. In the normal mouse retina, photoreceptoral and post-photoreceptoral ERG responses improved simultaneously from eye-opening until adult levels were achieved at approximately postnatal day (P) 30. Maturation of amino acid neurochemistry preceded the development of retinal function in the normal retina. Amino acid levels increased immediately from birth and reached stable levels by eye-opening. In contrast, in the rd1 mouse, both rod and cone pathway function rapidly reduced from eye-opening and by P21 became undetectable. Interestingly, at P18 cone responses were still comparable between the normal and degenerating retina. Before eye opening, the pattern of amino acid immunoreactivity in the rd1 retina was similar to the normal retina. Alterations in neurochemistry were observed after the onset of rod photoreceptor cell death. The most obvious change was the reduction in neurotransmitter immunoreactivity within the synaptic layers and some cell classes of the rd1 retina. Reduction of glutamine and glutamate was observed in Müller cells before established gliosis markers. Overall, these results suggest the rapid maturation of neurochemistry by eye opening followed by functional maturation by P30 in the normal retina. The dystrophic retina displays similar neurochemistry to control retina before eye opening but a subsequent decline.
Publisher: Informa UK Limited
Date: 09-2005
Publisher: Wiley
Date: 04-1993
DOI: 10.1111/J.1475-1313.1993.TB00445.X
Abstract: The effects of prolonged exposure to intense, short-wavelength light were studied in monkeys through the measurement of increment-threshold spectral sensitivity (ITSS) and threshold-versus-intensity (TVI) functions using a behavioural method. The long-term effect of intense blue-light exposure was to induce a short-wavelength (SW) sensitivity loss which did not depend on the intensity or chromatic composition of the adapting field. The TVI curves for short wavelength stimuli revealed an increase in test threshold without changes in field sensitivity. Since this SW sensitivity loss may generalize to characteristic colour vision defects found in many outer retinal diseases, models of acquired alterations of colour vision mechanisms are considered. These models describe probable changes in ITSS functions and TVI curves in diseases affecting the inner or outer retina as well as changes in dark adaptation.
Publisher: Springer Science and Business Media LLC
Date: 09-2022
DOI: 10.1038/S41598-022-18646-2
Abstract: Deep learning methods have enabled a fast, accurate and automated approach for retinal layer segmentation in posterior segment OCT images. Due to the success of semantic segmentation methods adopting the U-Net, a wide range of variants and improvements have been developed and applied to OCT segmentation. Unfortunately, the relative performance of these methods is difficult to ascertain for OCT retinal layer segmentation due to a lack of comprehensive comparative studies, and a lack of proper matching between networks in previous comparisons, as well as the use of different OCT datasets between studies. In this paper, a detailed and unbiased comparison is performed between eight U-Net architecture variants across four different OCT datasets from a range of different populations, ocular pathologies, acquisition parameters, instruments and segmentation tasks. The U-Net architecture variants evaluated include some which have not been previously explored for OCT segmentation. Using the Dice coefficient to evaluate segmentation performance, minimal differences were noted between most of the tested architectures across the four datasets. Using an extra convolutional layer per pooling block gave a small improvement in segmentation performance for all architectures across all four datasets. This finding highlights the importance of careful architecture comparison (e.g. ensuring networks are matched using an equivalent number of layers) to obtain a true and unbiased performance assessment of fully semantic models. Overall, this study demonstrates that the vanilla U-Net is sufficient for OCT retinal layer segmentation and that state-of-the-art methods and other architectural changes are potentially unnecessary for this particular task, especially given the associated increased complexity and slower speed for the marginal performance gains observed. Given the U-Net model and its variants represent one of the most commonly applied image segmentation methods, the consistent findings across several datasets here are likely to translate to many other OCT datasets and studies. This will provide significant value by saving time and cost in experimentation and model development as well as reduced inference time in practice by selecting simpler models.
Publisher: Oxford University Press (OUP)
Date: 11-2000
DOI: 10.1093/CERCOR/10.11.1132
Abstract: Glutamate is an important amino acid in the neocortex for metabolic and neurotransmitter functions. The objective of this study was to detect variations in cellular glutamate content using quantitative immunocytochemistry. We show that glutamate is present in almost all cortical cells and coexists with other amino acids such as aspartate, glutamine or gamma-aminobutyric acid (GABA). The patterns of aspartate and glutamine content suggests that there are no purely aspartatergic or glutaminergic neurons. GABAergic neurons showed variable levels of the precursors such as glutamate, glutamine and aspartate. Comparison of immunoreactive patterns between two cortical areas did not detect any statistically significant differences. The mean cellular intensity for GABA and glutamate was constant across different layers. Surprisingly, we found that GABAergic neurons could coexist with either low or high levels of glutamate, suggesting that metabolic levels of glutamate in these neurons could be variable. Alternatively, some GABA neurons may utilize both GABA and glutamate for neurotransmission. We show that when variations in amino acid content are separately mapped onto in idual cells, co-registration is a useful technique for reporting heterogeneity among cortical cells.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2015
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2018
DOI: 10.1097/OPX.0000000000001179
Abstract: This study resulted in the identification of an optic nerve head (ONH) feature associated with tilted optic discs, which might potentially contribute to ONH pathologies. Knowledge of such findings will enhance clinical insights and drive future opportunities to understand disease processes related to tilted optic discs. The aim of this study was to identify novel retinal nerve fiber layer (RNFL) anomalies by evaluating tilted optic discs using optical coherence tomography. An observed retinal nerve fiber protrusion was further investigated for association with other morphological or functional parameters. A retrospective review of 400 randomly selected adult patients with ONH examinations was conducted in a referral-only, diagnostic imaging center. After excluding other ONH pathologies, 215 patients were enrolled and evaluated for optic disc tilt and/or torsion. Gross anatomical ONH features, including size and rim or parapapillary region elevation, were assessed with stereoscopic fundus photography. Optical coherence tomography provided detailed morphological information of in idual retinal layers. Statistical analysis was applied to identify significant changes between in idual patient cohorts. A dome-shaped hyperreflective RNFL bulge, protruding into the neurosensory retina at the optic disc margins, was identified in 17 eyes with tilted optic discs. Available follow-up data were inconclusive regarding natural changes with this ONH feature. This RNFL herniation was significantly correlated with smaller than average optic disc size ( P = .005), congenital disc tilt ( P .0001), and areas of rim or parapapillary elevation ( P .0001). This study reports an RNFL protrusion associated with tilted optic discs, which has not previously been assessed as an independent ONH structure. The feature is predominantly related to congenital crowded, small optic discs and variable between patients. This study is an important first step to elucidate diagnostic capabilities of tilted disc morphological changes and understanding associated functional deficits.
Publisher: Wiley
Date: 29-11-2021
DOI: 10.1111/OPO.12919
Abstract: There is growing interest in functional testing for early/intermediate age‐related macular degeneration (iAMD). However, systematic evaluation of existing clinical functional tests is lacking. This systematic review examines evidence for using clinical automated perimetry in routine assessment of early/iAMD. PubMed, Web of Science Core Collection, and Embase were searched from inception to October 2020 to answer, is there evidence of visual field defects in early/iAMD, and if so, are early/iAMD visual field defects linked to real‐world patient outcomes? Articles using clinical automated perimetry (commercially accessible and non‐modified devices rotocols) were included. Microperimetry was excluded as this has yet to be incorporated into clinical guidelines. The primary outcome was global visual field indices including mean deviation (MD), pattern standard deviation (PSD), mean sensitivity (MS) and frequency of defects. The secondary outcome was any real‐world patient outcome including quality of life and/or activities of daily living indices. Twenty‐six studies were eligible for inclusion and all studies were observational. There was consistent evidence of worsened MD, PSD, MS and frequency of defects for early/iAMD compared to normal eyes under photopic, low‐photopic and scotopic conditions. Meta‐analysis of studies using standard automated perimetry (SAP) under photopic conditions revealed worsened MD (−1.52dB [−2.27, −0.78 dB]) and MS (−1.47dB [−2, −0.94 dB]) in early/iAMD compared to normal eyes, representing large statistical effect sizes but non‐clinically meaningful reductions. There was insufficient data for meta‐analyses regarding other clinical automated perimetry protocols. Only one study assessed a real‐world patient outcome (on‐road driving performance), with no significant link to visual field outcomes in early/iAMD. Significant reduction of global visual field indices is present in early/iAMD, but not clinically meaningful using SAP under photopic conditions. Translational relevance of visual field outcomes to patient outcomes in early/iAMD remains unclear. Thus, SAP under photopic conditions is unlikely to be useful for routine assessment of early/iAMD.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 16-04-2012
DOI: 10.1167/IOVS.11-8462
Abstract: To identify the distribution of creatine transporter (CRT) in the aged human retina and how this expression pattern is modified after retinal detachment. An affinity-purified antibody raised against the CRT was used in the immunohistochemical investigation. The anti-CRT antibody was colocalized with neuronal markers (calbindin, parvalbumin, Islet-1, calretinin, GAD₆₇, Go-alpha), glia markers (glutamine synthetase, glial fibrillary acid protein), and a blood vessel basal membrane marker (laminin). Confocal microscopy was used to visualize the labeling patterns in retinal sections. The level of CRT expression was determined in the retina using a semiquantification method. Immunohistochemical assessment of CRT expression in the normal aged retina revealed strong labeling in photoreceptor synaptic terminals and in inner and outer segments. Labeling was also observed on subpopulations of amacrine cells and ganglion cells as well as in the outer and inner plexiform layers. CRT labeling was observed in blood vessels, although was absent in glial cells. In retinal detachment, the CRT labeling pattern was maintained, although there was an apparent decrease in labeling in inner retina and an increase in CRT expression in photoreceptors. CRT is expressed in areas of intense metabolic activity, such as photoreceptors, selected cells in the inner retina, and sites of creatine transport into the retina (inner retinal blood vessels and retinal pigment epithelium). The absence of CRT to Müller cells harmonizes with the concept that glial cells are a biosynthetic source of creatine but not a source of creatine to other retinal neurons. The increased immunolabeling of CRT localized to the outer retina in retinal detachment suggests a regional metabolic remodeling occurring in photoreceptor cells.
Publisher: Informa UK Limited
Date: 07-2017
DOI: 10.1111/CXO.12551
Publisher: Informa UK Limited
Date: 04-01-2022
DOI: 10.1080/08164622.2021.1999771
Abstract: Ischaemic stroke is a major disease burden as well as a leading cause of death. Early signs of ischaemic stroke can manifest in the eye, placing primary eyecare practitioners in an important position to identify patients at risk of ischaemic stroke and initiate suitable referral pathways. The vascular supply to the brain is reviewed with reference to vision including the various retinal signs and ocular symptoms associated with transient ischaemic attacks and ischaemic stroke. Using a range of clinical cases, the erse clinical presentations of retinal embolic events, as well as other forms of vascular occlusion, are highlighted and the underlying pathophysiology is discussed. A succinct scheme for the assessment and management of ischaemic events for primary eye care practitioners is provided.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 11-10-2022
Publisher: Elsevier BV
Date: 02-2018
DOI: 10.1016/J.EXER.2017.10.008
Abstract: Retinal ischemia is involved in the pathogenesis of many major vision threatening diseases. Vinpocetine is a natural drug, which has a range of neuroprotective actions against retinal ischemia including modulating cation flow, improving metabolic activity and preventing apoptosis. The exact mechanism behind these actions remains unknown but may involve glutamate receptors, major components of the ischemic cascade. This study examined the effects of vinpocetine in association with specific ionotropic glutamate receptor agonists: N-methyl-D-aspartate (NMDA) and kainate. Vinpocetine's actions to improve cation channel permeability and cell marker immunoreactivity following ischemia appeared to be limited to NMDA activation with no changes observed following kainate stimulation. Vinpocetine's actions were lost in the presence of an NMDA receptor inhibitor further suggesting they may be secondary to NMDA receptor activation. NMDA receptor function was also necessary for vinpocetine's actions on glucose availability during ischemia but not lactate dehydrogenase (LDH) activity in the ischemic retina suggesting not all of vinpocetine's actions are linked to NMDA receptor function. These results may explain vinpocetine's effectiveness as a neuroprotective agent as the NMDA receptor is implicated in the pathogenesis of ischemia in a range of tissues of the central nervous system.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2018
DOI: 10.1097/OPX.0000000000001172
Abstract: This article shows that self-tonometry can provide robust measures of diurnal intraocular pressure (IOP) and also detect changes to IOP in response to treatment within a short period of monitoring. These advances in IOP monitoring may contribute to improved management of glaucoma patients and suspects. The aim of this study was to prospectively investigate the utility of rebound self-tonometry performed over several weeks for detecting diurnal IOP fluctuations in glaucoma patients and suspects and also initial response to topical treatment in glaucoma patients. Forty patients were recruited following glaucoma-specific examination. Subsequent to successful training with the iCare HOME tonometer, patients were instructed to measure IOP, in a sitting position, four times a day over 4 to 6 weeks. Date, time, laterality, and IOP downloaded from the tonometer and clinical examination data, including applanation IOP and corneal thickness, were analyzed. A user satisfaction survey was also administered at study completion. t Test and analysis of variance were used to compare groups and IOP across days. Pearson correlation was used to compare measurements to Goldmann applanation tonometry and IOP measurements from the first day/s to the overall mean IOP. Twenty-seven patients (18 suspects and 9 glaucoma patients) completed data collection. Patients self-measured IOP on 118 (±29) occasions for 40 (±7.4) days. Two dominant patterns of fluctuation were revealed: peak IOP upon awakening (n = 11) and at midday (n = 13). Diurnal IOP measured in the first 7 days showed strong correlation to diurnal IOP across the entire study period ( r 2 = 0.82, P .0001). Within 24 hours of treatment commencement (latanoprost 0.005% ophthalmic solution), IOP reduced from 23.9 (±5.2) to 16.1 (±2.6) mmHg. Overall, patients rated the instrument as easy to use, although difficulties with correct alignment were expressed. Rebound self-tonometry demonstrated utility for measuring diurnal IOP fluctuations in most patients, hence enhancing management of patient with or at risk of developing glaucoma.
Publisher: Informa UK Limited
Date: 07-03-2022
DOI: 10.1080/08820538.2022.2039222
Abstract: Certain peripheral retinal degenerations pose a significant risk to vision and require prompt detection and management. Other historically "benign" peripheral lesions are being recognised as clinically significant due to their associations with ocular and systemic disorders. Assessment and documentation of these entities however can be difficult due to challenges in visualisation of the peripheral retina. This review addresses this by providing a series of clinical ex les of these entities visualised with a variety of ocular imaging technologies. A literature search was performed in Embase, Medline, and Google Scholar. We identified and analysed all papers referring to peripheral retinal degenerations and the peripheral retina, as well as reference lists of retrieved articles until August 2019. Using ocular imaging technologies including ultra-widefield imaging and peripheral optical coherence tomography, we comprehensively describe current evidence and knowledge of a number of peripheral retinal degenerations and anomalies including microcystoid, pavingstone, lattice, snail track, snowflake and reticular pigmentary degenerations, peripheral drusen, white without pressure, retinal holes and vitreoretinal tufts. A summary of these entities is also provided as a short and easily interpretable chairside guide to facilitate the translation of this evidence base into clinical practice. While ocular technologies are useful in visualising peripheral retinal degenerations, the current evidence is fragmented throughout the literature and there is a paucity of information on imaging of "benign" peripheral lesions. This review facilitates a multimodal imaging approach to evaluating peripheral lesions.
Publisher: Elsevier BV
Date: 11-1999
DOI: 10.1016/S1350-9462(98)00036-6
Abstract: The dominant neurochemicals involved in encoding sensory information are the amino acid neurotransmitters, glutamate, gamma-aminobutyrate (GABA) and glycine, which mediate fast point-to-point synaptic transmission in the retina and other parts of the central nervous system. The relative abundance of these neurochemicals and the existence of neuronal and glial uptake mechanisms as well as a plethora of receptors support the key role these neurochemicals play in shaping neural information. However, in addition to subserving neurotransmitter roles, amino acids subserve normal metabolic,cellular functions, may be precursors for other amino acids, and may also be associated with protein synthesis. Post-embedding immunocytochemistry of small molecules has allowed the characterization of multiple amino acid profiles within subpopulations of neurons in the vertebrate retina. The general theme emerging from these studies is that the retinal through pathway uses glutamate as its neurotransmitter, and the lateral elements, GABA and/or glycine. Co-localization studies using quantitative immunocytochemistry have shown that virtually all neuronal space can be accounted for by the three dominant amino acids. In addition, co-localization studies have demonstrated that there are no purely aspartate, glutamine, alanine. leucine or ornithine immunoreactive neurons and thus these amino acids are likely to act as metabolites and may sustain glutamate production through a multitude of enzymatic pathways. The mapping of multiple cellular metabolic profiles during development or in degenerating retinas has shown that amino acid neurochemistry is a sensitive marker for metabolic activity. In the degenerating retina, (RCS retina), neurochemical anomalies were evident early in development (from birth), even before photoreceptors mature at PND6-8 implying a generalized metabolic dysfunction. Identification of metabolic anomalies within subpopulation of neurons is now possible and can be used to investigate a multitude of retinal functions including amino acid metabolic and neurochemical changes secondary to external insult as well as to expand our understanding of the intricate interrelationship between neurons and glia.
Publisher: Cambridge University Press (CUP)
Date: 07-2004
DOI: 10.1017/S0952523804214080
Abstract: Glutamate is a major neurotransmitter in the retina and other parts of the central nervous system, exerting its influence through ionotropic and metabotropic receptors. One ionotropic receptor, the N-methyl-D-aspartate (NMDA) receptor, is central to neural shaping, but also plays a major role during neuronal development and in disease processes. We studied the distribution pattern of different subunits of the NMDA receptor within the rat retina including quantifying the pattern of labelling for all the NR1 splice variants, the NR2A and NR2B subunits. The labelling pattern for the subunits was confined predominantly in the outer two-thirds of the inner plexiform layer. We also wanted to probe NMDA receptor function using an organic cation, agmatine (AGB) a marker for cation channel activity. Although there was an NMDA concentration-dependent increase in AGB labelling of amacrine cells and ganglion cells, we found no evidence of functional NMDA receptors on horizontal cells in the peripheral rabbit retina, nor in the visual streak where the type A horizontal cell was identified by GABA labelling. Basal AGB labelling within depolarizing bipolar cells was also noted. This basal bipolar cell AGB labelling was not modulated by NMDA and was completely abolished by the use of L-2-amino-4-phosphono-butyric acid, which is known to hyperpolarize retinal depolarizing bipolar cells. AGB is therefore not only useful as a probe of ligand-gated drive, but can also identify neurons that have constitutively open cationic channels. In combination, the NMDA receptor subunit distribution pattern and the AGB gating experiments strongly suggests that this ionotropic glutamate receptor is functional in the cone-driven pathway of the inner retina.
Publisher: Wiley
Date: 02-10-2015
DOI: 10.1111/OPO.12247
Abstract: To evaluate the influence of different clinical examination techniques, including optic nerve head (ONH) photography, visual field tests, and adjunct imaging on the diagnosis of glaucoma by Australian and New Zealand optometrists. The effect of a short-term, didactic teaching module on these is also explored. Clinical data of 30 patients previously seen at the Centre for Eye Health was collected and compiled into glaucoma diagnostic assessment modules. Each of six modules contained different combinations of clinical examination results and required a classification of the cases as normal, suspicious or glaucoma. A cohort of 54 Australian and New Zealand optometrists were recruited for the study and allocated into two cohorts. The intervention group completed a glaucoma training course prior to the assessment while the control group completed the assessment without additional training. Diagnostic accuracy was compared between modules and optometrist groups. High false negative rates were observed with ONH photography, which were drastically reduced with the addition of visual field, albeit at the cost of increased false positive rates. Addition of adjunct imaging techniques partially compensated for the increase in the false positive rate from the visual field, but had limited effect on false negative rate. Educational intervention resulted in larger improvement in the diagnostic ability when multiple imaging modalities were provided. The study highlighted the importance of combining both structural and functional assessments in glaucoma. Current imaging technology demonstrated limited usefulness for event diagnosis due to the persistent difficulties of defining structural and functional loss in glaucoma, thus highlighting the need for new glaucoma assessment techniques. Short-term didactic teaching programs may only result in limited improvement of glaucoma diagnostic ability in optometrists, and hence, it may need to be combined with long-term and/or non-didactic training components to obtain a greater effect.
Publisher: Springer Science and Business Media LLC
Date: 12-08-2019
DOI: 10.1038/S41598-019-48026-2
Abstract: Standard automated perimetry (SAP), the most common form of perimetry used in clinical practice, is associated with high test variability, impacting clinical decision making and efficiency. Contrast sensitivity isocontours (CSIs) may reduce test variability in SAP by identifying regions of the visual field with statistically similar patterns of change that can be analysed collectively and allow a point (disease)-to-CSI (normal) comparison in disease assessment as opposed to a point (disease)-to-point (normal) comparison. CSIs in the central visual field however have limited applicability as they have only been described using visual field test patterns with low, 6° spatial s ling. In this study, CSIs were determined within the central 20° visual field using the 10-2 test grid paradigm of the Humphrey Field Analyzer which has a high 2° s ling frequency. The number of CSIs detected in the central 20° visual field was greater than previously reported with low spatial s ling and stimulus size dependent: 6 CSIs for GI, 4 CSIs for GII and GIII, and 3 CSIs for GIV and GV. CSI number and distribution were preserved with age. Use of CSIs to assess visual function in age-related macular degeneration (AMD) found CSI guided analysis detected a significantly greater deviation in sensitivity of AMD eyes from normal compared to a standard clinical pointwise comparison (−1.40 ± 0.15 dB vs −0.96 ± 0.15 dB p 0.05). This work suggests detection of CSIs within the central 20° is dependent on s ling strategy and stimulus size and normative distribution limits of CSIs can indicate significant functional deficits in diseases affecting the central visual field such as AMD.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2017
DOI: 10.1097/OPX.0000000000000997
Abstract: Fundus autofluorescence (FAF) provides detailed insight into the health of the retinal pigment epithelium (RPE). This is highly valuable in age-related macular degeneration (AMD) as RPE damage is a hallmark of the disease. The purpose of this paper is to critically appraise current clinical descriptions regarding the appearance of AMD using FAF and to integrate these findings into a chair-side reference. A wide variety of FAF patterns have been described in AMD, which is consistent with the clinical heterogeneity of the disease. In particular, FAF imaging in early to intermediate AMD has the capacity to reveal RPE alterations in areas that appear normal on funduscopy, which aids in the stratification of cases and may have visually significant prognostic implications. It can assist in differential diagnoses and also represents a reliable, sensitive method for distinguishing reticular pseudodrusen. FAF is especially valuable in the detection, evaluation, and monitoring of geographic atrophy and has been used as an endpoint in clinical trials. In neovascular AMD, FAF reveals distinct patterns of classic choroidal neovascularization noninvasively and may be especially useful for determining which eyes are likely to benefit from therapeutic intervention. FAF represents a rapid, effective, noninvasive imaging method that has been underutilized, and incorporation into the routine assessment of AMD cases should be considered. However, the practicing clinician should also be aware of the limitations of the modality, such as in the detection of foveal involvement and in the distinction of phenotypes (hypo-autofluorescent drusen from small areas of geographic atrophy).
Publisher: Wiley
Date: 16-12-1996
DOI: 10.1002/(SICI)1096-9861(19961216)376:3<343::AID-CNE1>3.0.CO;2-2
Abstract: One new depsidone derivative, aspergillusidone H (
Publisher: OSA
Date: 2019
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2018
DOI: 10.1097/OPX.0000000000001286
Abstract: 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. 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. 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. 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. 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.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2013
Publisher: Wiley
Date: 27-11-2007
DOI: 10.1002/CNE.21561
Abstract: Tangential cell dispersion in the retina is a spacing mechanism that establishes a regular mosaic organization among cell types and contributes to their final positioning. The present study has used the X-inactivation transgenic mouse expressing the lacZ reporter gene on one X chromosome. Due to X chromosome inactivation, 50% of early progenitor cells express beta-galactosidase (beta-Gal) therefore, all cells derived from a particular beta-Gal-expressing progenitor cell can be identified in labeled columns. The radial segregation of clonally related beta-Gal-positive and beta-Gal-negative cells can be used to determine whether single cells transgress a clonal boundary in the retina. We investigated the extent to which particular cell classes tangentially disperse by analyzing the placement of labeled cells expressing particular markers at several ages and quantifying their tangential displacement. Retinal neurons expressing cell markers at postnatal day (P) 1 have a greater degree of tangential dispersion compared with amacrine and bipolar cells at P5-6. We also studied whether there is a functional correlation with these dispersion patterns by investigating the emergence of functional ionotropic glutamate receptors. To determine the degree of functional glutamate receptor activation, agmatine (AGB) was used in combination with cell-specific labeling. AGB permeates functional glutamate receptor channels following activation with alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), kainate or N-methyl-D-aspartate (NMDA). Within these receptor groups, high concentrations of AMPA, kainate, and NMDA are associated with a high degree of tangential dispersion in the adult. Developmentally, functional kainate and AMPA receptors were detected by P1 and were associated with tangentially dispersed cells. Functional NMDA receptors were not detected as early as kainate and AMPA receptors. These results indicate that cells generated early during development are more likely to disperse tangentially compared with those generated later in development. Therefore, functional AMPA and kainate receptors may play a critical role in tangentially displacing cell types.
Publisher: Springer Science and Business Media LLC
Date: 1992
DOI: 10.1007/BF00154376
Publisher: Wiley
Date: 17-02-2017
DOI: 10.1111/OPO.12355
Abstract: Goldmann size V ( GV ) test stimuli are less variable with a greater dynamic range and have been proposed for measuring contrast sensitivity instead of size III ( GIII ). Since GIII and GV operate within partial summation, we hypothesise that actual GV ( aGV ) thresholds could predict GIII ( pGIII ) thresholds, facilitating comparisons between actual GIII ( aGIII ) thresholds with pGIII thresholds derived from smaller GV variances. We test the suitability of GV for detecting visual field ( VF ) loss in patients with early glaucoma, and examine eccentricity‐dependent effects of number and depth of defects. We also hypothesise that stimuli operating within complete spatial summation (‘spatially equated stimuli’) would detect more and deeper defects. Sixty normal subjects and 20 glaucoma patients underwent VF testing on the Humphrey Field Analyzer using GI ‐V sized stimuli on the 30‐2 test grid in full threshold mode. Point‐wise partial summation slope values were generated from GI ‐V thresholds, and we subsequently derived pGIII thresholds using aGV . Difference plots between actual GIII ( aGIII ) and pGIII thresholds were used to compare the amount of discordance. In glaucoma patients, the number of ‘events’ (points below the 95% lower limit of normal), defect depth and global indices were compared between stimuli. 90.5% of pGIII and aGIII points were within ±3 dB of each other in normal subjects. In the glaucoma cohort, there was less concordance (63.2% within ±3 dB ), decreasing with increasing eccentricity. GIII found more defects compared to GV ‐derived thresholds, but only at outermost test locations. Greater defect depth was found using aGIII compared to aGV and pGIII , which increased with eccentricity. Global indices revealed more severe loss when using GIII compared to GV . Spatially equated stimuli detected the greatest number of ‘events’ and largest defect depth. Whilst GV may be used to reliably predict GIII values in normal subjects, there was less concordance in glaucoma patients. Similarities in ‘event’ detection and defect depth in the central VF were consistent with the fact that GIII and GV operate within partial summation in this region. Eccentricity‐dependent effects in ‘events’ and defect depth were congruent with changes in spatial summation across the VF and the increase in critical area with disease. The spatially equated test stimuli showed the greatest number of defective locations and larger sensitivity loss.
Publisher: Wiley
Date: 19-04-2023
DOI: 10.1002/CNE.25483
Abstract: This study sought to identify demographic variations in retinal thickness measurements from optical coherence tomography (OCT), to enable the calculation of cell density parameters across the neural layers of the healthy human macula. From macular OCTs ( n = 247), ganglion cell (GCL), inner nuclear (INL), and inner segment–outer segment (ISOS) layer measurements were extracted using a customized high‐density grid. Variations with age, sex, ethnicity, and refractive error were assessed with multiple linear regression analyses, with age‐related distributions further assessed using hierarchical cluster analysis and regression models. Models were tested on a naïve healthy cohort ( n = 40) with Mann–Whitney tests to determine generalizability. Quantitative cell density data were calculated from histological data from previous human studies. Eccentricity‐dependent variations in OCT retinal thickness closely resemble topographic cell density maps from human histological studies. Age was consistently identified as significantly impacting retinal thickness ( p = .0006, .0007, and .003 for GCL, INL and ISOS), with gender affecting ISOS only ( p .0001). Regression models demonstrated that age‐related changes in the GCL and INL begin in the 30th decade and were linear for the ISOS. Model testing revealed significant differences in INL and ISOS thickness ( p = .0008 and .0001 however, differences fell within the OCT's axial resolution. Qualitative comparisons show close alignment between OCT and histological cell densities when using unique, high‐resolution OCT data, and correction for demographics‐related variability. Overall, this study describes a process to calculate in vivo cell density from OCT for all neural layers of the human retina, providing a framework for basic science and clinical investigations.
Publisher: Informa UK Limited
Date: 11-2007
DOI: 10.1111/J.1444-0938.2007.00179.X
Abstract: This report describes the short- and long-term ocular signs and symptoms of a patient with an orbital blow-out fracture and discusses the differential diagnosis of vertical diplopia. A blow-out fracture occurs when blunt trauma is applied either directly to the eyeball itself or the orbital rim and usually results in a fracture of the orbital floor with consequential excavation and entrapment of orbital contents in the fracture. Vertical diplopia is a common presenting symptom for a blow-out fracture of the orbit but careful considerations should be given to other potential conditions leading to such diplopia. A patient is presented who suffered a blow-out fracture almost a decade earlier, secondary to blunt trauma to the globe. The clinical findings are provided immediately after the trauma, post-surgery and during a recent ocular examination.
Publisher: Elsevier BV
Date: 2017
DOI: 10.1016/J.EXER.2016.11.018
Abstract: Vinpocetine has been shown to have beneficial effects for tissues of the central nervous system subjected to ischemia and other related metabolic insults. We recently showed vinpocetine promotes glucose availability, prevents unregulated cation channel permeability and regulates glial reactivity when present during retinal ischemia. Less is known however about the ability of vinpocetine to protect against future ischemic insults. This study explores the effect of vinpocetine when used as a pre-treatment in an ex vivo model for retinal ischemia using cation channel permeability of agmatine (AGB) combined with immunohistochemistry as a measure for cell functionality. We found that vinpocetine pre-treatment reduced cation channel permeability and apoptotic marker immunoreactivity in the GCL and increased parvalbumin immunoreactivity of inner retinal neurons in the inner nuclear layer following ischemic insult. Vinpocetine pre-treatment also reduced Müller cell reactivity following ischemic insults of up to 120 min compared to untreated controls. Many of vinpocetine's effects however were transient in nature suggesting the drug can protect retinal neurons against future ischemic damage but may have limited long-term applications.
Publisher: Public Library of Science (PLoS)
Date: 13-03-2013
Publisher: Informa UK Limited
Date: 2015
DOI: 10.1111/CXO.12177
Abstract: Ophthalmic practitioners have to make a critical differential diagnosis in cases of an elevated optic nerve head. They have to discriminate between pseudopapilloedema (benign elevation of the optic nerve head) and true swelling of the optic nerve head. This decision has significant implications for appropriate patient management. Assessment of the optic disc prior to the advanced imaging techniques that are available today (particularly spectral domain optical coherence tomography and fundus autofluorescence), has mainly used diagnostic tools, such as funduscopy and retinal photography. As these traditional methods rely on the subjective assessment by the clinician, evaluation of the elevated optic nerve head to differentiate pseudopapilloedema from true swelling of the optic nerve head can be a challenge in clinical practice with patients typically referred for further neuroimaging investigation when the diagnosis is uncertain. The use of multimodal ocular imaging tools such as spectral domain optical coherence tomography, short wavelength fundus autofluorescence and ultrasonography, can potentially aid in the differentiation of pseudopapilloedema from true swelling of the optic nerve head, in conjunction with other clinical findings. By doing so, unnecessary patient costs and anxiety in the case of pseudopapilloedema can be reduced, and appropriate urgent referral and management in the case of true swelling of the optic nerve head can be initiated.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 02-04-2018
Abstract: To investigate the effect of stimulus size and disease status on the structure-function relationship within the central retina, we correlated the differential light sensitivity (DLS) with Goldmann stimulus size I to V (GI-V) and optical coherence tomography (OCT) derived in vivo ganglion cell count per stimulus area (GCc) within the macular area in normal subjects and patients with early glaucoma. Humphrey Field Analyzer 10-2 visual field data with GI through V and Spectralis OCT macular ganglion cell layer (GCL) thickness measurements were collected from normal and early glaucoma cohorts including 25 subjects each. GCc was calculated from GCL thickness data and correlated with DLSs for different stimulus sizes. Correlation coefficients attained with smaller stimulus size were higher compared to larger stimulus sizes in both normal (GI-GII: R2 = 0.41-0.43, GIII-GV: R2 = 0.16-0.41) and diseased cohorts (GI-GII: R2 = 0.33-0.41, GIII-GV: R2 = 0.19-0.36). Quadratic regression curves for combined GI to V data demonstrated high correlation (R2= 0.82-0.90) and differed less than 1 dB of visual sensitivity within the GCc range between cohorts. The established structure-function relationship was compatible with a histologically derived model correlation spanning the range predicted by stimulus sizes GI to GIII. Stimulus sizes within critical spatial summation area (GI-II) improved structure-function correlations in the central visual field. The structure-function relationship was identical in both normal and diseased cohort when GI to GV data were combined. Congruency of GI and GII structure-function correlation with those previously derived with GIII from more peripheral locations further suggests that the structure-function relationship is governed by the number of ganglion cell per stimulus area.
Publisher: Optica Publishing Group
Date: 10-1990
Abstract: Increment-threshold spectral-sensitivity (ITSS) functions and threshold-versus-intensity (tvi) curves were measured under white-light adaptation in rhesus monkeys. The tvi curves showed shape and test wavelength invariance, implying that three cone mechanisms were mediating detection. In general, the results were in agreement with the differential adaptation hypothesis proposed by Stiles that predicted spectral shape invariance of the cone mechanisms but overall changes in the shape of the spectral-sensitivity function with increases in the intensity of the adapting field. The principal changes occurring in the ITSS function as the level of adaptation increased involved a smaller loss in sensitivity of the short-wavelength and the long-wavelength peaks compared with the corresponding loss in sensitivity of the middle-wavelength peak. A three-channel model with an opponent L-M mechanism and a nonopponent L-M mechanism (both with S-cone input) and an independent S-cone mechanism described the ITSS data as well as other increment-threshold and suprathreshold data. The model values for the ITSS functions, along with parameters derived from the transformation of these data to cone-contrast coordinates, permitted the factoring out of first-site adaptation, second-site adaptation, and the relative strengths of contribution of the L and M cones within the opponent and nonopponent L-M channels.
Publisher: Informa UK Limited
Date: 03-2018
DOI: 10.1111/CXO.12607
Publisher: Informa UK Limited
Date: 09-2005
DOI: 10.1111/J.1444-0938.2005.TB06715.X
Abstract: Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries. With an ageing population, the prevalence of such a condition has resulted in a large proportion of the population relying on peripheral vision to undertake activities of daily living. Peripheral vision is not a scaled-down version of the fovea, simply requiring larger print or increased contrast for detection of objects or reading text. Even when print size is scaled and eye movements are minimised, the peripheral retina cannot perform at the level of the foveal region. Understanding how and why reading performance is limited as a function of eccentricity has important implications for how we approach rehabilitation of patients with central visual loss. This brief review of the extensive literature on reading with peripheral vision and the research aimed at better reading rehabilitation for low vision patients focuses on why many of the problems associated with the reduced reading capability of peripheral vision cannot be completely solved with magnification, reducing eye movements or modifying print.
Publisher: Wiley
Date: 11-2018
DOI: 10.1111/OPO.12589
Abstract: 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. 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. 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 ). 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.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 07-08-2019
DOI: 10.1167/TVST.8.4.20
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 28-01-2022
DOI: 10.1167/TVST.11.1.37
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 06-2003
DOI: 10.1167/IOVS.02-1054
Abstract: To consider how aerobic and anaerobic metabolic processes limit posthypoxemic decay in retinal function, measured by electroretinogram (ERG). The hypothesis that lowering metabolic demand would prolong endogenous metabolic stores was tested by comparing the rate of ERG decay in rats in dark- (n = 5) versus light-adapted (15 minutes, 112 cd/m(2), n = 5) conditions and with serial versus single (n = 5 at each of seven time points) light stimulation. Postmortem hypoxemia was induced by cervical dislocation. Glucose (10 and 100 mM) and glutamine or lactate (100 mM) were injected into the vitreous 10 minutes before hypoxemic insult, to consider glycolytic-oxidative versus oxidative metabolism, respectively. Lowering the metabolic drain by light adaptation or serial stimulation significantly improved the photoreceptoral saturated litude during the first 5 to 7.5 minutes after postmortem hypoxemia. Increasing substrate availability with exogenous glucose preloading delayed the loss of the photoreceptoral response, thereby extending the delay constant from 4.8 to 10.9 minutes. Postreceptoral litudes were not improved by any exogenous substrate. Providing glucose at 5 minutes after hypoxemia provided no benefits. Similar to glucose, glutamine and lactate loading significantly delayed photoreceptoral decay over the first 7.5 minutes, after which time glucose was the more effective substrate. The postmortem decay of photoreceptoral function reflects depletion of both endogenous oxygen and carbon substrate reserves. The findings provide evidence that a transition between aerobic and anaerobic metabolism occurs after approximately 8 minutes of complete hypoxemia.
Publisher: Informa UK Limited
Date: 05-2019
DOI: 10.1111/CXO.12847
Publisher: Springer Science and Business Media LLC
Date: 1998
DOI: 10.3758/BF03206869
Abstract: The characteristics of artificially induced anisometropic suppression were investigated in observers with normal and abnormal binocular vision (anisometropic amblyopia) by using a simple reaction time paradigm. Reaction time was measured as a function of stimulus intensity for various stimulus durations. For all conditions, the reaction time increased as stimulus intensity decreased toward threshold. We found that traditional techniques for modeling this trend were inadequate, so we developed a simple visuogram method for comparing these functions. Using this technique, reaction time versus intensity functions are shown to be shape-invariant for all conditions examined. This means that, although reaction times are longer during induced anisometropic suppression or in anisometropic amblyopia, they are the same if contrast is normalized to equate threshold. The shape-invariant nature of these functions is also consistent with the notion that a single mechanism mediates detection under these conditions. Temporal summation was investigated at both threshold (method of limits) and suprathreshold (criterion reaction time) levels. Again, because of shape invariance, the suprathreshold results mirror the threshold results. The critical duration (the duration at the intersection of the complete summation and zero summation regions) is not affected by any of the conditions. However, the critical intensity (the intensity for the zero summation region) is higher for the amblyopic eyes, as compared with the normal or nonamblyopic eyes. Induced anisometropic suppression always increases the critical intensity, with a smaller increase occurring for the amblyopic eyes. This suggests that amblyopic eyes do not have a need for strong suppression.
Publisher: Elsevier BV
Date: 08-1998
DOI: 10.1016/S0896-6273(00)80539-5
Abstract: Cell lineage analyses suggest that cortical neuroblasts are capable of undertaking both radial and tangential modes of cell movement. However, it is unclear whether distinct progenitors are committed to generating neuroblasts that disperse exclusively in either radial or tangential directions. Using highly unbalanced mouse stem cell chimeras, we have identified certain progenitors that are committed to one mode of cell dispersion only. Radially dispersed neurons expressed glutamate, the neurochemical signature of excitatory pyramidal cells. In contrast, tangential progenitors gave rise to widely scattered neurons that are predominantly GABAergic. These results suggest lineage-based mechanisms for early specification of certain progenitors to distinct dispersion pathways and neuronal phenotypes.
Publisher: Springer Science and Business Media LLC
Date: 06-05-2022
DOI: 10.1038/S41598-022-11070-6
Abstract: Drusen are a hallmark lesion of age-related macular degeneration (AMD) and changes in their area and/or volume are strongly associated with disease progression. Assessment of longitudinal change in drusen size in clinical practice however is limited to a single commercial tool or manual inspection by clinicians. In this study we analysed change in drusen area in 33 eyes with intermediate AMD across two separate visits using a novel technique known as multispectral pattern recognition for en face retinal images from various imaging modalities (infrared (815 nm), fundus autofluorescence (488 nm) and green (532 nm) scanning laser ophthalmoscopy). We found 91% (30/33 eyes) agreement in the direction of drusen change for multispectral pattern recognition relative to expert graders who graded eyes as having drusen progression, regression or being stable. Multispectral pattern recognition showed 100% sensitivity (22/22 eyes) and 73% specificity (8/11 eyes). In comparison, we found only 70% (23/33 eyes) agreement in the direction of drusen change with a commercially available change analysis software, the Cirrus Advanced RPE Analysis relative to expert graders, with a sensitivity 64% (14/22 eyes) and specificity of 82% (9/11 eyes). Total drusen area or amount of change between visits had no significant effect on agreement. This suggests multispectral pattern recognition can quantify longitudinal change in drusen area from multimodal imaging with greater congruency to expert graders than a commercially available platform based on a single imaging modality. Considering the association of drusen area and disease progression, this method could aid clinical assessment and monitoring of AMD.
Publisher: Informa UK Limited
Date: 03-2004
DOI: 10.1111/J.1444-0938.2004.TB03152.X
Abstract: Retinitis pigmentosa (RP) is a leading cause of human blindness due to degeneration of retinal photoreceptor cells. Causes of retinal degeneration include defects in the visual pigment, defects in the proteins important for photoreceptor function or in enzymes involved in initiating visual transduction. Despite the ersity of genetic mutations identified in inherited forms of retinal dystrophy, there is a common end result of photoreceptor death and functional blindness. In this review, pertinent anatomical and physiological pathways involved in RP and the underlying genetic mutations are outlined, including a discussion on the inheritance patterns revealed by advances in molecular biological techniques. Characteristics of progression rates of visual field loss and current management options will provide useful clinical guidelines for the management of patients with RP.
Publisher: Wiley
Date: 06-04-2009
DOI: 10.1002/CNE.22029
Abstract: Retinitis pigmentosa reflects a family of diseases that result in retinal photoreceptor death and functional blindness. The natural course of retinal changes secondary to photoreceptor degeneration involves anatomical remodeling (cell process alterations and soma displacement) and neurochemical remodeling. Anatomical remodeling predominantly occurs late in the disease process and cannot explain the significant visual deficits that occur very early in the disease process. Neurochemical remodeling includes modified glutamate receptor disposition and altered responses secondary to functional activation of glutamate receptors. We investigated the neurochemical remodeling of retinal neurons in the rd/rd (rd1) mouse retina by tracking the functional activation of glutamate receptors with a cation probe, agmatine. We provide evidence that bipolar cells and amacrine cells undergo selective remodeling of glutamate receptors during the early phases of retinal degeneration. These early neurochemical changes in the rd/rd mouse retina include the expression of aberrant functional ionotropic glutamate receptors on the cone ON bipolar cells from postnatal day 15 (P15), poor functional activation of metabotropic glutamate receptors on both rod and cone ON bipolar cells throughout development/degeneration, and poor functional activation of N-methyl-D-aspartate receptors on amacrine cells from P15. Our results suggest that major neurochemical remodeling occurs prior to anatomical remodeling, and likely accounts for the early visual deficits in the rd/rd mouse retina.
Publisher: Springer Science and Business Media LLC
Date: 28-10-2020
DOI: 10.1038/S41598-020-75599-0
Abstract: We aimed to evaluate methods of extracting optical coherence tomography (OCT)-derived macular ganglion cell-inner plexiform layer (GCIPL) thickness measurements over retinal locations corresponding to standard visual field (VF) test grids. A custom algorithm was developed to automatically extract GCIPL thickness measurements from locations corresponding to Humphrey Field Analyser 10-2 and 30-2 test grids over Goldmann II, III and V stimulus sizes from a healthy cohort of 478 participants. Differences between GCIPL thickness measurements based on VF test grids (VF-based paradigms) and the 8 × 8 grid, as per instrument review software, were analyzed, as were impacts of fovea to optic disc tilt and areas over which GCIPL thickness measurements were extracted. Significant differences between the VF-based paradigms and the 8 × 8 grid were observed at up to 55% of locations across the macula, with the greatest deviations at the fovea (median 25.5 μm, 95% CI 25.24–25.72 μm, P .0001). While significant correlations with fovea to optic disc tilt were noted at up to 33% of locations distributed 6°–8° from the foveal center, there were no marked differences in GCIPL thickness measurements between VF-based paradigms using different stimulus sizes. As such, standard high-density OCT measurement paradigms do not adequately reflect GCIPL measurements at retinal locations tested with standard VF patterns, with the central macular region contributing most to the observed differences and with further correction required for fovea to optic disc tilt. Spatial direction of GCIPL thickness measurements will improve future comparisons of structure and function, thereby improving methods designed to detect pathology affecting the inner retina.
Publisher: Elsevier BV
Date: 03-2012
DOI: 10.1016/J.NBD.2011.12.004
Abstract: Huntington's disease (HD) is a progressive neurological disease characterised by motor dysfunction, cognitive impairment and personality changes. Previous work in HD patients and animal models of the disease has also highlighted retinal involvement. This study characterised the changes in retinal structure and function early within the progression of disease using the R6/1 mouse model of HD. The retinal phenotype was observed to occur at the same time in the disease process as other neurological deficits such as motor dysfunction (by 13 weeks of age). There was a specific functional deficit in cone response to the electroretinogram and using immunocytochemical techniques, this dysfunction was found to be likely due to a progressive and complete loss of cone opsin and transducin protein expression by 20 weeks of age. In addition, there was an increase in Müller cell gliosis and the presence of ectopic rod photoreceptor terminals. This retinal remodelling is also observed in downstream neurons, namely the rod and cone bipolar cells. While R6/1 mice exhibit significant retinal pathology simultaneously with other more classical HD alterations, this doesn't lead to extensive cell loss. These findings suggest that in HD, cone photoreceptors are initially targeted, possibly via dysregulation of protein expression or trafficking and that this process is subsequently accompanied by increased retinal stress and neuronal remodelling also involving the rod pathway. As retinal structure and connectivity are well characterised, the retina may provide a useful model tissue in which to characterise the mechanisms important in the development of neuronal pathology in HD.
Publisher: Cambridge University Press (CUP)
Date: 07-1994
DOI: 10.1017/S0952523800003096
Abstract: Postembedding immunocytochemistry was used to determine the retinal distribution of the amino acid glutamine, and characterize amino acid signatures in the avian retinal ganglion cell layer. Glutamine is a potential precursor of glutamate and some glutamatergic neurons may use this amino acid to sustain production of glutamate for neurotransmission. Ganglion cells, cells in the inner nuclear layer, and some photoreceptors exhibited glutamine immunoreactivity of varying intensity. Ganglion cells demonstrated the highest level of immunoreactivity which indicates either slow glutamine turnover or active maintenance of a large standing glutamine pool relative to other glutamatergic neurons. Müller's cells in the avian retina are involved in glutamate uptake and carbon recycling by the rapid conversion of glutamate to glutamine, thus explaining the low glutamate and high glutamine immunoreactivity found throughout Müller's cells. Most chicken retinal ganglion cells are glutamate (E) and glutamine (Q) immunoreactive but display erse signatures with presumed functional subsets of cells displaying admixtures of E and Q with GABA (7) and/or glycine (G). The four major ganglion cell signatures are (1) EQ (2) EQγ (3) EQG and (4) EQγG.
Publisher: Wiley
Date: 21-12-2013
DOI: 10.1016/J.IJDEVNEU.2013.12.005
Abstract: This study characterizes the developmental patterns of seven key amino acids: glutamate, γ-amino-butyric acid (GABA), glycine, glutamine, aspartate, alanine and taurine in the mouse retina. We analyze amino acids in specific bipolar, amacrine and ganglion cell sub-populations (i.e. GABAergic vs. glycinergic amacrine cells) and anatomically distinct regions of photoreceptors and Müller cells (i.e. cell bodies vs. endfeet) by extracting data from previously described pattern recognition analysis. Pattern recognition statistically classifies all cells in the retina based on their neurochemical profile and surpasses the previous limitations of anatomical and morphological identification of cells in the immature retina. We found that the GABA and glycine cellular content reached adult-like levels in most neurons before glutamate. The metabolic amino acids glutamine, aspartate and alanine also reached maturity in most retinal cells before eye opening. When the overall amino acid profiles were considered for each cell group, ganglion cells and GABAergic amacrine cells matured first, followed by glycinergic amacrine cells and finally bipolar cells. Photoreceptor cell bodies reached adult-like amino acid profiles at P7 whilst Müller cells acquired typical amino acid profiles in their cell bodies at P7 and in their endfeet by P14. We further compared the amino acid profiles of the C57Bl/6J mouse with the transgenic X-inactivation mouse carrying the lacZ gene on the X chromosome and validated this animal model for the study of normal retinal development. This study provides valuable insight into normal retinal neurochemical maturation and metabolism and benchmark amino acid values for comparison with retinal disease, particularly those which occur during development.
Publisher: Informa UK Limited
Date: 06-09-2023
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 15-11-2021
Publisher: Springer Science and Business Media LLC
Date: 02-07-2020
DOI: 10.1038/S41598-020-67829-2
Abstract: The choroidal vascularity index (CVI) has been shown to be sensitive in detecting changes in choroidal angioarchitecture in a range of ocular diseases. However, changes in CVI in association with normal physiological aging and spatial distribution remains to be determined. This is significant as a range of ocular conditions with choroidal degeneration are associated with aging. In this study, we assessed CVI for 106 healthy eyes from 106 in iduals (range 21–78 years old, ~ 20 in iduals/decade) at 15 eccentricities across the macula (0, 230 µm, 460 µm, 690 µm, 1,150 µm, 1,380 µm and 2,760 µm from the fovea in the superior and inferior direction). Total choroidal area, luminal area and stromal area were all significantly decreased with age (p 0.001 for all parameters). CVI was also significantly decreased with age (p 0.01) and eccentricity. Fitting of quadratic regression curves to CVI as a function of age yielded a good fit for all eccentricities (r 2 = 0.55–0.80) and suggested a decrease in CVI from the ages of 33–43 years at a rate of 0.7–2.7% per decade. CVI was lower in the inferior versus superior retina at matching eccentricities and a significant difference in age-related decline of CVI with eccentricity only occurred in inferior locations. These findings suggest choroidal angioarchitecture declines from the 4th decade of life with potential eccentricity differences in the inferior and superior retina. Considering the number of age-related diseases with choroidal dysfunction, these results provide foundational knowledge to understand choroidal involvement in these diseases.
Publisher: Public Library of Science (PLoS)
Date: 06-07-2016
Publisher: Elsevier BV
Date: 2002
Publisher: Cambridge University Press (CUP)
Date: 05-04-2013
DOI: 10.1017/S0952523813000047
Abstract: The proline-23-histidine line 3 (P23H-3) transgenic rat carries a human opsin gene mutation leading to progressive photoreceptor loss characteristic of human autosomal dominant retinitis pigmentosa. The aim of the present study was to evaluate neurochemical modifications in the P23H-3 retina as a function of development and degeneration. Specifically, we investigated the ion channel permeability of photoreceptors by tracking an organic cation, agmatine (1-amino-4-guanidobutane, AGB), which permeates through nonspecific cation channels. We also investigated the activity of ionotropic glutamate receptors in distinct populations of bipolar, amacrine, and ganglion cells using AGB tracking in combination with macromolecular markers. We found elevated cation channel permeation in photoreceptors as early as postnatal day 12 (P12) suggesting that AGB labeling is an early indicator of impending photoreceptor degeneration. However, bipolar, amacrine, or ganglion cells displayed normal responses secondary to ionotropic glutamate receptor activation even at P138 when about one half of the photoreceptor layer was lost and apoptosis and gliosis were observed. These results suggest that possible therapeutic windows as downstream neurons in inner retina appear to retain normal function with regard to AGB permeation when photoreceptors are significantly reduced but not lost.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2018
DOI: 10.1097/OPX.0000000000001256
Abstract: Drusen are associated with retinal thinning in age-related macular degeneration (AMD). These changes, however, have mostly been examined at single time points, ignoring the evolution of drusen from emergence to regression. Understanding the full breadth of retinal changes associated with drusen will improve understanding of disease pathogenesis. The purpose of this study was to assess how the natural history of drusen affects retinal thickness, focusing on the photoreceptor and retinal pigment epithelium (RPE) layers. Spectral domain optical coherence tomography of subjects with intermediate AMD (n = 50) who attended the Centre for Eye Health, Sydney, Australia, for two separate visits (476 ± 16 days between visits) was extracted. Scans were automatically segmented with manufacturer software then assessed for drusen that had emerged, grown, or regressed between visits. For each identified lesion, the thickness of each retinal layer at the drusen peak and at adjacent drusen-free areas (150 μm nasal and temporal to the druse) was compared between visits. Before drusen emergence, the RPE was significantly thicker at the drusen site (14.2 ± 2.6%) compared with neighboring drusen-free areas. There was a 71% sensitivity of RPE thickening predicting drusen emergence. Once drusen emerged, significant thinning of all outer retinal layers was observed, consistent with previous studies. Drusen growth was significantly correlated with thinning of the outer retina ( r = −0.38, P .001). Drusen regression resulted in outer retinal layers returning to thicknesses not significantly different from baseline. The natural history of drusen is associated with RPE thickening before drusen emergence, thinning of the outer nuclear layer as well as photoreceptor and RPE layers proportional to drusen growth, and return to baseline thickness after drusen regression. These findings have useful clinical applications, providing a potential marker for predicting drusen emergence for AMD prognostic and intervention studies and highlighting that areas of normal retinal thickness in AMD may be former sites of regressed drusen.
Publisher: Oxford University Press (OUP)
Date: 16-09-2010
Abstract: The Reelin signaling pathway is essential for proper cortical development, but it is unclear to whether Reelin function is primarily important for cortical layering or neuron migration. It has been proposed that Reelin is perhaps required only for somal translocation but not glial-dependent locomotion. This implies that the location of neurons responding to Reelin is restricted to the outer regions of the cortical plate (CP). To determine whether Reelin is required for migration outside of the CP, we used time-lapse imaging to track the behavior of cells undergoing locomotion in the germinal zones. We focused on the migratory activity in the ventricular/subventricular zones where the first transition of bipolar to multipolar migration occurs and where functional Reelin receptors are known to be expressed. Despite Reelin loss, neurons had no difficulty in undergoing radial migration and indeed displayed greater migratory speed. Additionally, compared with the wild-type, reeler neurons displayed altered trajectories with greater deviation from a radial path. These results suggest that Reelin loss has early consequences for migration in the germinal zones that are portrayed as defective radial trajectories and migratory speeds. Together, these abnormalities can give rise to the increased cell dispersion observed in the reeler cortex.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 13-10-2017
Publisher: Informa UK Limited
Date: 11-2014
DOI: 10.1111/CXO.12194
Abstract: Eye health-care in Australia encompasses patients with chronic disorders being referred to ophthalmologists for detailed assessment and subsequent management. An increasing case load and relative decrease in ophthalmologists predicted over the next few years portend of an upcoming bottleneck in care delivery. To improve the efficiency and effectiveness of patient care within a rapidly changing health system, we propose that minor adjustments to existing services could improve the proficiency of resources. Such changes will require service providers to rethink their positions and roles and actively collaborate with each other for improved patient outcomes.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2014
Publisher: Springer Science and Business Media LLC
Date: 11-06-2021
DOI: 10.1038/S41598-021-89751-X
Abstract: Stereopsis provides critical information for the spatial visual perception of object form and motion. We used virtual reality as a tool to understand the role of global stereopsis in the visual perception of self-motion and spatial presence using virtual environments experienced through head-mounted displays (HMDs). Participants viewed radially expanding optic flow simulating different speeds of self-motion in depth, which generated the illusion of self-motion in depth (i.e., linear vection). Displays were viewed with the head either stationary (passive radial flow) or laterally swaying to the beat of a metronome (active conditions). Multisensory conflict was imposed in active conditions by presenting displays that either: (i) compensated for head movement (active compensation condition), or (ii) presented pure radial flow with no compensation during head movement (active no compensation condition). In Experiment 1, impairing stereopsis by anisometropic suppression in healthy participants generated declines in reported vection strength, spatial presence and severity of cybersickness. In Experiment 2, vection and presence ratings were compared between participants with and without clinically-defined global stereopsis. Participants without global stereopsis generated impaired vection and presence similarly to those found in Experiment 1 by subjects with induced stereopsis impairment. We find that reducing global stereopsis can have benefits of reducing cybersickness, but has adverse effects on aspects of self-motion perception in HMD VR.
Publisher: Springer Science and Business Media LLC
Date: 12-01-2021
DOI: 10.1038/S41598-020-79424-6
Abstract: Current descriptions of retinal thickness across normal age cohorts are mostly limited to global analyses, thus overlooking spatial variation across the retina and limiting spatial analyses of retinal and optic nerve disease. This retrospective cross-sectional study uses location-specific cluster analysis of 8 × 8 macular average grid-wise thicknesses to quantify topographical patterns and rates of normal, age-related changes in all in idual retinal layers of 253 eyes of 253 participants across various age cohorts (n = 23–69 eyes per decade). Most retinal layers had concentric spatial cluster patterns except the retinal nerve fibre layer (RNFL) which displayed a nasal, asymmetric radial pattern. Age-related thickness decline mostly occurred after the late 4th decade, described by quadratic regression models. The ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), and outer nuclear layer + Henle’s fibre layer (ONL +HFL ) were significantly associated with age ( p 0.0001 to 0.05), demonstrating similar rates of thickness decline (mean pooled slope = − 0.07 µm/year), while the IS/OS had lesser mean pooled thickness slopes for all clusters (− 0.04 µm/year). The RNFL, OPL, and RPE exhibited no significant age-related thickness change, and the RNFL were significantly associated with sex. Analysis using spatial clusters compared to the ETDRS sectors revealed more extensive spatial definition and less variability in the former method. These spatially defined, clustered normative data and age-correction functions provide an accessible method of retinal thickness analysis with more spatial detail and less variability than the ETDRS sectors, potentially aiding the diagnosis and monitoring of retinal and optic nerve disease.
Publisher: Wiley
Date: 27-10-2016
DOI: 10.1111/OPO.12322
Abstract: 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. 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. 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%). 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.
Publisher: Informa UK Limited
Date: 03-2018
DOI: 10.1111/CXO.12624
Abstract: Age-related macular degeneration is a common, complex and blinding eye disease. When early and intermediate levels of severity are detected in one or both eyes, there is a wide-ranging 0.4 to 53 per cent risk of progression to advanced disease in five years. In order to maximise visual outcomes for their patients, practising eye-care professionals must be able to stratify patients according to their risk of progression, intervene (for ex le by recommending smoking cessation or nutritional supplements and Amsler grid self-monitoring in intermediate disease) and monitor accordingly. With the aid of ocular imaging, a range of under-recognised yet meaningful risk factors have been identified. The purpose of this review is to assist the eye-care practitioner in stratifying the risk of progression in intermediate age-related macular degeneration using the range of established and emerging precursory signs that herald loss of vision.
Publisher: SPIE
Date: 27-02-2018
DOI: 10.1117/12.2293434
Publisher: Informa UK Limited
Date: 09-2020
DOI: 10.1111/CXO.12984
Abstract: The imaging characteristics of congenital grouped pigmentation of the retinal pigment epithelium (CGP-RPE) and its non-pigmented variant - grouped congenital albinotic retinal pigment epithelial spots (GCARPES) are poorly defined in the literature. Our case series reports their multimodal imaging characteristics across a spectrum of presentations. A retrospective review of patient records was conducted on patients seen at the Centre for Eye Health between January and December 2016. The multimodal imaging findings across four cases is described using optical coherence tomography (OCT), infrared imaging, ultra-widefield imaging, fundus photography and fundus autofluorescence (FAF). Case 1 is a 55-year-old female with a bilateral presentation of CGP-RPE showing typical features. Case 2 is a 28-year-old male with a classical presentation of GCARPES in the left eye. Case 3 is a 33-year-old female with unilateral CGP-RPE and an atypical solitary congenital hypertrophy of the retinal pigment epithelium (CHRPE) in the same eye. Case 4 is a unilateral presentation in an 11-year-old female with unusual characteristics. Ocular imaging characteristics of CGP-RPE lesions varied between patients: OCT showed visible RPE changes in cases 3 and 4 but not case 1. The pattern of FAF and infrared imaging also varied with most lesions displaying a pattern of hypo-autofluorescence, but some central lesions in case 3 exhibited hyper-autofluorescence. All lesions were visible with fundus photography. FAF can be helpful in alerting clinicians to the presence of lesions that may be difficult to visualise funduscopically and OCT can be helpful in differentiating between CGP-RPE and its variants from more sinister ocular conditions. All in all, these findings highlight the variable manifestation of CGP-RPE and its variants on multimodal imaging the diagnosis of CGP-RPE and its variants should remain based on its characteristic funduscopic appearance.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 20-09-2021
DOI: 10.1097/OPX.0000000000001806
Abstract: Intraocular pressure (IOP) profiling is an important component of the glaucoma examination. Two techniques for profiling are the water drinking test (WDT) and iCare HOME phasing, but the correlations between techniques and their ease of deployment have not been studied. These questions are important in determining suitability for clinical deployment. This study aimed to compare the IOP results of the WDT and iCare HOME phasing in patients with suspected or newly diagnosed glaucoma. Ninety-eight consecutive patients attending a glaucoma clinic underwent IOP profiling using both techniques. For the WDT, patients ingested 10 mL/kg body weight of water after a baseline applanation IOP measurement and then underwent serial IOP measurements approximately every 15 minutes, ceasing after 30 minutes of consecutive measurements within 3 mmHg of baseline. Patients successfully certified for self-administration of the iCare HOME were loaned the instrument for 1 week and instructed to take four measurements per day. Twenty-seven patients (28%) successfully obtained four measurements per day using iCare HOME, and 96 patients (98%) were able to complete the WDT. Intraocular pressure profiles showed no difference between the time for peak IOP and across nearly all IOP parameters obtained from profiling except for the standard deviation of IOP measurements obtained using the iCare HOME ( P = .005). There were moderate correlations between peak IOPs obtained using each technique ( r = 0.67, P = .001, right eye r = 0.66, P = .002, left eye) but no correlation between the daily range (iCare HOME) or peak-trough difference (WDT r = 0.21, P = .28, right eye r = 0.27, P = .02, left eye). Bland-Altman analysis returned similar results for peak and range. Intraocular pressure profiling using both techniques can reveal the peak IOP, and these measurements are strongly correlated. Most patients were unable to complete the iCare HOME according to the manufacturer's recommendations. Clinicians should select the most appropriate technique for each patient.
Publisher: Informa UK Limited
Date: 2002
DOI: 10.1111/J.1444-0938.2002.TB03069.X
Abstract: Retinal neural and glial cells share an intricate relationship that includes uptake and recycling of the amino acid neurotransmitters, glutamate and gamma-amino butyric acid (GABA), as well as metabolic links. The aim of this work was to determine the neurochemical and morphological changes induced by the removal of glucose but with the provision of exogenous glutamate in the isolated retinal preparation incubated under aerobic conditions. The carbon skeleton of glutamate can enter the tricarboxylic acid cycle as alpha-ketogluterate, providing an alternative metabolic substrate in cases of glucose deprivation. Isolated rat retinas were incubated in physiological media with and without glucose, using a range of glutamate concentrations to provide an alternative source of metabolic substrate. We conducted post-embedding immunocytochemistry and quantified the change in glutamate and GABA immunoreactivity within Müller cells under these different incubation conditions. The provision of glutamate with normal (6 mM) glucose levels resulted in a gradual accumulation of glutamate and GABA in Müller cells, with Müller loading when exogenous glutamate concentrations were above 0.1 mM. However, when these varying levels of glutamate were applied in the absence of glucose, glutamate accumulation in Müller cells was decreased compared to the 6 mM glucose condition and GABA accumulation in Müller cells was at a minimum at moderate (0.5 and 1 mM) glutamate levels. Under hypoglycaemic conditions, exogenous glutamate (0.5 to 1 mM) is rapidly metabolised by Müller cells to the extent that no glial loading is evident, despite the high concentrations. Normal neurochemical function appears to be maintained secondary to exogenous glutamate provision of 0.5 to 1 mM when glucose is not in the incubation medium, implying that glutamate can be used as an alternative metabolic substrate. We also show that Müller cells possess more rapid glutamate metabolic capabilities compared to the metabolism of GABA.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2001
DOI: 10.1097/00006324-200112000-00014
Abstract: We determined word acuity thresholds as a function of contrast and retinal eccentricity to determine the rate of threshold alteration in the normal retinal periphery. Subjects identified words presented foveally (0 degrees eccentricity) or above the point of fixation at retinal eccentricities of 0.5, 1, 2, 3, 6, and 8 degrees for three contrast levels of 10, 45, and 85%. A descending method of limits was used to determine thresholds for random four-letter words flashed for 90 ms at the different retinal eccentricities. For high-contrast letters, word acuity displayed threshold elevation in the periphery similar to previous reports and similar threshold elevation to those reported for vernier acuity. Lower contrast levels displayed different threshold change as a function of eccentricity, approaching levels reported for grating acuity. When comparing the relative elevation of word acuity thresholds for the different contrast levels (85 vs. 45% and 85 vs. 10%), both comparisons showed that the most rapid decline in word acuity threshold occurs within 2 degrees of the fovea. The peripheral retina displays a reduction in word acuity threshold that is dependent on letter contrast and shows a change similar to those reported for higher cortical functions such as vernier thresholds. The greatest word threshold elevation occurs within the central 2 degrees of the fovea.
Publisher: Wiley
Date: 15-04-1996
DOI: 10.1002/(SICI)1096-9861(19960415)367:4<518::AID-CNE4>3.0.CO;2-7
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 10-02-2022
DOI: 10.1167/TVST.11.2.20
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 18-05-2011
DOI: 10.1167/IOVS.10-6422
Abstract: To investigate how glutamate and glutamine levels are established in the aqueous humor by identifying the transporters and metabolism pathways that contribute to the differential accumulation of glutamate and glutamine between the distinct epithelial cell layers that constitute the ciliary body. Postembedding immunohistochemistry and silver intensification were used to quantify the relative distributions of glutamate, glutamine, and related amino acids (aspartate, alanine, GABA, and glycine) in the pigmented (PE) and nonpigmented (NPE) epithelial cells of the ciliary body. Fluorescent immunocytochemistry was used to localize Na(+)-dependent glutamate transporters (EAAT1-5), glutamine transporters (LAT1, LAT2, and b(0,+)AT), and the enzyme glutamine synthetase (GS) in the ciliary epithelium. Intravitreal injection of the GS inhibitor methionine sulfoximine (MSO) or the EAAT functional probe D-aspartate was used to modulate GS activity and indirectly monitor glutamate uptake from the aqueous, respectively. Although glutamate, glutamine, and alanine were preferentially accumulated in NPE relative to PE cells, no such differential distribution of aspartate, GABA, or glycine was observed. This differential distribution of amino acids was abolished by a single injection of MSO that caused a decrease in glutamine and an increase in glutamate levels in NPE compared with PE cells. This amino acid distribution plus an observed strong labeling of EAAT3 in the interface between the PE and the NPE cell layers indicate that EAAT3 mediates the uptake of glutamate from the blood. Weaker EAAT3 labeling of the basolateral membranes of NPE cells, coupled with the accumulation of injected D-aspartate by the ciliary epithelium, indicates that NPE cells also mediate glutamate uptake directly from the aqueous. In contrast, the basolateral localization of LAT1 and b(0,+)AT in NPE cells suggest that these transporters may mediate glutamine efflux from the NPE cells into the aqueous. The basolateral membrane localization of EAAT3 and LAT1/b(0,+)AT in NPE cells indicates that the low glutamate and high glutamine levels observed in the aqueous are determined by glutamate uptake and glutamine efflux, respectively. Furthermore, the concentration gradient for glutamine efflux appears to be generated by the active accumulation of glutamate by EAAT3, located in the apical membrane of NPE cells and the subsequent conversion of the accumulated glutamate to glutamine by GS in NPE cells. This suggests that in contrast to fluid transport, which uses both the PE and the NPE cell layers, the transepithelial transport of glutamine occurs primarily in the NPE cell layer.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 10-06-2021
DOI: 10.1167/TVST.10.7.9
Publisher: Informa UK Limited
Date: 09-2020
DOI: 10.1111/CXO.13030
Abstract: In ageing populations, the prevalence of chronic diseases such as glaucoma is projected to increase, placing additional demands on limited health-care resources. In the UK, the demand for secondary care in hospital eye clinics was inflated by high rates of false positive glaucoma referrals. Collaborative care models incorporating referral refinement, whereby glaucoma suspect referrals are triaged by suitably trained optometrists through further testing, can potentially reduce false positive referrals. This study examined the impact of a referral refinement model on the accuracy of glaucoma referrals in Australia. Optometrist-initiated glaucoma suspect referrals to the Glaucoma Management Clinic (Sydney, Australia) were prospectively recruited. Glaucoma suspect referrals arising from two pathways were eligible for inclusion, either directly from a community optometrist (standard care) or following comprehensive assessment at the Centre for Eye Health (referral refinement). Main outcome measures were the positive predictive value and false positive rate of referrals. The impact of referral letter content on management outcomes was also investigated. Of 464 referrals received between March 2015 and June 2018, 252 were for treatment of naïve glaucoma suspects and eligible for inclusion. Following ophthalmological assessment, 45.6 per cent (n = 115/252) were prescribed treatment for open angle glaucoma or ocular hypertension. Positive predictive value of community optometry referrals was 33.8 per cent (n = 25/74) and 50.6 per cent (n = 90/178) following referral refinement. The first visit discharge (false positive) rate was 26 per cent (n = 19/74) for community referrals compared to four per cent (n = 8/178) with referral refinement. Positive predictive value increased with the number of abnormal clinical examination findings associated with referral (χ Referral refinement can improve the diagnostic accuracy of optometry-initiated referrals for glaucoma suspects in Australia, thereby decreasing unnecessary referrals to hospital and other secondary clinics.
Publisher: Informa UK Limited
Date: 17-08-2022
DOI: 10.1080/08164622.2021.1965461
Abstract: Frontloaded visual field testing (twice per eye per session) is well-tolerated by patients and technicians, representing a viable strategy that can be implemented in routine clinical practice to capture enough clinical perimetry data for effective disease diagnosis, surveillance and management. To determine the experiences of patients and technicians following the implementation of frontloaded visual field testing (multiple tests per eye within the same session) in a glaucoma service. This was a retrospective, cross-sectional study. A written questionnaire was administered to patients (three questions) attending the glaucoma service at the Centre for Eye Health for glaucoma assessment and to their administering perimetry technicians (two questions). The questionnaire was administered after static automated perimetry (24-2 SITA-Faster on the Humphrey Field Analyzer) was performed twice for each eye (frontloaded) within the same session. Respondents were asked to provide a 1-5 Likert scale response to questions that targeted operational issues for frontloaded visual field testing. Responses were correlated against to demographic (age, gender, ethnicity) and clinical (diagnosis, refractive error, visual field indices, test duration) parameters. Approximately 90% of patient respondents agreed that frontloaded visual field testing was clearly explained to them, that they were comfortable during the test, and would prefer completing the tests at a single visit rather than returning to repeat the test. Most technician respondents were also able to keep their patients comfortable. 13% of technician respondents felt they ran late during the session, but on average, the total test duration for four visual field tests was 13 minutes, including breaks. There was no correlation found between demographic and clinical factors, and the responses. Frontloaded visual field testing was well-tolerated by patients and technicians. Strategies that may be helpful for other clinics to adopt this new paradigm are described.
Publisher: Informa UK Limited
Date: 09-11-2022
Publisher: Wiley
Date: 08-03-2021
DOI: 10.1111/OPO.12795
Abstract: A fundamental clinical skill is the recognition of artefacts within the outputs of advanced imaging modalities. However, current teaching programmes of healthcare practitioners are becoming increasingly challenged to provide practical exposure within an already crowded curriculum. This study evaluates the impact of a novel work‐integrated teaching model on the confidence and competence of clinicians in the use of optical coherence tomography (OCT) and the recognition of its artefacts. The outcomes were then used to develop a model to predict performance and guide teaching strategies. We prospectively evaluated a 6‐week clinical placement for final year optometry students within a diagnostic eye clinic in 2018‐2020. Participants completed a quiz on the identification of common OCT artefacts and rated their confidence levels on key areas of OCT application using a five‐point Likert scale. Both were completed before (pre‐rotation) and after (post‐rotation) the placement. The cohort was ided into two groups the first group was used to assess the impact of the placement and derive the prediction model for post‐placement performance, which was then validated against the second group. A significant improvement in detecting OCT imaging artefacts was seen upon completion of the placement, which was greater in participants with lower entry level performance. Across all OCT artefact subtypes, there was an improvement in detecting segmentation error, delineation error and media opacities. A model predicting post‐placement student performance was developed using entry level knowledge base as the key dependent variable. Self‐rated confidence improved across all domains of OCT application but was not found to be a direct predictor of actual performance. These results highlight the benefit of a work‐integrated learning programme on both academic performance and confidence whilst identifying entry level knowledge base as the key variable predicting improvement. Tailored teaching incorporating entering knowledge is the best predictor of improvement during clinical placements. Integrating clinicians into a work‐integrated setting with tailored teaching and comprehensive practical exposure can be an effective method for training future or current healthcare professionals.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 12-01-2015
DOI: 10.1167/15.1.6
Abstract: In the present study, we measured the extent of spatial summation in the detection of image contrast within the central 40° visual field. Contrast detection thresholds (in 28 observers) were measured for a spot of light of 10 different sizes [area: 0.03-1.92(°)(2)] at different retinal meridians (0°, 45°, 90°, 135°, 180°, 225°, 270°, and 315°) and eccentricities (0°, 5°, 10°, 15°, and 20°). Contrast detection thresholds were significantly affected by the size of the stimulus with sensitivity improving with stimulus size consistent with Ricco's law. Summation curves were similar across different spatial meridians, but the extent of spatial summation increased with retinal eccentricity consistent with previous reports. The size of the stimulus was also shown to affect contrast detection thresholds in the periphery. In particular, contrast detection thresholds decreased more rapidly with increasing eccentricity for a smaller target than a larger one. This difference in performance is accounted for by the accompanying change in Ac with eccentricity. In Experiment 2, we show that spatial uncertainty affected contrast detection, particularly at eccentric locations greater than 5°, such that cueing the location of the stimulus improved contrast thresholds. Spatial uncertainty improved overall performance but did not affect the estimates of the critical areas of summation. The results of the present study indicate that, due to spatial summation, detection performance is highly dependent on the size of the stimulus, its eccentric location, and spatial uncertainty. Future perimetric methodologies must consider these factors to improve detection sensitivity.
Publisher: Wiley
Date: 21-04-1997
DOI: 10.1002/(SICI)1096-9861(19970421)380:4<449::AID-CNE3>3.0.CO;2-1
Abstract: We used postembedding immunocytochemistry to determine the localisation of the amino acid neurotransmitters glutamate, gamma-aminobutyrate (GABA), and glycine, potential neurotransmitter precursors (aspartate and glutamine), and taurine in the rat retina during postnatal development. All amino acids investigated were present at birth however, only the inhibitory neurotransmitters GABA and glycine displayed neuronal localisation. GABA was localised in a sparse population of amacrine cells, and glycine immunoreactivity was found in cells within the ventricular zone that appeared to migrate through the neuroblastic layer. Glutamate labelling was diffuse across the retina until postnatal day (PND) 8. Localisation of glutamine was evident within Müller's cells by PND 6, in agreement with the known age of onset of glutamine synthetase activity. Based on the findings of uptake of radiolabelled glutamate and GABA by PND 8 and changes in immunoreactivity, we propose that Müller's cells evolve at PND 6-8 from their precursor cells, the radial glial cells. Evidence for differences in glutamate turnover in the infant retina was seen on examination of aspartate and glutamine immunoreactivity. Aspartate labelling was weak until PND 11, when ganglion cells and some amacrine cells were labelled. Unlike the mature retina, a large number of amacrine cells were glutamine immunoreactive in the PND 6 retina. One reason for the observed differences in precursor pooling may be a lack of neuronal neurotransmitter release and overall low metabolic activity. We also investigated the response of the developing retina to ischaemic insult to test the physiological hypoxia model of vascular development. Our findings are consistent with the hypothesis that the developing retina has increased tolerance to ischaemic insult. Our findings suggest that, although the retina is morphologically adult like by PND 8, there are differences in neurotransmitter turnover in the immature rat retina.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2015
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 17-10-2022
Publisher: Informa UK Limited
Date: 02-03-2021
Publisher: Informa UK Limited
Date: 09-2013
DOI: 10.1111/CXO.12011
Abstract: We localised amino acids in the mid-peripheral aged human retina and a retina that had undergone radiation treatment 10 years earlier. The distribution pattern of glutamate, γ-amino butyric acid (GABA), glycine, glutamine and taurine, reflected patterns established in the primate retina. The retina that had undergone radiation exposure displayed both anatomical and neurochemical remodelling. The proximal retina comprised around 40 to 45 per cent of the total retina and neuronal kinesis and aberrant neuronal projections were also present. Amino acid neurochemistry was strikingly different with Müller cells displaying GABA loading, glycinergic neurons displaced and displaying a very high level of glycine labelling. We conclude that radiation exposure triggered these changes in the human retina and likely reflects general remodelling of structure and function following ischaemic damage to endothelial cells.
Publisher: Informa UK Limited
Date: 05-2013
DOI: 10.1111/CXO.12015
Abstract: Advances in basic retinal anatomy, genetics, biochemical pathways and neurochemistry have not only provided a better understanding of retinal function but have also allowed us to link basic science to retinal disease. The link with disease allowed measures to be developed that now provide an opportunity to intervene and slow down or even restore sight in previously 'untreatable' retinal diseases. One of the critical advances has been the understanding of the retinal amino acid neurotransmitters, related amino acids, their metabolites and functional receptors. This review provides an overview of amino acid localisation in the retina and ex les of how retinal anatomy and amino acid neurochemistry directly links to understanding retinal disease. Also, the implications of retinal remodelling involving amino acid (glutamate) receptors are outlined in this review and insights are presented on how understanding of detrimental and beneficial retinal remodelling will provide better outcomes for patients using strategies for the preservation or restoration of vision. An internet-based database of retinal images of amino acid labelling patterns and other amino acid-related images in health and disease is located at www.aminoacidimmunoreactivity.com.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2020
DOI: 10.1097/OPX.0000000000001478
Abstract: Icare HOME rebound tonometry is increasingly adopted into clinical practice for IOP phasing of glaucoma patients and suspects. Because of measurement differences with applanation tonometry and diurnal fluctuations, interpretation of the IOP measured with Icare HOME phasing can be challenging. The purpose of this study was to use a large patient cohort to develop a practical, analytical tool for interpreting Icare HOME measurements with respect to applanation pressure. IOP measurements using the Icare HOME and an applanation tonometer were taken prospectively in 498 consecutive patients. Bland-Altman, frequency distribution, and linear regression analysis were applied to determine measurement differences. A novel criterion, Threshold Icare HOME IOP, was developed to assist identification of elevation above target applanation pressure, considering the expected diurnal variation and measurement variability. Icare HOME tended to underestimate applanation tonometry (mean bias, −1.7 mmHg 95% limits of agreement, −7.0 to +3.6). Overall, differences were within ±3 mmHg in 71.5% and ±5 mmHg in 92% of patients. Based on the novel criterion developed, Icare HOME measurements that exceed target applanation pressure by 6 mmHg or greater are generally outside the 95% limit of expected observations. The Threshold Icare HOME IOP is a novel and practical criterion that can assist clinicians in their interpretation of Icare HOME phasing measurements with respect to target applanation pressures. Elevation above the expected thresholds may prompt closer monitoring or even modifications to glaucoma management.
Publisher: Elsevier BV
Date: 06-2002
DOI: 10.1016/S0042-6989(02)00075-5
Abstract: Word recognition for Western languages shows an increased probability of a correct response when words are presented to the right of fixation. We considered whether this right bias was consistent at eccentricities superior and inferior to fixation and whether this bias can be altered by different presentation strategies. A right bias of up to approximately 0.9 degrees to the right of fixation was found when words were presented along one horizontal meridian. The eccentricities tested extended up to 8 degrees above and below the point of fixation. However, the right bias was reduced for stimulus conditions where the word was randomly presented within a mosaic containing all possible presentation locations. We have therefore demonstrated that reading habit (right bias) can be manipulated based upon experimental paradigm, strongly supporting the proposition that the left-right asymmetry is a consequence of attending to a particular area of visual space as part of the normal reading habit, rather than an innate superiority for word recognition of the right visual field or reduced visual performance.
Publisher: Cambridge University Press (CUP)
Date: 1999
DOI: 10.1017/S0952523899161108
Abstract: The high-affinity uptake of glutamate by glial cells and neurons of the central nervous system, including the retina, serves to inactivate synaptically released glutamate and maintains glutamate at low concentrations in the extracellular space. This uptake prevents accumulation of glutamate extracellularly and thus minimizes the possibility of glutamate neurotoxicity secondary to ischemic insult. One mechanism whereby glutamate neurotoxicity may occur in ischemic/hypoxic insult is through increased extracellular K + reversing the electrogenic glutamate uptake into retinal glial (Müller) cells. We investigated glial uptake of the amino acids glutamate, GABA, and D-aspartate in the intact isolated rat retina under high extracellular K + conditions and under conditions simulating ischemia. Immunocytochemical findings showed that uptake of glutamate and GABA by Müller cells in the intact isolated rat retina continues under conditions simulating ischemia and high extracellular K + conditions, and uptake of D-aspartate also continues under high K + conditions. However, under high K + conditions, the glutamate uptake system saturates at a lower concentration of exogenous glutamate than in the normal K + condition. These findings provide evidence that disruption of glutamate uptake by Müller cells is likely to be a significant contributing factor to excess glutamate accumulation in the extracellular space which can lead to neurotoxicity.
Publisher: Elsevier BV
Date: 11-2020
Publisher: Frontiers Media SA
Date: 09-04-2019
Publisher: Elsevier BV
Date: 10-2021
DOI: 10.1016/J.AJO.2021.04.019
Abstract: To assess the viability, in terms of time taken for testing and repeatability, of frontloading (performing multiple perimetric examinations) in a single clinic visit. Reliability enhancement analysis. A total of 329 healthy glaucoma suspect and glaucoma subjects within a glaucoma clinic undergoing perimetric testing using SITA-Faster twice for each eye within the same session were included. Global indices, pointwise sensitivity and probability scores, test duration, and reliability metrics were analysed. For both tests 9.1% of right eye and 6.7% of left eye results were unreliable, with 58.4% and 67.5% of right and left eyes achieving reliable results, respectively 83.8% of all subjects spent less than 20 minutes performing all tests. Differences in global indices, pointwise sensitivity and probability scores showed no systematic or clinically significant difference between tests one and two for each eye. There was also no systematic difference in the number of test locations identified as defective at the P < .05 level between tests. Test results that were unreliable tended to show more instances of a failed "cluster" criterion that were not repeatable. Frontloading using SITA-Faster was viable for obtaining sets of reliable, repeatable perimetric data in terms of conventional outputs, overcoming practical issues regarding low test reliability using singleton results and confirmation of visual field defects. Despite the need to remain cognisant of the reliability of SITA-Faster, frontloading using this algorithm may be a practical method for meeting recommendations for multiple perimetric data required to make confident inferences about glaucoma state and progression.
Publisher: Informa UK Limited
Date: 03-2020
DOI: 10.1111/CXO.12923
Abstract: Currently, no specific collaborative care pathway exists that distinguishes open angle glaucoma from narrow angle or angle closure disease. This study evaluates a newly developed referral and collaborative care pathway specifically for patients with angle closure spectrum disease. The medical records of consecutive patients referred to the Centre for Eye Health for glaucoma assessment were examined, six months before (Pre Suite) and after (Post Suite) the introduction of a novel referral pathway for anterior chamber angle assessment (Angle Suite). Patient demographic and clinical data, the referral letter and practitioner characteristics were extracted. Angle Suite (n = 77) patients had an appointment much sooner compared to Pre (n = 383) and Post Suite (n = 425) patients (p < 0.0001). Following the introduction of Angle Suites, there was a reduction of incidental angle closure disease found in routine, non-angle closure glaucoma assessment. Onward referral was required by 36.4 per cent of patients referred for suspected angle closure disease, while the rest could be discharged back into the community (13.0 per cent) or reviewed at the Centre for Eye Health (50.6 per cent). Multinomial logistic regression found that the presence of an angle description in the referral letter improved the true positive rate for angle closure disease (p < 0.0001). The clinical pathway may reduce the number of incidental angle closure patients and improved the timeliness of appropriate clinical care delivered to a subset of patients who may benefit from prompt medical attention. This pathway provides an opportunity for appropriately staffed and equipped collaborative care clinics to reduce the burden on tertiary level ophthalmic facilities.
Publisher: Springer Science and Business Media LLC
Date: 10-09-2020
DOI: 10.1038/S41598-020-71627-1
Abstract: Current tests for assessing metamorphopsia do not account for confounders such as perceptual filling-in and spatial redundancy, which affect its sensitivity and repeatability. This proof-of-concept study aimed to assess the performance of a novel laboratory-based psychophysical test (Line Sag Test, LST) which addresses these issues for quantification of metamorphopsia in idiopathic epiretinal membranes. The LST quantifies perpendicular metamorphopsia at three eccentricities (3°, 6°, and 9°) along eight meridians (45° steps). Metamorphopsia was assessed using the LST and Amsler grid and the hit rates of both tests for detecting metamorphopsia were compared. Normal metamorphopsia scores using the LST did not differ significantly from 0 and fell within one step-size (p = 0.500). The LST detected significantly more cases of metamorphopsia than the Amsler grid (14/21 versus 3/21) (p = 0.003). Similarly, significantly more cases of visual distortions in asymptomatic iERMs were detected using the LST than the Amsler grid (11/18 versus 0/18) (p = 0.008). The LST has a higher hit rate compared to the Amsler grid (67% versus 14%). This work demonstrates a psychophysically-robust functional test addressing perceptual confounders is more sensitive for quantifying and localising metamorphopsia in macular disease, particularly in asymptomatic disease.
Publisher: Wiley
Date: 25-03-2018
DOI: 10.1111/CEO.13187
Publisher: Wiley
Date: 10-2008
DOI: 10.1111/J.1460-9568.2008.06435.X
Abstract: The cystine/glutamate transporter (Xc-) is widely expressed in the central nervous system and is thought to play a role in glutamatergic neurotransmission by releasing low levels of glutamate. Although previous studies have localized the transporter throughout the retina, we now present results from localization and functional studies within the first synaptic layer, i.e. the outer plexiform layer. Using light and electron microscopy, we have localized the Xc- transporter to the ribbon complex of both rod and cone photoreceptors in the rat, cow, l rey, chicken and monkey retina, suggesting that the pre-synaptic expression of the Xc- transporter on the photoreceptor ribbon complex is phylogenetically preserved. The Xc- transporter does not appear to be located within the ribbon synapse of the inner plexiform layer. Developmentally, the evolution of distinct ribbon-shaped Xc- labelling in the outer plexiform layer parallels the known morphological and electrophysiological maturation of photoreceptors. Using the cation channel probe agmatine, we tracked cation fluxes within bipolar cells and therefore indirectly determined the modulation of glutamate release from photoreceptors. Such cystine-driven alteration in agmatine entry into bipolar cells can be modified by a specific metabotropic glutamate receptor 6 antagonist [(RS)-alpha-cyclopropyl-4-phosphonophenylglycine] and an Xc- transport inhibitor [(S)-4-carboxyphenylglycine]. The phylogenetic preservation of the transporter, its ultrastructural localization to the ribbon synapse and functional modulation of post-receptoral neurons collectively support a role for the Xc- transporter in glutamate neurotransmission in the outer retina of vertebrates. We have therefore proposed a model of glutamate release in the photoreceptor synapse that incorporates the Xc- transporter, which complements the established vesicular-mediated glutamate release.
Publisher: Wiley
Date: 23-11-2022
DOI: 10.1111/OPO.13065
Abstract: To analyse optical coherence tomography (OCT)‐derived inner nuclear layer (INL) and outer retinal complex (ORC) measurements relative to ganglion cell‐inner plexiform layer (GCIPL) measurements in glaucoma. Glaucoma participants ( n = 271) were categorised by 10‐2 visual field defect type. Differences in GCIPL, INL and ORC thickness were calculated between glaucoma and matched healthy eyes ( n = 548). Hierarchical cluster algorithms were applied to generate topographic patterns of retinal thickness change, with agreement between layers assessed using Cohen's kappa (κ). Differences in GCIPL, INL and ORC thickness within and outside GCIPL regions showing the greatest reductions and Spearman's correlations between layer pairs were compared with 10‐2 mean deviation (MD) and pattern standard deviation (PSD) to determine trends with glaucoma severity. Glaucoma participants with inferior and superior defects presented with concordant GCIPL and INL defects demonstrating mostly fair‐to‐moderate agreement (κ = 0.145–0.540), which was not observed in eyes with no or ring defects (κ = −0.067–0.230). Correlations ( r ) with MD and PSD were moderate and weak in GCIPL and INL thickness differences, respectively (GCIPL vs. MD r = 0.479, GCIPL vs. PSD r = −0.583, INL vs. MD r = 0.259, INL vs. PSD r = −0.187, p = .0001–0.002), and weak in GCIPL‐INL correlations (MD r = 0.175, p = 0.004 and PSD r = 0.154, p = 0.01). No consistent patterns in ORC thickness or correlations were observed. In glaucoma, concordant reductions in macular INL and GCIPL thickness can be observed, but reductions in ORC thickness appear unlikely. These findings suggest that trans‐synaptic retrograde degeneration may occur in glaucoma and could indicate the usefulness of INL thickness in evaluating glaucomatous damage.
Publisher: American Physiological Society
Date: 10-2005
DOI: 10.1152/AJPCELL.00137.2005
Abstract: Creatine and phosphocreatine are required to maintain ATP needed for normal retinal function and development. The aim of the present study was to determine the distribution of the creatine transporter (CRT) to gain insight to how creatine is transported into the retina. An affinity-purified antibody raised against the CRT was applied to adult vertebrate retinas and to mouse retina during development. Confocal microscopy was used to identify the localization pattern as well as co-localization patterns with a range of retinal neurochemical markers. Strong labeling of the CRT was seen in the photoreceptor inner segments in all species studied and labeling of a variety of inner neuronal cells (amacrine, bipolar, and ganglion cells), the retinal nerve fibers and sites of creatine transport into the retina (retinal pigment epithelium, inner retinal blood vessels, and perivascular astrocytes). The CRT was not expressed in Müller cells of any of the species studied. The lack of labeling of Müller cells suggests that neurons are independent of this glial cell in accumulating creatine. During mouse retinal development, expression of the CRT progressively increased throughout the retina until approximately postnatal day 10, with a subsequent decrease. Comparison of the distribution patterns of the CRT in vascular and avascular vertebrate retinas and studies of the mouse retina during development indicate that creatine and phosphocreatine are important for ATP homeostasis.
Publisher: Ubiquity Press, Ltd.
Date: 07-08-2020
DOI: 10.5334/IJIC.5470
Publisher: Wiley
Date: 17-10-2017
DOI: 10.1111/OPO.12413
Abstract: 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. 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. 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 . 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.
Publisher: Springer Science and Business Media LLC
Date: 02-2005
DOI: 10.1007/S00125-004-1639-5
Abstract: Glutamate recycling is a major function of retinal Muller cells. The aim of this study was to evaluate the expression and function of glutamate transporters during diabetes. Sprague-Dawley rats were rendered diabetic by a single dose of streptozotocin (50 mg/kg). Following 12 weeks of diabetes, immunolocalisation and mRNA expression of the two glial cell transporters, GLAST and EAAT4 were evaluated using indirect immunofluorescence and real-time PCR. The function of glutamate transport was investigated at 1, 4 and 12 weeks following induction of diabetes by measuring the level of uptake of the non-metabolisable glutamate analogue, D: -aspartate, into Muller cells. There was no difference in the localisation of either GLAST or EAAT4 during diabetes. Although there was a small apparent increase in expression of both GLAST and EAAT4 in diabetic retinae compared with controls this was not statistically significant. At 1, 4 and 12 weeks following diabetes, D: -aspartate immunoreactivity was significantly increased in Muller cells of diabetic rats compared to controls (p<0.001). The EC(50) was found to increase by 0.304 log units in diabetic Muller cells compared with controls, suggesting that glutamate uptake is twice as efficient. These data suggest that there are alterations in glutamate transport during diabetes. However, these changes are unlikely to play a significant role in glutamate-induced neuronal excitoxicity during diabetes. These results suggest that although Muller cells undergo gliosis at an early stage of diabetes, one of the most important functions for maintaining normal retinal function is preserved within the retina.
Publisher: Informa UK Limited
Date: 15-05-2012
DOI: 10.3109/02713683.2012.669509
Abstract: To assess the amino acid levels of the ciliary epithelium, aqueous and lens under normal conditions and secondary to ischaemia and reperfusion. We assessed the amino acids glutamate, glutamine, aspartate, alanine, gamma-amino butyric acid, glycine, arginine and taurine in albino Sprague-Dawley rats. Acute ischaemia was created in the eye and the different anterior eye components were assessed for amino acid levels. Quantitative immunocytochemistry was used to compare amino acid profiles within the ciliary processes immediately after ischaemia and after 4 days of reperfusion. Liquid chromatography was used to determine amino acid levels in the aqueous humour and quantitative immunocytochemistry to determine the location and alterations of amino acids in the lens 4 days after ischaemia/reperfusion. Elevated amino acid levels were evident in the ciliary epithelium immediately after ischaemia. After 4 days of reperfusion, decreased levels of glutamine, gamma-aminobutyric acid, glycine and arginine were evident in the ciliary epithelium, in particular the nonpigmented epithelial cells. The amino acid levels in the aqueous humour remained unchanged after ischaemia/reperfusion and thus showed considerable resilience to this kind of injury. However, significant reductions of glutamate, glutamine, alanine, glycine, arginine and taurine were observed in the lens 4 days after ischaemia/reperfusion. We propose a model to explain the maintenance of amino acid homeostasis in the aqueous humour despite altered levels in both the ciliary processes and lens.
Publisher: Society for Neuroscience
Date: 12-1990
DOI: 10.1523/JNEUROSCI.10-12-04006.1990
Abstract: Postembedding silver-intensified immunogold procedures reveal high levels of glutamate immunoreactivity in “vertical” elements of the goldfish retina: (1) Red-sensitive and green-sensitive cones display strong glutamate immunoreactivity, especially in their synaptic terminals, but blue-sensitive cones are poorly immunoreactive. (2) All type Mb (on-center) and Ma (off-center) mixed rod-cone bipolar cells and all identifiable cone bipolar cells are highly glutamate immunoreactive. We find no evidence for bipolar cells that lack glutamate immunoreactivity. (3) The majority of the somas in the ganglion cell layer and certain large cells of the amacrine cell layer resembling displaced ganglion cells are strongly glutamate immunoreactive. (4) Despite their high affinity symport of acidic amino acids, the endogenous levels of glutamate in Muller's cells are among the lowest in the retina. (5) GABAergic neurons possess intermediate levels of glutamate immunoreactivity. Quantitative immunocytochemistry coupled with digital image analysis allows estimates of intracellular glutamate levels. Photoreceptors and bipolar and ganglion cells contain from 1 to 10 mM glutamate. The bipolar and ganglion cell populations maintain high intracellular glutamate concentrations, averaging about 5 mM, whereas red-sensitive and green-sensitive cones apparently maintain lower levels. Importantly, photoreceptor glutamate levels are extremely volatile, and in vitro maintenance is required to preserve cone glutamate immunoreactivity in the goldfish. GABAergic horizontal and amacrine cells contain about 0.3–0.7 mM glutamate, which matches the values predicted from the Km of glutamic acid decarboxylase. Muller's cells and non-GABAergic amacrine cells contain less than 0.1 mM glutamate. Though Muller's cells are known to possess potent glutamate symport, they clearly possess equally potent mechanisms for maintaining low intracellular glutamate concentrations.
Publisher: Informa UK Limited
Date: 05-2017
DOI: 10.1111/CXO.12478
Publisher: Informa UK Limited
Date: 05-2014
DOI: 10.1111/CXO.12119
Abstract: This study investigated the referral pathways offered to patients with age-related macular degeneration (AMD), diabetic retinopathy (DR) or glaucoma (GL) by ophthalmologists and optometrists. Australian ophthalmologists and optometrists were surveyed regarding referral decisions to other eye-care specialists (inter- or intra-professional), general medical practitioners (GPs), low vision rehabilitation (LVR) and support services. Thematic analysis and concept mapping were applied to highlight current and ideal referral pathways. The survey was completed by 155 optometrists and 50 ophthalmologists and deemed representative of their respective professions in Australia. Not surprisingly, the vast majority of the participating optometrists (97 to 99 per cent) referred to ophthalmologists regardless of the underlying condition. Clear differences (Chi-square: p < 0.05) were observed in the referral patterns of optometrists and ophthalmologists to GPs and support services. General medical practitioner services were almost exclusively used for patients with DR, while AMD triggered a significantly higher referral rate to low vision rehabilitation and support services than the other two disorders. While ophthalmologists predominantly referred patients with AMD, DR or GL to low vision rehabilitation services, optometrists' referrals were highly skewed toward ophthalmology. Referrals to other supporting services by the two groups were not greatly used. The perceived referral pathways by the two eye-care professionals suggested a unidirectional route, potentially highlighting the need for a more collaborative approach that facilitates optimal use of eye health care and allied services.
Publisher: Elsevier BV
Date: 08-2003
DOI: 10.1016/S0014-4835(03)00132-5
Abstract: We wanted to determine the characteristics associated with electrophysiological and neurochemical changes secondary to ischemic insult as well as correlate these electrophysiological and neurochemical changes. A Ganzfeld source was used to elicit electroretinograms in anesthetized adult Sprague-Dawley rats. Following baseline recordings, one eye was removed for control quantitative amino acid immunocytochemistry, and ischemic insult was induced by cervical dislocation. Following the induction of ischemia, a single electroretinogram signal was collected at 1, 2, 4, 6, 8, 16, 32 or 64 min, after which the eye was removed for immunocytochemistry. The post-receptoral b-wave was undetectable after 1 min post-ischemia, whereas phototransduction declined more gradually and persisted for up to 16 min post-mortem. Both phototransduction saturated litude and sensitivity decayed with a similar time course (tc=3.06 (2.73, 3.48) versus 3.29 (2.61, 4.62)min). Significant elevation of amino acid neurotransmitter levels was not observed until 6 min post-mortem. Between 8 and 16 min post-ischemia, glutamate and GABA were significantly accumulated in neurons and Müller cells (p<0.05). Beyond 16 min, the neurotransmitter elevation in neurons and Müller cells was relatively attenuated. Aspartate immunoreactivity was significantly elevated at 4 and 6 min post-ischemia in neurons, prior to a change in any other amino acid. Moreover, of the amino acids assessed the post-ischemic change in aspartate immunoreactivity showed the best correlation with phototransduction decay (r2=0.68). Our findings show that complete impairment of phototransduction coincides with the accumulation of amino acid neurotransmitter. The correlation of aspartate immunoreactivity and phototransduction provides evidence of heightened glutamate oxidation during ischemic insult.
Publisher: Elsevier BV
Date: 2021
Publisher: Elsevier BV
Date: 04-2012
DOI: 10.1016/J.EXER.2012.02.009
Abstract: Rhegmatogenous retinal detachment is by far the most common indication for retinal surgery and a major cause of severe vision loss. Increased levels of glutamate found in the vitreous of human patients and persistent remodeling, even after reattachment, suggest substantial neurochemical, functional and anatomical changes have occurred in the detached retina. Therefore, this study was designed to characterize the morphological changes and glutamate receptor functionality in human rhegmatogenous retinal detachment. A cation channel permeating probe, agmatine (1-amino-4-guanidobutane AGB), was employed to track endogenous and kainate (KA) driven channel functionality combined with immunocytochemical characterization of cellular remodeling. In the detached retina increased AGB permeability was identified in the outer retina while there was a decrease in the inner retina in basal conditions. KA receptors exhibited increased AGB permeability in ON bipolar cells and decreased permeability in calbindin labeled inner retinal cells. All retinal detachment s les demonstrated ectopic synaptic protein expression, photoreceptor processes extending toward the inner retina, and other remodeling features of retinal degeneration. These anatomical changes have been demonstrated in animal studies and are novel features unreported in primary cases of human retinal detachment. We conclude that deafferentation in retinal detachment leads to alteration of the glutamatergic pathway.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 18-10-2021
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 03-06-2015
Abstract: To establish Ricco's critical area (Ac) using the 30-2 Humphrey visual field analyzer (HVFA) and thereby identify Goldmann test sizes that are within or outside complete spatial summation at all visual field testing locations. We also determined the suitability of using age normative data for different test sizes. Finally, by modifying current output measures (dB values), we provide a new method that allows comparison of contrast sensitivity when testing with different Goldmann test sizes within complete spatial summation. We used the HVFA in full threshold mode and measured thresholds for all five Goldmann test sizes in 12 observers. Normative data of Heijl et al. were used for age transformation and comparison. All the data converted to a 50-year-old equivalent lie within 1 SD of expected variance for all test locations of the 30-2 paradigm. We established Ac values at all locations of the 30-2 paradigm and showed a systematic increase in Ac as a function of increased visual field eccentricity, consistent with previous studies. Age does not appear to affect Ac or the slope of partial summation for a wide range of visual field eccentricities tested using the HVFA. By equating spatial summation, we propose a new metric, dB*, that returns a uniform sensitivity value for different test sizes that are operating within complete spatial summation (i.e., follow Ricco's law). We established that converting to age-equivalent thresholds and application of dB* principle advantageously allows comparison of data sets across age and test size at different locations of the visual field. By identifying the Ac across the visual field, it is now possible to systematically determine threshold changes across the 30-2 locations in ocular disease and further characterize the importance of testing within complete spatial summation in standard automated perimetry.
Publisher: Wiley
Date: 07-09-2021
DOI: 10.1111/OPO.12880
Abstract: Despite the importance of anterior chamber depth (ACD) measurements in disease and ageing, the repeatability and their threshold for change is not known. Our purpose was to determine the intra‐session repeatability of Pentacam Scheimpflug photography for measuring the ACD across the chamber width in healthy subjects and thus inform expected limits of normality. Pentacam Scheimpflug photography was used to obtain ACD measurements at 57 points across the central 8mm of the chamber width from one randomly selected eye of 130 healthy (normal vision and no ocular diseases, except age‐normal cataracts) subjects (median age 58.0 years, interquartile range 46.3–63.0 years 48 males, 82 females). Intra‐session ACD measurements were compared. Univariate and multivariate linear regression was performed to identify categorical and continuous variables demonstrating a significant relationship with ACD and its repeatability. Bland‐Altman analyses showed no directional or depth‐dependent bias in the difference between the first and second tests (mean bias −0.003 mm, 95% limits of agreement −0.115 to +0.109 mm). Multivariate analysis found gender to be a significant factor ( p 0.0001), but not age ( p = 0.69) nor ethnicity ( p = 0.65), although the model fit was poor ( R 2 = 0.004). There were no regional differences in repeatability measures found in males, but six locations in the superior aspect in females were found to be significantly different in their repeatability characteristics. Tolerance limits used to calculate the number of step sizes between and ‐year‐old age groups found 8.1–11.5 steps for females, and 7.5–9.2 steps for males. Scheimpflug imaging using the Pentacam has excellent intra‐session repeatability. Only gender appeared to affect repeatability characteristics, manifesting with a greater number of meaningful steps of change between two extremes of age range in females compared to males, which provides guidance for identifying clinically significant and measurable change between tests.
Publisher: Frontiers Media SA
Date: 29-07-2015
Publisher: Wiley
Date: 10-11-1997
DOI: 10.1002/(SICI)1096-9861(19971110)388:1<1::AID-CNE1>3.0.CO;2-5
Abstract: A thorough understanding of in idual characteristics of older adults during the COVID-19 pandemic is critical for managing the ongoing pandemic course and planning for the future pandemics. Here, we explore the impact of the COVID-19 pandemic on driving, social distancing, protective, and coping behaviors of older adults. This study reports data on participants aged above 65 whose driving behaviors are being monitored using Global Positioning System (GPS) devices. Participants completed a COVID-19 survey in May 2020. We found that older adults decreased their number of days driving, number of trips per day, as well as average driving speed, and had fewer speeding incidents following COVID-19 onset. We also show that female and African American older adults engaged in more positive coping and cleaning behaviors, and had greater decreases in the number of days driving during the pandemic. The findings highlight the importance of considering older adults' in idual characteristics for an equitable response to the COVID-19 pandemic.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 07-06-2018
DOI: 10.1167/TVST.7.3.17
Publisher: Informa UK Limited
Date: 13-01-2022
DOI: 10.1080/08164622.2021.2008791
Abstract: Misdiagnosis of retinal disease is a common problem in primary care that can lead to irreversible vision loss and false-positive referrals, resulting in inappropriate use of health services. Clinical decision support systems describe tools that leverage information technology to provide timely recommendations that assist clinicians in the decisions they make about the care of a patient. They, therefore, have the potential to reduce the rate of misdiagnosis by promoting evidence-based medicine and more effective and efficient healthcare. This narrative review aims to support primary care practitioners in better understanding the current and emerging capacity of clinical decision support systems in eye care. Different types of clinical decision support systems are discussed, using current ex les and evidence from the available literature to demonstrate how they may improve diagnostic effectiveness and aid the management of retinal disease. Comments are made on the future directions of clinical decision support in primary eye care and the potential applications of artificial intelligence.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 04-2021
DOI: 10.1167/IOVS.62.4.2
Publisher: Elsevier BV
Date: 2014
DOI: 10.1016/J.NEUINT.2014.01.003
Abstract: Vinpocetine is a natural drug which exerts neuroprotective effects in ischaemia of the brain through actions on cation channels, glutamate receptors and other pathways. This study investigated the effect of vinpocetine on cation channel permeability of inner retinal neurons after acute retinal metabolic insult. We focused on amacrine and ganglion cells immunoreactive for calretinin or parvalbumin due to their previously documented susceptibility to ischaemia. Using the probe, 1-amino-4-guanidobutane (AGB), we observed increased cation channel permeability across amacrine and ganglion cells under ischaemia and hypoglycaemia but not anoxia. Calretinin and parvalbumin immunoreactivity was also reduced during ischaemia and hypoglyacemia but not anoxia. Vinpocetine decreased AGB entry into ischaemic and hypoglycaemic ganglion cells indicating that the drug can modulate unregulated cation entry. In addition, vinpocetine prevented the loss of calretinin and parvalbumin immunoreactivity following ischaemia suggesting it may indirectly regulate intracellular calcium. Vinpocetine also reduced AGB permeability in selected amacrine and ganglion cell populations following N-methyl-D-aspartate (NMDA) but not kainate activation suggesting that vinpocetine's regulation of cation channel permeability may partly involve NMDA sensitive glutamate receptors.
Publisher: Elsevier BV
Date: 2012
DOI: 10.1016/J.EXER.2011.11.008
Abstract: Glutamate is the major neurotransmitter in the vertebrate retina. Neurons involved in the glutamate pathway express α-amino-3-hydroxyl-5-methylisoxazole-4-propionic acid (AMPA), kainic acid (KA) and N-methyl-D-aspartate (NMDA) receptors. Functional characterization of these ionotropic glutamate receptors can be achieved by using a cation channel permeating probe named agmatine (1-amino-4-guanidobutane AGB). Retinal mapping using this guanidinium analog has certain advantages including the immunocytochemical identification of a whole population of neurons expressing functional glutamate gated receptor channels. We have extended AGB studies into the functionality of ionotropic receptors in peripheral aged human retina to serve as a comparison for functional analysis of retinopathies such as retinal detachment. We probed the human retina with AGB after activation with AMPA, KA and NMDA. The results showed patterns of AGB entry into neurons consistent with those previously observed in subunit localization studies in adult mammalian retinae including primates. Application of 30 μM AMPA activated receptors in virtually all calretinin immunoreactive AII amacrine cells in the mid-peripheral human retina. About half of the AII amacrine cells showed AGB permeation after incubation with 50 μM KA. Some bipolar cells including DB3 OFF bipolar cells displayed functional KA receptors. Colocalization of AGB with parvalbumin labeled horizontal cells revealed functional KA and AMPA receptors with no responsiveness to NMDA activation. NMDA activation resulted in AGB labeling of ganglion cells and amacrine cells. The present study provides a description of functional ionotropic glutamate receptors in the aged mid-peripheral human retina.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 23-03-2018
DOI: 10.1167/TVST.7.2.8
Publisher: Informa UK Limited
Date: 19-09-2022
DOI: 10.1080/08164622.2021.1971490
Abstract: Structured record keeping improves documentation in age-related macular degeneration however, it may have a more limited effect on the management decisions of a group of already highly trained clinicians, especially in the context of other well-embedded clinical decision support tools. Structured record keeping has been associated with a range of advantages including improved history taking and communication, reduced number of unnecessary referrals, and enhanced diagnostic accuracy. The aim of this study was to examine the impact of a structured record keeping, quality improvement tool on recording, reporting and management congruency. A before and after retrospective record review study was performed in a single academic, intermediate-tier care institute in New South Wales, Australia. The structured record keeping tool intervention captured 31 items in addition to the prior pre-existing medical record: six items relating to historical risk factors, two items relating to patient activation, 13 items signifying core clinical signs, five items for change analysis and five items regarding the ongoing patient management plan. Two hundred medical records from 151 patients with age-related macular degeneration were analysed. There was a statistically significant improvement in the number of reports that explicitly specified the number of clinical structural risk factors (from 24 to 75% Fisher's exact p < 0.001) and risk of progression to advanced disease (from 71 to 84% p = 0.041) however, this documentation had no statistically significant effect on the report-recommended management plan and/or the final report-recommended review period. Disease-specific, structured record keeping improves the outgoing documentation of key clinical signs and is effective in prompting the transposition of these signs into a quantified risk progression score. It has limited value in improving management consistency among a group of highly trained eye care staff.
Publisher: Wiley
Date: 12-02-2015
DOI: 10.1111/OPO.12197
Abstract: Previous studies confirmed that optometrists have access to and confidence in applying clinical tests recommended for glaucoma assessment. Less is known about factors best predicting compliance with national clinical guidelines and thus by inference, the provision of suitable care by primary care ophthalmic practitioners. We utilised the unique two-tiered profession (therapeutic and non-therapeutic scope of practice) in Australia and New Zealand to assess the prospective adherence to glaucoma guidelines dependent on the clinician's background. Australian and New Zealand optometrists were surveyed on ophthalmic techniques for glaucoma assessment, criteria for the evaluation of the optic nerve head, glaucoma risk categories and review times while also recording background, training, and experience. Parameters identifying progression/conversion and patients' risk levels were analysed comparatively to ophthalmologists' opinions. Linear regression analysis identified variables significantly improving the likelihood of concordance with guidelines. Reported application of techniques complied well with glaucoma guidelines although gonioscopy and pachymetry, pupil dilation for optic nerve head examination, and acquisition of permanent records were less frequently employed. The main predictors for entry-level diagnostic standards were therapeutic endorsement together with the associated knowledge of relevant guidance and procedural confidence. Other findings suggested a potential underestimation in the value of optic disc size and intraocular pressure for the prediction of glaucoma risk, while optometrists more frequently relied on the outcomes of non-standardised automated perimetry and auxiliary imaging. Optometrists in Australia and New Zealand may not always exercise optimal clinical acumen regarding techniques/criteria for glaucoma diagnosis. Therapeutic endorsement was gradually adopted in different jurisdictions in various forms since 1999 and is mandatory for registration since late 2014. The result of the two-tiered optometric cohorts suggest that inclusion of therapeutic training as part of the core training is likely a key factor to enhanced compliance with glaucoma guidelines. Improved adherence to the current clinical standards should positively impact on the facilitation of appropriate glaucoma diagnosis and management. Obligatory knowledge and possibly accreditation of available guidelines might ensure a uniform standard in glaucoma testing protocols in concordance with compulsory entry-level skills.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 02-03-2018
DOI: 10.1167/TVST.7.2.1
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 20-09-2019
DOI: 10.1167/TVST.8.5.16
Publisher: Springer Science and Business Media LLC
Date: 21-01-2021
DOI: 10.1038/S41598-021-81554-4
Abstract: Glaucoma, a leading cause of blindness, is a multifaceted disease with several patho-physiological features manifesting in single fundus images (e.g., optic nerve cupping) as well as fundus videos (e.g., vascular pulsatility index). Current convolutional neural networks (CNNs) developed to detect glaucoma are all based on spatial features embedded in an image. We developed a combined CNN and recurrent neural network (RNN) that not only extracts the spatial features in a fundus image but also the temporal features embedded in a fundus video (i.e., sequential images). A total of 1810 fundus images and 295 fundus videos were used to train a CNN and a combined CNN and Long Short-Term Memory RNN. The combined CNN/RNN model reached an average F-measure of 96.2% in separating glaucoma from healthy eyes. In contrast, the base CNN model reached an average F-measure of only 79.2%. This proof-of-concept study demonstrates that extracting spatial and temporal features from fundus videos using a combined CNN and RNN, can markedly enhance the accuracy of glaucoma detection.
Publisher: American Physiological Society
Date: 03-2010
DOI: 10.1152/AJPCELL.00253.2009
Abstract: We determined the metabolic changes that precede cell death in the dystrophic proline-23-histidine (P23H) line 3 (P23H-3) rat retina compared with the normal Sprague-Dawley (SD) rat retina. Metabolite levels and metabolic enzymes were analyzed early in development and during the early stages of degeneration in the P23H-3 retina. Control and degenerating retinas showed an age-dependent change in metabolite levels and enzymatic activity, particularly around the time when phototransduction was activated. However, lactate dehydrogenase (LDH) activity was significantly higher in P23H-3 than SD retina before the onset of photoreceptor death. The creatine hosphocreatine system did not contribute to the increase in ATP, because phosphocreatine levels, creatine kinase, and expression of the creatine transporter remained constant. However, Na + -K + -ATPase and Mg 2+ -Ca 2+ -ATPase activities were increased in the developing P23H-3 retina. Therefore, photoreceptor apoptosis in the P23H-3 retina occurs in an environment of increased LDH, ATPase activity, and higher-than-normal ATP levels. We tested the effect of metabolic challenge to the retina by inhibiting monocarboxylate transport with α-cyano-4-hydroxycinnamic acid or systemically administering the phosphodiesterase inhibitor sildenafil. Secondary to monocarboxylate transport inhibition, the P23H-3 retina did not demonstrate alterations in metabolic activity. However, administration of sildenafil significantly reduced LDH activity in the P23H-3 retina and increased the number of terminal deoxynucleotidyl transferase biotin-dUPT nick end-labeled photoreceptor cells. Photoreceptor cells with a rhodopsin mutation display an increase in apoptotic markers secondary to inhibition of a phototransduction enzyme (phosphodiesterase), suggesting increased susceptibility to altered cation entry.
Publisher: Wiley
Date: 22-05-2022
DOI: 10.1111/OPO.12997
Abstract: To assess the accuracy of cluster analysis‐based models in predicting visual field (VF) defects from macular ganglion cell‐inner plexiform layer (GCIPL) measurements in glaucomatous and healthy cohorts. GCIPL measurements were extracted from posterior pole optical coherence tomography (OCT), from locations corresponding to central VF test grids. Models incorporating cluster analysis methods and corrections for age and fovea to optic disc tilt were developed from 493 healthy participants, and 5th and 1st percentile limits of GCIPL thickness were derived. These limits were compared with pointwise 5th and 1st percentile limits by calculating sensitivities and specificities in an additional 40 normal and 37 glaucomatous participants, as well as applying receiver operating characteristic (ROC) curve analyses to assess the accuracy of predicting VF results from co‐localised GCIPL measurements. Clustered models demonstrated globally low sensitivity, but high specificity in the glaucoma cohort (0.28–0.53 and 0.77–0.91, respectively), and high specificity in the healthy cohort (0.91–0.98). Clustered models showed similar sensitivities and superior specificities compared with pointwise methods (0.41–0.65 and 0.71–0.98, respectively). There were significant differences in accuracy between clusters, with relatively poor accuracy at peripheral macular locations ( p 0.0001 for all comparisons). Cluster analysis‐based models incorporating age correction and holistic consideration of fovea to optic disc tilt demonstrated superior performance in predicting VF results to pointwise methods in both glaucomatous and healthy eyes. However, relatively low sensitivity and poorer performance at the peripheral macula indicate that OCT in isolation may be insufficient to predict visual function across the macula accurately. With modifications to criteria for abnormality, the concepts suggested by the described normative models may guide prioritisation of VF assessment requirements, with the potential to limit excessive VF testing.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 27-05-2022
DOI: 10.1167/IOVS.63.5.36
Publisher: Wiley
Date: 06-05-2022
DOI: 10.1111/OPO.12991
Abstract: Age‐related macular degeneration (AMD) is a leading cause of vision loss. It is helpful for patients living with AMD to understand the prognosis, risk factors and management of their condition. Online education materials are a popular and promising channel for conveying this knowledge to patients with AMD. However, the quality of these materials—particularly with respect to qualities such as ‘understandability’ and ‘actionability’—is not yet known. This study assessed a collection of online materials about AMD based on these qualities of ‘understandability’ and ‘actionability’. Online education materials about AMD were sourced through Google from six English‐speaking nations: Australia, New Zealand, USA, UK, Ireland and Canada. Three Australian/New Zealand trained and registered optometrists participated in the grading of the ‘understandability’ and ‘actionability’ of online education materials using the Patient Education Materials Assessment Tool (PEMAT). This study analysed a total of 75 online materials. The mean ‘understandability’ score was 74% (range: 38%–94%). The ‘understandability’ PEMAT criterion U11 (calling for a summary of the key points) scored most poorly across all materials. The mean ‘actionability’ score was 49% (range: 0%–83%). The ‘actionability’ PEMAT criterion A26 (using ‘visual aids’ to make instructions easier to act on) scored most poorly across all materials. Most education materials about AMD are easy to understand, but difficult to act on, because of a lack of meaningful visual aids. We propose future enhancements to AMD education materials—including the use of summaries, visual aids and a habit tracker—to help patients with AMD improve their understanding of disease prognosis, risk factors and eye assessment schedule requirements.
Publisher: Wiley
Date: 30-05-2023
DOI: 10.1111/OPO.13168
Abstract: Age‐related macular degeneration (AMD) is a major cause of vision loss globally. Patients with AMD may not always understand or retain the information about AMD communicated by their eyecare practitioner. This study aims to explore the characteristics of effective health communication for AMD, from both patients' and eyecare practitioners' perspectives. The purpose is to provide a foundation for understanding how health communication for AMD could potentially be improved in the future. A total of 10 focus groups involving 17 patients with AMD and 17 optometrists were conducted via web conferencing. Each session was audio‐recorded, transcribed and analysed using the Grounded Theory Methodology. The five themes identified are as follows: (1) materials' quality, (2) materials' relevance, (3) contextualising for the in idual, (4) contextualising for the disease and (5) support network. Participants expressed concern about the unrealistic yet common depiction of vision loss in AMD as a black patch overlying common visual scenes. They also preferred education materials tailored to a specific disease stage and the regular opportunity to ask or answer questions. Longer appointment durations and peer support (from family, friends or others with AMD) were also valued. Optometrists are encouraged to focus on three over‐arching dimensions when counselling patients with AMD in routine clinical practice: (1) curating and using disease and stage‐specific, impactful education materials, (2) their chairside verbal communication techniques and (3) AMD‐specific opportunities for care coordination among patient family and friends, peers and other multidisciplinary members of the care support team.
Publisher: Wiley
Date: 1993
DOI: 10.1111/J.1475-1313.1993.TB00427.X
Abstract: Spectral sensitivity defects, associated with chronic elevated intraocular pressure (IOP) produced by Argon laser trabeculoplasty, were studied in monkeys. Increment-threshold spectral sensitivity (ITSS) and threshold versus intensity (TVI) functions were measured using a behavioural model. Elevated IOP resulted in short wavelength (SW) sensitivity losses characteristic of many ocular diseases. The amount of SW sensitivity loss for ITSS functions depended upon the intensity level and chromatic composition of the background field. The optimum condition identifying the greatest SW sensitivity reduction was a yellow background of moderate intensity (100-1000 Td). In the early stages of experimental glaucoma, the cone mechanisms and the rod mechanism typically showed decreased test and field sensitivities. The SW cone pathway has slightly greater threshold elevation (approximately 0.3 log unit) compared to the rod and cone pathways. On the other hand, in the advanced stages of experimental glaucoma, the largest sensitivity losses were in the longer-wavelength, red-green opponent mechanisms, with the rod and SW cone pathways showing smaller losses. The similarities of the colour vision anomalies in this animal model with those of patients with glaucoma, provides support for its use as an experimental model for human glaucoma.
Publisher: Wiley
Date: 12-08-2003
DOI: 10.1002/CNE.10830
Abstract: The N-methyl-D-aspartate (NMDA) responses of neurons from within the inner rabbit retina were mapped using a channel permeable cation, 1-amino-4-guanidobutane (agmatine, AGB). Serial sections were subsequently probed with immunoglobulins targeting AGB, glutamate, gamma-aminobutyric acid (GABA), and glycine to visualize the NMDA responses of neurochemical subpopulations of neurons. Most inner retinal subpopulations of neurons demonstrated an NMDA concentration-dependent increase in activation. This NMDA-induced activation displayed a distinct pattern, with the most sensitive class to least sensitive class ranking being GC > GABA cAC > GABA/Gly cAC > Gly cAC > GABA dAC (GC, ganglion cells AC, amacrine cells c, conventional d, displaced Gly, glycine). The variable NMDA response may reflect differences in NMDA receptor subunit disposition or differences in receptor density. In addition to the variable NMDA activation pattern, we found that virtually all ganglion cells (87%) showed NMDA-gated AGB entry, compared with only 58% of amacrine cells. We conclude that a large cohort of amacrine cells do not possess functional NMDA receptors. In addition to most ganglion cells being activated by NMDA, a large subpopulation displayed the highest sensitivity to NMDA application. The functional significance of this finding is that the ganglion cell population will be the first neuronal class to be susceptible to glutamate-induced neurotoxicity mediated through the NMDA receptor. The addition of betaxolol significantly reduced NMDA-mediated AGB entry into most neuronal groups (ganglion cells, GABA, and glycine amacrine cells), with the greatest effect being on ganglion cells. Betaxolol had no significant effect on NMDA-gated entry of AGB on the GABA/Gly amacrine cell population.
Publisher: American Physiological Society
Date: 05-2015
DOI: 10.1152/AJPCELL.00291.2014
Abstract: Vinpocetine protects against a range of degenerative conditions and insults of the central nervous system via multiple modes of action. Little is known, however, of its effects on metabolism. This may be highly relevant, as vinpocetine is highly protective against ischemia, a process that inhibits normal metabolic function. This study uses the ischemic retina as a model to characterize vinpocetine's effects on metabolism. Vinpocetine reduced the metabolic demand of the retina following ex vivo hypoxia and ischemia to normal levels based on lactate dehydrogenase activity. Vinpocetine delivered similar effects in an in vivo model of retinal ischemia-reperfusion, possibly through increasing glucose availability. Vinpocetine's effects on glucose also appeared to improve glutamate homeostasis in ischemic Müller cells. Other actions of vinpocetine following ischemia-reperfusion, such as reduced cell death and improved retinal function, were possibly a combination of the drug's actions on metabolism and other retinal pathways. Vinpocetine's metabolic effects appeared independent of its other known actions in ischemia, as it recovered retinal function in a separate metabolic model where the glutamate-to-glutamine metabolic pathway was inhibited in Müller cells. The results of this study indicate that vinpocetine mediates ischemic damage partly through altered metabolism and has potential beneficial effects as a treatment for ischemia of neuronal tissues.
Publisher: Elsevier BV
Date: 12-2013
DOI: 10.1016/J.EXPNEUROL.2013.09.007
Abstract: Pattern recognition has been used for the complete and statistically rigid classification of retinal neurons in vertebrates such as the adult cat, primate, rat and goldfish. Here, we label the mouse retina with antibodies against seven amino acids and use pattern recognition to characterize distinct retinal neurochemical cell classes based on their unique amino acid signatures. We followed the development of the cell classes in the X-inactivation transgenic mouse expressing the lacZ reporter gene on one X-chromosome. This mouse allows clonally related cells to be identified through differential β-galactosidase activity due to random X-chromosome inactivation. Pattern recognition analysis partitioned the retina into nine neuronal classes at birth, increasing to 19 classes at eye opening and 26 classes by adulthood. Emergence of new cell classes was partly attributed to new neuron types and partly to the splitting of classes from early ages from refinement of their amino acid profiles. All six GABAergic amacrine cell classes and most ganglion cell classes appeared by P7 whilst all the glycinergic amacrine cell classes did not appear till adulthood. Separable bipolar cell classes were not detected till eye opening. Photoreceptor cell classes were detected at P3 but inner and outer segments did not form separable classes until adulthood. More importantly, we show that cells which share common amino acid profiles also shared cell dispersion patterns. GABAergic amacrine cell classes with conventional and displaced counterparts transgressed clonal boundaries whereas GABAergic amacrine cell classes found exclusively in the inner nuclear layer and all glycinergic amacrine cell classes did not transgress. Ganglion cells displayed both dispersion patterns. This study provides a comprehensive neurochemical atlas of the developing mouse retina, tracking the amino acid levels within distinct neuronal populations and highlighting unique migratory patterns within subpopulations of inner retinal neurons.
Publisher: Wiley
Date: 22-12-2006
DOI: 10.1002/CNE.20813
Abstract: The mammalian retina contains as many as 50-60 unique cell types, many of which have been identified using various neurochemical markers. Retinal neurons express N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxyl-5-methylisoxazole-4-propionic acid (AMPA), and kainic acid (KA) receptor subunits in various mixtures, densities, and spatial distributions. Ionotropic glutamatergic drive in retinal neurons can be mapped using a cation channel permeant guanidinium analog called agmatine (1-amino-4-guanidobutane AGB). This alternative approach to physiologically characterize neurons in the retina was introduced by Marc (1999, J Comp Neurol 407:47-64, 407:65-76), and allows the simultaneous mapping of responses of glutamate receptor-gated channels from an entire population of neurons. Unlike previous AGB studies, we colocalized AGB with various macromolecular markers using direct and indirect immunofluorescence to characterize the glutamate agonist sensitivities of specific cell types. Activation with NMDA, AMPA, and KA resulted in AGB entry into neurons in a dose-dependent manner and was consistent with previous receptor subunit localization studies. Consistent with the various morphological phenotypes encompassed by the calbindin and calretinin immunoreactive cells, we observed various functional phenotypes revealed by AGB labeling. Not all calbindin or calretinin immunoreactive cells showed ligand-evoked AGB permeation. A small proportion either did not possess functional glutamate receptors, required higher activation thresholds, or express functional channels impermeable to AGB. AMPA and KA activation of bipolar cells resulted in AGB permeation into the hyperpolarizing variety only. We also studied the glutamate ligand-gating properties of 3[alpha1-3]-fucosyl-N-acetyl-lactosamine (CD15) immunoreactive cells and show functional responses consistent with receptor subunit gene expression patterns. CD15-immunoreactive bipolar cells only responded to AMPA but not KA. The CD15 immunoreactive amacrine cells demonstrated an identical selectivity to AMPA activation, but were also responsive to NMDA. Finally, localization of AGB secondary to glutamate receptor activation was visualized with a permanent reaction product.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2019
DOI: 10.1097/OPX.0000000000001432
Abstract: In our intermediate-tier glaucoma care clinic, we demonstrate fair to moderate agreement in gonioscopy examination between optometrists and ophthalmologists, but excellent agreement when considering open versus closed angles. We highlight the need for increased consistency in the evaluation and recording of angle status using gonioscopy. The consistency of gonioscopy results obtained by different clinicians is not known but is important in moving toward practice modalities such as telemedicine and collaborative care clinics. The purpose of this study was to evaluate the description and concordance of gonioscopy results among different practitioners. The medical records of 101 patients seen within a collaborative care glaucoma clinic who had undergone gonioscopic assessment by two clinicians (one optometrist and either one general ophthalmologist [n = 50] or one glaucoma specialist [n = 51]) were reviewed. The gonioscopy records were evaluated for their descriptions of deepest structure seen, trabecular pigmentation, iris configuration, and other features. These were compared between clinicians (optometrist vs. ophthalmologist) and against the final diagnosis. Overall, 51.9 and 59.8% of angles were graded identically in terms of deepest visible structure when comparing between optometrist versus general ophthalmologist and optometrist versus glaucoma specialist, respectively. The concordance increased when considering ±1 of the grade (67.4 and 78.5%, respectively), and agreement with the final diagnosis was high ( %). Variations in angle grading other than naming structures were observed (2.0, 30, and 3.9% for optometrist, general ophthalmologist, and glaucoma specialist, respectively). Most of the time, trabecular pigmentation or iris configuration was not described. Fair to moderate concordance in gonioscopy was achieved between optometrists and ophthalmologists in a collaborative care clinic in which there is consistent feedback and clinical review. To move toward unified medical records and a telemedicine model, improved consistency of record keeping and angle description is required.
Publisher: Elsevier BV
Date: 11-2014
DOI: 10.1016/J.EXER.2014.08.014
Abstract: Sildenafil, the active ingredient in Viagra, has been reported to cause transient visual disturbance from inhibition of phosphodiesterase 6 (PDE6), a key enzyme in the visual phototransduction pathway. This study investigated the effects of sildenafil on the rd1(+/-) mouse, a model for carriers of Retinitis Pigmentosa which exhibit normal vision but may have a lower threshold for cellular stress caused by sildenafil due to a heterozygous mutation in PDE6. Sildenafil caused a dose-dependent decrease in electroretinogram (ERG) responses of normal mice which mostly recovered two days post administration. In contrast, rd1(+/-) mice exhibited a significantly reduced photoreceptor and a supernormal bipolar cell response to sildenafil within 1 h of treatment. Carrier mice retinae took two weeks to return to baseline levels suggesting sildenafil has direct effects on both the inner and outer retina and these effects differ significantly between normal and carrier mice. Anatomically, an increase in expression of the early apoptotic marker, cytochrome C in rd1(+/-) mice indicated that the effects of sildenafil on visual function may lead to degeneration. The results of this study are significant considering approximately 1 in 50 people are likely to be carriers of recessive traits leading to retinal degeneration.
Publisher: Elsevier BV
Date: 10-2021
Publisher: Elsevier BV
Date: 2005
Publisher: Wiley
Date: 2006
DOI: 10.1002/CNE.21225
Abstract: Ionotropic glutamate receptors have been associated with early development of the visual process by regulating cell differentiation, cell motility, and synaptic contacts. We determined the expression of functional ionotropic glutamate receptors during development of the mouse retina by assessing 1-amino-4-guanidobutane (agmatine AGB) immunolabelling after application of a range of glutamate analogs. Colocalization of AGB with calretinin and islet-1 allowed the identification of functional receptors in neurochemically defined neurons. Activation with kainate (KA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), and N-methyl-D-aspartate (NMDA) resulted in AGB entry into neurons consistent with that found previous receptor subunit localization studies in the developing retina. Temporal analysis revealed that application of 50 microM KA activated receptors as early as embryonic day 18 in the ventricular zone and in the ganglion cell layer, whereas 30 muM AMPA activated cells predominantly in the ganglion cell layer. Cholinergic amacrine cells showed functional KA and AMPA receptors upon their insertion into the conventional amacrine cell layer from postnatal day 1 (P1). OFF cone bipolar cells showed functional KA receptors from P6, at a developmental age when they are known to make contact with ganglion cells. NMDA activation led to diffuse AGB labeling at birth among cells in the ganglion cell layer, whereas, at P1, regularly spaced cholinergic amacrine cells in the conventional amacrine cell layer started to be responsive to NMDA. Non-NMDA receptors were first to show functional activation in the developing retina, and cholinergic amacrine cells displayed functional ionotropic glutamate receptors after reaching their final destination.
Publisher: Wiley
Date: 11-2000
DOI: 10.1111/J.1469-7793.2000.00591.X
Abstract: It is well accepted that in rod photoreceptors the photoproducts generated by a bleach cause desensitisation during dark adaptation. We examine whether this notion holds for cones. A model of cone dark adaptation is developed based on the equivalent background concept. The underlying theory of the model relies on a series of assumptions that link psychophysically determined detection thresholds to cone phototransduction. Correction of thresholds for the reduced quantum-catching ability of the cones (due to the depletion of photopigment caused by a bleaching light) is an important aspect of the model. Foveal detection thresholds were measured for a small test flash presented on a large steady background field or presented alone after adapting to the background field. Test and background fields were monochromatic, with wavelengths closely matched to promote detection by the luminance mechanism. The model provided a good description of the data collected under these conditions. Parameters of the model were similar for all wavelengths and each observer, as were the derived equivalent background relationships. Analysis of previously published data for Stiles' pi5 mechanism gave analogous results. The model is made up of two components. The early (fast) component is likely to be due to the direct action of the cone equivalent of inactivated Rh* on the G-protein cascade and/or the reverse reaction of the cone equivalent of inactivated Rh* to Rh*. The later (slow) component may be due to the direct action of cone opsin on the G-protein cascade.
Publisher: Public Library of Science (PLoS)
Date: 03-03-2016
Publisher: Public Library of Science (PLoS)
Date: 17-01-2018
Publisher: BMJ
Date: 04-2020
DOI: 10.1136/BMJOPEN-2019-034699
Abstract: Diabetic eye disease is a leading cause of blindness but can be mitigated by regular eye assessment. A framework of issues, developed from the literature of barriers to eye assessment, was used to structure an examination of perceptions of a new model of care for diabetic retinopathy from the perspective of staff using the model, and health professionals referring patients to the new service. Multimethod: interviews and focus groups, and a separate survey. A new clinic based on an integrated model of care was established at a hospital in outer metropolitan Sydney, Australia in 2017. Funded jointly by Centre for Eye Health (CFEH) and the hospital, the clinic was equipped and staffed by optometrists who work alongside the ophthalmologists in the existing hospital eye clinic. Five (of seven) hospital staff working in the clinic (ophthalmologists and administrative officers) or referring to it from other departments (endocrinologists) nine optometrists from CFEH who developed or worked in the clinic 10 community-based optometrists as potential referrers. The new clinic was considered to have addressed known barriers to eye assessment, including access, assistance for patients unable/unwilling to organise eye checks and efficient management of human resources. The clinic optimised known drivers of this model of care: providing clear scope of practice and protocols for shared care between optometrists and ophthalmologists, good communication between referrers and eye professionals and a collegial approach promoting interprofessional trust. Remaining areas of concern were few referrals from general practitioners, fewer referrals from hospital endocrinologists than expected and issues with stretched administrative capacity. There were also perceived mismatches between the priorities of hospital management and aims of the clinic. The new model was considered to have addressed many of the barriers to assessment. While there remain issues with the model, there were also unexpected benefits.
Publisher: Wiley
Date: 15-07-1990
Abstract: Dopaminergic and glycinergic interplexiform cells (IPCs) in the goldfish retina were impregnated by using two new Golgi protocols. The two cell types have markedly different morphological characteristics: Dopaminergic IPCs have primary dendrites that descend into and stratify in the inner plexiform layer, where they give rise to processes that project to the outer plexiform layer. Conversely, glycinergic IPCs have primary dendrites that ascend to the outer plexiform layer and from this dendritic arbor, many processes then project into the inner plexiform layer. The apparent coverage of dopaminergic IPCs is almost four times that of glycinergic IPCs. Even so, the coverage of each glycinergic IPC in the outer plexiform layer allows it to provide an accurate copy of the S-space to the inner plexiform layer. Considering the known GABAergic and glycinergic synaptologies in the inner plexiform layer, the glycinergic IPC must form a major element in the retinal circuitry of the goldfish.
Publisher: Wiley
Date: 29-08-2007
DOI: 10.1002/CNE.21470
Abstract: Studies of retinal ischemia/reperfusion indicate a disparity between the anatomical and functional results while a large number of rod bipolar cells remain postischemia, there is a significant reduction in the litude of the scotopic b-wave of the electroretinogram (ERG). We investigated the alterations in photoreceptor-bipolar cell signaling following ischemia/reperfusion and suggest a mechanism for the decrease in b-wave litude. A cation channel probe (agmatine, 1-amino-4-guanidobutane, AGB) was used to assess cellular ion channel activity in neurochemically identified cells secondary to endogenous glutamate release or pharmacological manipulations. By applying the "neurochemical truth point" principle (Sun et al. [2007a] J Comp Neurol, this issue), we have been able to confirm the loss of specific subpopulations of neurons. ERG was used to assess gross retinal function, with parameters of the ERG model providing insight into changes in the phototransduction cascade and sensitivity of postreceptoral glutamate receptors. Following ischemia/reperfusion, rod bipolar cells maintained 2-amino-4-phosphonobutyric acid-responsive metabotropic glutamate receptors and displayed no change in sensitivity to flashes of light as assessed by ERG. Therefore, the loss in b-wave litude is likely due to alterations in photoreceptoral glutamate release detected as a change in postsynaptic AGB permeation into rod bipolar cells. Bipolar cell to amacrine cell signaling was also altered. The robust AGB entry into cholinergic amacrine cells was virtually absent in retinas that had undergone ischemia/reperfusion but remained in the AII amacrine cells. Such results suggest a loss of glutamate receptors and/or a change in receptor subunit expression in subpopulations of inner retinal neurons. Although many cells retain their characteristic neurochemical labeling following ischemia/reperfusion, caution should be used when assuming cells participate in functional retinal circuits based solely on the persistence of neurochemical labeling.
Publisher: Cambridge University Press (CUP)
Date: 11-1999
DOI: 10.1017/S0952523899166161
Abstract: Glutamate and γ-aminobutyric acid (GABA) are the dominant amino acids in the retina and brain. The manufacturing and degradation pathways of both of these amino acids are intricately linked with the tricarboxylic acid cycle leading to rapid redistribution of these amino acids after metabolic insult. Postmortem ischemia in mammalian retina predominantly results in a loss of glutamate and GABA from neurons and accumulation of these amino acids within Müller cells. This accumulation of glutamate and GABA in Müller cells may occur as a result of increased release of these neurotransmitters from neurons, and decreased degradation. Quantification of the semisaturation value (half-maximal response) for glutamate and GABA Müller cell loading during postmortem ischemia indicated a shorter semisaturation value for GABA than glutamate. Such changes are consistent with a single aerobically dependent GABA-degradation pathway, and the existence of multiple glutamate-degradation pathways. Comparison with the in vitro ischemic model showed similar qualitative characteristics, but a markedly increased semisaturation time for glutamate and GABA Müller cell loading (a factor of 5–10) in the postmortem ischemia model. We interpret these differences to indicate that the in vitro condition provides a more immediate and/or severe ischemic insult. In the postmortem ischemia model, the delayed glial cell loading implies the availability of internal stores of both glucose and/or oxygen. Increased glial and neuronal immunoreactivity for the amino acids involved in transamination reactions, aspartate, alanine, leucine, and ornithine was observed, indicating a potential shift in the equilibrium of transamination reactions associated with glutamate production. These findings provide evidence that, in the rat retina, there are multiple pathways subserving glutamate production/degradation that include a multitude of transamination reactions. Further evidence is therefore provided to support a role for all four amino acids in glutamate metabolism within a variety of retinal neurons and glia.
Publisher: Elsevier BV
Date: 12-2005
DOI: 10.1016/J.VISRES.2005.07.025
Abstract: Excitation mapping is a method of visualizing the signaling history of neurons with permeant organic cations. It is compatible with high-resolution imaging, allowing concurrent visualization of all neuronal classes and their glutamate-gated excitation histories. Excitation mapping documents the stability and precision of neuronal signaling within a given neuronal class, arguing that single unit electrophysiological s ling accurately reflects neuronal ersity. We here review the theory of excitation mapping, provide methods and protocol links outline imaging concepts provide parametric data on the temporal range and physiological sensitivity of excitation mapping and show that immunocytochemical methods for macromolecules are compatible with excitation mapping.
Publisher: Springer Science and Business Media LLC
Date: 02-12-2022
DOI: 10.1038/S41433-022-02227-8
Abstract: The purpose of this project was to systematically review and meta-analyse studies assessing the diagnostic accuracy of optical coherence tomography angiography (OCTA) and optical coherence tomography (OCT) for myopic choroidal neovascularisation (mCNV). Fluorescein angiography (FA) was accepted as the reference standard. PUBMED and EMBASE were searched from inception to March 2021 for studies evaluating the test accuracy of OCTA and/or OCT for diagnosing mCNV. The Preferred Reporting Items for Systematic Reviews and Meta-analyses of Diagnostic Test Accuracy Studies guideline was followed, and the Grading of Recommendations, Assessment, Development and Evaluation approach was used to frame clinical recommendations. Pooled estimates of test accuracy were obtained using a bivariate model. Of 410 studies assessed for eligibility, 3 studies were identified that compared OCTA to FA and 3 studies were identified that compared spectral domain (SD) OCT to FA. All studies had at least one major methodological flaw leading to an overall high risk of bias. On meta-analysis, the pooled sensitivity of OCTA was 0.89 (95% CI 0.78–0.94) and pooled specificity was 0.93 (95% CI 0.79–0.98). The pooled sensitivity of SD-OCT was 0.99 (95% CI 0.91–1.00). Due to uncertainty in in idual studies, the pooled specificity of SD-OCT could not be estimated. OCTA can reliably diagnose mCNV in clinically suspected patients, however, SD-OCT may not reliably establish a positive diagnosis of mCNV. Future large, prospective studies with improvements in conduct and reporting are needed to strengthen these clinical recommendations.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2015
Publisher: American Physiological Society
Date: 07-2010
Publisher: Wiley
Date: 10-2004
DOI: 10.1111/J.1442-9071.2004.00885.X
Abstract: Alterations in retinal amino acid neurochemistry are an indicator of metabolic function. Glutamate is the primary excitatory amino acid neurotransmitter within the retina, and excessive levels of glutamate can potentially cause excitotoxicity, in particular, through the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor. Anomalies in NMDA receptor function have been implicated as causing many neurodegenerative disorders, and overactivation leads to neuronal death secondary to metabolic insult. Several pharmaceutical agents have been proposed as potential neuroprotective agents against excitotoxicity (e.g. betaxolol), yet any effects such drugs have on retinal neurochemistry have not been determined. Therefore, the aim of this study was to quantify the changes in retinal amino acid neurochemistry secondary to the application of NMDA with and without betaxolol. Functional NMDA channel activation was confirmed in both amacrine and ganglion cells by quantifying the entry into these neurones of a channel permeable probe (agmatine: 1-amino-4-guanidobutane [AGB]). By probing serial thin sections with immunoglobulins targeting AGB, glutamate, gamma-aminobutyric acid (GABA) and glycine, it was possible to simultaneously study the neurochemical characteristic as well as the NMDA-evoked AGB responses of different neurochemical populations of inner retinal neurones. The authors have previously shown no accumulation of glutamate or GABA within Muller cells following NMDA application. Herein they report altered GABA and glycine immunoreactivity, but not glutamate immunoreactivity within neurones of the amacrine and ganglion cell layers following NMDA application. Finally, the addition of betaxolol did not significantly alter the normal neurochemistry of the retina. The retina possesses intrinsic mechanisms that allow it to maintain metabolic integrity during short periods of high NMDA application.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2015
Publisher: Elsevier BV
Date: 09-2023
Publisher: Springer Science and Business Media LLC
Date: 08-09-2010
DOI: 10.1007/S10633-009-9193-6
Abstract: Retinopathy of prematurity is a devastating vascular disease of premature infants. A number of studies indicate that retinal function is affected in this disease. Using the rat model of oxygen-induced retinopathy, it is possible to explore more fully the complex relationship between neuronal, glial and vascular pathology in this condition. This review examines the structural and functional changes that occur in the rat retina following oxygen-induced retinopathy. We highlight that vascular pathology in rats is characterized by aberrant growth of blood vessels into the vitreous at the expense of blood vessel growth into the body of the retina. Moreover, amino acid neurochemistry, a tool for examining neuronal changes in a spatially complete manner reveals widespread changes in amacrine and bipolar cells. In addition, neurochemical anomalies within inner retinal neurons are highly correlated with the absence of retinal vessels. The key cell types that link blood flow with neuronal function are macroglia. Macroglia cells, which in the retina include astrocytes and Müller cells, are affected by oxygen-induced retinopathy. Astrocyte loss occurs in the peripheral retina, while Müller cells show signs of reactive gliosis that is highly localized to regions that are devoid of intraretinal blood vessels. Finally, we propose that treatments, such as blockade of the renin-angiotensin system, that not only targets pathological angiogenesis, but that also promotes re-vascularization of the retina are likely to prove important in the treatment of those with retinopathy of prematurity.
Publisher: Wiley
Date: 19-05-2016
DOI: 10.1111/OPO.12295
Abstract: 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. 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). 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. 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.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 19-04-2022
DOI: 10.1167/TVST.11.4.18
Publisher: Wiley
Date: 23-09-2009
DOI: 10.1111/J.1471-4159.2009.06354.X
Abstract: Glutamate is a major neurotransmitter in the CNS but is also a key metabolite intimately coupled to amino acid production/degradation. We consider the effect of inhibition of two key glutamate metabolic enzymes: glutamine synthetase (GS) and aspartate aminotransferase on retinal function assessed using the electroretinogram to consider photoreceptoral (a-wave) and post-receptoral (b-wave) litudes. Quantitative immunocytochemistry was used to assess amino acid levels within photoreceptors, ganglion and Müller cells secondary to GS inhibition. Intravitreal injections of methionine sulfoximine reduced GS immunoreactivity in the rat retina. Additionally, glutamate and its precursor aspartate was reduced in photoreceptors and ganglion cells, but elevated in Müller cells. This reduction in neuronal glutamate was consistent with a deficit in neurotransmission (-75% b-wave reduction). Exogenous glutamine supply completely restored the b-wave, whereas other amino acid substrates (lactate, pyruvate, alpha-ketoglutarate, and succinate) only partially restored the b-wave (16-20%). Inhibition of the aminotranferases using aminooxyacetic acid had no effect on retinal function. However, aminooxyacetic acid application after methionine sulfoximine further reduced the b-wave (from -75% to -92%). The above data suggest that de novo glutamate synthesis involving aspartate aminotransferase can partially sustain neurotransmission when glutamate recycling is impaired. We also show that altered glutamate homeostasis results in a greater change in amino acid distribution in ganglion cells compared with photoreceptors.
Publisher: Wiley
Date: 17-02-2005
DOI: 10.1111/J.1471-4159.2004.02976.X
Abstract: Changes in oxygen and/or glucose availability may result in altered levels of ATP production and amino acid levels, and alteration in lactic acid production. However, under certain metabolic insults, the retina demonstrates considerable resilience and maintains ATP production, and/or retinal function. We wanted to investigate whether this resilience would be reflected in alterations in the activity of key enzymes of retinal metabolism, or enzymes associated with amino acid production that may supply their carbon skeleton for energy production. Enzymatic assays were conducted to determine the activity of key retinal metabolic enzymes total ATPase and Na(+)/K(+)-ATPase, aspartate aminotransferase and lactate dehydrogenase. In vitro anoxia led to an increase in retinal lactate dehydrogenase activity and to a decrease in retinal aspartate aminotransferase activity, without significant changes in Na(+)/K(+)-ATPase activity. In vivo inhibition of glutamine synthetase resulted in a short-term significant decrease in retinal aspartate aminotransferase activity. An increase in retinal aspartate aminotransferase and lactate dehydrogenase activities was accompanied by altered levels of amino acids in neurons and glia after partial inhibition of glial metabolism, implying that short- and long-term up- and down-regulation of key metabolic enzymes occurs to supply carbon skeletons for retinal metabolism. ATPase activity does not appear to fluctuate under the metabolic stresses employed in our experimental procedures.
Publisher: Informa UK Limited
Date: 25-02-2021
Publisher: Elsevier BV
Date: 09-2016
DOI: 10.1016/J.EXER.2016.01.002
Abstract: Macromolecular cell markers are essential for the classification and characterization of the highly complex and cellularly erse vertebrate retina. Although a plethora of markers are described in the current literature, the immunoreactivity of these markers in normal human tissue has not been fully determined. This is problematic as they are quintessential to the characterization of morphological changes associated with human retinal disease. This review provides an overview of the macromolecular markers currently available to assess human retinal cell types. We draw on immunohistochemical studies conducted in our laboratories to describe marker immunoreactivity in human retina alongside comparative descriptions in non-human tissues. Considering the growing number of eye banks services offering healthy and diseased human retinal tissue, this review provides a point of reference for future human retina studies and highlights key species specific disease applications of some macromolecular markers.
Publisher: Elsevier BV
Date: 03-1997
DOI: 10.1016/S0042-6989(96)00187-3
Abstract: In order to better understand the nature of long-wavelength (L) and middle-wavelength (M) cone input into spectral sensitivity functions and determine the reliability with which it is possible to predict L:M cone inputs, we developed analytical methods to determine confidence intervals for L:M cone input for spectral sensitivity functions or data transformed to cone-contrast space. Spectral sensitivity functions measured by direct heterochromatic brightness matches are dominated by the L/M opponent channel over most of the spectral range. For detection of large/ long test stimuli, spectral sensitivity functions show a characteristic "notch" at the adapting wavelength, with the L/M opponent channel dominating most of the spectral range. Flicker increment threshold (FIT) spectral sensitivity functions display many of the characteristics of the luminance flicker mechanism described by Stromeyer et al. (1987). [Vision Research, 27, 1113-1137]. Previous modelling of FIT spectral sensitivity functions proposed a 2:1 L:M cone input for most of testing conditions. We show that FIT spectral sensitivity functions are dominated by L cones but show L cone suppression under bright red adapting fields. For the fitted spectral sensitivity functions or simulated data sets, we found small confidence intervals for L:M cone input into the L/M opponent channel and conclude that it is possible to reliably predict L:M cone input ratios. However, for similar data sets of additive spectral sensitivity functions, we found large confidence intervals for L:M cone input ratios and conclude that it is not possible reliably predict L:M cone input into the L/M non-opponent channel using available spectral sensitivity functions.
Publisher: Wiley
Date: 04-06-2013
DOI: 10.1002/CNE.23307
Abstract: We studied the anatomical remodeling and gliosis of retinal Müller cells in the rd/rd mouse model of photoreceptor degeneration. A computational calculation of glutamine synthetase immunoreactivity was developed so we could specifically quantify changes in Müller cell anatomy between control mice (C57Bl/6) and the dystrophic strain. We found no change in the number of Müller cell somata between mice strains, indicating no cell proliferation as a function of development and degeneration. The retinal area occupied by the total Müller cell body (soma and processes) was significantly less in the rd/rd mouse retina compared with control mice. When only the outer retina was considered, we found rd/rd Müller cell processes were dramatically reduced during the cone phase of photoreceptor degeneration. However, at older ages an increase in Müller cell processes was seen. Conversely, glial fibrillary acidic protein (GFAP) expression showed a significant increase during cone degeneration followed by a reduction in older ages. Müller cell electrophysiology, particularly K(+) currents and membrane potential, was similar between rd/rd and control Müller cells during cone degeneration. Together, these results show that glial remodeling in the rd/rd retina follows separate phases-an initial conservative glial response involving the loss of Müller cells processes, hyperexpression of GFAP, and preservation of normal electrophysiology followed by an active growth of Müller cell processes, glial seal formation, and attenuation of GFAP expression after complete photoreceptor loss.
Publisher: Wiley
Date: 25-04-2016
DOI: 10.1111/OPO.12283
Publisher: Wiley
Date: 04-06-2013
DOI: 10.1002/CNE.23305
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 09-11-2016
DOI: 10.1167/16.14.5
Abstract: In the present study, we measured the extent of statokinetic dissociation (SKD) in normal observers and then equated the psychophysical tasks into a two-interval forced choice (2IFC) procedure. In Experiment 1, we used the Humphrey visual field analyzer in static perimetry and automated kinetic perimetry modes to measure contrast sensitivity thresholds and the Goldmann manual kinetic perimeter to measure isopters. This was carried out using a Goldmann size II target. Goldmann kinetic perimetry was performed manually with both inward (peripheral to center) and outward (center to periphery) directions of movement to deduce an "average" isopter. This revealed the presence of SKD when superimposed upon the map of static contrast threshold results. There was no evidence of any contribution of examiner technique or instrument-specific differences to SKD. In Experiment 2, we determined the psychometric curves plotting proportion seen as a function of stimulus eccentricity with static and kinetic stimuli with a 2IFC procedure and method of constant stimuli. In an additional experiment, we also showed that subjects were able to reliably discriminate whether a stimulus was static, moving inward, or moving outward, and hence, comparisons could be made between static and kinetic perimetry tasks. Overall, by making the task objective and reducing criterion bias, eccentricity thresholds were equated across static and kinetic perimetry methods hence, no evidence of SKD was seen. We suggest SKD is inherent to the differences in methodology of threshold measurement in conventional static and kinetic perimetry and in idual criterion bias.
Publisher: Wiley
Date: 14-08-2020
DOI: 10.1111/OPO.12721
Abstract: Studies examining the anterior chamber angle and angle closure disease often compare quantitative angle information obtained using anterior segment optical coherence tomography (ASOCT) with one of several ordinal scales derived using gonioscopy. We test the assumption that the ordinal gonioscopic angle grades have equal step sizes and can be analysed using metric statistics. The medical records of 214 consecutive patients who were referred for assessment of the anterior chamber angle were prospectively examined using gonioscopy and ASOCT (Spectralis Optical Coherence Tomography, OCT, www.heidelbergengineering.com ). Anterior chamber angle parameters (angle opening distance, AOD, and trabecular‐iris space area, TISA at 500 and 750 microns) were extracted from ASOCT images using a semi‐automated segmentation algorithm written on MATLAB ( www.mathworks.com ). We first matched the quantitative values for each gonioscopic grade (0–4, from no structures visible to ciliary body visible) and described the frequency distributions to determine separability. We then applied a grade‐agnostic clustering algorithm to determine the concordance between algorithm‐clustered groups (using solely quantitative data) and those obtained using gonioscopy. The frequency distributions of the quantitative ASOCT parameters for each angle grade were mostly non‐parametric and displayed unique distribution characteristics, with a floor effect seen for grade 0 and the lack of a ceiling effect seen for grades 3 and 4. Although we found significant differences in quantitative values across the five angle grades using the frequency distributions, some pairwise comparisons were indistinguishable (such as grades 0 and 1, and grades 3 and 4) due to the overlaps in distributions. On average, differences in quantitative values were consistent between gonioscopic grade steps, but there remained substantial variability that confounds prediction of change between ordinal steps. The clustering algorithm showed approximately 10% of cases with the same group assignment as that of the gonioscopic grade, improving slightly to 30% when the top 5% of quantitative data were excluded from analysis. Our results do not necessarily support the assumption that the ordinal scales used in gonioscopy can be interpreted using an interval scale. We highlight the need for better methods of describing the course and risk of angle closure spectrum disease to identify disease progression and conversion, where gonioscopy remains the gold standard.
Publisher: Optica Publishing Group
Date: 11-1991
Abstract: The effects of chromatic adaptation on the opponent interactions of cone mechanisms were investigated by using increment-threshold spectral-sensitivity (ITSS) functions and threshold-versus-radiance (TVR) curves in rhesus monkey subjects. The TVR curves showed shape- and field-sensitivity invariance for both 580- and 500-nm adapting backgrounds and indicated that three cone mechanisms were mediating detection over moderate adapting-field intensity levels. Differential adaptation between the long-wavelength-sensitive (L) and the middle-wavelength-sensitive (M) opponent (L - M) and nonopponent (L + M) channels and the short-wavelength-sensitive (S) channel caused changes in the shape of the ITSS function as the adapting-field intensity was increased without changes in the level of cone interaction. Chromatic adaptation also resulted in significant changes in the shape of the ITSS functions, but it still exhibited characteristic L-M opponent interactions. Converting ITSS data to cone-contrast coordinates for R-G adapting fields indicated that the relative contribution of the L and M cones at the second site was approximately equal (detection contour slope approximately 1). Consequently, most of the changes in the shape of ITSS functions under chromatic adaptation are explained by the von Kries adaptation principle. ITSS functions on a green background also exhibited opponent interactions between S cones and longer-wavelength cones. The cone-contrast coordinates, when expressed for S cones, showed that the inhibitory interactions occur because the S-cone signal subtracts from both M and L cones.
Publisher: Wiley
Date: 25-11-2015
DOI: 10.1111/CEO.12466
Abstract: Optimizing patient management will reduce unnecessary vision loss in glaucoma through early detection. One method is the introduction of collaborative care schemes between optometrists and ophthalmologists. We conducted a retrospective study to evaluate the impact of the Centre for Eye Health (CFEH) on glaucoma patient outcomes and management in primary optometric care. Patients referred to CFEH by optometrists for a glaucoma assessment were eligible for this study if written consent was provided (500 participants were randomly chosen). Clinical data were classified according to disease risk and implemented patient care and analysed against the original diagnosis and patient parameters, followed by statistical analysis. Two main parameters were evaluated suitable referral of patients for glaucoma condition assessment and appropriate implementation of follow-up care. The majority of patients referred for glaucoma assessment (86.2%) were classified as glaucoma suspects or likely to have glaucoma, indicating suitable referral of patients for a CFEH evaluation. Further, the involvement of CFEH resulted in a false positive rate of 7.8% for those patients who proceeded to ophthalmological care. However, long-term optometric patient care was not maintained for up to a third of primarily lower risk patients. The investigated collaborative eye health-care model led to a substantial improvement in appropriate referrals of glaucoma patients to ophthalmologists and could be suitable for optimizing patient care and utilization of resources. Improvement in follow-up of patients by optometrists is required to minimize inappropriately discontinued patient care.
Publisher: Wiley
Date: 23-08-2016
DOI: 10.1002/CNE.24084
Publisher: Elsevier BV
Date: 11-2023
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 03-02-2021
DOI: 10.1167/IOVS.62.2.4
Publisher: Elsevier BV
Date: 07-2018
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 02-2004
DOI: 10.1167/IOVS.03-0695
Abstract: To test the proposal that inhibiting monocarboxylate transport in the rat retina results in altered retinal function measured using the electroretinogram (ERG) and to evaluate the efficacy of exogenous metabolic substrates to restore any functional deficit. Full-field white-flash ERGs were measured after monocarboxylate transport inhibition with intravitreal injection of alpha-cyano-4-hydroxycinnamic acid (4-CIN, 10 mM), and functional recovery was assessed after the introduction of various exogenous metabolic substrates (10 mM): lactate, pyruvate, alpha-ketoglutarate, alanine, succinate, and glutamine. The efficacy of glutamine as a metabolic substrate was also considered in the presence of phosphate-activated glutaminase inhibition (6-diazo-5-oxo-norleucin, 10 mM) or aminotransferase inhibition (aminooxyacetic acid, 10 mM). Pyruvate and alanine recovery was also assessed after aminooxyacetic acid application. 4-CIN application resulted in an increased phototransduction litude but a mild reduction of gain. A greater reduction of postreceptoral b-wave and oscillatory potential litudes (80%) was observed, along with delayed implicit times (35 ms). Partial recovery of b-wave litudes was achieved with exogenous lactate (24%), pyruvate (27%), alpha-ketoglutarate (27%), alanine (25%), and succinate (26%), whereas glutamine provided 62% recovery. However, none of the substrates improved phototransduction gain. Both 6-diazo-5-oxo-norleucin and aminooxyacetic acid completely suppressed the glutamine-induced b-wave recovery. Aminooxyacetic acid also abolished the b-wave recovery from 4-CIN afforded by pyruvate and alanine. The greater loss of the b-wave and oscillatory potentials may reflect preferential routing of amino acid carbon skeletons to oxidative metabolic pathways, which in turn reduces glutamate availability for neurotransmission between photoreceptors and ON-bipolar cells. The reduction in log S provides evidence that inhibition of monocarboxylate transport produced some metabolic dysfunction in the rat.
Publisher: Informa UK Limited
Date: 03-2014
DOI: 10.1111/CXO.12102
Abstract: The aim was to obtain an overview of general medical practitioner (GP) referral pathways to ocular health care and allied services for people identified with age-related macular degeneration (AMD), diabetic retinopathy (DR) or glaucoma (GL). A questionnaire was developed to survey GPs in Australia. Questions included demographic information and referral patterns to ocular and health service providers. The survey was posted to 1,050 randomly selected GPs across Australia. Fifty-eight GPs participated in this study amounting to a 6.5 per cent response rate. Nearly all GPs referred patients to ophthalmologists (AMD: 98 per cent DR: 98 per cent GL: 95 per cent). A smaller proportion of GPs also referred to low vision rehabilitation (LVR) services (AMD: 34 per cent DR: 33 per cent GL: 22 per cent), optometrists (AMD: 26 per cent DR: 34 per cent GL: 31 per cent), or support services (AMD: 17 per cent DR: 40 per cent GL: 19 per cent). For the three tested conditions, there were no statistically significant differences in the proportions of GPs, who referred to ophthalmologists (p = 0.43), optometrists (p = 0.48) or to low vision rehabilitation services (p = 0.31). The proportion of GPs who referred to support services was significantly higher for patients diagnosed with DR than AMD or GL (p < 0.05). The majority of GPs referred patients with AMD, DR or GL to ophthalmologists. Fewer GPs considered referrals to optometrists, low vision rehabilitation or support services. General practitioners may need to be more aware about the central role of optometrists in the delivery of primary eye health care. In the interest of optimising eye care, closer working relationships between GPs and optometrists should be fostered.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-1990
DOI: 10.1097/00006324-199003000-00004
Abstract: A classroom assessment of color vision characteristics of children with low vision was conducted using a battery of tests. The results showed 75% of the children failed one or more tests, although only 24% had a moderate or severe color vision defect. Comparisons with the low vision clinic color vision assessment showed that many of the children were not identified as being color vision defective. Considering the use of color-coded information in education, greater emphasis on color vision evaluations in routine low vision examinations is recommended.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 20-06-2017
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 16-05-2022
DOI: 10.1167/TVST.11.5.13
Publisher: Wiley
Date: 30-10-2010
DOI: 10.1002/CNE.22205
Abstract: Retinopathy of prematurity (ROP) is characterized by deficits in the scotopic pathway, although the cellular locus for these deficits is not clear. Here we examined neurochemical and cellular changes that develop during oxygen-induced retinopathy, a model of ROP. In addition, we examined whether treatment with the angiotensin II type-1 receptor inhibitor, valsartan, prevented these changes. Newborn Sprague-Dawley rats were exposed from postnatal day (P) 0 to 11 to 80%:20% O(2) (22:2 hr/day) and then room air until P18. Valsartan (40 mg/kg/day) was administered from P12-P18. Pattern recognition analysis of overlapping amino acid profiles was used to provide a statistically robust and spatially complete classification of neural elements for each experimental condition. Classification yielded 12 neuronal theme classes in controls and nine classes following ROP. ROP was associated with a reduction in the number of amacrine and bipolar cell theme classes. The reduction in theme classes was confirmed as true neuronal loss by quantifying anatomical changes and using an apoptotic marker. ROP was associated with shifts in amino acid levels across all neuronal populations except for horizontal cells. A reduction in the density of glycine-immunoreactive amacrine cells, and particularly parvalbumin-immunoreactive AII amacrine cells, was observed following ROP. Valsartan treatment during ROP prevented loss of theme classes and loss of AII amacrine cells. This study suggests that deficits in scotopic vision during ROP may be associated with loss of AII amacrine cells. In addition, this study highlights the potential of AT(1)R blockade in preventing neuronal anomalies in this condition.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 02-04-2018
Abstract: To develop a proof-of-concept, computational method for the quantification and classification of fundus images in intermediate age-related macular degeneration (AMD). Multispectral, unsupervised pattern recognition was applied to 184 fundus images from 10 normal and 36 intermediate AMD eyes. The imaging results of preprocessed, grayscale images from three modalities (infrared, green, and fundus autofluorescence scanning laser ophthalmoscopy) were automatically classified into various clusters sharing a common spectral signature, using a k-means clustering algorithm. Class separability was calculated by using transformed ergence (DT). The classification results for large drusen, pigmentary abnormalities, and areas unaffected by AMD were compared against three expert observers for concordance, and to calculate sensitivity and specificity. Multispectral, unsupervised pattern recognition successfully identified a finite number of AMD-specific, statistically separable signatures in eyes with intermediate AMD. By using a correct classification criterion of >83% for identical clusters and a total of 1693 expert annotations, the sensitivity and specificity of multispectral pattern recognition for the detection of AMD lesions was 74% and 98%, respectively. Large drusen and pigmentary abnormalities were correctly classified in 75% and 68% of instances, respectively. We describe herein a novel approach for the classification of multispectral images in intermediate AMD. Automated classification of intermediate AMD, using multispectral pattern recognition, has moderate sensitivity and high specificity, when compared against clinical experts. The methods described may have a future role in AMD screening or monitoring.
Publisher: Society for Neuroscience
Date: 02-2006
DOI: 10.1523/JNEUROSCI.3651-05.2006
Abstract: We tested the response of interneurons to the absence of Reelin signaling or p35 in the mouse neocortex. We provide three independent strands of evidence to demonstrate that layering of late-born (but not early-born) interneurons is regulated by Reelin signaling. First, early-born and late-born interneurons behaved differently in mice lacking Reelin or disabled 1 (Dab1). Early-born interneurons showed layer inversion, whereas late-born interneurons did not demonstrate layer inversion but were randomly distributed across the cortex. Second, in p35 mutant brains (in which Reelin signaling is intact), late-born interneurons are appropriately positioned in the upper layers despite the malpositioning of all other cortical neurons in these mice. Third, transplanted late-born interneuron precursors (wild type) into Dab1 −/− cortices showed appropriate upper layer segregation. Together, these results indicate that, in the absence of Reelin signaling, late-born interneurons fail to laminate properly, and this is restored in an environment in which Reelin signaling is intact. These studies suggest different mechanisms for the stratification of cortical interneurons. Whereas the early-born interneurons appear to be associated with projection neuron layering, late-born interneurons rely on Reelin signaling for their correct lamination.
Publisher: Wiley
Date: 29-08-2007
DOI: 10.1002/CNE.21478
Abstract: We established a metabolic and functional profile map of the normal rat retina, given the premise that: 1) amino acid neurochemistry reflects metabolic integrity and cellular identity, and 2) the permeation of a cation channel probe, agmatine (1-amino-4-guanidobutane, AGB), reflects cation channel functionality. The purpose was to provide a unique method of simultaneously assessing the metabolic and functional characteristics of the normal retina, upon which a comparison can be made to disease models. Quantitative pattern recognition analysis of overlapping amino acid and AGB expression profiles was used to provide a statistically robust classification of all neural elements according to their metabolic and functional characteristics. This classification was spatially complete and with single-cell resolution. The resulting classification demonstrated 28 statistically separable theme classes dominated by characteristic glutamate, GABA, glycine, and/or taurine profiles, with each of the neuronal theme classes containing further subtypes. The inclusion of a functional parameter (AGB mapping) in the classification process nearly doubled the number of neural elements that could be ascribed a neurochemical/cation profile, compared to when amino acid labeling was used alone. Strong endogenous glutamate gated AGB labeling was observed in horizontal cells, rod bipolar cells, cholinergic amacrine cells, and AII amacrine cells. The resulting amino acid and AGB profile matrix constitutes a nomogram for assessing cellular responses to experimental challenges in models of ocular disease.
Publisher: Wiley
Date: 25-03-2023
DOI: 10.1111/OPO.13129
Abstract: To determine whether there are quantifiable structural or functional differences that can distinguish between high‐tension glaucoma (HTG intraocular pressure [IOP] 21 mm Hg) and low‐tension glaucoma (LTG IOP ≤ 21 mm Hg) at diagnosis. This was a retrospective, cross‐sectional study. Clinical results of one eye from 90 newly diagnosed HTG and 319 newly diagnosed LTG patients (117 with very‐low‐tension glaucoma [vLTG ≤15 mm Hg] and 202 with middling LTG [mLTG mm Hg, ≤21 mm Hg]) were extracted, which included relevant demographic covariates of glaucoma, quantitative optical coherence tomography (including the optic nerve head, retinal nerve fibre layer and ganglion cell‐inner plexiform layer) measurements and standard automated perimetry global metrics. We used binary logistic regression analysis to identify statistically significant clinical parameters distinguishing between phenotypic groups for inclusion in principal component (PC) (factor) analysis (PCA). The separability between each centroid for each cohort was calculated using the Euclidean distance ( d ( x , y )). The binary logistic regression comparing HTG and all LTG identified eight statistically significant clinical parameters. Subsequent PCA results included three PCs with an eigenvalue . PCs 1 and 2 accounted for 21.2% and 20.2% of the model, respectively, with a d( x , y ) = 0.468, indicating low separability between HTG and LTG. The analysis comparing vLTG, mLTG and HTG identified 15 significant clinical parameters, which were subsequently grouped into five PCs. PCs 1 and 2 accounted for 24.1% and 17.8%, respectively. The largest separation was observed between vLTG and HTG (d( x , y ) = 0.581), followed by vLTG and mLTG (d( x , y ) = 0.435) and lastly mLTG and HTG (d( x , y ) = 0.210). Conventional quantitative structural or functional parameters could not distinguish between pressure‐defined glaucoma phenotypes at the point of diagnosis and are therefore not contributory to separating cohorts. The overlap in findings highlights the heterogeneity of the primary open‐angle glaucoma clinical presentations among pressure‐defined groups at the cohort level.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 10-02-2015
Abstract: Drusen alters retinal architecture in early age-related macular degeneration (AMD). However, abnormalities also may exist in drusen-free areas of the AMD retina. This study examines retinal thickness above drusen relative to drusen-free areas in the same patient and a normal population. Patients with early to intermediate AMD (n = 122) or no disease (n = 30) were examined at the Center for Eye Health. Spectral domain optical coherence tomography (SD-OCT) scans through single, isolated druse (n = 125) or confluent drusen (n = 54) were obtained. The thickness of in idual retinal layers was measured above the druse and in a drusen-free area, 150 μm from the drusen edge. Intraeye comparisons found total retinal thickness above drusen was 16 ± 0.6% less than drusen-free areas. Thinning was mostly in the retinal pigment epithelium hotoreceptor layer (32 ± 1% reduction) and the outer nuclear layer (22 ± 1% reduction). Confluent drusen showed similar thinning of the outer retina as well as inner retina loss (5%). Thinning was strongly correlated with drusen height, but only modestly correlated with drusen width. When compared to the normal population, retinal thickness above drusen and drusen-free areas were significantly reduced. We confirm outer retina thinning above drusen in early/intermediate AMD compared to drusen-free areas in the same retina or a normal population. Interestingly, drusen-free areas in AMD patients were not the same as control patients suggesting "normal" areas of the AMD retina are abnormal. The strong correlation between retinal thinning and drusen height, rather than width, suggests current grading systems for AMD may need refinement.
Publisher: Wiley
Date: 22-05-2022
DOI: 10.1111/OPO.13006
Abstract: To determine the usefulness of Humphrey Field Analyser (HFA) SITA‐Faster 24–2 gaze tracker outputs on interpreting intra‐visit visual field (VF) result pairs. Analysis of 1380 right–left eye pairs and 1432 pairs of test 1‐test 2 intrasession VF results of patients seen within a university‐based glaucoma service was undertaken to understand gaze deviation distributions. Output gaze tracker results were aggregated into total ticks, sum of litudes and average litudes. Correlations between visual field indices (mean deviation [MD], “events” and overall hill of vision) and independent variables (age and test order) were performed using one eye from each subject. There was no association of test order (right–left, test 1‐test 2) with eye movements. There was a significant, but weak correlation between eye movements and age ( r = 0.16). Correlations of eye movements with MD were driven by more severe MD values. There were no significant correlations between intrasession difference in eye movements and the change in MD, number of “events” and hill of vision, or in the root mean square of sensitivity and total deviation values. There was also no significant correlation between gaze tracker outputs and another commonly used “reliability” metric, false positive rate. Eye movement parameters as currently reported by the HFA do not appear to be correlated with key sensitivity parameters when considering the repeatability of intrasession SITA‐Faster 24–2 VF results. Thus, current gaze tracker outputs do not appear to provide clinically meaningful information for interpretation of intra‐visit visual field results that cannot already be garnered using other strategies.
Publisher: Elsevier BV
Date: 12-2019
Publisher: Wiley
Date: 29-08-2007
DOI: 10.1002/CNE.21481
Abstract: We quantitatively tracked the recovery in amino acid labeling and cation channel functionality within distinct retinal elements for up to 2 weeks after an ischemic insult. Pattern recognition analysis of multiple amino acid and agmatine (a cation channel probe 1-amino-4-guanidobutane AGB) immunocytochemical patterns was used to classify all neural elements within the retina. This classification was spatially complete and with single-cell resolution. By 48 hours of reperfusion the amino acid labeling pattern of virtually all cell populations had returned to near preischemic levels, with the exception of glutamine and alanine levels, which remained significantly higher in many cell populations. Classification resulted in a total of 18 statistically separable theme classes (including neurons, glia, and extraretinal classes), a reduction of 10 theme classes from the normal retina (Sun et al. [ 2007a, b] J Comp Neurol, this issue). In addition to the known selective losses of amacrine cell types within the inner nuclear layer, we now demonstrate a selective loss of theme classes representing cone bipolar cells within the bipolar cell population. While there was a recovery in the amino acid labeling pattern, there were persistent cation channel gating anomalies (as reflected by AGB labeling) within several theme classes, including the theme class representing all the remaining rod bipolar cells, suggesting aberrant neuronal function secondary to metabolic insult.
Publisher: SPIE
Date: 03-03-2017
DOI: 10.1117/12.2253980
Publisher: Wiley
Date: 09-07-2020
DOI: 10.1111/OPO.12714
Abstract: To identify patterns of age‐, gender‐ and refractive‐ related changes in Scheimpflug‐based anterior chamber depth across the central 8 mm of chamber width, to derive normative models, potentially useful for angle closure disease diagnosis. This was a retrospective, cross‐sectional study. Scheimpflug photography was used to obtain anterior chamber depth measurements at 57 points across the central 8 mm of the chamber width from one eye of each healthy subject (male Caucasians ( n = 189), female Caucasians ( n = 186), male Asians ( n = 165) and female Asians ( n = 181)). Sliding window and nonlinear regression analysis was used to identify the age‐related changes in chamber depth. Hierarchical cluster analysis was used to identify test locations with statistically identical age‐related shifts, which were used to perform age‐correction for all subjects, resulting in normative distributions of chamber depth across the chamber width. The model was examined with and without the contribution of spherical equivalent refractive error. Distinct clusters, demonstrating statistically indistinguishable age‐related changes of chamber depth over time, were identified. These age‐related changes followed a nonlinear regression (fifth or sixth order polynomial). Females tended to have a greater rate of chamber depth shallowing. Incorporating refractive error into the model produced minimal changes to the fit relative to the ground truth. Comparisons with cut‐offs for angle closure from the literature showed that ageing alone was insufficient for identifying angle closure disease. Age‐, ethnicity‐ and gender‐related differences need to be acknowledged in order to utilise anterior chamber depth data for angle closure disease diagnosis correctly. Ageing alone does not adequately account for the angle closure disease process.
No related grants have been discovered for Michael Kalloniatis.