scholarly journals Medical Management of Glaucoma in the 21st Century from a Canadian Perspective

2016 ◽  
Vol 2016 ◽  
pp. 1-22 ◽  
Author(s):  
Paul Harasymowycz ◽  
Catherine Birt ◽  
Patrick Gooi ◽  
Lisa Heckler ◽  
Cindy Hutnik ◽  
...  
Keyword(s):  
Medical Management ◽  
Vision Loss ◽  
Ganglion Cells ◽  
Field Testing ◽  
Retinal Nerve Fibre Layer ◽  
Retinal Ganglion ◽  
Canadian Perspective ◽  
Recent Developments ◽  
Nerve Fibre Layer

Glaucoma is a medical term describing a group of progressive optic neuropathies characterized by degeneration of retinal ganglion cells and retinal nerve fibre layer and resulting in changes in the optic nerve head. Glaucoma is a leading cause of irreversible vision loss worldwide. With the aging population it is expected that the prevalence of glaucoma will continue to increase. Despite recent advances in imaging and visual field testing techniques that allow establishment of earlier diagnosis and treatment initiation, significant numbers of glaucoma patients are undiagnosed and present late in the course of their disease. This can lead to irreversible vision loss, reduced quality of life, and a higher socioeconomic burden. Selection of therapeutic approaches for glaucoma should be based on careful ocular examination, patient medical history, presence of comorbidities, and awareness of concomitant systemic therapies. Therapy should also be individualized to patients’ needs and preferences. Recent developments in this therapeutic field require revisiting treatment algorithms and integration of traditional and novel approaches in order to ensure optimal visual outcomes. This article provides an overview of recent developments and practice trends in the medical management of glaucoma in Canada. A discussion of the surgical management is beyond the scope of this paper.

scholarly journals A Retinal Biophysical Biomarker for Amyotrophic Lateral Sclerosis (ALS)

2021 ◽  
Author(s):  
Maryam Amin Mohammed Amin
Keyword(s):  
Nerve Fibre ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Retinal Nerve Fibre Layer ◽  
Retinal Ganglion ◽  
Axonal Pathology ◽  
Fibre Layer ◽  
Nerve Fibre Layer ◽  
Als Patients ◽  
Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is an incurable motor neuron disease with no current valid diagnostic imaging biomarkers. The retina is an extension of the central nervous system and axonal transport defects have been documented in various neurodegenerative diseases. This study reports evidence of axonal pathology in the retina of ALS patients using an interdisciplinary approach that includes the neuropathological study of retinal sections in ALS patients expanded to the optical characteristics of the whole retina preparations using eye imaging technology. The histopathological examination of retina sections revealed round profiles in the retinal nerve fibre layer in 10 out 10 ALS patients and in 4 out of 10 age-matched control patients. All 10 ALS patients showed increased phosphorylated neurofilament immunoreactivity in the retinal nerve fibre layer compared to all 10 control patients. Retinal imaging of whole globes and retina flat-mounts by blue reflectance retinal funduscopy and optical coherence tomography revealed hyper-reflective profiles in the retinal nerve fibre layer. For the first time, approximately 1µm retinal ganglion cells axons were visualized in immunofluorescence stained retina flat-mounts using near-infrared retina fundus imaging and Image Mapping Spectrometer. These findings suggest axonal pathology in retinal ganglion cells and its potential use as a novel non-invasive ocular imaging biomarker for ALS.

scholarly journals A Retinal Biophysical Biomarker for Amyotrophic Lateral Sclerosis (ALS)

2021 ◽  
Author(s):  
Maryam Amin Mohammed Amin
Keyword(s):  
Nerve Fibre ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Retinal Nerve Fibre Layer ◽  
Retinal Ganglion ◽  
Axonal Pathology ◽  
Fibre Layer ◽  
Nerve Fibre Layer ◽  
Als Patients ◽  
Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is an incurable motor neuron disease with no current valid diagnostic imaging biomarkers. The retina is an extension of the central nervous system and axonal transport defects have been documented in various neurodegenerative diseases. This study reports evidence of axonal pathology in the retina of ALS patients using an interdisciplinary approach that includes the neuropathological study of retinal sections in ALS patients expanded to the optical characteristics of the whole retina preparations using eye imaging technology. The histopathological examination of retina sections revealed round profiles in the retinal nerve fibre layer in 10 out 10 ALS patients and in 4 out of 10 age-matched control patients. All 10 ALS patients showed increased phosphorylated neurofilament immunoreactivity in the retinal nerve fibre layer compared to all 10 control patients. Retinal imaging of whole globes and retina flat-mounts by blue reflectance retinal funduscopy and optical coherence tomography revealed hyper-reflective profiles in the retinal nerve fibre layer. For the first time, approximately 1µm retinal ganglion cells axons were visualized in immunofluorescence stained retina flat-mounts using near-infrared retina fundus imaging and Image Mapping Spectrometer. These findings suggest axonal pathology in retinal ganglion cells and its potential use as a novel non-invasive ocular imaging biomarker for ALS.

Image Sharpness and Contrast Tuning in the Early Visual Pathway

2017 ◽  
Vol 27 (08) ◽  
pp. 1750045 ◽  
Author(s):  
Eduardo Sánchez ◽  
Rubén Ferreiroa ◽  
Adrián Arias ◽  
Luis M. Martínez
Keyword(s):  
Functional Organization ◽  
Ganglion Cells ◽  
Receptive Fields ◽  
Local Contrast ◽  
Retinal Ganglion ◽  
Image Sharpness ◽  
Image Processing Techniques ◽  
Thalamic Relay ◽  
Processing Techniques

The center–surround organization of the receptive fields (RFs) of retinal ganglion cells highlights the presence of local contrast in visual stimuli. As RF of thalamic relay cells follow the same basic functional organization, it is often assumed that they contribute very little to alter the retinal output. However, in many species, thalamic relay cells largely outnumber their retinal inputs, which diverge to contact simultaneously several units at thalamic level. This gain in cell population as well as retinothalamic convergence opens the door to question how information about contrast is transformed at the thalamic stage. Here, we address this question using a realistic dynamic model of the retinothalamic circuit. Our results show that different components of the thalamic RF might implement filters that are analogous to two types of well-known image processing techniques to preserve the quality of a higher resolution version of the image on its way to the primary visual cortex.

scholarly journals Oxidative Stress in Optic Neuropathies

Antioxidants ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1538
Author(s):  
Berta Sanz-Morello ◽  
Hamid Ahmadi ◽  
Rupali Vohra ◽  
Sarkis Saruhanian ◽  
Kristine Karla Freude ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Optic Neuropathy ◽  
Vision Loss ◽  
Ganglion Cells ◽  
Redox System ◽  
Ischemic Optic Neuropathy ◽  
Retinal Ganglion ◽  
Oxidative Stress Biomarkers ◽  
Optic Disc Drusen ◽  
Advanced Stages

Increasing evidence indicates that changes in the redox system may contribute to the pathogenesis of multiple optic neuropathies. Optic neuropathies are characterized by the neurodegeneration of the inner-most retinal neurons, the retinal ganglion cells (RGCs), and their axons, which form the optic nerve. Often, optic neuropathies are asymptomatic until advanced stages, when visual impairment or blindness is unavoidable despite existing treatments. In this review, we describe systemic and, whenever possible, ocular redox dysregulations observed in patients with glaucoma, ischemic optic neuropathy, optic neuritis, hereditary optic neuropathies (i.e., Leber’s hereditary optic neuropathy and autosomal dominant optic atrophy), nutritional and toxic optic neuropathies, and optic disc drusen. We discuss aspects related to anti/oxidative stress biomarkers that need further investigation and features related to study design that should be optimized to generate more valuable and comparable results. Understanding the role of oxidative stress in optic neuropathies can serve to develop therapeutic strategies directed at the redox system to arrest the neurodegenerative processes in the retina and RGCs and ultimately prevent vision loss.

OCT Angiography of the Central Macular Capillary Network in Glaucoma Patients and Healthy Controls

2018 ◽  
Vol 235 (04) ◽  
pp. 436-444
Author(s):  
Olena Müller ◽  
Margarita G. Todorova ◽  
Torsten Schlote
Keyword(s):  
Optical Coherence Tomography ◽  
Structural Changes ◽  
Ganglion Cells ◽  
Retinal Nerve Fibre Layer ◽  
Vessel Density ◽  
Healthy Controls ◽  
Optical Coherence ◽  
Significant Difference ◽  
Nerve Fibre Layer ◽  
And Control

Abstract Purpose We aimed to investigate central macular microvasculature by optical coherence tomography angiography (OCTA) and to analyse its relation to alterations in classical parameters of optical coherence tomography (OCT) in glaucoma patients. Methods Using OCTA (Avanti incl. AngioVue; Optovue, Inc., Fremont, CA), the superficial flow (SF) and the superficial non-flow (SNF) area of the macula, as well as the S-ETDRS (based on Early Treatment Diabetic Retinopathy charts). and S-grid vessel density (zones 1 – 9) of the macula, were evaluated in 27 glaucoma patients (49 eyes) and compared to those of 27 age-matched healthy controls (50 eyes; p = 0.253). The interactions between OCTA parameters representing macular microvasculature and classical OCT measurements of the circumpapillary retinal nerve fibre layer (RNFL) and macular ganglion cells (mGCC) were analysed within groups (linear mixed-effects model). Results SF, SNF, and S-ETDRS vessel density exhibited no significant difference between the glaucoma and control groups (all p ≥ 0.158). However, within the glaucoma group, decreased RNFL and mGCC thickness correlated significantly with decreased S-ETDRS density (zones 1; 2 – 9, p ≤ 0.033). The same held true for the interactions between the RNFL and mGCC thickness with S-grid density (zones 1 – 3; 6 – 9; p ≤ 0.033). For perimetric glaucoma patients, subgroup analyses demonstrated significantly reduced density maps of superficial foveal flow as well as significant interactions between OCT and OCTA parameters; this was not the case within the preperimetric group. Conclusions Even if the central macular microvasculature, as measured by SF and SNF, is found preserved in glaucoma, the strong positive relation between the central microvascular and structural changes in OCTA and OCT indicates that there are alterations in central macular microvasculature in subclinical glaucoma.

scholarly journals Loss of Responses to Visual But Not Electrical Stimulation in Ganglion Cells of Rats With Severe Photoreceptor Degeneration

2009 ◽  
Vol 102 (6) ◽  
pp. 3260-3269 ◽  
Author(s):  
Chris Sekirnjak ◽  
Clare Hulse ◽  
Lauren H. Jepson ◽  
Pawel Hottowy ◽  
Alexander Sher ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Retinal Ganglion Cells ◽  
Vision Loss ◽  
Ganglion Cells ◽  
Transgenic Rat ◽  
Direct Electrical Stimulation ◽  
Retinal Ganglion ◽  
Photoreceptor Degeneration ◽  
Wild Type ◽  
Light Responses

Retinal implants are intended to help patients with degenerative conditions by electrically stimulating surviving cells to produce artificial vision. However, little is known about how individual retinal ganglion cells respond to direct electrical stimulation in degenerating retina. Here we used a transgenic rat model to characterize ganglion cell responses to light and electrical stimulation during photoreceptor degeneration. Retinas from pigmented P23H-1 rats were compared with wild-type retinas between ages P37 and P752. During degeneration, retinal thickness declined by 50%, largely as a consequence of photoreceptor loss. Spontaneous electrical activity in retinal ganglion cells initially increased two- to threefold, but returned to nearly normal levels around P600. A profound decrease in the number of light-responsive ganglion cells was observed during degeneration, culminating in retinas without detectable light responses by P550. Ganglion cells from transgenic and wild-type animals were targeted for focal electrical stimulation using multielectrode arrays with electrode diameters of ∼10 microns. Ganglion cells were stimulated directly and the success rate of stimulation in both groups was 60–70% at all ages. Surprisingly, thresholds (∼0.05 mC/cm2) and latencies (∼0.25 ms) in P23H rat ganglion cells were comparable to those in wild-type ganglion cells at all ages and showed no change over time. Thus ganglion cells in P23H rats respond normally to direct electrical stimulation despite severe photoreceptor degeneration and complete loss of light responses. These findings suggest that high-resolution epiretinal prosthetic devices may be effective in treating vision loss resulting from photoreceptor degeneration.

Evaluation of the Optic Nerve and Retinal Nerve Fibre Layer in Myopic Individuals

2012 ◽  
Vol 06 (05) ◽  
pp. 280
Author(s):  
Ahmad A Aref ◽  
Donald L Budenz ◽  
◽  
Keyword(s):  
Nerve Fibre ◽  
False Positive Rate ◽  
Field Testing ◽  
Retinal Nerve Fibre Layer ◽  
Histopathological Study ◽  
Glaucomatous Optic Neuropathy ◽  
Neuroretinal Rim ◽  
Fibre Layer ◽  
Nerve Fibre Layer

Clinical discrimination between myopic tilted optic discs and glaucomatous optic neuropathy is often challenging, especially when considering that myopia is a risk factor for the development of glaucoma. Myopic tilted discs are usually larger than average, with associated relative cupping and thinner neuroretinal rim tissue. Histopathological study has revealed thinner parapapillary retinal tissue in these eyes. Optical coherence tomography (OCT)-measured average retinal nerve fibre layer (RNFL) thickness has been found to decrease with longer axial length and higher myopic refractive error. Parapapillary RNFL quadrant and clock-hour analyses result in a higher false-positive rate in myopic eyes. Careful slit-lamp examination, quality baseline stereoscopic disc photographs and frequent serial visual field testing are essential to the follow-up of myopic individuals with suspected glaucoma. A novel diagnostic parameter, OCT-derived ganglion cell analysis, may prove to be useful in the diagnosis and follow-up of these individuals.

scholarly journals PTEN Expression Regulates Gap Junction Connectivity in the Retina

2021 ◽  
Vol 15 ◽  
Author(s):  
Ashley M. Chen ◽  
Shaghauyegh S. Azar ◽  
Alexander Harris ◽  
Nicholas C. Brecha ◽  
Luis Pérez de Sevilla Müller
Keyword(s):  
Gap Junction ◽  
Retinal Ganglion Cells ◽  
Vision Loss ◽  
Ganglion Cells ◽  
Dendritic Structure ◽  
Amacrine Cells ◽  
Mouse Retina ◽  
Retinal Ganglion ◽  
Cell Coupling ◽  
Cell Degeneration

Manipulation of the phosphatase and tensin homolog (PTEN) pathway has been suggested as a therapeutic approach to treat or prevent vision loss due to retinal disease. In this study, we investigated the effects of deleting one copy of Pten in a well-characterized class of retinal ganglion cells called α-ganglion cells in the mouse retina. In Pten+/– retinas, α-ganglion cells did not exhibit major changes in their dendritic structure, although most cells developed a few, unusual loop-forming dendrites. By contrast, α-ganglion cells exhibited a significant decrease in heterologous and homologous gap junction mediated cell coupling with other retinal ganglion and amacrine cells. Additionally, the majority of OFF α-ganglion cells (12/18 cells) formed novel coupling to displaced amacrine cells. The number of connexin36 puncta, the predominant connexin that mediates gap junction communication at electrical synapses, was decreased by at least 50% on OFF α-ganglion cells. Reduced and incorrect gap junction connectivity of α-ganglion cells will affect their functional properties and alter visual image processing in the retina. The anomalous connectivity of retinal ganglion cells would potentially limit future therapeutic approaches involving manipulation of the Pten pathway for treating ganglion cell degeneration in diseases like glaucoma, traumatic brain injury, Parkinson’s, and Alzheimer’s diseases.

scholarly journals Epiretinal stimulation with local returns enhances selectivity at cellular resolution

2018 ◽  
Author(s):  
Victoria H. Fan ◽  
Lauren E. Grosberg ◽  
Sasidhar S. Madugula ◽  
Pawel Hottowy ◽  
Wladyslaw Dabrowski ◽  
...  
Keyword(s):  
Ganglion Cells ◽  
Electrode Array ◽  
Artificial Vision ◽  
Retinal Ganglion ◽  
Retinal Neurons ◽  
Cellular Resolution ◽  
Electrode Recording ◽  
Current Spread ◽  
Evoked Activity

AbstractObjectiveEpiretinal prostheses are designed to restore vision in people blinded by photoreceptor degenerative diseases, by directly activating retinal ganglion cells (RGCs) using an electrode array implanted on the retina. In present-day clinical devices, current spread from the stimulating electrode to a distant return electrode often results in the activation of many cells, potentially limiting the quality of artificial vision. In the laboratory, epiretinal activation of RGCs with cellular resolution has been demonstrated with small electrodes, but distant returns may still cause undesirable current spread. Here, the ability of local return stimulation to improve the selective activation of RGCs at cellular resolution was evaluated.ApproachA custom multi-electrode array (512 electrodes, 10 μm diameter, 60 μm pitch) was used to simultaneously stimulate and record from RGCs in isolated primate retina. Stimulation near the RGC soma with a single electrode and a distant return was compared to stimulation in which the return was provided by six neighboring electrodes.Main resultsLocal return stimulation enhanced the capability to activate cells near the central electrode (<30 μm) while avoiding cells farther away (>30 μm). This resulted in an improved ability to selectively activate ON and OFF cells, including cells encoding immediately adjacent regions in the visual field.SignificanceThese results suggest that a device that restricts the electric field through local returns could optimize activation of neurons at cellular resolution, improving the quality of artificial vision.Novelty & SignificanceThe effectiveness of local return stimulation for enhancing the electrical activation of retinal neurons was tested using high-density multi-electrode recording and stimulation in isolated macaque retina. The results suggest that local returns may reduce unwanted evoked activity and thus optimize the selectivity of stimulation at cellular resolution. Similar patterns could be implemented in a future high-resolution prosthesis to permit a more faithful replication of normal retinal activity for the treatment of incurable blindness.

scholarly journals Current Medical Therapy and Future Trends in the Management of Glaucoma Treatment

2020 ◽  
Vol 2020 ◽  
pp. 1-14 ◽  
Author(s):  
Barbara Cvenkel ◽  
Miriam Kolko
Keyword(s):  
Ganglion Cells ◽  
Retinal Ganglion ◽  
Future Trends ◽  
Neuroprotective Agents ◽  
Sustained Drug Delivery ◽  
Progressive Loss ◽  
Neuroprotective Therapy ◽  
Rate Of Progression ◽  
New Treatment

Glaucoma is a neurodegenerative disease characterized by progressive loss of retinal ganglion cells and their axons. Lowering of intraocular pressure (IOP) is currently the only proven treatment strategy for glaucoma. However, some patients show progressive loss of visual field and quality of life despite controlled IOP which indicates that other factors are implicated in glaucoma. Therefore, approaches that could prevent or decrease the rate of progression and do not rely on IOP lowering have gained much attention. Effective neuroprotection has been reported in animal models of glaucoma, but till now, no neuroprotective agents have been clinically approved. The present update provides an overview of currently available IOP-lowering medications. Moreover, potential new treatment targets for IOP-lowering and neuroprotective therapy are discussed. Finally, future trends in glaucoma therapy are addressed, including sustained drug delivery systems and progress toward personalized medicine.

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