-
Cells Aug 2023Age-related macular degeneration (AMD) is the leading cause of vision loss and visual impairment in people over 50 years of age. In the current therapeutic landscape,... (Review)
Review
Age-related macular degeneration (AMD) is the leading cause of vision loss and visual impairment in people over 50 years of age. In the current therapeutic landscape, intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapies have been central to the management of neovascular AMD (also known as wet AMD), whereas treatments for geographic atrophy have lagged behind. Several therapeutic approaches are being developed for geographic atrophy with the goal of either slowing down disease progression or reversing sight loss. Such strategies target the inflammatory pathways, complement cascade, visual cycle or neuroprotective mechanisms to slow down the degeneration. In addition, retinal implants have been tried for vision restoration and stem cell therapies for potentially a dual purpose of slowing down the degeneration and restoring visual function. In particular, therapies focusing on the complement pathway have shown promising results with the FDA approved pegcetacoplan, a complement C3 inhibitor, and avacincaptad pegol, a complement C5 inhibitor. In this review, we discuss the mechanisms of inflammation in AMD and outline the therapeutic landscapes of atrophy AMD. Improved understanding of the various pathway components and their interplay in this complex neuroinflammatory degeneration will guide the development of current and future therapeutic options, such as optogenetic therapy.
Topics: Humans; Middle Aged; Geographic Atrophy; Angiogenesis Inhibitors; Wet Macular Degeneration; Vascular Endothelial Growth Factor A; Visual Acuity; Inflammation
PubMed: 37626902
DOI: 10.3390/cells12162092 -
Biomedical Papers of the Medical... Sep 2023A case report of a 40-year-old patient with tuberculosis treated with ethambutol is described. Within six months of starting treatment, there was a painless sudden...
PURPOSE
A case report of a 40-year-old patient with tuberculosis treated with ethambutol is described. Within six months of starting treatment, there was a painless sudden decline in visual function. Despite the known complications of ethambutol treatment, it was discontinued after another three months.
METHODS
In the case report, we highlight the damage to the dominantly peripheral visual pathways. Using electrophysiological examinations, we showed a significant alteration in the optic nerves. Optical Coherence Tomography (OCT) showed progressive loss of vessel density and nerve fibre layer of retinal ganglion cells. Perimetric examination showed both a central decrease in sensitivity and mainly scotomas in the temporal parts of the visual fields. Although there was improvement in visual fields over time, OCT findings indicated progression of ethambutol-induced optic neuropathy (EON). Magnetic Resonance Imaging confirmed the alteration in the peripheral part of the visual pathway (intraorbital, intracranial parts of optic nerves, chiasma, and optic tracts).
CONCLUSION
Even though EON is not an unknown complication, new cases still occur and, unfortunately, with an irreversible course. Therefore, it is important to draw attention constantly to this complication and to consider it not only in ophthalmologists' surgeries.
Topics: Humans; Adult; Ethambutol; Antitubercular Agents; Optic Nerve Diseases; Optic Nerve; Tuberculosis; Tomography, Optical Coherence
PubMed: 35582729
DOI: 10.5507/bp.2022.022 -
NeuroImage Oct 2023Visual illusions have long been used to study visual perception and contextual integration. Neuroimaging studies employ illusions to identify the brain regions involved... (Meta-Analysis)
Meta-Analysis Review
Visual illusions have long been used to study visual perception and contextual integration. Neuroimaging studies employ illusions to identify the brain regions involved in visual perception and how they interact. We conducted an Activation Likelihood Estimation (ALE) meta-analysis and meta-analytic connectivity modeling on fMRI studies using static and motion illusions to reveal the neural signatures of illusory processing and to investigate the degree to which different areas are commonly recruited in perceptual inference. The resulting networks encompass ventral and dorsal regions, including the inferior and middle occipital cortices bilaterally in both types of illusions. The static and motion illusion networks selectively included the right posterior parietal cortex and the ventral premotor cortex respectively. Overall, these results describe a network of areas crucially involved in perceptual inference relying on feed-back and feed-forward interactions between areas of the ventral and dorsal visual pathways. The same network is proposed to be involved in hallucinogenic symptoms characteristic of schizophrenia and other disorders, with crucial implications in the use of illusions as biomarkers.
Topics: Humans; Illusions; Likelihood Functions; Neural Networks, Computer; Visual Perception; Head
PubMed: 37591478
DOI: 10.1016/j.neuroimage.2023.120335 -
Expert Opinion on Pharmacotherapy 2023With the recent FDA approvals of pegcetacoplan (SYFOVRE, Apellis Pharmaceuticals) and avacincaptad pegol (IZERVAY, Astellas Pharmaceuticals), modulation of the... (Review)
Review
INTRODUCTION
With the recent FDA approvals of pegcetacoplan (SYFOVRE, Apellis Pharmaceuticals) and avacincaptad pegol (IZERVAY, Astellas Pharmaceuticals), modulation of the complement system has emerged as a promising therapeutic approach for slowing progression of geographic atrophy (GA) in AMD.
AREAS COVERED
This article reviews the current understanding of the complement system, its role in AMD, and the various complement-targeting therapies in development for the treatment of GA, including monoclonal antibodies, aptamers, protein analogs, and gene therapies. Approved and investigational agents have largely focused on interfering with the activity of complement components 3 and 5, owing to their central roles in the classical, lectin, and alternative complement pathways. Other investigational therapies have targeted formation of membrane attack complex (a terminal step in the complement cascade which leads to cell lysis), complement factors H and I (which serve regulatory functions in the alternative pathway), complement factors B and D (within the alternative pathway), and complement component 1 (within the classical pathway). Clinical trials investigating these agents are summarized, and the potential benefits and limitations of these therapies are discussed.
EXPERT OPINION
Targeting the complement system is a promising therapeutic approach for slowing the progression of GA in AMD, potentially improving visual outcomes. However, increased risk of exudative conversion must be considered, and further research is required to identify clinical criteria and best practices for initiating complement inhibitor therapy for GA.
Topics: Humans; Macular Degeneration; Geographic Atrophy; Immunologic Factors; Therapies, Investigational; Pharmaceutical Preparations
PubMed: 37691588
DOI: 10.1080/14656566.2023.2257604 -
Frontiers in Neuroscience 2023The thalamus acts as an interface between the periphery and the cortex, with nearly every sensory modality processing information in the thalamocortical circuit. Despite... (Review)
Review
The thalamus acts as an interface between the periphery and the cortex, with nearly every sensory modality processing information in the thalamocortical circuit. Despite well-established thalamic nuclei for visual, auditory, and tactile modalities, the key thalamic nuclei responsible for innocuous thermosensation remains under debate. Thermosensory information is first transduced by thermoreceptors located in the skin and then processed in the spinal cord. Temperature information is then transmitted to the brain through multiple spinal projection pathways including the spinothalamic tract and the spinoparabrachial tract. While there are fundamental studies of thermal transduction via thermosensitive channels in primary sensory afferents, thermal representation in the spinal projection neurons, and encoding of temperature in the primary cortical targets, comparatively little is known about the intermediate stage of processing in the thalamus. Multiple thalamic nuclei have been implicated in thermal encoding, each with a corresponding cortical target, but without a consensus on the role of each pathway. Here, we review a combination of anatomy, physiology, and behavioral studies across multiple animal models to characterize the thalamic representation of temperature in two proposed thermosensory information streams.
PubMed: 37901427
DOI: 10.3389/fnins.2023.1210949 -
International Journal of Molecular... Oct 2023Glaucoma is the leading cause of blindness worldwide. It is classically associated with structural and functional changes in the optic nerve head and retinal nerve fiber... (Review)
Review
Glaucoma is the leading cause of blindness worldwide. It is classically associated with structural and functional changes in the optic nerve head and retinal nerve fiber layer, but the damage is not limited to the eye. The involvement of the central visual pathways and disruption of brain network organization have been reported using advanced neuroimaging techniques. The brain structural changes at the level of the areas implied in processing visual information could justify the discrepancy between signs and symptoms and underlie the analogy of this disease with neurodegenerative dementias, such as Alzheimer's disease, and with the complex group of pathologies commonly referred to as "disconnection syndromes." This review aims to summarize the current state of the art on the use of advanced neuroimaging techniques in glaucoma and Alzheimer's disease, highlighting the emerging biomarkers shared by both diseases.
Topics: Humans; Alzheimer Disease; Magnetic Resonance Imaging; Glaucoma; Neuroimaging; Brain; Biomarkers
PubMed: 37834380
DOI: 10.3390/ijms241914932 -
Eye (London, England) Aug 2023Historically, distinct mitochondrial syndromes were recognised clinically by their ocular features. Due to their predilection for metabolically active tissue,... (Review)
Review
Historically, distinct mitochondrial syndromes were recognised clinically by their ocular features. Due to their predilection for metabolically active tissue, mitochondrial diseases frequently involve the eye, resulting in a range of ophthalmic manifestations including progressive external ophthalmoplegia, retinopathy and optic neuropathy, as well as deficiencies of the retrochiasmal visual pathway. With the wider availability of genetic testing in clinical practice, it is now recognised that genotype-phenotype correlations in mitochondrial diseases can be imprecise: many classic syndromes can be associated with multiple genes and genetic variants, and the same genetic variant can have multiple clinical presentations, including subclinical ophthalmic manifestations in individuals who are otherwise asymptomatic. Previously considered rare diseases with no effective treatments, considerable progress has been made in our understanding of mitochondrial diseases with new therapies emerging, in particular, gene therapy for inherited optic neuropathies.
Topics: Humans; Syndrome; Mitochondrial Diseases; Mitochondria; Optic Nerve Diseases; Retinal Diseases
PubMed: 37185957
DOI: 10.1038/s41433-023-02523-x -
Advanced Materials (Deerfield Beach,... Feb 2024The development of artificial intelligence has posed a challenge to machine vision based on conventional complementary metal-oxide semiconductor (CMOS) circuits owing to... (Review)
Review
The development of artificial intelligence has posed a challenge to machine vision based on conventional complementary metal-oxide semiconductor (CMOS) circuits owing to its high latency and inefficient power consumption originating from the data shuffling between memory and computation units. Gaining more insights into the function of every part of the visual pathway for visual perception can bring the capabilities of machine vision in terms of robustness and generality. Hardware acceleration of more energy-efficient and biorealistic artificial vision highly necessitates neuromorphic devices and circuits that are able to mimic the function of each part of the visual pathway. In this paper, we review the structure and function of the entire class of visual neurons from the retina to the primate visual cortex within reach (Chapter 2) are reviewed. Based on the extraction of biological principles, the recent hardware-implemented visual neurons located in different parts of the visual pathway are discussed in detail in Chapters 3 and 4. Furthermore, valuable applications of inspired artificial vision in different scenarios (Chapter 5) are provided. The functional description of the visual pathway and its inspired neuromorphic devices/circuits are expected to provide valuable insights for the design of next-generation artificial visual perception systems.
Topics: Animals; Artificial Intelligence; Visual Pathways; Vision, Ocular; Computers; Visual Perception; Primates
PubMed: 37435995
DOI: 10.1002/adma.202301986