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Developmental Biology Aug 2021The basic structure of the eye, which is crucial for visual function, is established during the embryonic process of optic cup morphogenesis. Molecular pathways of... (Review)
Review
The basic structure of the eye, which is crucial for visual function, is established during the embryonic process of optic cup morphogenesis. Molecular pathways of specification and patterning are integrated with spatially distinct cell and tissue shape changes to generate the eye, with discrete domains and structural features: retina and retinal pigment epithelium enwrap the lens, and the optic fissure occupies the ventral surface of the eye and optic stalk. Interest in the underlying cell biology of eye morphogenesis has led to a growing body of work, combining molecular genetics and imaging to quantify cellular processes such as adhesion and actomyosin activity. These studies reveal that intrinsic machinery and spatiotemporally specific extrinsic inputs collaborate to control dynamics of cell movements and morphologies. Here we consider recent advances in our understanding of eye morphogenesis, with a focus on the mechanics of eye formation throughout vertebrate systems, including insights and potential opportunities using organoids, which may provide a tractable system to test hypotheses from embryonic models.
Topics: Actomyosin; Animals; Cell Movement; Eye; Humans; Lens, Crystalline; Morphogenesis; Optic Disk; Organogenesis; Retina; Retinal Pigment Epithelium; Signal Transduction; Vertebrates
PubMed: 33811855
DOI: 10.1016/j.ydbio.2021.03.023 -
Romanian Journal of Ophthalmology 2021Idiopathic intracranial hypertension (IIH) is a neuro-ophthalmological syndrome of unknown cause that can be vision-threatening, so an early diagnosis is crucial. We...
Idiopathic intracranial hypertension (IIH) is a neuro-ophthalmological syndrome of unknown cause that can be vision-threatening, so an early diagnosis is crucial. We reported a case of a 68-year-old asymptomatic male referred with a cataract in his right eye (OD). Best-corrected visual acuity (BCVA) was 70 letters (20/ 40) in the OD and 85 letters (20/ 20) in the left eye (OS). Ophthalmological examination revealed a significant nuclear cataract in the OD that explained the visual acuity. Fundus imaging showed a faint nasal margin elevation of the optic disc of both eyes (OU). Optical coherence tomography (OCT) revealed a sectorial retinal nerve fiber layer (RNFL) atrophy in the inferior quadrant in the OS. Nevertheless, visual field (VF) did not demonstrate defects. Neuroimaging was normal and examination of CSF revealed an opening pressure of 500 mmH2O. A diagnosis of IIH was confirmed and acetazolamide 250 mg twice daily was recommended. After 12 months of follow-up, RNFL thickness remained stable and VF did not confirm defects. A routine eye examination was the onset of IIH in our case. Thus, the ophthalmologist played a crucial role in the early diagnosis of this syndrome. Papilledema is usually a key criterion for IIH, so after its detection, exclusion diagnosis and treatment should be initiated in order to avoid permanent visual loss.
Topics: Aged; Humans; Male; Optic Disk; Papilledema; Pseudotumor Cerebri; Retinal Ganglion Cells; Tomography, Optical Coherence
PubMed: 34179586
DOI: 10.22336/rjo.2021.37 -
Translational Vision Science &... Jul 2020To use multimodal retinal images (including quantitative fundus autofluorescence [QAF]) for spectral-domain optical coherence tomography (SD-OCT)-based image...
PURPOSE
To use multimodal retinal images (including quantitative fundus autofluorescence [QAF]) for spectral-domain optical coherence tomography (SD-OCT)-based image registration and alignment. For each age decade of healthy adults, normative fine-grained QAF retinal maps are generated and advanced methods for QAF image analysis are applied.
METHODS
Multimodal retinal images were obtained from 103 healthy subjects (age 19-77 years; unremarkable retina/macula, age-appropriate clear optic media). Custom written FIJI plugins enabled: (1) determination of the fovea in SD-OCT and the edge of the optic disc in infrared (IR) images; (2) alignment and superimposition of multimodal retinal images based on foveal and optic disc position; (3) plotting of normative QAF retinal maps for each decade; and (4) comparison of individual retinas with normative retinas of different decades using newly introduced analysis patterns (QAF97, freehand tool).
RESULTS
SD-OCT based image registration enables easy image registration, alignment, and analysis of different modalities (QAF, IR, and SD-OCT here reported). In QAF, intensities significantly increase with age with two major inclines between the third/fourth and seventh/eighth decades. With aging, the parafoveal area of maximum QAF intensity slightly shifts from temporal-superior to temporal. Compared with standard QAF analysis, refined QAF analysis patterns reveal a more detailed analysis of QAF, especially in the diseased retina.
CONCLUSIONS
Age-related QAF normative retinal maps can be used to directly compare and classify individual's QAF intensities. Advanced QAF analysis tools will further help to interpret autofluorescence changes in normal aging and in the diseased retina in a multimodal imaging setting.
TRANSLATIONAL RELEVANCE
Advanced methods for QAF analysis link basic findings with clinical observations in normal aging and in the diseased macula.
Topics: Adult; Aged; Fluorescein Angiography; Humans; Middle Aged; Optic Disk; Optical Imaging; Retina; Tomography, Optical Coherence; Young Adult
PubMed: 32855849
DOI: 10.1167/tvst.9.8.2 -
JCI Insight Jun 2023Over 30 million people worldwide suffer from untreatable vision loss and blindness associated with childhood-onset and age-related eye diseases caused by photoreceptor...
Over 30 million people worldwide suffer from untreatable vision loss and blindness associated with childhood-onset and age-related eye diseases caused by photoreceptor (PR), retinal pigment epithelium (RPE), and choriocapillaris (CC) degeneration. Recent work suggests that RPE-based cell therapy may slow down vision loss in late stages of age-related macular degeneration (AMD), a polygenic disease induced by RPE atrophy. However, accelerated development of effective cell therapies is hampered by the lack of large-animal models that allow testing safety and efficacy of clinical doses covering the human macula (20 mm2). We developed a versatile pig model to mimic different types and stages of retinal degeneration. Using an adjustable power micropulse laser, we generated varying degrees of RPE, PR, and CC damage and confirmed the damage by longitudinal analysis of clinically relevant outcomes, including analyses by adaptive optics and optical coherence tomography/angiography, along with automated image analysis. By imparting a tunable yet targeted damage to the porcine CC and visual streak - with a structure similar to the human macula - this model is optimal for testing cell and gene therapies for outer retinal diseases including AMD, retinitis pigmentosa, Stargardt, and choroideremia. The amenability of this model to clinically relevant imaging outcomes will facilitate faster translation to patients.
Topics: Humans; Animals; Swine; Child; Retina; Retinal Degeneration; Retinal Pigment Epithelium; Macular Degeneration
PubMed: 37288665
DOI: 10.1172/jci.insight.157654 -
Clinical & Experimental Optometry Jan 2020We live in a three-dimensional world and the human eye can focus images from a wide range of distances by adjusting the power of the eye's lens (accommodation).... (Review)
Review
We live in a three-dimensional world and the human eye can focus images from a wide range of distances by adjusting the power of the eye's lens (accommodation). Progressive senescent changes in the lens ultimately lead to a complete loss of this ability by about age 50, which then requires alternative strategies to generate high-quality retinal images for far and close viewing distances. This review paper highlights the biomimetic properties and underlying optical mechanisms of induced anisometropia, small apertures, dynamic lenses, and multi-optic lenses in ameliorating the visual consequences of presbyopia. Specifically, the advantages and consequences of non-liner neural summation leveraged in monovision treatments are reviewed. Additionally, the value of a small pupil is quantified, and the impact of pinhole pupil location and their effects on neural sensitivity are examined. Different strategies of generating multifocal optics are also examined, and specifically the interaction between ocular and contact or intraocular lens aberrations and their effect on resulting image quality are simulated. Interestingly, most of the novel strategies for aiding presbyopic and pseudophakic eyes (for example, monovision, multifocality, pinhole pupils) have emerged naturally via evolution in a range of species.
Topics: Accommodation, Ocular; Anisometropia; Contact Lenses; Eyeglasses; Humans; Optics and Photonics; Presbyopia; Pupil; Visual Acuity
PubMed: 31734940
DOI: 10.1111/cxo.12987 -
Asia-Pacific Journal of Ophthalmology...Structural and functional alterations in the microcirculation by systemic hypertension can cause significant organ damage at the eye, heart, brain, and kidneys. As the...
Structural and functional alterations in the microcirculation by systemic hypertension can cause significant organ damage at the eye, heart, brain, and kidneys. As the retina is the only tissue in the body that allows direct imaging of small vessels, the relationship of hypertensive retinopathy signs with development of disease states in other organs have been extensively studied; large-scale epidemiological studies using fundus photography and advanced semi-automated analysis software have reported the association of retinopathy signs with hypertensive end-organ damage includes the following: stroke, dementia, and coronary heart disease. Although yielding much useful information, the vessels assessed from fundus photographs remain limited to the larger retinal arterioles and venules, and abnormalities observed may not be that of the earliest changes. Newer imaging modalities such as optical coherence tomography angiography and adaptive optics technology, which allow a greater precision in the structural quantification of retinal vessels, including capillaries, may facilitate the assessment and management of these patients. The advent of deep learning technology has also augmented the utility of fundus photographs to help create diagnostic and risk stratification systems. Particularly, deep learning systems have been shown in several large studies to be able to predict multiple cardiovascular risk factors, major adverse cardiovascular events within 5 years, and presence of coronary artery calcium, from fundus photographs alone. In the future, combining deep learning systems with the imaging precision offered by optical coherence tomography angiography and adaptive optics could pave way for systems that are able to predict adverse clinical outcomes even more accurately.
Topics: Fluorescein Angiography; Fundus Oculi; Humans; Hypertension; Retina; Retinal Vessels; Tomography, Optical Coherence
PubMed: 35533334
DOI: 10.1097/APO.0000000000000509 -
Investigative Ophthalmology & Visual... Aug 2023To assess the clinical characteristics of focal temporal optic disc microvasculature dropout (MvD-D) in primary open-angle glaucoma (POAG) patients.
PURPOSE
To assess the clinical characteristics of focal temporal optic disc microvasculature dropout (MvD-D) in primary open-angle glaucoma (POAG) patients.
METHODS
One hundred and eighty-seven eyes of 187 POAG patients having MvD-D on Swept-Source optical coherence tomography angiography (SS-OCTA) were enrolled. Three groups were categorized according to the presence of temporal MvD-D within the upper and lower 45° of the fovea-Bruch's membrane (BM) opening axis: focal temporal MvD-D (Group 1, isolated focal temporal MvD-D; 44 eyes), supero/inferotemporal MvD-D (Group 2, MvD-D only in superotemporal or inferotemporal sector; 78 eyes), and diffuse temporal MvD-D (Group 3, MvD-D spanning ≥ 2 consecutive sectors, at least one of which being temporal sector; 65 eyes).
RESULTS
Group 1 had a significantly longer axial length and β-zone parapapillary atrophy without BM. There also was a larger horizontal tilt angle and ovality index than the other two groups (P < 0.001). Group 1 had a significantly thinner retinal nerve fiber layer (RNFL) in the temporal sector than did Group 2 (P < 0.001), despite similar thicknesses in all other areas (P > 0.05). Group 3 had significantly worse visual field mean deviation and thinner RNFL than the other two groups in all areas other than the nasal, temporal, and superotemporal sectors (P < 0.05).
CONCLUSIONS
Focal temporal MvD-D detected by SS-OCTA was associated with a longer axial length and related subsequent morphological changes of the optic disc and parapapillary area. This suggests that stretching of the optic disc consequent on axial elongation may lead to absence of temporal optic disc microvasculature.
Topics: Humans; Optic Disk; Glaucoma, Open-Angle; Intraocular Pressure; Retinal Ganglion Cells; Tomography, Optical Coherence; Microvessels
PubMed: 37540177
DOI: 10.1167/iovs.64.11.6 -
Eye (London, England) Feb 2023The retina and the optic nerve are considered extensions of the central nervous system (CNS) and thus can serve as the window for evaluation of CNS disorders. Spectral... (Review)
Review
The retina and the optic nerve are considered extensions of the central nervous system (CNS) and thus can serve as the window for evaluation of CNS disorders. Spectral domain optical coherence tomography (OCT) allows for detailed evaluation of the retina and the optic nerve. OCT can non-invasively document changes in single retina layer thickness and structure due to neuronal and retinal glial cells (RGC) modifications in systemic and local inflammatory and neurodegenerative diseases. These can include evaluation of retinal nerve fibre layer and ganglion cell complex, hyper-reflective retinal spots (HRS, sign of activated microglial cells in the retina), subfoveal neuroretinal detachment, disorganization of the inner retinal layers (DRIL), thickness and integrity of the outer retinal layers and choroidal thickness. This review paper will report the most recent data on the use of OCT as a non invasive imaging biomarker for evaluation of the most common systemic neuroinflammatory and neurodegenerative/neurocognitive disorders in the adults and in paediatric population. In the adult population the main focus will be on diabetes mellitus, multiple sclerosis, optic neuromyelitis, neuromyelitis optica spectrum disorders, longitudinal extensive transverse myelitis, Alzheimer and Parkinson diseases, Amyotrophic lateral sclerosis, Huntington's disease and schizophrenia. In the paediatric population, demyelinating diseases, lysosomal storage diseases, Nieman Pick type C disease, hypoxic ischaemic encephalopathy, human immunodeficiency virus, leukodystrophies spinocerebellar ataxia will be addressed.
Topics: Adult; Humans; Child; Tomography, Optical Coherence; Retinal Ganglion Cells; Neuroinflammatory Diseases; Retina; Neuromyelitis Optica; Biomarkers
PubMed: 35428871
DOI: 10.1038/s41433-022-02056-9 -
Eye (London, England) Feb 2024To characterize choroidal vascular changes in children with different refractive status.
OBJECTIVES
To characterize choroidal vascular changes in children with different refractive status.
METHODS
A study including 5864 children aged 6-9 years was performed to investigate the choroidal vascular index (CVI) in myopic, emmetropic and hyperopic eyes. Each participant had a comprehensive ocular examination with cycloplegic autorefraction performed, axial length (AL) measured and Swept Source-Optical Coherence Tomography (SS-OCT) scans acquired. Choroidal thickness (ChT) was measured by built-in software, and CVI was calculated using a previously validated self-developed algorithm.
RESULTS
The mean ChT and CVI were 275.88 ± 53.34 μm and 34.91 ± 3.83 in the macula region, and 191.96 ± 46.28 μm and 32.35 ± 4.21 in the peripapillary region. CVI was significantly lowest for myopes, followed by emmetropes and hyperopes (P < 0.001). CVI varied between different sectors separated by the Early Treatment of Diabetic Retinopathy Study (ETDRS) grid (P < 0.001). Macular CVI decreased horizontally from nasal to temporal quadrant with lowest in center fovea, and vertically from superior to inferior quadrants. Peripapillary CVI was highest in the nasal and lowest in the inferior sector. Multiple regression showed that spherical equivalent (SE), AL, intraocular pressure (IOP), ChT, age, and gender were significantly related to CVI (P < 0.05).
CONCLUSIONS
In children, the distribution of CVI in the posterior pole is not uniform. A decreased CVI was observed from hyperopia to myopia and was associated with decreased SE, elongated AL, and choroidal thinning. Further study of changes in CVI during myopia onset and progression is required to better understand the role of the choroidal vasculature in myopia development.
Topics: Child; Humans; Fovea Centralis; Refraction, Ocular; Macula Lutea; Myopia; Hyperopia; Choroid; Tomography, Optical Coherence
PubMed: 37770533
DOI: 10.1038/s41433-023-02743-1 -
Proceedings of the National Academy of... Dec 2020Microglia are resident central nervous system macrophages and the first responders to neural injury. Until recently, microglia have been studied only in animal models...
Microglia are resident central nervous system macrophages and the first responders to neural injury. Until recently, microglia have been studied only in animal models with exogenous or transgenic labeling. While these studies provided a wealth of information on the delicate balance between neuroprotection and neurotoxicity within which these cells operate, extrapolation to human immune function has remained an open question. Here we examine key characteristics of retinal macrophage cells in live human eyes, both healthy and diseased, with the unique capabilities of our adaptive optics-optical coherence tomography approach and owing to their propitious location above the inner limiting membrane (ILM), allowing direct visualization of cells. Our findings indicate that human ILM macrophage cells may be distributed distinctly, age differently, and have different dynamic characteristics than microglia in other animals. For example, we observed a macular pattern that was sparse centrally and peaked peripherally in healthy human eyes. Moreover, human ILM macrophage density decreased with age (∼2% of cells per year). Our results in glaucomatous eyes also indicate that ILM macrophage cells appear to play an early and regionally specific role of nerve fiber layer phagocytosis in areas of active disease. While we investigate ILM macrophage cells distinct from the larger sample of overall retinal microglia, the ability to visualize macrophage cells without fluorescent labeling in the live human eye represents an important advance for both ophthalmology and neuroscience, which may lead to novel disease biomarkers and new avenues of exploration in disease progression.
Topics: Biomarkers; Disease Susceptibility; Glaucoma; Humans; Macrophages; Macula Lutea; Microglia; Molecular Imaging; Neuroprotection; Optical Imaging; Retina; Tomography, Optical Coherence
PubMed: 33168747
DOI: 10.1073/pnas.2010943117