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Progress in Retinal and Eye Research Sep 2023Myopic axial elongation is associated with various non-pathological changes. These include a decrease in photoreceptor cell and retinal pigment epithelium (RPE) cell... (Review)
Review
Myopic axial elongation is associated with various non-pathological changes. These include a decrease in photoreceptor cell and retinal pigment epithelium (RPE) cell density and retinal layer thickness, mainly in the retro-equatorial to equatorial regions; choroidal and scleral thinning pronounced at the posterior pole and least marked at the ora serrata; and a shift in Bruch's membrane opening (BMO) occurring in moderately myopic eyes and typically in the temporal/inferior direction. The BMO shift leads to an overhang of Bruch's membrane (BM) into the nasal intrapapillary compartment and BM absence in the temporal region (i.e., parapapillary gamma zone), optic disc ovalization due to shortening of the ophthalmoscopically visible horizontal disc diameter, fovea-optic disc distance elongation, reduction in angle kappa, and straightening/stretching of the papillomacular retinal blood vessels and retinal nerve fibers. Highly myopic eyes additionally show an enlargement of all layers of the optic nerve canal, elongation and thinning of the lamina cribrosa, peripapillary scleral flange (i.e., parapapillary delta zone) and peripapillary choroidal border tissue, and development of circular parapapillary beta, gamma, and delta zone. Pathological features of high myopia include development of macular linear RPE defects (lacquer cracks), which widen to round RPE defects (patchy atrophies) with central BM defects, macular neovascularization, myopic macular retinoschisis, and glaucomatous/glaucoma-like and non-glaucomatous optic neuropathy. BM thickness is unrelated to axial length. Including the change in eye shape from a sphere in emmetropia to a prolate (rotational) ellipsoid in myopia, the features may be explained by a primary BM enlargement in the retro-equatorial/equatorial region leading to axial elongation.
Topics: Humans; Axial Length, Eye; Myopia; Choroid; Optic Disk; Bruch Membrane; Tomography, Optical Coherence
PubMed: 36585290
DOI: 10.1016/j.preteyeres.2022.101156 -
Survey of Ophthalmology 2023Tamoxifen (TAM) is a selective estrogen receptor modulator that is used in the treatment of breast cancer. As there are estrogen receptors in the retina, retinal pigment... (Review)
Review
Tamoxifen (TAM) is a selective estrogen receptor modulator that is used in the treatment of breast cancer. As there are estrogen receptors in the retina, retinal pigment epithelium, and choroid, these tissues may also be affected by TAM. We describe the reported effects of TAM on the retina and choroid. Medical databases were searched using relevant keywords and the results were extracted and pooled. The incidence of retinal/choroidal toxicity ranged from 0.9% to 12%. There was a wide range for the time of exposure before the development of TAM retinopathy (3 weeks to 13 years). While functional measurements may be appropriate for assessment of TAM retinopathy, they have not been effective for screening patients. There is no generally accepted screening modality, but serial funduscopy and optical coherence tomography imaging seem to be the most reasonable approach for detecting early TAM-induced retinal toxicity.
Topics: Humans; Retinal Diseases; Retina; Retinal Pigment Epithelium; Choroid; Tamoxifen; Tomography, Optical Coherence
PubMed: 36781026
DOI: 10.1016/j.survophthal.2023.02.003 -
Molecular Neurodegeneration Sep 2023Retinal ganglion cell (RGC) death in glaucoma and other optic neuropathies results in irreversible vision loss due to the mammalian central nervous system's limited... (Review)
Review
Retinal ganglion cell (RGC) death in glaucoma and other optic neuropathies results in irreversible vision loss due to the mammalian central nervous system's limited regenerative capacity. RGC repopulation is a promising therapeutic approach to reverse vision loss from optic neuropathies if the newly introduced neurons can reestablish functional retinal and thalamic circuits. In theory, RGCs might be repopulated through the transplantation of stem cell-derived neurons or via the induction of endogenous transdifferentiation. The RGC Repopulation, Stem Cell Transplantation, and Optic Nerve Regeneration (RReSTORe) Consortium was established to address the challenges associated with the therapeutic repair of the visual pathway in optic neuropathy. In 2022, the RReSTORe Consortium initiated ongoing international collaborative discussions to advance the RGC repopulation field and has identified five critical areas of focus: (1) RGC development and differentiation, (2) Transplantation methods and models, (3) RGC survival, maturation, and host interactions, (4) Inner retinal wiring, and (5) Eye-to-brain connectivity. Here, we discuss the most pertinent questions and challenges that exist on the path to clinical translation and suggest experimental directions to propel this work going forward. Using these five subtopic discussion groups (SDGs) as a framework, we suggest multidisciplinary approaches to restore the diseased visual pathway by leveraging groundbreaking insights from developmental neuroscience, stem cell biology, molecular biology, optical imaging, animal models of optic neuropathy, immunology & immunotolerance, neuropathology & neuroprotection, materials science & biomedical engineering, and regenerative neuroscience. While significant hurdles remain, the RReSTORe Consortium's efforts provide a comprehensive roadmap for advancing the RGC repopulation field and hold potential for transformative progress in restoring vision in patients suffering from optic neuropathies.
Topics: Animals; Humans; Retinal Ganglion Cells; Optic Nerve Diseases; Retina; Brain; Cell Differentiation; Mammals
PubMed: 37735444
DOI: 10.1186/s13024-023-00655-y -
Proceedings of the National Academy of... Aug 2023Although the visual system extends through the brain, most vision loss originates from defects in the eye. Its central element is the neural retina, which senses light,...
Although the visual system extends through the brain, most vision loss originates from defects in the eye. Its central element is the neural retina, which senses light, processes visual signals, and transmits them to the rest of the brain through the optic nerve (ON). Surrounding the retina are numerous other structures, conventionally divided into anterior and posterior segments. Here, we used high-throughput single-nucleus RNA sequencing (snRNA-seq) to classify and characterize cells in six extraretinal components of the posterior segment: ON, optic nerve head (ONH), peripheral sclera, peripapillary sclera (PPS), choroid, and retinal pigment epithelium (RPE). Defects in each of these tissues are associated with blinding diseases-for example, glaucoma (ONH and PPS), optic neuritis (ON), retinitis pigmentosa (RPE), and age-related macular degeneration (RPE and choroid). From ~151,000 single nuclei, we identified 37 transcriptomically distinct cell types, including multiple types of astrocytes, oligodendrocytes, fibroblasts, and vascular endothelial cells. Our analyses revealed a differential distribution of many cell types among distinct structures. Together with our previous analyses of the anterior segment and retina, the data presented here complete a "Version 1" cell atlas of the human eye. We used this atlas to map the expression of >180 genes associated with the risk of developing glaucoma, which is known to involve ocular tissues in both anterior and posterior segments as well as the neural retina. Similar methods can be used to investigate numerous additional ocular diseases, many of which are currently untreatable.
Topics: Humans; Transcriptome; Endothelial Cells; Optic Disk; Glaucoma; Optic Nerve; Sclera
PubMed: 37566633
DOI: 10.1073/pnas.2306153120 -
Progress in Retinal and Eye Research Jul 2023Wnt signaling comprises a group of complex signal transduction pathways that play critical roles in cell proliferation, differentiation, and apoptosis during... (Review)
Review
Wnt signaling comprises a group of complex signal transduction pathways that play critical roles in cell proliferation, differentiation, and apoptosis during development, as well as in stem cell maintenance and adult tissue homeostasis. Wnt pathways are classified into two major groups, canonical (β-catenin-dependent) or non-canonical (β-catenin-independent). Most previous studies in the eye have focused on canonical Wnt signaling, and the role of non-canonical signaling remains poorly understood. Additionally, the crosstalk between canonical and non-canonical Wnt signaling in the eye has hardly been explored. In this review, we present an overview of available data on ocular non-canonical Wnt signaling, including developmental and functional aspects in different eye compartments. We also discuss important changes of this signaling in various ocular conditions, such as keratoconus, aniridia-related keratopathy, diabetes, age-related macular degeneration, optic nerve damage, pathological angiogenesis, and abnormalities in the trabecular meshwork and conjunctival cells, and limbal stem cell deficiency.
Topics: Humans; Wnt Signaling Pathway; beta Catenin; Conjunctiva; Cell Differentiation; Trabecular Meshwork
PubMed: 36443219
DOI: 10.1016/j.preteyeres.2022.101149 -
Annual Review of Vision Science Sep 2023Proper eye structure is essential for visual function: Multiple essential eye tissues must take shape and assemble into a precise three-dimensional configuration.... (Review)
Review
Proper eye structure is essential for visual function: Multiple essential eye tissues must take shape and assemble into a precise three-dimensional configuration. Accordingly, alterations to eye structure can lead to pathological conditions of visual impairment. Changes in eye shape can also be adaptive over evolutionary time. Eye structure is first established during development with the formation of the optic cup, which contains the neural retina, retinal pigment epithelium, and lens. This crucial yet deceptively simple hemispherical structure lays the foundation for all later elaborations of the eye. Building on descriptions of the embryonic eye that started with hand drawings and micrographs, the field is beginning to identify mechanisms driving dynamic changes in three-dimensional cell and tissue shape. A combination of molecular genetics, imaging, and pharmacological approaches is defining connections among transcription factors, signaling pathways, and the intracellular machinery governing the emergence of this crucial structure.
Topics: Animals; Vertebrates; Retina; Retinal Pigment Epithelium; Vision, Low; Morphogenesis
PubMed: 37040791
DOI: 10.1146/annurev-vision-100720-111125 -
Survey of Ophthalmology 2024Intraretinal or subretinal fluid in the peripapillary area can be clinically visualized in conditions such as peripapillary choroidal neovascularization, optic disc pit... (Review)
Review
Intraretinal or subretinal fluid in the peripapillary area can be clinically visualized in conditions such as peripapillary choroidal neovascularization, optic disc pit maculopathy, and optic nerve head tumors and granulomas. Optical coherence tomography (OCT) helps to visualize peripapillary fluid in many other chorioretinal conditions such as peripapillary pachychoroid syndrome, posterior uveitis, central retinal vein occlusion, malignant hypertension, hypotonic maculopathy as well as neuro-ophthalmological conditions such as glaucoma, microcystic macular edema and disc edema due papilledema, non-arteritic anterior ischemic optic neuropathy, neuroretinitis, and diabetic papillopathy. Often, the differential diagnosis of peripapillary fluid is a bit tricky and may lead to misdiagnosis and improper management. We describe a diagnostic algorithm for peripapillary fluid on OCT and outline the salient features and management of these conditions.
Topics: Humans; Tomography, Optical Coherence; Optic Disk; Subretinal Fluid; Diagnosis, Differential; Retinal Diseases
PubMed: 38016521
DOI: 10.1016/j.survophthal.2023.11.004 -
Survey of Ophthalmology 2023Most eyes start with a hypermetropic refractive error at birth, but the growth rates of the ocular components, guided by visual cues, will slow in such a way that this... (Review)
Review
Most eyes start with a hypermetropic refractive error at birth, but the growth rates of the ocular components, guided by visual cues, will slow in such a way that this refractive error decreases during the first 2 years of life. Once reaching its target, the eye enters a period of stable refractive error as it continues to grow by balancing the loss in corneal and lens power with the axial elongation. Although these basic ideas were first proposed over a century ago by Straub, the exact details on the controlling mechanism and the growth process remained elusive. Thanks to the observations collected in the last 40 years in both animals and humans, we are now beginning to get an understanding how environmental and behavioral factors stabilize or disrupt ocular growth. We survey these efforts to present what is currently known regarding the regulation of ocular growth rates.
Topics: Animals; Infant, Newborn; Humans; Eye; Refractive Errors; Lens, Crystalline; Vision, Ocular; Cornea; Refraction, Ocular
PubMed: 36796457
DOI: 10.1016/j.survophthal.2023.02.002 -
Current Opinion in Ophthalmology Nov 2023This article reviewed and summarized recent published data on ocular imaging findings and treatment of posterior segment manifestations of ocular metastasis. (Review)
Review
PURPOSE OF REVIEW
This article reviewed and summarized recent published data on ocular imaging findings and treatment of posterior segment manifestations of ocular metastasis.
RECENT FINDINGS
Advanced ocular imaging can help differentiate ocular metastases from other mimicking lesions, including primary intraocular tumors or infections. Recently, case reports have demonstrated the successful use of targeted systemic therapy to achieve local control of vitreous and choroidal metastases.
SUMMARY
Metastasis can lead to a wide variety of posterior segment ocular manifestations. The choroid is the most common metastatic site, whereas tumor metastasizing to the retina and optic disc are rare. Patients with possible metastatic eye disease are recommended to undergo extensive investigation to determine the underlying primary cancer and ongoing systemic metastases. Currently, there is no consensus on the treatment strategy. Treatment generally includes systemic chemotherapy in combination with local treatment, such as radiotherapy, laser therapy, or anti-vascular endothelial growth factor (anti-VEGF) treatment.
Topics: Humans; Choroid; Retina; Eye Diseases; Eye Neoplasms; Diagnostic Imaging
PubMed: 37556166
DOI: 10.1097/ICU.0000000000000988 -
Retinal Cases & Brief Reports Jan 2024To report a case of peripapillary subretinal fluid associated with a ridge-shaped morphology surrounding the optic disk, which we termed ridge-shaped peripapilla.
PURPOSE
To report a case of peripapillary subretinal fluid associated with a ridge-shaped morphology surrounding the optic disk, which we termed ridge-shaped peripapilla.
METHODS
Case report.
RESULTS
A 6-year-old girl with mild-to-moderate myopia was referred for an abnormal fundus appearance of the left eye. Fundus examination of the left eye showed a vertical whitish elevation just temporal to the disk with pigment clumping. Spectral domain optical coherence tomography of the left eye showed an elevation of the fundus at the temporal edge of the disk with thinning of the choroid overlying the thickened scleral protrusion and a serous subretinal fluid. Fluorescein angiography of the left eye showed a hyperfluorescent area without leakage at the temporal edge of the disk, indicative of retinal pigment epithelium atrophy. There was no sign of choroidal neovascularization. Based on the fluorescein angiography and optical coherence tomography findings, the protrusion of the sclera seemed to result in overlying choroidal thinning with choroidal blood flow disturbances, and consequent retinal pigment epithelium atrophy, leading to the subretinal fluid.
CONCLUSION
This case highlights an unusual presentation of ridge-shaped peripapilla, characterized by inward convexity of the peripapillary area with a ridge-shaped morphology and localized thickening of the peripapillary sclera, in eyes with myopia.
Topics: Female; Humans; Child; Choroid; Fundus Oculi; Optic Disk; Tomography, Optical Coherence; Atrophy; Myopia; Fluorescein Angiography
PubMed: 36007179
DOI: 10.1097/ICB.0000000000001308