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Antioxidants (Basel, Switzerland) Sep 2021Increasing evidence indicates that changes in the redox system may contribute to the pathogenesis of multiple optic neuropathies. Optic neuropathies are characterized by... (Review)
Review
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.
PubMed: 34679672
DOI: 10.3390/antiox10101538 -
Eye (London, England) Jan 2021The pachychoroid disease spectrum encompasses seven major retinal conditions including central serous chorioretinopathy (CSC), polypoidal choroidal vasculopathy (PCV),... (Review)
Review
The pachychoroid disease spectrum encompasses seven major retinal conditions including central serous chorioretinopathy (CSC), polypoidal choroidal vasculopathy (PCV), and pachychoroid neovasculopathy or type I macular neovascularisation (MNV) secondary to chronic persistent thickening and dysfunction of the choroidal vasculature. Drusen are focal yellow-white deposits of extracellular debris, which consist of complement proteins, esterified and nonesterified cholesterol, apolipoproteins, carbohydrates, and trace elements, above the retinal pigment epithelium (RPE) or between the RPE and Bruch's membrane. Although drusen are an essential disease precursor of advanced age-related macular degeneration (AMD), a new entity "pachydrusen" has been identified to be associated with some of the enitites that constitute the pachychoroid spectrum. It remains to be determined what the exact differences are between soft drusen, pseudodrusen, and pachydrusen in terms of phenotype, genotype, and pathogenesis. Improving our knowledge in these areas will inevitably improve our understanding of their clinical significance especially as in disease prediction in AMD and the pachychroid spectrum disorders. It remains controversial whether PCV is a subtype of AMD. Understanding the pathogenesis of different types of drusen may also help in addressing if phenotype and/or genotype of type 1 MNV associated with pachychoroid are similar to type 1 MNV related to AMD. Furthermore, because pachydrusen links two pachychoroid diseases, CSC and PCV, it is also of great interest to investigate if CSC is an early stage or a predictor of PCV in future research. In this review, we share our experience in clinical practice and the latest published evidence-based literature to emphasize the differences and similarities in morphology, pathogenesis, and clinical significance of drusen and pachydrusen, a new member of the pachychoroid spectrum disorders.
Topics: Central Serous Chorioretinopathy; Choroid; Fluorescein Angiography; Humans; Retina; Retinal Drusen
PubMed: 33208847
DOI: 10.1038/s41433-020-01265-4 -
Scientific Reports Apr 2021The natural history and clinical significance of pachydrusen is unclear. This study aims to compare the longitudinal changes of eyes with pachydrusen and soft drusen and...
The natural history and clinical significance of pachydrusen is unclear. This study aims to compare the longitudinal changes of eyes with pachydrusen and soft drusen and progression to exudative macular neovascularisation (MNV). Patients with a diagnosis of MNV in one eye only and the fellow eye was selected as the study eye. Study eyes were required to have pachydrusen or soft drusen on fundus photographs and follow up of at least 2 years or until exudative MNV occurred. Systematic grading was performed at baseline and change in drusen area and onset of exudative MNV recorded over the period of follow up. A total of 75 eyes from 75 patients (29 with pachydrusen and 46 with soft drusen) were included. There was no difference in the rate of progression to exudative MNV in the soft and pachydrusen groups (13.3% versus 24.1%, p = 0.38). Pachydrusen, as compared to soft drusen, was associated with polypoidal choroidal vasculopathy subtype (85.7% versus 16.7%, p < 0.01) and the location of exudation was co-localised with soft drusen but not with pachydrusen. There was a higher rate of increase in soft drusen area compared to pachydrusen area (27.7 ± 31.9%/year versus 8.7 ± 12.4%/year respectively, p < 0.01). We found no difference in the proportion of eyes that developed exudative MNV in this study however characterisation of drusen evolution patterns revealed a strong association with exudative MNV subtype.
Topics: Aged; Choroidal Neovascularization; Disease Progression; Female; Humans; Macular Degeneration; Male; Retinal Drusen; Tomography, Optical Coherence
PubMed: 33820941
DOI: 10.1038/s41598-021-87083-4 -
Eye (London, England) May 2018The first descriptions of ageing macula disorder (AMD), be it under other names, appeared in 1855 and 1868. The earliest accounts of AMD linked the presence of drusen... (Review)
Review
The first descriptions of ageing macula disorder (AMD), be it under other names, appeared in 1855 and 1868. The earliest accounts of AMD linked the presence of drusen with visual loss. It took a century before these connections between drusen and AMD were generally accepted by medical science and in clinical articles. The first signs of AMD appear in the region of the choriocapillaris, Bruch's membrane and the retinal pigment epithelium. The pathogenesis of drusen and of AMD is still uncertain. This is reflected in the wide variation in nomenclature of both, since the first publications.
Topics: History, 19th Century; History, 20th Century; History, 21st Century; Humans; Macular Degeneration; Retinal Drusen; Terminology as Topic
PubMed: 29424832
DOI: 10.1038/eye.2017.298 -
Clinical Ophthalmology (Auckland, N.Z.) 2017Age-related macular degeneration (AMD) is a leading cause of vision loss in patients >50 years old. The hallmark of the disease is represented by the accumulation of... (Review)
Review
Age-related macular degeneration (AMD) is a leading cause of vision loss in patients >50 years old. The hallmark of the disease is represented by the accumulation of extracellular material between retinal pigment epithelium and the inner collagenous layer of Bruch's membrane, called drusen. Although identified almost 30 years ago, reticular pseudodrusen (RPD) have been recently recognized as a distinctive phenotype. Unlike drusen, they are located in the subretinal space. RPD are strongly associated with late AMD, especially geographic atrophy, type 2 and 3 choroidal neovascularization, which, in turn, are less common in typical AMD. RPD identification is not straightforward at fundus examination, and their identification should employ at least 2 different imaging modalities. In this narrative review, we embrace all aspects of RPD, including history, epidemiology, histology, imaging, functional test, natural history and therapy.
PubMed: 29033536
DOI: 10.2147/OPTH.S130165 -
Biomolecules Sep 2020Fibulin-3 (also known as EGF-containing fibulin extracellular matrix protein 1 (EFEMP1)) is a secreted extracellular matrix glycoprotein, encoded by the gene that... (Review)
Review
Fibulin-3 (also known as EGF-containing fibulin extracellular matrix protein 1 (EFEMP1)) is a secreted extracellular matrix glycoprotein, encoded by the gene that belongs to the eight-membered fibulin protein family. It has emerged as a functionally unique member of this family, with a diverse array of pathophysiological associations predominantly centered on its role as a modulator of extracellular matrix (ECM) biology. Fibulin-3 is widely expressed in the human body, especially in elastic-fibre-rich tissues and ocular structures, and interacts with enzymatic ECM regulators, including tissue inhibitor of metalloproteinase-3 (TIMP-3). A point mutation in causes an inherited early-onset form of macular degeneration called Malattia Leventinese/Doyne honeycomb retinal dystrophy (ML/DHRD). genetic variants have also been associated in genome-wide association studies with numerous complex inherited phenotypes, both physiological (namely, developmental anthropometric traits) and pathological (many of which involve abnormalities of connective tissue function). Furthermore, expression changes are implicated in the progression of numerous types of cancer, an area in which fibulin-3 has putative significance as a therapeutic target. Here we discuss the potential mechanistic roles of fibulin-3 in these pathologies and highlight how it may contribute to the development, structural integrity, and emergent functionality of the ECM and connective tissues across a range of anatomical locations. Its myriad of aetiological roles positions fibulin-3 as a molecule of interest across numerous research fields and may inform our future understanding and therapeutic approach to many human diseases in clinical settings.
Topics: Animals; Disease Models, Animal; Extracellular Matrix; Extracellular Matrix Proteins; Genome-Wide Association Study; Humans; Optic Disk Drusen
PubMed: 32911658
DOI: 10.3390/biom10091294 -
Journal of Clinical Medicine Apr 2024Drusen are one of the most characteristic pathologies of precursor lesion of age-related macular degeneration (AMD). Drusen comprise a yellowish white substance that... (Review)
Review
Drusen are one of the most characteristic pathologies of precursor lesion of age-related macular degeneration (AMD). Drusen comprise a yellowish white substance that accumulates typically under the retinal pigment epithelium (RPE), and their constituents are lipids, complement, amyloid, crystallin, and others. In the past, many researchers have focused on drusen and tried to elucidate the pathophysiology of AMD because they believed that disease progression from early AMD to advanced AMD might be based on drusen or drusen might cause AMD. In fact, it is well established that drusen are the hallmark of precursor lesion of AMD and a major risk factor for AMD progression mainly based on their size and number. However, the existence of advanced AMD without drusen has long been recognized. For example, polypoidal choroidal vasculopathy (PCV), which comprises the majority of AMD cases in Asians, often lacks drusen. Thus, there is the possibility that drusen might be no more than a biomarker of AMD and not a cause of AMD. Now is the time to reconsider the relationship between AMD and drusen. In this review, we focus on early AMD pathogenesis based on basic research from the perspective of cholesterol metabolism and hypoxic response in the retina, and we discuss the role of drusen.
PubMed: 38731137
DOI: 10.3390/jcm13092608 -
Survey of Ophthalmology 2016Optic disk drusen occur in 0.4% of children and consist of acellular intracellular and extracellular deposits that often become calcified over time. They are typically... (Review)
Review
Optic disk drusen occur in 0.4% of children and consist of acellular intracellular and extracellular deposits that often become calcified over time. They are typically buried early in life and generally become superficial, and therefore visible, later in childhood, at the average age of 12 years. Their main clinical significance lies in the ability of optic disk drusen, particularly when buried, to simulate true optic disk edema. Misdiagnosing drusen as true disk edema may lead to an invasive and unnecessary workup for elevated intracranial pressure. Ancillary testing, including ultrasonography, fluorescein angiography, fundus autofluorescence, and optical coherence tomography, may aid in the correct diagnosis of optic disk drusen. Complications of optic disk drusen in children include visual field defects, hemorrhages, choroidal neovascular membrane, nonarteritic anterior ischemic optic neuropathy, and retinal vascular occlusions. Treatment options for these complications include ocular hypotensive agents for visual field defects and intravitreal anti-vascular endothelial growth factor agents for choroidal neovascular membranes. In most cases, however, children with optic disk drusen can be managed by observation with serial examinations and visual field testing once true optic disk edema has been excluded.
Topics: Child; Fluorescein Angiography; Fundus Oculi; Global Health; Humans; Incidence; Optic Disk; Optic Disk Drusen; Tomography, Optical Coherence; Visual Acuity; Visual Fields
PubMed: 27033945
DOI: 10.1016/j.survophthal.2016.03.007 -
Neuro-ophthalmology (Aeolus Press) Dec 2018Optic nerve head drusen are benign acellular calcium concretions that usually form early in life, just anterior to the lamina cribrosa. Improving imaging using optical... (Review)
Review
Optic nerve head drusen are benign acellular calcium concretions that usually form early in life, just anterior to the lamina cribrosa. Improving imaging using optical coherence tomography suggests they are common and may be present in many clinically normal discs. These drusen may change in appearance in early life, but are generally stable in adulthood, and may be associated with visual field defects, anterior ischaemic optic neuropathy, or rarer complications. Based on long-term clinical data and optical coherence tomography, we propose a refined hypothesis as to the cause of optic disc drusen. Here we summarise recent findings and suggest future studies to better understand the forces involved.
PubMed: 30524490
DOI: 10.1080/01658107.2018.1444060 -
Graefe's Archive For Clinical and... Jul 2022To investigate retinal sensitivity changes in eyes with pure cuticular drusen.
PURPOSE
To investigate retinal sensitivity changes in eyes with pure cuticular drusen.
METHODS
Multimodal imaging and microperimetry (37-loci grid) data were examined retrospectively to evaluate functional changes in eyes with pure cuticular drusen. Mean sensitivity in the cuticular drusen cohort was compared to age-matched normals. An age- and loci-specific normative reference was created to analyse localised sensitivity deviation.
RESULTS
The mean number loci with relative scotoma in the cuticular drusen cohort (n = 27, mean [SD] age: 48.5 [12.4] years) referenced to normal eyes (n = 80, 53.5 [14.6] years) was 5.5 (95% confidence interval 3.0 to 8.1). However, mean sensitivity was not statistically different to the age-matched normal cohort (95% CI, - 2.3 to + 3.4 dB). The 37-loci grid was stratified into three rings of the approximately same number of loci, and the percentage of cuticular drusen eyes with pointwise deviation was significantly lower in the inner compared to the middle ring (12.3 [5.3]% vs. 17.3 [5.1]%, p < 0.05).
CONCLUSIONS
Eyes with cuticular drusen demonstrated relative scotoma, but mean sensitivity was not affected. Pointwise sensitivity provides a more robust measure of retinal sensitivity than mean sensitivity in cuticular drusen and should be assessed both in the clinic and in future clinical trials.
Topics: Bruch Membrane; Eye Diseases, Hereditary; Humans; Middle Aged; Retinal Drusen; Retrospective Studies; Scotoma; Tomography, Optical Coherence
PubMed: 35129629
DOI: 10.1007/s00417-022-05570-4