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Cureus May 2023Age-related macular degeneration (AMD) is a significant cause of blindness globally. With the exponential rise in the aging population, AMD is the third leading cause of... (Review)
Review
Age-related macular degeneration (AMD) is a significant cause of blindness globally. With the exponential rise in the aging population, AMD is the third leading cause of visual impairment worldwide. Neovascular AMD (nAMD; Wet AMD) and geographical atrophy (GA, late-stage dry AMD) are the advanced AMD accountable for substantial cases of visual deterioration among the elderly. Our review of the literature depicted that notable risk factors include cigarette smoking, nutritional elements, cardiovascular disorders, and genetic markers, including genes regulating complement, lipid, and angiogenic pathways. Some studies have suggested a relative decline in the proportion of AMD cases in the last two decades attributable to novel diagnostic and therapeutic modalities. Accurate diagnosis is the result of a combination of clinical examination and imaging techniques, including retinal photography, angiography, and optical coherence tomography. The incorporation of dietary antioxidant supplements, explicitly lutein, slows the progression of the disease in advanced stages. The induction of vascular endothelial growth factor (VEGF) inhibitors in the treatment of neovascular AMD, often combined with other modalities, has shown an immensely favorable prognosis. Research to integrate gene therapy and regenerative techniques using stem cells is underway to further mitigate AMD-associated morbidity. It is imperative to establish screening and therapeutic guidelines for AMD to curtail the future social and financial burden and improve the diminishing quality of life among the elderly.
PubMed: 37388610
DOI: 10.7759/cureus.39624 -
International Journal of Molecular... Jun 2023Accumulation of 7-ketocholesterol (7KC) occurs in age-related macular degeneration (AMD) and was found previously to promote fibrosis, an untreatable cause of vision...
Accumulation of 7-ketocholesterol (7KC) occurs in age-related macular degeneration (AMD) and was found previously to promote fibrosis, an untreatable cause of vision loss, partly through induction of endothelial-mesenchymal transition. To address the hypothesis that 7KC causes mesenchymal transition of retinal pigment epithelial cells (RPE), we exposed human primary RPE (hRPE) to 7KC or a control. 7KC-treated hRPE did not manifest increased mesenchymal markers, but instead maintained RPE-specific proteins and exhibited signs of senescence with increased serine phosphorylation of histone H3, serine/threonine phosphorylation of mammalian target of rapamycin (p-mTOR), p16 and p21, β-galactosidase labeling, and reduced LaminB1, suggesting senescence. The cells also developed senescence-associated secretory phenotype (SASP) determined by increased IL-1β, IL-6, and VEGF through mTOR-mediated NF-κB signaling, and reduced barrier integrity that was restored by the mTOR inhibitor, rapamycin. 7KC-induced p21, VEGF, and IL-1β were inhibited by an inhibitor of protein kinase C. The kinase regulates IQGAP1 serine phosphorylation. Furthermore, after 7KC injection and laser-induced injury, mice with an IQGAP1 serine 1441-point mutation had significantly reduced fibrosis compared to littermate control mice. Our results provide evidence that age-related accumulation of 7KC in drusen mediates senescence and SASP in RPE, and IQGAP1 serine phosphorylation is important in causing fibrosis in AMD.
Topics: Animals; Humans; Mice; Cellular Senescence; Choroidal Neovascularization; Fibrosis; Macular Degeneration; Mammals; Phosphorylation; Retinal Pigment Epithelium; TOR Serine-Threonine Kinases; Vascular Endothelial Growth Factor A; ras GTPase-Activating Proteins
PubMed: 37373423
DOI: 10.3390/ijms241210276 -
Antioxidants (Basel, Switzerland) May 2023The seminal role of autophagy during age-related macular degeneration (AMD) lies in the clearance of a number of reactive oxidative species that generate dysfunctional... (Review)
Review
The seminal role of autophagy during age-related macular degeneration (AMD) lies in the clearance of a number of reactive oxidative species that generate dysfunctional mitochondria. In fact, reactive oxygen species (ROS) in the retina generate misfolded proteins, alter lipids and sugars composition, disrupt DNA integrity, damage cell organelles and produce retinal inclusions while causing AMD. This explains why autophagy in the retinal pigment epithelium (RPE), mostly at the macular level, is essential in AMD and even in baseline conditions to provide a powerful and fast replacement of oxidized molecules and ROS-damaged mitochondria. When autophagy is impaired within RPE, the deleterious effects of ROS, which are produced in excess also during baseline conditions, are no longer counteracted, and retinal degeneration may occur. Within RPE, autophagy can be induced by various stimuli, such as light and naturally occurring phytochemicals. Light and phytochemicals, in turn, may synergize to enhance autophagy. This may explain the beneficial effects of light pulses combined with phytochemicals both in improving retinal structure and visual acuity. The ability of light to activate some phytochemicals may further extend such a synergism during retinal degeneration. In this way, photosensitive natural compounds may produce light-dependent beneficial antioxidant effects in AMD.
PubMed: 37371913
DOI: 10.3390/antiox12061183 -
Biomolecules May 2023Age-related macular degeneration (AMD) causes vision loss in the elderly population. Dry AMD leads to the formation of Drusen, while wet AMD is characterized by cell... (Review)
Review
Age-related macular degeneration (AMD) causes vision loss in the elderly population. Dry AMD leads to the formation of Drusen, while wet AMD is characterized by cell proliferation and choroidal angiogenesis. The retinal pigment epithelium (RPE) plays a key role in AMD pathogenesis. In particular, helioreceptor renewal depends on outer segment phagocytosis of RPE cells, while RPE autophagy can protect cells from oxidative stress damage. However, when the oxidative stress burden is too high and homeostasis is disturbed, the phagocytosis and autophagy functions of RPE become damaged, leading to AMD development and progression. Hence, characterizing the roles of RPE cell phagocytosis and autophagy in the pathogenesis of AMD can inform the development of potential therapeutic targets to prevent irreversible RPE and photoreceptor cell death, thus protecting against AMD.
Topics: Aged; Humans; Phagocytosis; Autophagy; Macular Degeneration; Oxidative Stress; Epithelial Cells; Retinal Pigments
PubMed: 37371481
DOI: 10.3390/biom13060901 -
European Journal of Epidemiology Sep 2023Genetic variants in ABCA1 are associated with higher concentrations of high-density lipoprotein (HDL) cholesterol. Higher HDL cholesterol concentrations are...
Genetic variants in ABCA1 are associated with higher concentrations of high-density lipoprotein (HDL) cholesterol. Higher HDL cholesterol concentrations are observationally and genetically associated with higher risk of age-related macular degeneration (AMD). However, whether amino acid-changing genetic variants in ABCA1 associated with high HDL cholesterol concentrations confer a higher risk of AMD in the general population is currently unknown. We tested this hypothesis. The study included 80,972 individuals (1,370 AMD cases) from the Copenhagen General Population Study (CGPS) and 9,584 individuals (142 AMD cases) from the Copenhagen City Heart Study (CCHS) with 10 to 18 years of follow-up. We created an HDL cholesterol weighted allele score based on amino acid-changing ABCA1 variants with a minor allele frequency above 0.001 and divided it into tertiles. The study included 55% women. Mean age was 58 years. The ABCA1 allele score for the third versus the first tertile was associated with HRs (95% confidence intervals (CIs)) of 1.30 (1.14-1.49) for all-cause AMD, 1.26 (1.06-1.50) for nonneovascular AMD, and 1.31 (1.12-1.53) for neovascular AMD in a multivariable adjusted model. On a continuous scale, higher concentrations of genetically determined HDL cholesterol were associated with higher risk of all-cause AMD, nonneovascular AMD, and neovascular AMD in an age- and sex adjusted model and in a multivariable adjusted model. In conclusion, amino acid-changing genetic variants in ABCA1 associated with higher HDL cholesterol concentrations were also associated with higher risk of AMD, suggesting a role for ABCA1 in AMD pathogenesis.
Topics: Female; Humans; Male; Middle Aged; Amino Acids; Angiogenesis Inhibitors; Cholesterol, HDL; Vascular Endothelial Growth Factor A; Visual Acuity; Wet Macular Degeneration; ATP Binding Cassette Transporter 1
PubMed: 37335386
DOI: 10.1007/s10654-023-01021-4 -
Frontiers in Neuroscience 2023The retina represents a critical ocular structure. Of the various ophthalmic afflictions, retinal pathologies have garnered considerable scientific interest, owing to...
INTRODUCTION
The retina represents a critical ocular structure. Of the various ophthalmic afflictions, retinal pathologies have garnered considerable scientific interest, owing to their elevated prevalence and propensity to induce blindness. Among clinical evaluation techniques employed in ophthalmology, optical coherence tomography (OCT) is the most commonly utilized, as it permits non-invasive, rapid acquisition of high-resolution, cross-sectional images of the retina. Timely detection and intervention can significantly abate the risk of blindness and effectively mitigate the national incidence rate of visual impairments.
METHODS
This study introduces a novel, efficient global attention block (GAB) for feed forward convolutional neural networks (CNNs). The GAB generates an attention map along three dimensions (height, width, and channel) for any intermediate feature map, which it then uses to compute adaptive feature weights by multiplying it with the input feature map. This GAB is a versatile module that can seamlessly integrate with any CNN, significantly improving its classification performance. Based on the GAB, we propose a lightweight classification network model, GABNet, which we develop on a UCSD general retinal OCT dataset comprising 108,312 OCT images from 4686 patients, including choroidal neovascularization (CNV), diabetic macular edema (DME), drusen, and normal cases.
RESULTS
Notably, our approach improves the classification accuracy by 3.7% over the EfficientNetV2B3 network model. We further employ gradient-weighted class activation mapping (Grad-CAM) to highlight regions of interest on retinal OCT images for each class, enabling doctors to easily interpret model predictions and improve their efficiency in evaluating relevant models.
DISCUSSION
With the increasing use and application of OCT technology in the clinical diagnosis of retinal images, our approach offers an additional diagnostic tool to enhance the diagnostic efficiency of clinical OCT retinal images.
PubMed: 37332865
DOI: 10.3389/fnins.2023.1143422 -
Journal of Visualized Experiments : JoVE May 2023A progression sequence for age-related macular degeneration (AMD) learned from optical coherence tomography (OCT)-based multimodal (MMI) clinical imaging could add...
A progression sequence for age-related macular degeneration (AMD) learned from optical coherence tomography (OCT)-based multimodal (MMI) clinical imaging could add prognostic value to laboratory findings. In this work, ex vivo OCT and MMI were applied to human donor eyes prior to retinal tissue sectioning. The eyes were recovered from non-diabetic white donors aged ≥80 years old, with a death-to-preservation time (DtoP) of ≤6 h. The globes were recovered on-site, scored with an 18 mm trephine to facilitate cornea removal, and immersed in buffered 4% paraformaldehyde. Color fundus images were acquired after anterior segment removal with a dissecting scope and an SLR camera using trans-, epi-, and flash illumination at three magnifications. The globes were placed in a buffer within a custom-designed chamber with a 60 diopter lens. They were imaged with spectral domain OCT (30° macula cube, 30 µm spacing, averaging = 25), near-infrared reflectance, 488 nm autofluorescence, and 787 nm autofluorescence. The AMD eyes showed a change in the retinal pigment epithelium (RPE), with drusen or subretinal drusenoid deposits (SDDs), with or without neovascularization, and without evidence of other causes. Between June 2016 and September 2017, 94 right eyes and 90 left eyes were recovered (DtoP: 3.9 ± 1.0 h). Of the 184 eyes, 40.2% had AMD, including early intermediate (22.8%), atrophic (7.6%), and neovascular (9.8%) AMD, and 39.7% had unremarkable maculas. Drusen, SDDs, hyper-reflective foci, atrophy, and fibrovascular scars were identified using OCT. Artifacts included tissue opacification, detachments (bacillary, retinal, RPE, choroidal), foveal cystic change, an undulating RPE, and mechanical damage. To guide the cryo-sectioning, OCT volumes were used to find the fovea and optic nerve head landmarks and specific pathologies. The ex vivo volumes were registered with the in vivo volumes by selecting the reference function for eye tracking. The ex vivo visibility of the pathology seen in vivo depends on the preservation quality. Within 16 months, 75 rapid DtoP donor eyes at all stages of AMD were recovered and staged using clinical MMI methods.
Topics: Humans; Aged, 80 and over; Tomography, Optical Coherence; Macular Degeneration; Retina; Multimodal Imaging
PubMed: 37306417
DOI: 10.3791/65240 -
Ophthalmology. Retina Oct 2023To elucidate the clinical characteristics and progression rate of geographic atrophy (GA) associated with age-related macular degeneration (AMD) in a Japanese population. (Observational Study)
Observational Study
PURPOSE
To elucidate the clinical characteristics and progression rate of geographic atrophy (GA) associated with age-related macular degeneration (AMD) in a Japanese population.
DESIGN
Retrospective, multicenter, observational study.
PARTICIPANTS
A total of 173 eyes from 173 patients from 6 university hospitals in Japan were included. Of 173 study eyes, 101 eyes from 101 patients were included in the follow-up group. All patients were Japanese, aged ≥ 50 years and had definite GA associated with AMD in at least 1 eye.
METHODS
The GA area was measured semiautomatically using fundus autofluorescence (FAF) images. In the follow-up group followed for > 6 months with FAF images, the GA progression rate was calculated by 2 methods: mm per year and mm per year using the square-root transformation (SQRT) strategy. Simple and multiple linear regression analyses were used to identify the baseline factors associated with the GA progression rate.
MAIN OUTCOME MEASURES
Clinical characteristics of GA and the GA progression rate.
RESULTS
The mean age was 76.8 ± 8.8 years, and 109 (63.0%) were males. Sixty-two (35.8%) patients had bilateral GA. The mean GA area was 3.06 ± 4.00 mm (1.44 ± 1.00 mm [SQRT]). Thirty-eight eyes (22.0%) were classified as having pachychoroid GA. Drusen and reticular pseudodrusen were detected in 115 (66.5%) and 73 (42.2%) eyes, respectively. The mean subfoveal choroidal thickness was 194.7 ± 105.5 μm. In the follow-up group (follow-up period: 46.2 ± 28.9 months), the mean GA progression rate was 1.01 ± 1.09 mm per year (0.23 ± 0.18 mm/year [SQRT]). In the multivariable analysis, the baseline GA area (SQRT; P = 0.002) and the presence of reticular pseudodrusen (P < 0.001) were significantly associated with a greater GA progression rate (SQRT).
CONCLUSIONS
Certain clinical characteristics of GA in Asian populations may differ from those in White populations. Asian patients with GA showed male dominance and relatively thicker choroid than White patients. There was a group with GA without drusen but with features of pachychoroid. The GA progression rate in this Asian population was relatively lower than that in White populations. Large GA and reticular pseudodrusen were associated with a greater GA progression rate.
FINANCIAL DISCLOSURE(S)
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
Topics: Humans; Male; Aged; Aged, 80 and over; Female; Geographic Atrophy; Retrospective Studies; East Asian People; Fluorescein Angiography; Macular Degeneration; Retinal Drusen
PubMed: 37302656
DOI: 10.1016/j.oret.2023.06.004 -
Ophthalmology Science Dec 2023To determine the interreader agreement for reticular pseudodrusen (RPD) assessment on combined infrared reflectance (IR) and OCT imaging in the early stages of...
PURPOSE
To determine the interreader agreement for reticular pseudodrusen (RPD) assessment on combined infrared reflectance (IR) and OCT imaging in the early stages of age-related macular degeneration across a range of different criteria to define their presence.
DESIGN
Interreader agreement study.
PARTICIPANTS
Twelve readers from 6 reading centers.
METHODS
All readers evaluated 100 eyes from individuals with bilateral large drusen for the following: (1) the presence of RPD across a range of different criteria and (2) the number of Stage 2 or 3 RPD lesions (from 0 to ≥ 5 lesions) on an entire OCT volume scan and on a selected OCT B-scan. Supportive information was available from the corresponding IR image.
MAIN OUTCOME MEASURES
Interreader agreement, as assessed by Gwet's first-order agreement coefficient (AC).
RESULTS
When evaluating an entire OCT volume scan, there was substantial interreader agreement for the presence of any RPD, any or ≥ 5 Stage 2 or 3 lesions, and ≥ 5 definite lesions on IR images corresponding to Stage 2 or 3 lesions (AC = 0.60-0.72). On selected OCT B-scans, there was also moderate-to-substantial agreement for the presence of any RPD, any or ≥ 5 Stage 2 or 3 lesions (AC = 0.58-0.65) and increasing levels of agreement with increasing RPD stage (AC = 0.08, 0.56, 0.78, and 0.99 for the presence of any Stage 1, 2, 3, and 4 lesions, respectively). There was substantial agreement regarding the number of Stage 2 or 3 lesions on an entire OCT volume scan (AC = 0.68), but only fair agreement for this evaluation on selected B-scans (AC = 0.30).
CONCLUSIONS
There was generally substantial or near-substantial-but not near-perfect-agreement for assessing the presence of RPD on entire OCT volume scans or selected B-scans across a range of differing RPD criteria. These findings underscore how interreader variability would likely contribute to the variability of findings related to the clinical associations of RPD. The low levels of agreement for assessing RPD number on OCT B-scans underscore the likely challenges of quantifying RPD extent with manual grading.
FINANCIAL DISCLOSURES
Proprietary or commercial disclosure may be found after the references.
PubMed: 37292179
DOI: 10.1016/j.xops.2023.100325 -
BMC Ophthalmology Jun 2023This study aimed to report eleven cases of non-neovascular pachychoroid disease with hyperreflective material (HRM) that occurred in Japanese patients.
BACKGROUND
This study aimed to report eleven cases of non-neovascular pachychoroid disease with hyperreflective material (HRM) that occurred in Japanese patients.
METHODS
A retrospective review of data from eleven patients who had non-neovascular retinal pigment epithelium (RPE) protrusion with HRM in the neurosensory retina between March 2017 and June 2022 was conducted. Clinical examination, color fundus photography, fluorescein angiography, spectral-domain optical coherence tomography (SD-OCT), and OCT angiography data were analyzed. Main outcome measures were patient characteristics, changes in SD-OCT findings, and symptom outcomes.
RESULTS
All cases had RPE protrusion and HRM with dilated choroidal veins, which were characteristic of pachychoroid disease. However, none of the cases had macular neovascularization (MNV). In 9 eyes (81.8%), HRM improved spontaneously without intervention and resulted in alterations in RPE, referred to as pachychoroid pigment epitheliopathy (PPE) or focal choroidal excavation (FCE). In these cases, symptoms such as metamorphopsia and distortion improved without treatment. In the remaining two cases (18.2%), HRM still persisted during the follow-up period.
CONCLUSION
There are some cases of non-neovascular pachychoroid disorder with HRM, which might be a new entity of pachychoroid spectrum disease or an early stage of PPE or FCE. These cases should not be misdiagnosed as MNV, and careful observation is necessary.
Topics: Humans; Choroid; Retinal Pigment Epithelium; Fluorescein Angiography; Tomography, Optical Coherence; Neovascularization, Pathologic; Retrospective Studies
PubMed: 37280611
DOI: 10.1186/s12886-023-03011-2