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Investigative Ophthalmology & Visual... Jan 2024To assess the relationship between choriocapillaris (CC) loss and the development of nascent geographic atrophy (nGA) using optical coherence tomography angiography... (Observational Study)
Observational Study
PURPOSE
To assess the relationship between choriocapillaris (CC) loss and the development of nascent geographic atrophy (nGA) using optical coherence tomography angiography (OCTA) imaging.
METHODS
In total, 105 from 62 participants with bilateral large drusen, without late age-related macular degeneration (AMD) or nGA at baseline, were included in this prospective, longitudinal, observational study. Participants underwent swept-source OCTA imaging at 6-month intervals. CC flow deficit percentage (FD%) and drusen volume measurements were determined for the visit prior to nGA development or the second-to-last visit if nGA did not develop. Global and local analyses, the latter based on analyses within superpixels (120 × 120-µm regions), were performed to examine the association between CC FD% and future nGA development.
RESULTS
A total of 15 (14%) eyes from 12 (19%) participants developed nGA. There was no significant difference in global CC FD% at the visit prior to nGA development between eyes that developed nGA and those that did not (P = 0.399). In contrast, CC FD% was significantly higher in superpixels that subsequently developed nGA compared to those that did not (P < 0.001), and a model utilizing CC FD% was significantly better at predicting foci of future nGA development at the superpixel level than a model using drusen volume alone (P ≤ 0.040).
CONCLUSIONS
This study showed that significant impairments in CC blood flow could be detected locally prior to the development of nGA. These findings add to our understanding of the pathophysiologic changes that occur with atrophy development in AMD.
Topics: Humans; Tomography, Optical Coherence; Geographic Atrophy; Prospective Studies; Choroid; Macular Degeneration; Angiography
PubMed: 38236187
DOI: 10.1167/iovs.65.1.33 -
Biomedical Optics Express Jan 2024Effective biomarkers are required for assessing the progression of age-related macular degeneration (AMD), a prevalent and progressive eye disease. This paper presents a...
Deep-learning-based automated measurement of outer retinal layer thickness for use in the assessment of age-related macular degeneration, applicable to both swept-source and spectral-domain OCT imaging.
Effective biomarkers are required for assessing the progression of age-related macular degeneration (AMD), a prevalent and progressive eye disease. This paper presents a deep learning-based automated algorithm, applicable to both swept-source OCT (SS-OCT) and spectral-domain OCT (SD-OCT) scans, for measuring outer retinal layer (ORL) thickness as a surrogate biomarker for outer retinal degeneration, e.g., photoreceptor disruption, to assess AMD progression. The algorithm was developed based on a modified TransUNet model with clinically annotated retinal features manifested in the progression of AMD. The algorithm demonstrates a high accuracy with an intersection of union (IoU) of 0.9698 in the testing dataset for segmenting ORL using both SS-OCT and SD-OCT datasets. The robustness and applicability of the algorithm are indicated by strong correlation (r = 0.9551, P < 0.0001 in the central-fovea 3 mm-circle, and r = 0.9442, P < 0.0001 in the 5 mm-circle) and agreement (the mean bias = 0.5440 um in the 3-mm circle, and 1.392 um in the 5-mm circle) of the ORL thickness measurements between SS-OCT and SD-OCT scans. Comparative analysis reveals significant differences (P < 0.0001) in ORL thickness among 80 normal eyes, 30 intermediate AMD eyes with reticular pseudodrusen, 49 intermediate AMD eyes with drusen, and 40 late AMD eyes with geographic atrophy, highlighting its potential as an independent biomarker for predicting AMD progression. The findings provide valuable insights into the ORL alterations associated with different stages of AMD and emphasize the potential of ORL thickness as a sensitive indicator of AMD severity and progression.
PubMed: 38223170
DOI: 10.1364/BOE.512359 -
Frontiers in Ophthalmology 2023Age related macular degeneration (AMD) causes legal blindness worldwide, with few therapeutic targets in early disease and no treatments for 80% of cases. Extracellular...
INTRODUCTION
Age related macular degeneration (AMD) causes legal blindness worldwide, with few therapeutic targets in early disease and no treatments for 80% of cases. Extracellular deposits, including drusen and subretinal drusenoid deposits (SDD; also called reticular pseudodrusen), disrupt cone and rod photoreceptor functions and strongly confer risk for advanced disease. Due to the differential cholesterol composition of drusen and SDD, lipid transfer and cycling between photoreceptors and support cells are candidate dysregulated pathways leading to deposit formation. The current study explores this hypothesis through a comprehensive lipid compositional analysis of SDD.
METHODS
Histology and transmission electron microscopy were used to characterize the morphology of SDD. Highly sensitive tools of imaging mass spectrometry (IMS) and nano liquid chromatography tandem mass spectrometry (nLC-MS/MS) in positive and negative ion modes were used to spatially map and identify SDD lipids, respectively. An interpretable supervised machine learning approach was utilized to compare the lipid composition of SDD to regions of uninvolved retina across 1873 IMS features and to automatically discern candidate markers for SDD. Immunohistochemistry (IHC) was used to localize secretory phospholipase A2 group 5 (PLA2G5).
RESULTS
Among the 1873 detected features in IMS data, three lipid classes, including lysophosphatidylcholine (LysoPC), lysophosphatidylethanolamine (LysoPE) and lysophosphatidic acid (LysoPA) were observed nearly exclusively in SDD while presumed precursors, including phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidic acid (PA) lipids were detected in SDD and adjacent photoreceptor outer segments. Molecular signals specific to SDD were found in central retina and elsewhere. IHC results indicated abundant PLA2G5 in photoreceptors and retinal pigment epithelium (RPE).
DISCUSSION
The abundance of lysolipids in SDD implicates lipid remodeling or degradation in deposit formation, consistent with ultrastructural evidence of electron dense lipid-containing structures distinct from photoreceptor outer segment disks and immunolocalization of secretory PLA2G5 in photoreceptors and RPE. Further studies are required to understand the role of lipid signals observed in and around SDD.
PubMed: 38186747
DOI: 10.3389/fopht.2023.1258734 -
Ophthalmology Science 2024To examine the effectiveness of a targeted high-density microperimetry testing strategy for detecting visual sensitivity abnormalities in eyes with nascent geographic...
PURPOSE
To examine the effectiveness of a targeted high-density microperimetry testing strategy for detecting visual sensitivity abnormalities in eyes with nascent geographic atrophy (nGA) when compared with standard central microperimetry testing.
DESIGN
Observational study.
PARTICIPANTS
Three-hundred and twenty-one eyes from 176 individuals with nonneovascular age-related macular degeneration (AMD).
METHODS
Thirty-five eyes from 33 participants underwent targeted high-density microperimetry testing of atrophic lesions (either nGA or geographic atrophy [GA]) within a 1.75° radius (or approximately 1000 μm diameter) region. Another cohort of 286 eyes from 143 participants with bilateral large drusen at baseline underwent standard microperimetry testing of the central 6 radius region at 6-monthly intervals for up to 36 months and thus included eyes that developed nGA and GA over the follow-up. All eyes underwent 2 tests at each visit to evaluate intrasession measurement repeatability.
MAIN OUTCOME MEASURES
Magnitude of visual sensitivity abnormalities based on mean sensitivity (MS), pointwise sensitivity standard deviation (PSD), and the number of test locations with a threshold of ≤ 10 decibels (dB; or deep defects) in eyes with nGA, compared between eyes that underwent targeted high-density microperimetry testing and standard central microperimetry testing.
RESULTS
The magnitude of visual sensitivity abnormalities based on MS, PSD and the number of deep defects were all significantly greater in eyes with nGA using targeted, high-density microperimetry testing compared with eyes with nGA using standard central microperimetry testing (all < 0.001) and were all significantly less than eyes with GA using targeted, high-density microperimetry testing (all ≤ 0.004). The intrasession coefficient of repeatability, where 95% of the test-retest differences are expected to occur, for MS in eyes with atrophic changes was 0.9 dB with the targeted, high-density microperimetry testing, and 1.8 dB with standard central microperimetry testing.
CONCLUSIONS
Targeted, high-density microperimetry testing enabled the detection of a significantly greater magnitude of visual sensitivity abnormalities in eyes with nGA than standard microperimetry testing.
FINANCIAL DISCLOSURES
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
PubMed: 38170082
DOI: 10.1016/j.xops.2023.100419 -
Ophthalmology and Therapy Feb 2024This study aimed to compare the integrity of the hyperreflective layer of the inner choroid in eyes with and without drusen.
INTRODUCTION
This study aimed to compare the integrity of the hyperreflective layer of the inner choroid in eyes with and without drusen.
METHODS
Swept-source optical coherence tomography images of patients with drusen and normal controls were reviewed. Using a line plot of ImageJ, choroidal reflectivity was measured at the subfovea, and the integrity of the hyperreflective layer of the inner choroid was determined.
RESULTS
In total, 63 eyes with drusen and 30 control eyes without drusen were included. The integrity of the hyperreflective layer of the inner choroid was preserved in 81.0% of eyes with drusen and 93.3% of normal controls. The proportion of eyes with the hyperreflective layer did not differ between eyes with and without drusen. Of the 63 subjects with drusen, this hyperreflective layer was observed in all 28 eyes (100%) with pachydrusen but only in 68.6% of the 35 eyes with soft drusen, and its prevalence was significantly different (P = 0.001).
CONCLUSION
The prevalence of the hyperreflective layer between the choriocapillaris and medium or large choroidal vessels in eyes with soft drusen differed from that in eyes with pachydrusen. These findings support the suggestion that changes within the choroidal stroma may be involved in the pathogenesis of age-related macular degeneration.
PubMed: 38113024
DOI: 10.1007/s40123-023-00865-z -
International Journal of Ophthalmology 2023To assess the agreement of optical coherence tomography (OCT) algorithm-based retinal pigment epithelium -Bruch's membrane complex volume (RBV) with fundus...
AIM
To assess the agreement of optical coherence tomography (OCT) algorithm-based retinal pigment epithelium -Bruch's membrane complex volume (RBV) with fundus photograph-based age-related macular degeneration (AMD) grading.
METHODS
Digital color fundus photographs (CFPs) and spectral domain OCT images were acquired from 96 elderly subjects. CFPs were graded according to Age-Related Eye Disease Study (AREDS) classification. OCT image segmentation and RBV data calculation were done with Orion™ software. Univariate and multivariate analyses were performed to find out whether AMD lesion features associated with higher RBVs.
RESULTS
RBV correlated with AMD grading (=0.338, =0.001), the correlation was slightly stronger in early AMD (=52; =0.432, =0.001). RBV was higher in subjects with early AMD compared with those with no AMD lesions evident in fundus photographs (1.05±0.20 0.96±0.13 mm, =0.023). In multivariate analysis higher RBVs were associated significantly with higher total drusen (=0.388, =0.027) and pigmentation areas (=0.319, =0.020) in fundus photographs, whereas depigmentation area (=-0.295, =0.015) associated with lower RBV.
CONCLUSION
RBV correlate with AMD grading status, with a stronger association in patients with moderate, non-late AMD grades. This effect is driven mostly by lesions with drusen or pigmentation. Lesions with depigmentation tend to have lower values. RBV is more comprehensive measurement of the key area of AMD pathogenesis, compared to sole drusen volume analysis. RBV measurements are independent on grader variations and offer a possibility to quantify early and middle grade AMD lesions in a research setting, but may not substitute fundus photograph-based grading in the whole range of AMD spectrum.
PubMed: 38028508
DOI: 10.18240/ijo.2023.11.14 -
Heliyon Nov 2023Worldwide, age-related macular degeneration (AMD) is a multifactorial progressive fundus disorder that can cause vision impairment and severe central blindness in older... (Review)
Review
Worldwide, age-related macular degeneration (AMD) is a multifactorial progressive fundus disorder that can cause vision impairment and severe central blindness in older adults. Currently, there are no approved prevention or treatment strategies for non-exudative AMD. While targeting VEGF is the main therapeutic approach to delay the degeneration process in exudative AMD, a significant number of patients show insensitivity or ineffectiveness to anti-VEGF therapy. Despite years of research, the exact mechanism underlying drusen formation and macular atrophy in AMD remains unknown. In the pathogenesis of AMD, lncRNAs play crucial roles, as discussed in this paper. This review focuses on the function of dysregulated lncRNAs and the mechanisms by which specific molecules target these lncRNAs in AMD. The analysis reveals that lncRNAs primarily regulate the progression of AMD by mediating apoptosis, epithelial-mesenchymal transition (EMT), dedifferentiation, and oxidative stress in choroidal vascular endothelial cells, retinal pigment epithelium (RPE) cells, and photoreceptors. Consequently, the regulation of apoptosis, dedifferentiation, EMT, and other processes by lncRNAs has emerged as a crucial focus in AMD research.These findings contribute to our understanding of the role of lncRNAs in AMD and their potential as valuable biomarkers. Furthermore, they highlight the need for further basic and clinical studies to explore the value of lncRNAs as biomarkers and potential therapeutic targets for AMD.
PubMed: 38027818
DOI: 10.1016/j.heliyon.2023.e22307 -
Case Reports in Ophthalmology 2023Doyne honeycomb retinal dystrophy (DHRD), or autosomal dominant radial drusen, is a genetic disease caused by pathogenic variants of the epidermal growth factor...
INTRODUCTION
Doyne honeycomb retinal dystrophy (DHRD), or autosomal dominant radial drusen, is a genetic disease caused by pathogenic variants of the epidermal growth factor (EGF)-containing fibulin-like extracellular matrix protein 1 gene and is characterized by the formation of subretinal drusenoid deposits. In a previous study, we reported the short-term beneficial effects of nanosecond laser treatment (2RT) on retinal function in DHRD. The aim of the present report was to describe the findings of a long-term follow-up of retinal structure/function in a small case series of patients with DHRD who underwent 2RT treatment.
CASE PRESENTATION
Three DHRD patients (case 1, male and cases 2 and 3, two sister females, age range 41-46) with pathogenic variant (c.1033C>T; p.R345W) and drusenoid deposits at the posterior pole were examined at baseline and after 2RT treatment, at regular intervals (every 2-4 months) up to 30 months. All 3 patients underwent one or two treatment sessions in one or both eyes during the follow-up period. Case 3 was treated with only the left eye (LE). Each patient underwent a full ophthalmologic examination, spectral domain optical coherence tomography (OCT), central perimetry with frequency doubling technology, and mesopic and photopic Ganzfeld electroretinograms. Compared to baseline findings, during follow-up, visual acuity improved in both eyes in case 1 and LE in case 2, while it decreased in the right eye in case 2 and LE in case 3; perimetric sensitivity was stable in case 1 and improved in both eyes in cases 2 and 3; and electroretinogram amplitude improved in cases 1 and 2 and was stable in case 3 (both eyes). OCT central macular thickness and retinal structure were stable in all cases. None of the patients had treatment-related side effects.
CONCLUSION
This is the first report showing that in a long-term follow-up, 2RT treatment in DHRD may improve or stabilize some retinal function parameters without significant structural changes.
PubMed: 38023612
DOI: 10.1159/000534579 -
Pharmaceutics Nov 2023Age-related macular degeneration (AMD) is the main cause of blindness in developed countries. AMD is characterized by the formation of drusen, which are lipidic...
Age-related macular degeneration (AMD) is the main cause of blindness in developed countries. AMD is characterized by the formation of drusen, which are lipidic deposits, between retinal pigment epithelium (RPE) and the choroid. One of the main molecules accumulated in drusen is 7-Ketocholesterol (7KCh), an oxidized-cholesterol derivative. It is known that 7KCh induces inflammatory and cytotoxic responses in different cell types and the study of its mechanism of action is interesting in order to understand the development of AMD. Sterculic acid (SA) counteracts 7KCh response in RPE cells and could represent an alternative to improve currently used AMD treatments, which are not efficient enough. In the present study, we determine that 7KCh induces a complex cell death signaling characterized by the activation of necrosis and an alternative pyroptosis mediated by P2X7, p38 and GSDME, a new mechanism not yet related to the response to 7KCh until now. On the other hand, SA treatment can successfully attenuate the activation of both necrosis and pyroptosis, highlighting its therapeutic potential for the treatment of AMD.
PubMed: 38004569
DOI: 10.3390/pharmaceutics15112590 -
Scientific Reports Nov 2023Ultra-widefield retinal imaging is increasingly used in ophthalmology and optometry practices to image patients identifying peripheral abnormalities. However, the...
Ultra-widefield retinal imaging is increasingly used in ophthalmology and optometry practices to image patients identifying peripheral abnormalities. However, the clinical relevance of these peripheral retinal abnormalities is unclear. This cross-sectional study aims to firstly validate a new grading system, secondly, assess the prevalence of peripheral retinal abnormalities in retinal patients, and finally understand how peripheral findings may associate with retinal disease. Ultra-widefield pseudocolor fundus images were taken from the eyes of clinic patients. Demographic data and clinical diagnosis for each patient was noted. The grading system was validated using masked retinal specialists. Logistic regression identified associations between retinal disease and peripheral retinal findings. Using the grading system, inter-observer agreement was 76.1% with Cohen's Kappa coefficient 0.542 (p < 0.0001) and the test-retest agreement was 95.1% with Kappa 0.677(p < 0.0001). 971 images were included, with 625 eyes (64.4%) having peripheral abnormalities. Peripheral drusen was the most common abnormality (n = 221, 22.76%) and correlated with age-related macular degeneration (p < 0.001). Novel correlations were also identified between diabetic retinopathy and retinal pigmentation as well as pigmentary degeneration. This study provides a validated system for identifying peripheral abnormalities and adds to literature highlighting peripheral retinal associations with retinal disease which would benefit from further study.
Topics: Humans; Cross-Sectional Studies; Prevalence; Retina; Fundus Oculi; Retinal Drusen; Fluorescein Angiography
PubMed: 37993580
DOI: 10.1038/s41598-023-47761-x