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Ophthalmology and Therapy Oct 2023To describe subclinical angioid streaks (AS) as a frequent, peculiar age-related macular degeneration (AMD) phenotype, comparing features of eyes with subclinical AS...
INTRODUCTION
To describe subclinical angioid streaks (AS) as a frequent, peculiar age-related macular degeneration (AMD) phenotype, comparing features of eyes with subclinical AS with those of eyes with AMD without AS.
METHODS
This was a retrospective, observational study. Among a patient cohort with AMD, we selected patients without known causes for AS whose eyes showed signs of angioid streaks (AS) on structural optical coherence tomography (OCT) but not on fundus examination. Selected OCT features of AS were Bruch's membrane (BM) breaks and large BM dehiscences.
RESULTS
Among 543 eyes of 274 patients with AMD (mean ± standard deviation: 82 ± 7 years), 73 eyes of 46 patients (81 ± 7 years; p = 0.432) showed AS features on OCT (OCT AS) that were not visible on fundus examination. Estimated prevalence of subclinical age-related AS was 13.4% (95% confidence interval 10.3-16.3%) in this AMD population. Fifty-three eyes (73%) with AS features were affected by peripapillary atrophy, often with a "petaloid-like" pattern, similar to typical features of AS disease. Almost all cases (97%) presented reticular pseudodrusen (RPD), with (41%) or without (59%) drusen showing a significant difference in RPD prevalence in OCT AS eyes in comparison to AMD eyes without subclinical AS using generalized estimating equations (P < 0.001). Among the 73 subclinical AS cases, 71 were affected by late AMD (57 with macular neovascularization, 14 with geographic atrophy), showing a more advanced AMD stage in comparison with AMD eyes without subclinical AS (P < 0.001). The following OCT features were disclosed: BM breaks in 100% of cases and BM dehiscences in 37%.
CONCLUSIONS
Subclinical AS in eyes with AMD is a peculiar phenotype of the disease, with features suggesting a primary involvement of Bruch's membrane and clinical similarities with mild, late-onset pseudoxanthoma elasticum.
PubMed: 37542615
DOI: 10.1007/s40123-023-00778-x -
Sensors (Basel, Switzerland) Jul 2023Deposition of calcium-containing minerals such as hydroxyapatite and whitlockite in the subretinal pigment epithelial (sub-RPE) space of the retina is linked to the...
Deposition of calcium-containing minerals such as hydroxyapatite and whitlockite in the subretinal pigment epithelial (sub-RPE) space of the retina is linked to the development of and progression to the end-stage of age-related macular degeneration (AMD). AMD is the most common eye disease causing blindness amongst the elderly in developed countries; early diagnosis is desirable, particularly to begin treatment where available. Calcification in the sub-RPE space is also directly linked to other diseases such as Pseudoxanthoma elasticum (PXE). We found that these mineral deposits could be imaged by fluorescence using tetracycline antibiotics as specific stains. Binding of tetracyclines to the minerals was accompanied by increases in fluorescence intensity and fluorescence lifetime. The lifetimes for tetracyclines differed substantially from the known background lifetime of the existing natural retinal fluorophores, suggesting that calcification could be visualized by lifetime imaging. However, the excitation wavelengths used to excite these lifetime changes were generally shorter than those approved for retinal imaging. Here, we show that tetracycline-stained drusen in human retinas may be imaged by fluorescence lifetime contrast using multiphoton (infrared) excitation. For this pilot study, ten eyes from six anonymous deceased donors (3 female, 3 male, mean age 83.7 years, range 79-97 years) were obtained with informed consent from the Maryland State Anatomy Board with ethical oversight and approval by the Institutional Review Board.
Topics: Male; Humans; Female; Aged; Aged, 80 and over; Tetracycline; Pilot Projects; Retina; Macular Degeneration; Anti-Bacterial Agents
PubMed: 37514920
DOI: 10.3390/s23146626 -
Bioengineering (Basel, Switzerland) Jul 2023Accurate noninvasive diagnosis of retinal disorders is required for appropriate treatment or precision medicine. This work proposes a multi-stage classification network...
Accurate noninvasive diagnosis of retinal disorders is required for appropriate treatment or precision medicine. This work proposes a multi-stage classification network built on a multi-scale (pyramidal) feature ensemble architecture for retinal image classification using optical coherence tomography (OCT) images. First, a scale-adaptive neural network is developed to produce multi-scale inputs for feature extraction and ensemble learning. The larger input sizes yield more global information, while the smaller input sizes focus on local details. Then, a feature-rich pyramidal architecture is designed to extract multi-scale features as inputs using DenseNet as the backbone. The advantage of the hierarchical structure is that it allows the system to extract multi-scale, information-rich features for the accurate classification of retinal disorders. Evaluation on two public OCT datasets containing normal and abnormal retinas (e.g., diabetic macular edema (DME), choroidal neovascularization (CNV), age-related macular degeneration (AMD), and Drusen) and comparison against recent networks demonstrates the advantages of the proposed architecture's ability to produce feature-rich classification with average accuracy of 97.78%, 96.83%, and 94.26% for the first (binary) stage, second (three-class) stage, and all-at-once (four-class) classification, respectively, using cross-validation experiments using the first dataset. In the second dataset, our system showed an overall accuracy, sensitivity, and specificity of 99.69%, 99.71%, and 99.87%, respectively. Overall, the tangible advantages of the proposed network for enhanced feature learning might be used in various medical image classification tasks where scale-invariant features are crucial for precise diagnosis.
PubMed: 37508850
DOI: 10.3390/bioengineering10070823 -
Journal of Imaging Jul 2023The current advancement towards retinal disease detection mainly focused on distinct feature extraction using either a convolutional neural network (CNN) or a...
The current advancement towards retinal disease detection mainly focused on distinct feature extraction using either a convolutional neural network (CNN) or a transformer-based end-to-end deep learning (DL) model. The individual end-to-end DL models are capable of only processing texture or shape-based information for performing detection tasks. However, extraction of only texture- or shape-based features does not provide the model robustness needed to classify different types of retinal diseases. Therefore, concerning these two features, this paper developed a fusion model called 'Conv-ViT' to detect retinal diseases from foveal cut optical coherence tomography (OCT) images. The transfer learning-based CNN models, such as Inception-V3 and ResNet-50, are utilized to process texture information by calculating the correlation of the nearby pixel. Additionally, the vision transformer model is fused to process shape-based features by determining the correlation between long-distance pixels. The hybridization of these three models results in shape-based texture feature learning during the classification of retinal diseases into its four classes, including choroidal neovascularization (CNV), diabetic macular edema (DME), DRUSEN, and NORMAL. The weighted average classification accuracy, precision, recall, and F1 score of the model are found to be approximately 94%. The results indicate that the fusion of both texture and shape features assisted the proposed Conv-ViT model to outperform the state-of-the-art retinal disease classification models.
PubMed: 37504817
DOI: 10.3390/jimaging9070140 -
Translational Vision Science &... Jul 2023Intermediate age-related macular degeneration (iAMD) is a risk factor for progression to advanced stages, but rates of progression vary between individuals. Predicting...
PURPOSE
Intermediate age-related macular degeneration (iAMD) is a risk factor for progression to advanced stages, but rates of progression vary between individuals. Predicting individual risk is advantageous for programing timely and effective treatment and for patient stratification into future clinical trials.
METHODS
We conducted a prospective and noninterventional study following patients with iAMD for 24 months. Optical coherence tomography parameters related with drusen, hyper-reflective foci (HRF), presence of incomplete retinal pigment epithelial and outer retinal atrophy (iRORA) and ellipsoid zone (EZ) status were explored at the baseline. Patients were reclassified at the end of the follow-up period and divided according to their progression. A risk prediction model for progression to late AMD was developed.
RESULTS
A total of 135 patients were enrolled in the study and 30.4% developed late disease. A multivariate logistic regression model was created using those optical coherence tomography parameters, further optimized by backward feature elimination. Parameters offering the best fit in prediction progression were presence of iRORA, EZ status, drusen area and presence of HRF. iRORA is the feature that provides a higher probability of developing late AMD (odds ratio, 12.91; P = 0.000), followed by EZ disruption status (odds ratio, 3.54; P = 0.0018). The area under the receiver operating characteristic curve calculated for the testing set was 0.77 (95% confidence interval, 0.56-0.98).
CONCLUSIONS
The combination of iRORA and EZ disruption constitute a high risk of progression to complete RORA within 2 years.
TRANSLATIONAL RELEVANCE
We propose a practical and useful model to help clinicians in their daily practice in predicting individual progression to advanced AMD.
Topics: Humans; Prospective Studies; Macular Degeneration; Tomography, Optical Coherence
PubMed: 37490304
DOI: 10.1167/tvst.12.7.22 -
Orphanet Journal of Rare Diseases Jul 2023To determine whether the rare NLRP3-Associated Autoinflammatory Disease (NLRP3-AID) is associated with retinal changes and to assess the ocular involvement.
PURPOSE
To determine whether the rare NLRP3-Associated Autoinflammatory Disease (NLRP3-AID) is associated with retinal changes and to assess the ocular involvement.
METHODS
A retrospective cohort study of 20 patients(40 eyes) diagnosed with rare NLRP3-AID at Peking Union Medical College Hospital, from April 2015 to August 2022. Patients underwent a comprehensive ophthalmological examination, including visual acuity, intraocular pressure examination, slit-lamp examination, fundus photography, optical coherence tomography(OCT), and fluorescence angiography (FA). Some patients also underwent optical coherence tomography angiography (OCTA).
RESULTS
This study analyzed 40 eyes of 20 patients (11 [55.0%] male; median age, 25.0 years [range, 12-52 years]) and 13 patients (26 eyes, 65%) demonstrated ocular involvement. The most common ophthalmologic manifestation was conjunctivitis (22 eyes, 84.6%), followed by papilledema (14 eyes, 53.8%), retinopathy (10 eyes, 38.5%), optic atrophy (6 eyes, 23.1%), uveitis (4 eyes, 15.4%), reduced pupil light reflex (3 eyes, 11.5%) and cataracts (2 eyes, 7.7%). Ocular involvement was bilateral in 11 patients (55.0%). Five kinds of retinal lesions were seen in 5 patients (10 eyes, 25%) with NLRP3-AID, including peripheral retinal vascular leakage, microaneurysms, macular ischemia, macular epiretinal membrane formation and drusen.
CONCLUSIONS
Peripheral retinal vascular leakage, macular ischemia, microaneurysms and drusen are newly identified retinal findings in patients with NLRP3-AID, which suggests the importance of detailed retinal examination in these patients.
Topics: Humans; Male; Adult; Female; NLR Family, Pyrin Domain-Containing 3 Protein; Retrospective Studies; Microaneurysm; Retinal Diseases; Tomography, Optical Coherence; Ischemia; Hereditary Autoinflammatory Diseases
PubMed: 37480029
DOI: 10.1186/s13023-023-02815-1 -
Genes & Nutrition Jul 2023Age-related macular degeneration (AMD) is one of the major causes of vision loss. Early AMD needs to be taken seriously, but the causal effects of lipid biomarkers on...
BACKGROUND
Age-related macular degeneration (AMD) is one of the major causes of vision loss. Early AMD needs to be taken seriously, but the causal effects of lipid biomarkers on early AMD remain unclear.
METHODS
In this study, two-sample Mendelian randomization (MR) analysis was performed to systematically assess the causal relationships between seven serum lipid biomarkers (apolipoprotein A (ApoA), apolipoprotein B (ApoB), total cholesterol (CHOL), high-density lipoprotein cholesterol (HDL-C), direct low-density lipoprotein cholesterol (LDL-C), lipoprotein A [Lp(a)], and triglycerides (TG)) and risk of early AMD. In total, 14,034 cases and 91,214 controls of European ancestry were included in the analysis (number of SNPs = 11,304,110).
RESULTS
MR estimates revealed that a higher HDL-C level is strongly associated with increased risk of early AMD (OR = 1.25, 95% CI: 1.15-1.35, P = 2.61 × 10). In addition, level of ApoA is also positively associated with risk of early AMD (OR = 2.04, 95% CI: 1.50-2.77, P = 6.27 × 10). Conversely, higher levels of TG significantly decrease the risk of early AMD (OR = 0.77, 95% CI: 0.71-0.84, P = 5.02 × 10). Sensitivity analyses further supported these associations. Moreover, multivariable MR analyses, adjusted for the effects of correlated lipid biomarkers, yielded similar results.
CONCLUSION
This study identifies causal relationships between elevated circulating HDL-C/ApoA levels and increased risk of early AMD, in addition to finding that TG specifically reduces the risk of early AMD. These findings contribute to a better understanding of the role of lipid metabolism in drusen formation, particularly in early AMD development.
PubMed: 37479984
DOI: 10.1186/s12263-023-00730-5 -
Ophthalmology. Retina Dec 2023To investigate the ability of retromode imaging technology to visualize drusen-like deposits (DLDs) in the macular region of healthy individuals without retinal... (Observational Study)
Observational Study
PURPOSE
To investigate the ability of retromode imaging technology to visualize drusen-like deposits (DLDs) in the macular region of healthy individuals without retinal diseases. Additionally, the correlation between subject age and the density of DLDs was assessed and their topographic distribution was evaluated.
DESIGN
Prospective, observational, cross-sectional study SUBJECTS: Healthy volunteers (aged ≥ 35 years) without macular diseases.
METHODS
This study evaluated macular images in healthy adults using color fundus photography (FP) and retromode imaging. Two masked graders counted the number of DLDs identifiable with each modality. The standardized ETDRS concentric rings were adopted to divide DLDs based on their topographic distribution.
MAIN OUTCOME MEASURES
Comparison of the number of DLDs detected with each imaging modality. The association between DLDs and age. The topographic distribution of macular DLDs with retromode imaging.
RESULTS
The study included 91 eyes of 52 healthy volunteers (mean ± standard deviation age, 57.9 ± 10.9 years; range, 36-82 years). Overall, at least 1 DLD was present in 63.74% of eyes on color FP and 96.71% on retromode. Retromode imaging allowed detection of significantly more DLDs compared with color FP within the ETDRS grid (median [interquartile range], 4 [1-14] vs. 0 [0-0] respectively; P < 0.001). The density of DLDs was higher in the outer and inner rings compared with the central subfield (relative risk [RR], 16.70; 95% confidence interval [CI], 10.3-27.3 vs. RR 17.1; 95% CI, 10.5-27.6, respectively). Age was significantly correlated with DLDs density in all 3 sectors (all P < 0.05).
CONCLUSIONS
Retromode technology allowed the detection of a significantly higher number of DLDs compared with FP in the macula of healthy individuals. This noninvasive imaging modality could be used to investigate the effect of the aging process on the macula, fostering a better understanding of the pathophysiology of age-related macular diseases.
FINANCIAL DISCLOSURE(S)
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
Topics: Adult; Aged; Humans; Middle Aged; Cross-Sectional Studies; Macular Degeneration; Prospective Studies; Retina; Retinal Drusen
PubMed: 37479086
DOI: 10.1016/j.oret.2023.07.012 -
Eye (London, England) Jan 2024Microvascular alterations and choroidal impairment are emerging as a pathologic pathway in age-related macular degeneration (AMD). This study aimed to evaluate the... (Observational Study)
Observational Study
BACKGROUND/OBJECTIVES
Microvascular alterations and choroidal impairment are emerging as a pathologic pathway in age-related macular degeneration (AMD). This study aimed to evaluate the central macular choriocapillaris (CC) in eyes with subretinal drusenoid deposits (SDD) and the retinal microvasculature in patients with early AMD phenotypes.
SUBJECTS/METHODS
This was an institutional, multicentric observational cross-sectional study. Ninety-nine eyes of 99 subjects; 33 eyes with SDD only, 33 eyes with conventional drusen (CD) only, and 33 eyes of healthy age-matched subjects were included. Comprehensive ophthalmologic examination and optical coherence tomography angiography (OCTA) was performed. The central macular flow area of the CC was analysed in the SDD group and the vessel density of the retinal superficial capillary plexus (SCP) and deep capillary plexus (DCP) was analysed in the SDD and CD groups using automated OCTA output parameters.
RESULTS
The flow area of the CC in the SDD group was significantly reduced (p ≤ 0.001) with respect to the healthy control group. There was a trend of reduction of vessel density of the SCP and the DCP in the SDD and CD group with respect to controls, although this did not reach statistical significance.
CONCLUSIONS
OCTA data in the present report corroborate the role of vascular damage in early AMD with CC impairment in the central macular area in eyes with SDD.
Topics: Humans; Choroid; Cross-Sectional Studies; Fluorescein Angiography; Macular Degeneration; Retina; Retinal Drusen; Retinal Vessels; Tomography, Optical Coherence
PubMed: 37419959
DOI: 10.1038/s41433-023-02654-1