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DeepSeeNet: A Deep Learning Model for Automated Classification of Patient-based Age-related Macular Degeneration Severity from Color Fundus Photographs
摘要： In assessing the severity of age-related macular degeneration (AMD), the Age-Related Eye Disease Study (AREDS) Simplified Severity Scale predicts the risk of progression to late AMD. However, its manual use requires the time-consuming participation of expert practitioners. Although several automated deep learning systems have been developed for classifying color fundus photographs (CFP) of individual eyes by AREDS severity score, none to date has used a patient-based scoring system that uses images from both eyes to assign a severity score. Design: DeepSeeNet, a deep learning model, was developed to classify patients automatically by the AREDS Simplified Severity Scale (score 0e5) using bilateral CFP. Participants: DeepSeeNet was trained on 58 402 and tested on 900 images from the longitudinal follow-up of 4549 participants from AREDS. Gold standard labels were obtained using reading center grades. Methods: DeepSeeNet simulates the human grading process by first detecting individual AMD risk factors (drusen size, pigmentary abnormalities) for each eye and then calculating a patient-based AMD severity score using the AREDS Simplified Severity Scale. Main Outcome Measures: Overall accuracy, specificity, sensitivity, Cohen’s kappa, and area under the curve (AUC). The performance of DeepSeeNet was compared with that of retinal specialists. Results: DeepSeeNet performed better on patient-based classification (accuracy ? 0.671; kappa ? 0.558) than retinal specialists (accuracy ? 0.599; kappa ? 0.467) with high AUC in the detection of large drusen (0.94), pigmentary abnormalities (0.93), and late AMD (0.97). DeepSeeNet also outperformed retinal specialists in the detection of large drusen (accuracy 0.742 vs. 0.696; kappa 0.601 vs. 0.517) and pigmentary abnormalities (accuracy 0.890 vs. 0.813; kappa 0.723 vs. 0.535) but showed lower performance in the detection of late AMD (accuracy 0.967 vs. 0.973; kappa 0.663 vs. 0.754). Conclusions: By simulating the human grading process, DeepSeeNet demonstrated high accuracy with increased transparency in the automated assignment of individual patients to AMD risk categories based on the AREDS Simplified Severity Scale. These results highlight the potential of deep learning to assist and enhance clinical decision-making in patients with AMD, such as early AMD detection and risk prediction for developing late AMD. DeepSeeNet is publicly available on https://github.com/ncbi-nlp/DeepSeeNet.
关键词： deep learning,age-related macular degeneration,automated classification,AREDS Simplified Severity Scale,color fundus photographs
更新于2025-09-23 15:22:29
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Visual Acuity at Presentation in the Second Eye versus First Eye in Patients with Exudative Age-Related Macular Degeneration
摘要： Purpose: To assess the difference in best-corrected visual acuity (BCVA) at presentation between the first and second eye in patients with bilateral neovascular age-related macular degeneration (AMD). Methods: We reviewed the charts of all patients who had a clinical examination for neovascular AMD at the University Eye Clinic of Creteil in January 2013. We retrospectively analyzed demographic and clinical data for 264 patients. Results: In the fellow eye, choroidal neovascularization (CNV) developed in 75/264 patients (28.4%) with a time interval between the 2 events of 30.3 months (range 6-145). Data were available on 65 patients: 14/65 (21.5%) were asymptomatic, 24/65 (36.9%) had BCVA >20/40, whereas at the time of CNV diagnosis in the first eye, no patient was asymptomatic (p<0.0001), and 11/65 (16.9%) eyes had BCVA >20/40 (p<0.0001). The mean BCVA of the first affected eye was 0.68 (±0.41) logarithm of minimum angle of resolution (logMAR) and the mean BCVA for the second eye was 0.36 (±0.29) logMAR (p<0.0001). Conclusions: The BCVA at the time of diagnosis of CNV was higher in the second eye than in the first affected eye. This was possibly due to several factors including systematic bilateral examination in follow-up of unilateral exudative AMD that allowed detection of 20% of cases.
关键词： Patient management,Optical coherence tomography,Visual acuity,Age-related macular degeneration
更新于2025-09-23 15:22:29
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Age-related differences in the prevalence of subtypes of Neovascular age-related macular degeneration in the first diagnosed eye
摘要： Purpose To evaluate age-related differences in the prevalence of subtypes of neovascular age-related macular degeneration (AMD) in the first diagnosed eye. Methods This retrospective, observational study included 1099 eyes of 1099 patients diagnosed with neovascular AMD. The neovascular AMD cases were classified into three subtypes: typical neovascular AMD, polypoidal choroidal vasculopathy (PCV), and type 3 neovascularization. The patients were divided into four groups, according to age: > 50 and < 60 years, ≥ 60 and < 70 years, ≥ 70 and < 80 years, and ≥ 80 years. Difference in the prevalence of three AMD subtypes was evaluated among the four age groups. Results In the age group > 50 and < 60 years, 34 (25.0%) and 102 patients (75.0%) were diagnosed with typical neovascular AMD and PCV, respectively. In the age group ≥ 60 and < 70 years, 90 (28.1%), 206 (64.4%), and 24 patients (7.5%) were diagnosed with typical neovascular AMD, PCV, and type 3 neovascularization, respectively. In the age group ≥ 70 and < 80 years, the corresponding numbers were 200 (41.9%), 197 (41.3%), and 80 (16.8%), respectively; in the age group ≥80 years, the corresponding values were 83 (50.0%), 39 (23.5%), and 44 (26.5%), respectively. A significant difference was observed in the prevalence of the subtypes of neovascular AMD among the four age groups (chi-square test, P < 0.001). Conclusion Subtype prevalence in newly diagnosed neovascular AMD differs significantly according to age. This result suggests that different pathophysiology may be involved in the development of different subtypes of neovascular AMD.
关键词： Retinal angiomatous proliferation,Polypoidal choroidal vasculopathy,Choroidal neovascularization,Type 3 neovascularization,Age-related macular degeneration
更新于2025-09-23 15:22:29
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Multimodal imaging based biomarkers predictive of early and late response to anti-VEGFs during the first year of treatment for neovascular age-related macular degeneration
摘要： Purpose. — To evaluate baseline predictive markers of early and late anatomical response to anti-vascular endothelial growth factor (anti-VEGF) treatment in patients with neovascular age-related macular degeneration (nAMD). Methods. — The records of the nAMD patients who underwent intravitreal ranibizumab or aflibercept treatment, received the 3 monthly loading doses, and completed a follow-up period of 12 months were included retrospectively. The anatomical treatment response at month 3 (early) and between month 3 and 12 (late) was classified as good, intermediate or poor. Baseline demographic, fluorescein angiography, and optical coherence tomography findings were compared among the three groups. Results. — One hundred and ten eyes (74.3%) showed good, 18 (12.2%) showed intermediate and 20 (13.5%) showed poor anatomical response at month 3, and 114 eyes (77.0%) showed good, 27 (18.2%) showed intermediate and 7 (4.7%) showed poor anatomical response between month 3 and month 12. Of the evaluated parameters, drug type (better in aflibercept), showed a statistically significant difference in regards to anatomical outcomes at both the early and late periods (P = 0.02 and P = 0.03). The greatest linear dimension of choroidal neovascularization (CNV) and presence of peaked pigment epithelial detachment (PED) were important factors for early anatomical anti-VEGF treatment response. Conclusion. — Larger CNV and the presence of a peaked PED appeared to be associated with a good early response, and the drug type seemed to be associated with both early and late poor anatomical response of anti-VEGF treatment in nAMD patients. Aflibercept appears to be more effective than ranibizumab in regards to the percentage of patients with better anatomical response in both the early and late treatment periods.
关键词： Optical coherence tomography,Ranibizumab,Age-related macular degeneration,Aflibercept,Fluorescein angiography
更新于2025-09-23 15:22:29
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Efficacy of aflibercept on exudative age-related macular degeneration in patients exhibiting complete ranibizumab resistance and tachyphylaxis
摘要： Purpose: The present study compared the efficacy of aflibercept for neovascular age-related macular degeneration (NV-AMD) in patients with complete ranibizumab resistance and tachyphylaxis. Methods: Forty-four eyes of 38 neovascular age-related macular degeneration patients were evaluated. Eyes were divided into a complete resistance group (n=23 eyes) and tachyphylaxis group (n=21 eyes). Results: After three injections, eight (38.1%) patients in the tachyphylaxis group and nine (39.1%) in the complete resistance group presented with macular dryness. After the first injection of aflibercept, the mean visual acuity improved significantly in the tachyphylaxis group (p=0.018) but remained unchanged in the complete resistance group (p=0.37). There was a non-significant trend towards improved mean visual acuity in both groups after the second and third injections relative to the acuity at the final visit for ranibizumab treatment. In the tachyphylaxis group, the presence of subfoveal pigmented epithelium detachment (PED) decreased significantly after intravitreal aflibercept treatment. Conclusions: Although treatment with aflibercept yielded generally positive anatomical results in both groups, no significant increase in visual acuity was achieved.
关键词： Tachyphylaxis,Ranibizumab,Angiogenesis inhibitors,Vascular endothelial growth factor A,Macular degeneration
更新于2025-09-23 15:21:21
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Generating iPSC-Derived Choroidal Endothelial Cells to Study Age-Related Macular Degeneration
摘要： PURPOSE. Age-related macular degeneration (AMD), the most common cause of incurable blindness in the western world, is characterized by the dysfunction and eventual death of choroidal endothelial (CECs), RPE, and photoreceptor cells. Stem cell–based treatment strategies designed to replace photoreceptor and RPE cells currently are a major scienti?c focus. However, the success of these approaches likely also will require replacement of the underlying, supportive choroidal vasculature. The purpose of this study was to generate stem cell–derived CECs to develop ef?cient differentiation and transplantation protocols. METHODS. Dermal ?broblasts from the Tie2-GFP mouse were isolated and reprogrammed into two independent induced pluripotent stem cell (iPSC) lines via viral transduction of the transcription factors Oct4, Sox2, Klf4, and c-Myc. Tie2-GFP iPSCs were differentiated into CECs using a coculture method with either the RF6A CEC line or primary mouse CECs. Induced pluripotent stem cell–derived CECs were characterized via RT-PCR and immunocytochemistry for EC- and CEC-speci?c markers. RESULTS. Induced pluripotent stem cells generated from mice expressing green ?uorescent protein (GFP) under control of the endothelial Tie2 promoter display classic pluripotency markers and stem cell morphology. Induced pluripotent stem cell–derived CECs express carbonic anhydrase IV, eNOS, FOXA2, PLVAP, CD31, CD34, ICAM-1, Tie2, TTR, VE-cadherin, and vWF. CONCLUSIONS. Induced pluripotent stem cell–derived CECs will be a valuable tool for modeling of choriocapillaris-speci?c insults in AMD and for use in future choroidal endothelial cell replacement approaches.
关键词： choroidal endothelial cells,induced pluripotent stem cells,macular degeneration
更新于2025-09-23 15:21:01
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Nanoparticulate Transscleral Ocular Drug Delivery
摘要： Ocular drug delivery is one of the most challenging areas of drug delivery due to the unique mostly avascular nature of the major eye structures and presence of two blood barriers. Effectiveness of a more conventional systemic delivery falls short due to low drug levels in the eye tissue. Periocular approaches require penetration of fibrous sclera and present their own limitations. Utilization of nanotechnology presents new avenue of drug system development with potential to penetrate protective barriers and sustain ample tissue saturation. More specifically, transscleral delivery permits a range of applications in targeted delivery, gene, stem cell, protein and peptides, oligonucleotide, and ribozyme therapies. The exciting range of current applications is expounded in this review.
关键词： Drug delivery systems,Drug delivery,Nanotechnology,Ocular delivery,Transscleral delivery,Macular degeneration,Nanoparticle,Retina
更新于2025-09-23 15:21:01
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Retinal Thickness Changes throughout the Natural History of Drusen in Age-related Macular Degeneration
摘要： SIGNIFICANCE: Drusen are associated with retinal thinning in age-related macular degeneration (AMD). These changes, however, have mostly been examined at single time points, ignoring the evolution of drusen from emergence to regression. Understanding the full breadth of retinal changes associated with drusen will improve understanding of disease pathogenesis. PURPOSE: The purpose of this study was to assess how the natural history of drusen affects retinal thickness, focusing on the photoreceptor and retinal pigment epithelium (RPE) layers. METHODS: Spectral domain optical coherence tomography of subjects with intermediate AMD (n = 50) who attended the Centre for Eye Health, Sydney, Australia, for two separate visits (476 ± 16 days between visits) was extracted. Scans were automatically segmented with manufacturer software then assessed for drusen that had emerged, grown, or regressed between visits. For each identified lesion, the thickness of each retinal layer at the drusen peak and at adjacent drusen-free areas (150 μm nasal and temporal to the druse) was compared between visits. RESULTS: Before drusen emergence, the RPE was significantly thicker at the drusen site (14.2 ± 2.6%) compared with neighboring drusen-free areas. There was a 71% sensitivity of RPE thickening predicting drusen emergence. Once drusen emerged, significant thinning of all outer retinal layers was observed, consistent with previous studies. Drusen growth was significantly correlated with thinning of the outer retina (r = ?0.38, P < .001). Drusen regression resulted in outer retinal layers returning to thicknesses not significantly different from baseline. CONCLUSIONS: The natural history of drusen is associated with RPE thickening before drusen emergence, thinning of the outer nuclear layer as well as photoreceptor and RPE layers proportional to drusen growth, and return to baseline thickness after drusen regression. These findings have useful clinical applications, providing a potential marker for predicting drusen emergence for AMD prognostic and intervention studies and highlighting that areas of normal retinal thickness in AMD may be former sites of regressed drusen.
关键词： spectral domain optical coherence tomography,drusen,age-related macular degeneration,retinal thickness
更新于2025-09-23 15:21:01
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Changes in Retinal Layer Thickness in the?Contralateral Eye of Patients with Unilateral Neovascular Age-Related Macular Degeneration
摘要： To evaluate the thickness of the outer retinal layers and its relationship with visual function in fellow eyes of participants with unilateral neovascular age-related macular degeneration (AMD). Design: Longitudinal study. Participants: We enrolled 105 subjects with unilateral neovascular AMD from 3 clinical centers in Europe. Methods: The fellow eye, without advanced AMD, was selected for the study. Subjects were followed up with visits occurring every 6 months for 2 years. Spectral domain optical coherence tomography volume scans were collected at 3 clinical sites, in Belfast, Northern Ireland; Coimbra, Portugal; and Milan, Italy. Detailed manual segmentation of outer retinal layers was performed using the custom-designed and validated grading software 3D OCTOR. Thickness measurements for neurosensory retina, photoreceptor layer (PRL) outer segments, retinal pigment epithelium plus drusen (RPEtdrusen) complex, and choroidal layers from each sector of the standard macular grid were obtained. Measures of vison were distance visual acuity, near visual acuity, Smith-Kettlewell Institute low-luminance acuity score, and reading speed. Subjects were grouped based on the presence or absence of subretinal drusenoid deposits (SDDs) for further analysis. Main Outcome Measures: Change in thickness of retinal layers and change in measures of vision. Results: In all, 85 eyes were included in the analysis. The average duration of follow-up was 20.5 (cid:2) 5.8 months. By the ?nal visit, the RPEtdrusen complex was signi?cantly thinner when compared with baseline (29.7 mm vs. 34.09 mm; P ? 0.03). Low-luminance de?cit was signi?cantly worse at the ?nal visit (P < 0.001) and correlated with PRL outer segment thickness (r ? 0.33; P ?0.02). The RPEtdrusen complex was signi?cantly thicker in eyes with SDDs compared with that in those without SDDs (30.67 mm vs. 28.64 mm; P ? 0.02). PRL outer segments became signi?cantly thinner over time in eyes with SDDs compared with those in eyes without SDDs. Conclusions: The RPEtdrusen complex layer becomes thinner over time in fellow eyes of subjects with unilateral neovascular AMD. The rate of PRL outer segment thinning was higher in eyes with SDDs than in eyes without SDDs. These ?ndings are preliminary steps in the identi?cation of early biomarkers for detecting and monitoring the progression of AMD. Ophthalmology Retina 2018;-:1e10 a 2018 Published by Elsevier Inc. on behalf of the American Academy of Ophthalmology
关键词： spectral domain optical coherence tomography,visual function,retinal layer thickness,subretinal drusenoid deposits,age-related macular degeneration
更新于2025-09-23 15:21:01
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Predictive Value of the OCT Double-Layer Sign for Identifying Subclinical Neovascularization in Age-Related Macular Degeneration
摘要： Purpose: Structural optical coherence tomography (OCT) images from eyes with non-exudative age-related macular degeneration (AMD) were graded for the presence of a double layer sign to determine if the double-layer sign predicted subclinical macular neovascularization (MNV). Design: Prospective, observational study. Participants: Non-exudative AMD patients with and without subclinical MNV identified by swept source OCT angiography (SS-OCTA). Methods: Subjects were enrolled prospectively into a SS-OCTA imaging study. A set of test scans with and without subclinical MNV was compiled to assess the ability of trained graders to identify non-exudative type 1 MNV. The graders only evaluated the structural OCT B-scans of those eyes. The presence of a double-layer sign was used as a predictive sign for subclinical type 1 MNV. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) from two separate gradings were calculated and compared. Main Outcome Measures: The association between the presence of a double-layer sign and subclinical type 1 MNV. Results: One hundred eyes with non-exudative AMD from 94 patients were used for this study. The test set contained 64 eyes with intermediate AMD (iAMD), which included 20 eyes with subclinical MNV, and 36 eyes with late AMD, which included 13 eyes with subclinical MNV. Two junior graders read the scans separately then reached a consensus grading. They detected a double-layer sign in 24 out of 33 eyes with subclinical MNV and did not detect a double-layer sign in 56 out of 67 eyes without MNV. Their sensitivity, specificity, PPV, and NPV were 73%, 84%, 69%, and 86%, respectively. The senior grader detected a double-layer sign in 29 out of 33 eyes with subclinical MNV and did not detect a double-layer sign in 58 out of 67 eyes without MNV, achieving a sensitivity, specificity, PPV, and NPV as 88%, 87%, 76%, and 94%, respectively. For all graders, there were statistically significant associations between the type 1 MNV and the double-layer sign (P < 0.001). Conclusions: The double-layer sign on structural OCT B-scans was associated with subclinical type 1 MNV and can be used to identify these lesions with good predictive values in eyes with non-exudative AMD.
关键词： OCT double-layer sign,age-related macular degeneration,SS-OCTA imaging,subclinical neovascularization
更新于2025-09-23 15:21:01