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Spatial Interpolation Enables Normative Data Comparison in Gaze-Contingent Microperimetry
摘要： PURPOSE. To demonstrate methods that enable visual field sensitivities to be compared with normative data without restriction to a fixed test pattern. METHODS. Healthy participants (n ? 60, age 19–50) undertook microperimetry (MAIA-2) using 237 spatially dense locations up to 138 eccentricity. Surfaces were fit to the mean, variance, and 5th percentile sensitivities. Goodness-of-fit was assessed by refitting the surfaces 1000 times to the dataset and comparing estimated and measured sensitivities at 50 randomly excluded locations. A leave-one-out method was used to compare individual data with the 5th percentile surface. We also considered cases with unknown fovea location by adding error sampled from the distribution of relative fovea–optic disc positions to the test locations and comparing shifted data to the fixed surface. RESULTS. Root mean square (RMS) difference between estimated and measured sensitivities were less than 0.5 dB and less than 1.0 dB for the mean and 5th percentile surfaces, respectively. Root mean square differences were greater for the variance surface, median 1.4 dB, range 0.8 to 2.7 dB. Across all participants 3.9% (interquartile range, 1.8–8.9%) of sensitivities fell beneath the 5th percentile surface, close to the expected 5%. Positional error added to the test grid altered the number of locations falling beneath the 5th percentile surface by less than 1.3% in 95% of participants. CONCLUSIONS. Spatial interpolation of normative data enables comparison of sensitivity measurements from varied visual field locations. Conventional indices and probability maps familiar from standard automated perimetry can be produced. These methods may enhance the clinical use of microperimetry, especially in cases of nonfoveal fixation.
关键词： fundus perimetry,microperimetry,normative database,AMD,gaze-contingent
更新于2025-09-23 15:23:52
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[Lecture Notes in Computer Science] Advances in Soft Computing Volume 10632 (16th Mexican International Conference on Artificial Intelligence, MICAI 2017, Enseneda, Mexico, October 23-28, 2017, Proceedings, Part I) || A Survey of Machine Learning Approaches for Age Related Macular Degeneration Diagnosis and Prediction
摘要： Age Related Macular Degeneration (AMD) is a complex disease caused by the interaction of multiple genes and environmental factors. AMD is the leading cause of visual dysfunction and blindness in developed countries, and a rising cause in underdeveloped countries. Currently, retinal images are studied in order to identify drusen in the retina. The classification of these images allows to support the medical diagnosis. Likewise, genetic variants and risk factors are studied in order to make predictive studies of the disease, which are carried out with the support of statistical tools and, recently, with Machine Learning (ML) methods. In this paper, we present a survey of studies performed in complex diseases under both approaches, especially for the case of AMD. We emphasize the approach based on the genetic variants of individuals, as it is a support tool for the prevention of AMD. According to the vision of personalized medicine, disease prevention is a priority to improve the quality of life of people and their families, as well as to avoid the inherent health burden.
关键词： Predictive diagnosis,Machine Learning,Classification,Automated diagnosis,Pattern recognition,AMD
更新于2025-09-23 15:23:52
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Characterization of Rod Function Phenotypes Across a Range of Age-Related Macular Degeneration Severities and Subretinal Drusenoid Deposits
摘要： PURPOSE. To examine spatial changes in rod-mediated function in relationship to local structural changes across the central retina in eyes with a spectrum of age-related macular degeneration (AMD) disease severity. METHODS. Participants were categorized into five AMD severity groups based on fundus features. Scotopic thresholds were measured at 14 loci spanning 6° to 18° along the vertical meridian from one eye of each of 42 participants (mean = 71.7 ± 9.9 years). Following a 30% bleach, dark adaptation was measured at eight loci (4° to 12°). Rod intercept time (RIT) was defined from the time to detect a ?3.1 log cd/m2 stimulus. RITslope was defined from the linear fit of RIT with decreasing retinal eccentricity. The presence of subretinal drusenoid deposits (SDD), ellipsoid (EZ) band disruption, and drusen at the test loci was evaluated using optical coherence tomography. RESULTS. Scotopic thresholds indicated greater rod function loss in the macula, which correlated with increasing AMD group severity. RITslope, which captures the spatial change in the rate of dark adaptation, increased with AMD severity (P < 0.0001). Three rod function phenotypes emerged: RF1, normal rod function; RF2, normal scotopic thresholds but slowed dark adaptation; and RF3, elevated scotopic thresholds with slowed dark adaptation. Dark adaptation was slowed at all loci with SDD or EZ band disruption, and at 32% of loci with no local structural changes. CONCLUSIONS. Three rod function phenotypes were defined from combined measurement of scotopic threshold and dark adaptation. Spatial changes in dark adaptation across the macula were captured with RITslope, which may be a useful outcome measure for functional studies of AMD.
关键词： age-related macular degeneration,RIT,SDD,scotopic thresholds,dark adaptation,rod intercept time,subretinal drusenoid deposits,AMD
更新于2025-09-23 15:22:29
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Three-year results of a modified photodynamic therapy procedure (Ironing PDT) for age-related macular degeneration patients with large lesions
摘要： Background: To evaluate the effect of photodynamic therapy (PDT) using a modified procedure on exudative age-related macular degeneration having been conventionally difficult to treat. Methods: The medical records of eight consecutive patients (eight eyes) with age-related macular degeneration treated with modified PDT were reviewed retrospectively. Modified PDT was used for the lesions that could not be covered by conventional use of PDT, either because the lesion was too large or too close to the optic disc. A moving PDT laser spot at constant speed, for 83 seconds, was used to cover the entire lesion, and was named 'Ironing PDT.' This retrospective study was performed with informed patient consent. It was approved by the Institutional Review Board of Kansai Medical University. Results: No exudation could be found 36 months after treatment in five eyes (62.5%). There was no significant difference between the best-corrected visual acuity before PDT (0.95 logMAR) and after PDT (1.09 logMAR). The logMAR best-corrected visual acuity was improved in one eye, maintained in five eyes, and deteriorated in two eyes. Conclusion: Ironing PDT decreased subfoveal fluid and preserved visual acuity in some patients with age-related macular degeneration difficult to treat with conventional therapy.
关键词： PCV,modified PDT,large lesions,PDT,Ironing PDT,AMD
更新于2025-09-23 15:22:29
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Protective effect of RIPK1-inhibitory compound in in vivo models for retinal degenerative disease
摘要： Receptor interacting protein kinase 1 (RIPK1) plays a key role in necroptosis, which is a type of programmed necrosis that is involved in ocular diseases, including glaucoma and dry age-related macular degeneration (AMD). We previously introduced RIPK1-inhibitory compound (RIC), which has biochemical characteristics and a mode of action that are distinct from those of the prototype RIPK1 inhibitor necrostatin-1. The intraperitoneal administration of RIC exerts a protective effect on retinal ganglion cells against a glaucomatous insult. In this study, we examined the protective effect of RIC on retinal pigment epithelium (RPE) against sodium iodate (SI) insult, which is associated with dry AMD pathogenesis. The eye drop administration of RIC that reached on the retina prevented RPE loss in SI-induced retinal degeneration. RIC consistently demonstrated retinal protection in the funduscopy and electroretinogram analyses in SI-injected rabbits and iodoacetic acid-treated mini-pigs. Moreover, the in vivo protective effects of RIC were superior to those of ACU-4429 and doxycycline, which are other medications investigated in clinical trials for the treatment of dry AMD, and RIC did not induce retinal toxicity following topical administration in rats. Collectively, RIC displayed excellent retinal penetration and prevented retinal degeneration in the pathogenesis of dry AMD with a high in vivo efficacy.
关键词： RPE protection,Receptor interacting protein kinase1 (RIPK1),Dry AMD,Topical application,Retinal degeneration,RIPK1-inhibitory compound (RIC)
更新于2025-09-23 15:21:01
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Quantifying Disrupted Outer Retinal-Subretinal Layer in SD-OCT Images in Choroidal Neovascularization
摘要： We reported a fully automated method to identify and quantify the thickness of the outer retinal-subretinal (ORSR) layer from clinical spectral-domain optical coherence tomography (SD-OCT) scans of choroidal neovascularization (CNV) due to exudative age-related macular degeneration (eAMD). A total of 23 subjects with CNV met eligibility. Volumetric SD-OCT scans of 23 eyes were obtained (Zeiss Cirrus, 200 3 200 3 1024 voxels). In a subset of eyes, scans were repeated. The OCT volumes were analyzed using our standard parameters and using a 3-dimensional (3D) graph-search approach with an adaptive cost function. A retinal specialist graded the segmentation as generally accurate, local segmentation inaccuracies, or failure. Reproducibility on repeat scans was analyzed using root mean square coef?cient of variation (RMS CV) of the average ORSR thickness. Using a standard segmentation approach, 1/23 OCT segmentations was graded generally accurate and 22/23 were failure(s). With the adaptive method 21/23 segmentations were graded generally accurate; 2/23 were local segmentation inaccuracies and none was a failure. The intermethod quality of segmentation was signi?cantly different (P << 0.001). The average ORSR thickness measured on CNV patients (78.0 lm; 95% con?dence interval [CI], 72.5–83.4 lm) is signi?cantly larger (P << 0.001) than normal average ORSR layer thickness (51.5 6 3.3 lm). The RMS CV was 8.1%. We have developed a fully automated 3D method for segmenting the ORSR layer in SD-OCT of patients with CNV from eAMD. Our method can quantify the ORSR layer thickness in the presence of ?uid, which has the potential to augment management accuracy and ef?ciency of anti-VEGF treatment.
关键词： imaging,OCT,retina,choroidal neovascularization,AMD
更新于2025-09-23 15:21:01
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Autofluorescence Lifetimes in Geographic Atrophy in Patients With Age-Related Macular Degeneration
摘要： PURPOSE. To investigate fluorescence lifetime characteristics in patients with geographic atrophy (GA) in eyes with age-related macular degeneration and to correlate the measurements with clinical data and optical coherence tomography (OCT) findings. METHODS. Patients with GA were imaged with a fluorescence lifetime imaging ophthalmoscope. Retinal autofluorescence lifetimes were measured in a short and a long spectral channel (498–560 nm and 560–720 nm). Mean retinal fluorescence lifetimes were analyzed within GA and the surrounding retina, and data were correlated with best corrected visual acuity and OCT measurements. RESULTS. Fluorescence lifetime maps of 41 eyes of 41 patients (80 ± 7 years) with GA were analyzed. Mean lifetimes within areas of atrophy were prolonged by 624 ± 276 ps (+152%) in the short spectral channel and 418 ± 186 ps (+83%) in the long spectral channel compared to the surrounding tissue. Autofluorescence lifetime abnormalities in GA occurred with particular patterns, similar to those seen in fundus autofluorescence intensity images. Within the fovea short mean autofluorescence lifetimes were observed, presumably representing macular pigment. Short lifetimes were preserved even in the absence of foveal sparing but were decreased in patients with advanced retinal atrophy in OCT. Short lifetimes in the fovea correlated with better best corrected visual acuity in both spectral channels. CONCLUSIONS. This study established that autofluorescence lifetime changes in GA present with explicit patterns. We hypothesize that the short lifetimes seen within the atrophy may be used to estimate damage induced by atrophy and to monitor disease progression in the context of natural history or interventional therapeutic studies.
关键词： GA,geographic atrophy,ophthalmic imaging,fundus autofluorescence,fluorescence lifetimes,AMD,age-related macular degeneration
更新于2025-09-19 17:15:36
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Proteomic Profiles in Advanced Age-Related Macular Degeneration Using an Aptamer-Based Proteomic Technology
摘要： Purpose: To explore top-ranked plasma proteins related to neovascular age-related macular degeneration (AMD) and geographic atrophy (GA), and explore pathways related to neovascular AMD and GA. Methods: We conducted a pilot study of patients with neovascular AMD (n = 10), GA (n = 10), and age-matched cataract controls (n = 10) who were recruited into an AMD registry. We measured 4001 proteins in ethylenediaminetetraacetic acid plasma samples using an aptamer-based proteomic technology. Relative concentrations of each of 4001 proteins were log (base 2) transformed and compared between cases of neovascular AMD and GA versus controls using linear regression. Pathway analysis was conducted using pathways downloaded from Reactome. Results: In this pilot study, higher levels of vinculin and lower levels of CD177 were found in patients with neovascular AMD compared with controls. Neuregulin-4 was higher and soluble intercellular adhesion molecule-1 was lower in patients with GA compared with controls. For neovascular AMD, cargo trafficking to the periciliary membrane, fibroblast growth factor receptor 3b ligand binding and activation, and vascular endothelial growth factor–related pathways were in the top ranked pathways. The top-ranked pathways for GA included several related to ErbB4 signaling. Conclusions: We found different proteins and different pathways associated with neovascular AMD and GA. Vinculin and some of the top-ranked pathways have been previously associated with AMD, whereas others have not been described.
关键词： neovascular AMD,aptamer-based technologies,geographic atrophy,proteomics
更新于2025-09-19 17:15:36
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The Effects of Anti‐VEGF and Kinin B1 Receptor Blockade on Retinal Inflammation in Laser‐Induced Choroidal Neovascularization
摘要： BACKGROUND AND PURPOSE Age-related macular degeneration (AMD) is a complex multifactorial neurodegenerative disease treated by anti-VEGF intravitreal injections. As inflammation has a potential pathological role in retinal degeneration, the pro-inflammatory kallikrein-kinin system might be a relevant alternative pharmacological target. The present study investigated the effects of anti-VEGF and anti-B1R treatments on the inflammatory mechanisms in a rat model of choroidal neovascularization (CNV). EXPERIMENTAL APPROACH Immediately after laser-induced CNV, Long-Evans rats were treated by eye-drop application of a B1R antagonist (R-954) or by intravitreal injection of B1R siRNA or anti-VEGF antibodies. The impact of treatments on gene expression of inflammatory mediators, CNV lesion regression, and the integrity of the blood-retinal barrier was measured ten days later in the retina. B1R and VEGF-R2 cellular localization was also investigated. KEY RESULTS The three treatments had significant inhibitory effects on CNV-induced retina alterations. Anti-VEGF and R-954 significantly alleviated CNV-induced upregulation of B1R, B2R, TNF-α, and ICAM-1. Anti-VEGF additionally reversed the upregulation of VEGF-A, VEGF-R2, HIF-1α, MCP-1 and VCAM-1, whereas R-954 inhibited gene expression of IL-1β and COX-2. Enhanced retinal vascular permeability was abolished by anti-VEGF and significantly reduced by R-954 and B1R siRNA treatments. Leukocyte adhesion was also impaired by anti-VEGF and B1R inhibition. B1R occurred on astrocytes and endothelial cells. CONCLUSION AND IMPLICATIONS B1R and VEGF pathways are both involved in retinal inflammation and damage in laser-induced CNV. The non-invasive and self-administration of B1R antagonists on the surface of the cornea by eye-drops might be an important asset for the treatment of AMD.
关键词： microglia,AMD,retinal pigmented epithelium,VEGF,kinin B1 receptor,retina,angiogenesis
更新于2025-09-16 10:30:52
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Comparison of Neovascular Lesion Area Measurements From Different Swept-Source OCT Angiographic Scan Patterns in Age-Related Macular Degeneration
摘要： PURPOSE. We compared area measurements for the same neovascular lesions imaged using swept source optical coherence tomography angiography (SS-OCTA) and enlarging scan patterns. METHODS. Patients with neovascular age-related macular degeneration were imaged using a 100-kHz SS-OCTA instrument (PLEX Elite 9000). The scanning protocols included the 3 3 3, 6 3 6, 9 3 9, and 12 3 12 mm ?elds of view. Two groups were studied. Group 1 included small lesions contained within the 3 3 3 mm scan, and Group 2 included larger lesions that were fully contained within the 6 3 6 mm scan. RESULTS. A total of 30 eyes of 26 patients were enrolled in Group 1 and 30 eyes of 25 patients were enrolled in Group 2. In Group 1, the automated mean lesion area measurements were 1.11 (SD ? 0.78), 1.14 (SD ? 0.80), and 1.27 (SD ? 0.82) mm2 for the 3 3 3, 6 3 6, and 12 3 12 mm scans, respectively (ANOVA P < 0.001; post hoc comparisons, P ? 0.184, 3 3 3 vs. 6 3 6 mm; P < 0.001 for the other two pairs). In Group 2, the automated mean lesion area measurements were 5.43 (SD ? 2.56), 5.53 (SD ? 2.48), and 5.49 (SD ? 2.65) mm2 for the 6 3 6, 9 3 9, and 12 3 12 mm scans, respectively (ANOVA P ? 0.435; post-hoc comparisons, P ? 0.062, 6 3 6 vs. 9 3 9 mm; P ? 0.553, 6 3 6 vs. 12 3 12 mm; P ? 0.654, 9 3 9 vs. 12 3 12 mm). CONCLUSIONS. The similarity in lesion area measurements across different scan patterns suggests that SS-OCTA imaging can be used to follow quantitatively the enlargement of choroidal neovascularization as the disease progresses.
关键词： neovascular AMD,optical coherence tomography angiography,swept-source OCTA,quantified measurement comparison,choroidal neovascularization
更新于2025-09-10 09:29:36