Optimisation of an automated drusen-quantifying software for the analysis of drusen distribution in patients with age-related macular degeneration.
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ABSTRACT:
SUBMITTER: Ong BB
PROVIDER: S-EPMC3625998 | biostudies-other | 2013 Apr
REPOSITORIES: biostudies-other
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Project description:Drusen are hallmarks of early and intermediate age-related macular degeneration (AMD) but their quantification remains a challenge. We compared automated drusen volume measurements between different OCT devices. We included 380 eyes from 200 individuals with bilateral intermediate (iAMD, n = 126), early (eAMD, n = 25) or no AMD (n = 49) from the MACUSTAR study. We assessed OCT scans from Cirrus (200 × 200 macular cube, 6 × 6 mm; Zeiss Meditec, CA) and Spectralis (20° × 20°, 25 B-scans; 30° × 25°, 241 B-scans; Heidelberg Engineering, Germany) devices. Sensitivity and specificity for drusen detection and differences between modalities were assessed with intra-class correlation coefficients (ICCs) and mean difference in a 5 mm diameter fovea-centered circle. Specificity was > 90% in the three modalities. In eAMD, we observed highest sensitivity in the denser Spectralis scan (68.1). The two different Spectralis modalities showed a significantly higher agreement in quantifying drusen volume in iAMD (ICC 0.993 [0.991-0.994]) than the dense Spectralis with Cirrus scan (ICC 0.807 [0.757-0.847]). Formulae for drusen volume conversion in iAMD between the two devices are provided. Automated drusen volume measures are not interchangeable between devices and softwares and need to be interpreted with the used imaging devices and software in mind. Accounting for systematic difference between methods increases comparability and conversion formulae are provided. Less dense scans did not affect drusen volume measurements in iAMD but decreased sensitivity for medium drusen in eAMD.Trial registration: ClinicalTrials.gov NCT03349801. Registered on 22 November 2017.
| S-EPMC9763254 | biostudies-literature
Project description:IntroductionThe purpose of this study was to build an automated age-related macular degeneration (AMD) colour fundus photography (CFP) recognition method that incorporates confounders (other ocular diseases) and normal age-related changes by using drusen masks for spatial feature supervision.MethodsA range of clinical sources were used to acquire 7588 CFPs. Contrast limited adaptive histogram equalisation was used for pre-processing. ResNet50 was used as the backbone network, and a spatial attention block was added to integrate prior knowledge of drusen features into the backbone. The evaluation metrics used were sensitivity, specificity and F1 score, which is the harmonic mean of precision and recall (sensitivity) and area under the receiver-operating characteristic (AUC). Fivefold cross-validation was performed, and the results compared with four other methods.ResultsExcellent discrimination results were obtained with the algorithm. On the public dataset (n = 6565), the proposed method achieved a mean (SD) sensitivity of 0.54 (0.09), specificity of 0.99 (0.00), F1 score of 0.62 (0.06) and AUC of 0.92 (0.02). On the private dataset (n = 1023), the proposed method achieved a sensitivity of 0.92 (0.02), specificity of 0.98 (0.01), F1 score of 0.92 (0.01) and AUC of 0.98 (0.01).ConclusionThe proposed drusen-aware model outperformed baseline and other vessel feature-based methods in F1 and AUC on the AMD/normal CFP classification task and achieved comparable results on datasets that included other diseases that often confound classification. The method also improved results when a five-category grading protocol was used, thereby reflecting discriminative ability of the algorithm within a real-life clinical setting.
| S-EPMC10946718 | biostudies-literature
Project description:PURPOSE: To examine the cross-sectional relationship between drusen, late age-related macular degeneration (AMD), and cognitive function. METHODS; We included 2149 stroke-free participants from the population-based Tromsø Study in Norway. Retinal photographs were graded for presence of drusen and AMD. Cognitive function was assessed using the verbal memory test (short verbal memory), digit-symbol coding test (processing speed), and the tapping test (psychomotor tempo). We assessed the relationship between drusen, late AMD, and cognitive test scores, adjusted for potential confounders. RESULTS: Late AMD was associated with decreased performance in the verbal memory test (standardized β=-0.23, 95% confidence interval (CI): -0.51 to -0.01). Intermediate and large drusen were associated with decreased performance in the digit-symbol coding test (standardized β=-0.14 and -0.19, 95% CIs: -0.23 to -0.05 and -0.29 to -0.09, respectively). Participants with large drusen were more likely to have test scores in the lowest quartile of the digit-symbol coding test (odds ratio (OR)=1.9, 95% CI: 1.1-3.5) and the tapping test (OR=1.6, 95% CI: 1.0-2.6), but not in the verbal memory test (OR=1.0, 95% CI: 0.6-1.6). CONCLUSIONS: The findings suggest a relationship between drusen deposition and reduced cognitive function. Although the relationships between drusen, late AMD, and the cognitive test results varied in strength and significance across the types of cognitive test, and may partly have been caused by residual confounding, it is not unlikely that a genuine but weaker relationship exists between drusen deposition and cognitive decline.
| S-EPMC3831136 | biostudies-other
Project description:Autosomal dominant radial drusen (ADRD), also termed Malattia Leventinese and Doyne honeycomb retinal dystrophy, causes early-onset vision loss because of mutation in EFEMP1. Drusen in an exceedingly rare ADRD human donor eye was compared with eyes affected with age-related macular degeneration (AMD). This study also elucidated whether variations in high-risk AMD genotypes modify phenotypic severity of ADRD.Morphologic and histochemical analyses of drusen in one ADRD donor and seven AMD donors. Evaluation of complement factor H (CFH) and ARMS2/HTRA1 alleles in a cohort of 25 subjects with ADRD.Autosomal dominant radial drusen had unique onion skin-like lamination but otherwise shared many compositional features with hard, nodular drusen and/or diffuse soft drusen with basal deposits. Autosomal dominant radial drusen also possessed collagen type IV, an extracellular matrix protein that is absent in age-related drusen. Antibodies directed against the membrane attack complex showed robust labeling of ADRD. Vitronectin and amyloid P were present in drusen of both types. High-risk alleles in the CFH and ARMS2/HTRA1 genes were not associated with increasing ADRD severity.Drusen from ADRD and AMD exhibit overlap of some major constituents, but ADRD exhibit distinct alterations in the extracellular matrix that are absent in AMD.
| S-EPMC5513174 | biostudies-literature
Project description:We tested the hypothesis that large areas of small hard drusen (diameter <63 μm) and intermediate drusen (diameter 63-124 μm) are associated with the incidence of age-related macular degeneration (AMD). Eyes of 3344 older adults with at least 2 consecutive visits spaced 5 years apart over a 20-year period were included. A 6-level severity scale including no drusen, 4 levels of increasing area (from minimal [<2596 μm(2)] to large [>9086 μm(2)]) of only small hard drusen, and intermediate drusen was used. The 5-year incidence of AMD was 3% in eyes at the start of the interval with no, minimal, small, and moderate areas of only small drusen and 5% and 25% for eyes with large area of only small drusen and intermediate drusen, respectively. Compared to eyes with a moderate area of small drusen, the odds ratio (OR) of developing AMD in eyes with a large area of only small drusen was 1.8 (P<.001). Compared to eyes with large area of only small drusen, eyes with intermediate drusen had an OR of 5.5 (P<0.001) of developing AMD. Our results are consistent with our hypothesis that large areas of only small drusen are associated with the incidence of AMD.
| S-EPMC4402933 | biostudies-literature
Project description:This study aimed to describe the clinical characteristics of age-related macular degeneration (AMD) eyes with both cuticular drusen (CD) and reticular pseudodrusen (RPD). Clinical records of patients diagnosed with CD or RPD with multimodal imaging was reviewed for patients diagnosed with both CD and RPD. The distribution patterns of CD (macular and diffuse type) and RPD (localized, intermediate, and diffuse type), presence of soft drusen, large drusen (> 200 µm), variant subretinal drusenoid deposits, and macular complications were investigated. Of the 220 eyes of 110 patients diagnosed with CD and 926 eyes of 463 patients diagnosed with RPD, 13 eyes of seven patients met the diagnostic criteria for both CD and RPD. The mean age at initial presentation was 71.4 ± 8.8 years and six patients were female. The mean subfoveal choroidal thickness was 143.8 ± 25.1 µm. The distribution of CD was of the macular type in all eyes. Distribution of RPD was localized in 11 eyes (84.6%) and intermediate in two eyes (15.4%). Soft drusen, large drusen, and variant subretinal drusenoid deposits were present in 13 (100%), 12 (92.3%) and, seven (53.8%) eyes, respectively. Macular neovascularization was observed in two eyes (15.4%). CD and RPD can coexist in eyes with AMD. Multimodal imaging should be used for AMD eyes with features suggestive of CD and RPD, considering the high likelihood of developing late AMD.
| S-EPMC8983695 | biostudies-literature
Project description:Drusen are extracellular deposits that accumulate below the retinal pigment epithelium on Bruch's membrane and are risk factors for developing age-related macular degeneration (AMD). The progression of AMD might be slowed or halted if the formation of drusen could be modulated. To work toward a molecular understanding of drusen formation, we have developed a method for isolating microgram quantities of drusen and Bruch's membrane for proteome analysis. Liquid chromatography tandem MS analyses of drusen preparations from 18 normal donors and five AMD donors identified 129 proteins. Immunocytochemical studies have thus far localized approximately 16% of these proteins in drusen. Tissue metalloproteinase inhibitor 3, clusterin, vitronectin, and serum albumin were the most common proteins observed in normal donor drusen whereas crystallin was detected more frequently in AMD donor drusen. Up to 65% of the proteins identified were found in drusen from both AMD and normal donors. However, oxidative protein modifications were also observed, including apparent crosslinked species of tissue metalloproteinase inhibitor 3 and vitronectin, and carboxyethyl pyrrole protein adducts. Carboxyethyl pyrrole adducts are uniquely generated from the oxidation of docosahexaenoate-containing lipids. By Western analysis they were found to be more abundant in AMD than in normal Bruch's membrane and were found associated with drusen proteins. Carboxymethyl lysine, another oxidative modification, was also detected in drusen. These data strongly support the hypothesis that oxidative injury contributes to the pathogenesis of AMD and suggest that oxidative protein modifications may have a critical role in drusen formation.
| S-EPMC137479 | biostudies-literature
Project description:We evaluated automated OCT-derived drusen volume measures in a population-based study (n?=?4,512) aged ?40 years, and its correlation with conventional color fundus photographs (CFP)-derived early AMD features. Participants had protocol-based assessment to capture medical and ocular history, genotyping for SNPs in CFH, ARMS2, and CETP, CFP-based AMD grading and automated drusen volume based on SD-OCT using built-in software (Cirrus OCT advanced RPE analysis software). Significantly fewer eyes with early AMD features (drusen, hyperpigmentation, soft or reticular drusen) had drusen volume?=?0?mm3 (p?<?0.001). In eyes with drusen volume?>?0?mm3, increasing AMD severity was associated with increase in drusen volume (correlation coefficient 0.17, p?<?0.001). However 220 (59.14%) of 372 participants with AMD based on CFP grading had drusen volume?=?0?mm3. Factors associated with drusen volume included age (OR 1.42 per 5 years, 95% confidence interval [CI] 2.76, 4.48), systolic blood pressure (OR1.00, 95% CI 1.00, 1.01), ethnic Malay (OR 1.54, 95% CI 1.29, 1.83) and Chinese (OR 1.66, 95% CI 1.37, 2.01) compared to Indian. The ARMS2 rs10490924 T allele was associated with increased drusen volume in subjects with AMD (multivariable adjusted OR1.54, 95% CI 1.08, 2.19). Automated OCT-derived drusen volume is correlated with CFP-based AMD grading in many, but not all subjects. However the agreement is not good. These two modalities provide complementary information and should be incorporated into future studies.
| S-EPMC6113205 | biostudies-literature
Project description:To investigate the relationship of drusen and photoreceptor abnormalities in African-American (AA) patients with intermediate non-neovascular age-related macular degeneration (AMD).AA patients with intermediate AMD (n?=?11; age 52-77 years) were studied with spectral-domain optical coherence tomography. Macular location and characteristics of large drusen (?125?µm) were determined. Thickness of photoreceptor laminae was quantified overlying drusen and in other macular regions. A patient with advanced AMD (age 87) was included to illustrate the disease spectrum.In this AA patient cohort, the spectrum of changes known to occur in AMD, including large drusen, sub-retinal drusenoid deposits and geographic atrophy, were identified. In intermediate AMD eyes (n?=?17), there were 183 large drusen, the majority of which were pericentral in location. Overlying the drusen there was significant thinning of the photoreceptor outer nuclear layer (termed ONL(+)) as well as the inner and outer segments (IS?+?OS). The reductions in IS?+?OS thickness were directly related to ONL(+) thickness. In a fraction (?8%) of paradrusen locations with normal lamination sampled within ?280?µm of peak drusen height, ONL(+) was significantly thickened compared to age and retinal-location-matched normal values. Topographical maps of the macula confirmed ONL thickening in regions neighboring and distant to large drusen.We confirm there is a pericentral distribution of drusen across AA-AMD maculae rather than the central localization in Caucasian AMD. Reductions in the photoreceptor laminae overlying drusen are evident. ONL(+) thickening in some macular areas of AA-AMD eyes may be an early phenotypic marker for photoreceptor stress.
| S-EPMC4489141 | biostudies-literature
Project description:Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in elderly people worldwide. Cuticular drusen (CD) is a clinical subtype of AMD, which typically displays an earlier age at onset, and has a strong genetic component. Genetic studies support a role for rare sequence variants in CD susceptibility, and rare sequence variants in the CFH gene have been identified in 8.8% of CD cases. To further explore the role of rare variants in CD, we performed whole exome sequencing (WES) in 14 affected members of six families and 12 sporadic cases with CD. We detected rare sequence variants in CFH and FBLN5, which previously were shown to harbor rare variants in patients with CD. In addition, we detected heterozygous rare sequence variants in several genes encoding components of the extracellular matrix (ECM), including FBLN1, FBLN3/EFEMP1, FBLN5, FBLN6/HMCN1, FBN2, and COL15A1. Two rare pathogenic variants were identified in the COL15A1 gene: one in a sporadic case and another was found to segregate in a family with six affected individuals with CD. In addition, two rare pathogenic variants were identified in the FGL1 gene in three unrelated CD cases. These findings suggest that alterations in the ECM and in the coagulation pathway may play a role in the pathogenesis of CD. The identified candidate genes require further analyses in larger cohorts to confirm their role in the CD subtype of AMD. No evidence was found of rare sequence variants in a single gene that segregate with CD in the six families, suggesting that the disease is genetically heterogeneous.
| S-EPMC4805164 | biostudies-literature