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European Journal of Ophthalmology Nov 2020Bruch's membrane, an extracellular matrix located between the retinal pigment epithelium and the choroid, plays a vital role as structural and functional support to the... (Review)
Review
Bruch's membrane, an extracellular matrix located between the retinal pigment epithelium and the choroid, plays a vital role as structural and functional support to the retinal pigment epithelium. Dysfunction of Bruch's membrane in both age-related macular degeneration and other ocular diseases is caused mostly by extracellular matrix degeneration, deposit formation, and angiogenesis. Although these factors are dealt in greater detail with respect to the cells that are degenerated such as the retinal pigment epithelium and the endothelial cells, the pathology involving the Bruch's membrane is often underrated. Since in most of the macular degenerations early degenerative changes are also observed in the Bruch's membrane, addressing only the cellular component without the underlying membrane will not yield an ideal clinical benefit. This review aims to discuss the factors and the mechanisms affecting the integrity of the Bruch's membrane, which would aid in developing an effective therapy for these pathologies.
Topics: Bruch Membrane; Choroid; Humans; Macular Degeneration; Retinal Pigment Epithelium
PubMed: 32345040
DOI: 10.1177/1120672120919337 -
Eye (London, England) Feb 2022Lipid-rich drusen are the sine qua non of age-related macular degeneration (AMD), the leading cause of blindness in older adults in the developed world. Efforts directed... (Review)
Review
Lipid-rich drusen are the sine qua non of age-related macular degeneration (AMD), the leading cause of blindness in older adults in the developed world. Efforts directed at uncovering effective therapeutic strategies have led to the hypothesis that altered lipid metabolism may play a pathogenic role in AMD. This hypothesis is supported by the fact that: (1) drusen, the hallmark histopathologic feature of AMD, are composed of lipids, (2) polymorphisms of genes involved in lipid homeostasis are associated with increased odds of AMD, (3) metabolomics studies show that patients with AMD have alterations in metabolites from lipid pathways, and (4) alterations in serum lipid profiles as a reflection of systemic dyslipidemia are associated with AMD. There is strong evidence that statins, which are well described for treating dyslipidemia and reducing risk associated with cardiovascular disease, may have a role for treating certain cohorts of AMD patients, but this has yet to be conclusively proven. Of interest, the specific changes in serum lipoprotein profiles associated with decreased cardiovascular risk (i.e., high HDL levels) have been shown in some studies to be associated with increased risk of AMD. In this review, we highlight the evidence that supports a role for altered lipid metabolism in AMD and provide our perspective regarding the remaining questions that need to be addressed before lipid-based therapies can emerge for specific cohorts of AMD patients.
Topics: Aged; Dyslipidemias; Humans; Lipid Metabolism; Lipids; Macular Degeneration; Metabolomics
PubMed: 35017697
DOI: 10.1038/s41433-021-01780-y -
Survey of Ophthalmology 2020An 84-year-old woman with a history of dry age-related macular degeneration presented with an acute inability to read, but intact writing ability (pure alexia or alexia...
An 84-year-old woman with a history of dry age-related macular degeneration presented with an acute inability to read, but intact writing ability (pure alexia or alexia without agraphia). She denied any difficulty speaking, paresthesias, or hemiparesis. Her visual acuity was 20/20 in each eye. Macular examination, optical coherence tomography, and fluorescein angiography demonstrated the previously diagnosed macular drusen and geographic atrophy of the retinal pigment epithelium consistent with the dry form of age-related macular degeneration both eyes. Automated perimetry revealed a right homonymous hemianopsia. Neuroimaging confirmed a left occipital ischemic infarction with involvement of the splenium of the corpus callosum producing the classic disconnection syndrome of alexia without agraphia.
Topics: Aged, 80 and over; Alexia, Pure; Corpus Callosum; Diagnosis, Differential; Female; Hemianopsia; Humans; Magnetic Resonance Imaging; Visual Acuity
PubMed: 30953621
DOI: 10.1016/j.survophthal.2019.03.008 -
Scientific Reports Apr 2022This study aimed to describe the clinical characteristics of age-related macular degeneration (AMD) eyes with both cuticular drusen (CD) and reticular pseudodrusen...
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.
Topics: Choroid; Female; Fluorescein Angiography; Humans; Macular Degeneration; Retina; Retinal Drusen; Tomography, Optical Coherence
PubMed: 35383241
DOI: 10.1038/s41598-022-09608-9 -
Scientific Reports Apr 2021The natural history and clinical significance of pachydrusen is unclear. This study aims to compare the longitudinal changes of eyes with pachydrusen and soft drusen and...
The natural history and clinical significance of pachydrusen is unclear. This study aims to compare the longitudinal changes of eyes with pachydrusen and soft drusen and progression to exudative macular neovascularisation (MNV). Patients with a diagnosis of MNV in one eye only and the fellow eye was selected as the study eye. Study eyes were required to have pachydrusen or soft drusen on fundus photographs and follow up of at least 2 years or until exudative MNV occurred. Systematic grading was performed at baseline and change in drusen area and onset of exudative MNV recorded over the period of follow up. A total of 75 eyes from 75 patients (29 with pachydrusen and 46 with soft drusen) were included. There was no difference in the rate of progression to exudative MNV in the soft and pachydrusen groups (13.3% versus 24.1%, p = 0.38). Pachydrusen, as compared to soft drusen, was associated with polypoidal choroidal vasculopathy subtype (85.7% versus 16.7%, p < 0.01) and the location of exudation was co-localised with soft drusen but not with pachydrusen. There was a higher rate of increase in soft drusen area compared to pachydrusen area (27.7 ± 31.9%/year versus 8.7 ± 12.4%/year respectively, p < 0.01). We found no difference in the proportion of eyes that developed exudative MNV in this study however characterisation of drusen evolution patterns revealed a strong association with exudative MNV subtype.
Topics: Aged; Choroidal Neovascularization; Disease Progression; Female; Humans; Macular Degeneration; Male; Retinal Drusen; Tomography, Optical Coherence
PubMed: 33820941
DOI: 10.1038/s41598-021-87083-4 -
The British Journal of Ophthalmology Sep 2022To provide a comprehensive multimodal retinal imaging characterisation of patients with North Carolina macular dystrophy (NCMD).
BACKGROUND/AIM
To provide a comprehensive multimodal retinal imaging characterisation of patients with North Carolina macular dystrophy (NCMD).
METHODS
Clinical evaluation and retinal imaging in six families.
RESULTS
Twenty-one subjects showed phenotypic characteristics of NCMD . Small drusen-like deposits were found in all affected individuals, either tightly grouped in the macula, or surrounding atrophic or fibrotic macular alterations. These small subretinal lesions showed an increased fundus autofluorescence and were associated with only mild irregularities on optical coherence tomography imaging. Similar drusen-like deposits were regularly seen in the peripheral fundus, predominantly temporally and often with a radial distribution. Two patients showed a bilateral chorioretinal atrophy and two had a macular neovascularisation (MNV). Findings from follow-up examinations were available from 11 patients. The retinal phenotype remained overall stable, except for two patients: one patient with atrophy showed a distinct growth of the atrophic lesions on longitudinal AF imaging over a review period of 14 years. One patient with MNV showed a unilateral decline of best-corrected visual acuity. Genetic testing identified the single nucleotide variant chr6:100040987G>C upstream of the gene in all family members with NCMD phenotype.
CONCLUSION
Patients with NCMD show a characteristic retinal phenotype and distribution of drusen that differ from drusen in patients with age-related macular degeneration. Although the prognosis of this developmental condition is overall better than for other macular diseases with drusen, patients may be at risk of developing MNV or enlargement of pre-existing atrophy.
Topics: Atrophy; Corneal Dystrophies, Hereditary; Fluorescein Angiography; Humans; Pedigree; Phenotype; Retinal Drusen; Tomography, Optical Coherence
PubMed: 33785507
DOI: 10.1136/bjophthalmol-2021-318815 -
Retina (Philadelphia, Pa.) Feb 2024To investigate the imaging features preceding the occurrence of type 3 (T3) macular neovascularization (MNV) using tracked spectral-domain optical coherence tomography.
PURPOSE
To investigate the imaging features preceding the occurrence of type 3 (T3) macular neovascularization (MNV) using tracked spectral-domain optical coherence tomography.
METHOD
From a cohort of eyes with T3 MNV and ≥ 12 months of previously tracked spectral-domain optical coherence tomography, T3 lesions that developed above soft drusen were selected for optical coherence tomography analysis. Retinal imaging findings at the location where type T3 MNV occurred were analyzed at each follow-up until the onset of T3 MNV. The following optical coherence tomography parameters were assessed: drusen size (height and width), outer nuclear layer/Henle fiber layer thickness at the drusen apex, and the presence of intraretinal hyperreflective foci, retinal pigment epithelium disruption, incomplete retinal pigment epithelium and outer retina atrophy, and complete retinal pigment epithelium and outer retina atrophy.
RESULTS
From a cohort of 31 eyes with T3 MNV, T3 lesions developed above soft drusen in 20 eyes (64.5%). Drusen showed progressive growth ( P < 0.001) associated with outer nuclear layer/Henle fiber ( P < 0.001) thinning before T3 MNV. The following optical coherence tomography features were identified preceding the occurrence of T3 MNV, typically at the apex of the drusenoid lesion: disruption of the external limiting membrane/ellipsoid zone and/or the retinal pigment epithelium, hyperreflective foci, and incomplete retinal pigment epithelium and outer retina atrophy/complete retinal pigment epithelium and outer retina atrophy.
CONCLUSION
The results demonstrate specific anatomic alterations preceding the occurrence of T3 MNV that most commonly originates above soft drusen. Drusen growth, reduced outer nuclear layer/Henle fiber thickness, and retinal pigment epithelium atrophy at the drusen apex precede the development of T3 MNV. Identifying these optical coherence tomography features should warrant close monitoring for identification of T3 MNV, which can benefit from prompt intravitreal anti-vascular endothelial growth factor therapy.
Topics: Humans; Macular Degeneration; Retina; Retinal Drusen; Retinal Pigment Epithelium; Tomography, Optical Coherence; Fluorescein Angiography; Atrophy; Retrospective Studies
PubMed: 37756671
DOI: 10.1097/IAE.0000000000003945 -
Japanese Journal of Ophthalmology Jan 2023Drusen are extracellular material considered a precursor lesion to advanced age-related macular degeneration (AMD), located either on the retinal pigment epithelium... (Review)
Review
Drusen are extracellular material considered a precursor lesion to advanced age-related macular degeneration (AMD), located either on the retinal pigment epithelium (RPE) or the sub-RPE; they contain various proteins associated with inflammation and lipids. Previous studies suggest that the lifecycle of drusen varies depending on drusen type and size. In general, conventional drusen grow and aggregate/coalesce in the first stage, and in the second stage, they regress with or without showing RPE atrophy. The risk of advanced AMD also varies depending on the drusen and drusenoid deposit types' along with their size and RPE abnormalities. In eyes with macular neovascularization (MNV), specific drusen/drusenoid deposits are closely associated with the MNV subtype. Recently, pachychoroid-associated drusen (pachydrusen) were proposed and clinical findings regarding this entity have been accumulating, as more attention is focused on drusen as well as pachychoroid diseases. With the advance in imaging modalities, various modalities can show specific characteristics depending on drusen types. To assess the risk of advanced AMD, it is essential for physicians to have accurate clinical knowledge about each druse/drusenoid lesion and correctly evaluate its imaging characteristics using multimodal imaging. This review summarizes the latest clinical knowledge about each druse/drusenoid lesions and documents their imaging characteristics on multimodal imaging, allowing clinicians to better manage patients and stratify the risk of developing advanced AMD. The most representative cases are illustrated, which can be helpful in the differential diagnosis of drusen and drusenoid deposits.
Topics: Humans; Macular Degeneration; Retinal Drusen; Tomography, Optical Coherence; Retinal Pigment Epithelium; Multimodal Imaging; Fluorescein Angiography
PubMed: 36477878
DOI: 10.1007/s10384-022-00943-y -
Cureus Jul 2023Background Age-related macular degeneration (AMD), diabetic retinopathy (DR), drusen, choroidal neovascularization (CNV), and diabetic macular edema (DME) are...
Background Age-related macular degeneration (AMD), diabetic retinopathy (DR), drusen, choroidal neovascularization (CNV), and diabetic macular edema (DME) are significant causes of visual impairment globally. Optical coherence tomography (OCT) imaging has emerged as a valuable diagnostic tool for these ocular conditions. However, subjective interpretation and inter-observer variability highlight the need for standardized diagnostic approaches. Methods This study aimed to develop a robust deep learning model using artificial intelligence (AI) techniques for the automated detection of drusen, CNV, and DME in OCT images. A diverse dataset of 1,528 OCT images from Kaggle.com was used for model training. The performance metrics, including precision, recall, sensitivity, specificity, F1 score, and overall accuracy, were assessed to evaluate the model's effectiveness. Results The developed model achieved high precision (0.99), recall (0.962), sensitivity (0.985), specificity (0.987), F1 score (0.971), and overall accuracy (0.987) in classifying diseased and healthy OCT images. These results demonstrate the efficacy and efficiency of the model in distinguishing between retinal pathologies. Conclusion The study concludes that the developed deep learning model using AI techniques is highly effective in the automated detection of drusen, CNV, and DME in OCT images. Further validation studies and research efforts are necessary to evaluate the generalizability and integration of the model into clinical practice. Collaboration between clinicians, policymakers, and researchers is essential for advancing diagnostic tools and management strategies for AMD and DR. Integrating this technology into clinical workflows can positively impact patient care, particularly in settings with limited access to ophthalmologists. Future research should focus on collecting independent datasets, addressing potential biases, and assessing real-world effectiveness. Overall, the use of machine learning algorithms in conjunction with OCT imaging holds great potential for improving the detection and management of drusen, CNV, and DME, leading to enhanced patient outcomes and vision preservation.
PubMed: 37565126
DOI: 10.7759/cureus.41615 -
Translational Vision Science &... Dec 2020To investigate the structure-function relationship in eyes with drusen with mesopic and scotopic microperimetry.
PURPOSE
To investigate the structure-function relationship in eyes with drusen with mesopic and scotopic microperimetry.
METHODS
We analyzed structural and functional data from 43 eyes with drusen. Functional data were acquired with mesopic and scotopic two-color (red and cyan) microperimetry. Normative values were calculated using data from 56 healthy eyes. Structural measurements were green autofluorescence and dense macular optical coherence tomography scans. The latter were used to calculate the retinal pigment epithelium elevation (RPE-E) and the photoreceptor reflectivity ratio (PRR). The pointwise structure-function relationship was measured with linear mixed models having the log-transformed structural parameters as predictors and the sensitivity loss (SL, deviation from normal) as the response variable.
RESULTS
In the univariable analysis, the structural predictors were all significantly correlated ( < 0.05) with the SL in the mesopic and scotopic tests. In a multivariable model, mesopic microperimetry yielded the best structure-function relationship. All predictors were significant ( < 0.05), but the predictive power was weak (best = 0.09). The relationship was improved when analyzing locations with abnormal RPE-E (best = 0.18).
CONCLUSIONS
Mesopic microperimetry shows better structure-function relationship compared to scotopic microperimetry; the relationship is weak, likely due to the early functional damage and the small number of tested locations affected by drusen. The relationship is stronger when locations with drusen are isolated for the mesopic and scotopic cyan test.
TRANSLATIONAL RELEVANCE
These results could be useful to devise integrated structure-function methods to detect disease progression in intermediate age-related macular degeneration.
Topics: Humans; Macular Degeneration; Retina; Retinal Drusen; Tomography, Optical Coherence; Visual Field Tests
PubMed: 33442497
DOI: 10.1167/tvst.9.13.43