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Investigative Ophthalmology & Visual... Sep 2023Choroidal vascular changes occur with normal aging and age-related macular degeneration (AMD). Here, we evaluate choroidal thickness and vascularity in aged rhesus...
PURPOSE
Choroidal vascular changes occur with normal aging and age-related macular degeneration (AMD). Here, we evaluate choroidal thickness and vascularity in aged rhesus macaques to better understand the choroid's role in this nonhuman primate model of AMD.
METHODS
We analyzed optical coherence tomography (OCT) images of 244 eyes from 122 rhesus macaques (aged 4-32 years) to measure choroidal thickness (CT) and choroidal vascularity index (CVI). Drusen number, size, and volume were measured by semiautomated annotation and segmentation of OCT images. We performed regression analyses to determine any association of CT or CVI with age, sex, and axial length and to determine if the presence and volume of soft drusen impacted these choroidal parameters.
RESULTS
In rhesus macaques, subfoveal CT decreased with age at 3.2 µm/y (R2 = 0.481, P < 0.001), while CVI decreased at 0.66% per year (R2 = 0.257, P < 0.001). Eyes with soft drusen exhibited thicker choroid (179.9 ± 17.5 µm vs. 162.0 ± 27.9 µm, P < 0.001) and higher CVI (0.612 ± 0.051 vs. 0.577 ± 0.093, P = 0.005) than age-matched control animals. Neither CT or CVI appeared to be associated with drusen number, size, or volume in this cohort. However, some drusen in macaques were associated with underlying choroidal vessel enlargement resembling pachydrusen in human patients with AMD.
CONCLUSIONS
Changes in the choroidal vasculature in rhesus macaques resemble choroidal changes in human aging, but eyes with drusen exhibit choroidal thickening, increased vascularity, and phenotypic characteristics of pachydrusen observed in some patients with AMD.
Topics: Humans; Animals; Macaca mulatta; Retrospective Studies; Retina; Choroid; Aging; Macular Degeneration; Retinal Drusen; Tomography, Optical Coherence
PubMed: 37773500
DOI: 10.1167/iovs.64.12.44 -
BioRxiv : the Preprint Server For... Nov 2023In age-related macular degeneration (AMD) and Sorsby's fundus dystrophy (SFD), lipid-rich deposits known as drusen accumulate under the retinal pigment epithelium (RPE)....
PURPOSE
In age-related macular degeneration (AMD) and Sorsby's fundus dystrophy (SFD), lipid-rich deposits known as drusen accumulate under the retinal pigment epithelium (RPE). Drusen may contribute to photoreceptor and RPE degeneration in AMD and SFD. We hypothesize that stimulating β-oxidation in RPE will reduce drusen accumulation. Inhibitors of acetyl-CoA carboxylase (ACC) stimulate β-oxidation and diminish lipid accumulation in fatty liver disease. In this report we test the hypothesis that an ACC inhibitor, Firsocostat, limits the accumulation of lipid deposits in cultured RPE cells.
METHODS
We probed metabolism and cellular function in mouse RPE-choroid, human fetal- derived RPE cells, and induced pluripotent stem cell-derived RPE cells. We used C6-glucose and C16-palmitate to determine the effects of Firsocostat on glycolytic, Krebs cycle, and fatty acid metabolism. C labeling of metabolites in these pathways were analyzed using gas chromatography-linked mass spectrometry. We quantified ApoE and VEGF release using enzyme-linked immunosorbent assays. Immunostaining of sectioned RPE was used to visualize ApoE deposits. RPE function was assessed by measuring the trans-epithelial electrical resistance (TEER).
RESULTS
ACC inhibition with Firsocostat increases fatty acid oxidation and remodels lipid composition, glycolytic metabolism, lipoprotein release, and enhances TEER. When human serum is used to induce sub-RPE lipoprotein accumulation, fewer lipoproteins accumulate with Firsocostat. In a culture model of Sorsby's fundus dystrophy, Firsocostat also stimulates fatty acid oxidation, improves morphology, and increases TEER.
CONCLUSIONS
Firsocostat remodels intracellular metabolism and improves RPE resilience to serum-induced lipid deposition. This effect of ACC inhibition suggests that it could be an effective strategy for diminishing drusen accumulation in the eyes of patients with AMD.
PubMed: 37986876
DOI: 10.1101/2023.11.07.566117 -
Asia-Pacific Journal of Ophthalmology... 2024Decades of studies on age-related macular degeneration (AMD), cardiovascular disease and stroke have not found consistent associations between AMD and systemic vascular... (Review)
Review
Decades of studies on age-related macular degeneration (AMD), cardiovascular disease and stroke have not found consistent associations between AMD and systemic vascular disease. This study suggests that there is in fact no general relationship, but instead a strong, specific association between only the subretinal drusenoid deposit (SDD) phenotype of AMD on retinal imaging and certain co-existent vascular diseases that are high risk for compromised cardiac output or internal carotid artery stenosis. Future screening initiatives for these high -risk vascular diseases (HRVDs) with fast, inexpensive retinal imaging could make a significant contribution to public health and save lives. Likewise, screening patients with known HRVDs for unrecognized AMD of the SDD form could enable needed treatment and save vision.
Topics: Humans; Retinal Drusen; Cardiovascular Diseases; Tomography, Optical Coherence; Macular Degeneration; Vascular Diseases; Fluorescein Angiography
PubMed: 38244930
DOI: 10.1016/j.apjo.2024.100036 -
Eye (London, England) Dec 2023To evaluate the quantitative impact of drusen and hyperreflective foci (HRF) volumes on mesopic retinal sensitivity in non-exudative age-related macular degeneration...
OBJECTIVES
To evaluate the quantitative impact of drusen and hyperreflective foci (HRF) volumes on mesopic retinal sensitivity in non-exudative age-related macular degeneration (AMD).
METHODS
In a standardized follow-up scheme of every three months, retinal sensitivity of patients with early or intermediate AMD was assessed by microperimetry using a custom pattern of 45 stimuli (Nidek MP-3, Gamagori, Japan). Eyes were consecutively scanned using Spectralis SD-OCT (20° × 20°, 1024 × 97 × 496). Fundus photographs obtained by the MP-3 allowed to map the stimuli locations onto the corresponding OCT scans. The volume and mean thickness of drusen and HRF within a circle of 240 µm centred at each stimulus point was determined using automated AI-based image segmentation algorithms.
RESULTS
8055 individual stimuli from 179 visits from 51 eyes of 35 consecutive patients were matched with the respective OCT images in a point-to-point manner. The patients mean age was 76.85 ± 6.6 years. Mean retinal sensitivity at baseline was 25.7 dB. 73.47% of all MP-spots covered drusen area and 2.02% of MP-spots covered HRF. A negative association between retinal sensitivity and the volume of underlying drusen (p < 0.001, Estimate -0.991 db/µm) and HRF volume (p = 0.002, Estimate -5.230 db/µm) was found. During observation time, no eye showed conversion to advanced AMD.
CONCLUSION
A direct correlation between drusen and lower sensitivity of the overlying photoreceptors can be observed. For HRF, a small but significant correlation was shown, which is compromised by their small size. Biomarker quantification using AI-methods allows to determine the impact of sub-clinical features in the progression of AMD.
Topics: Humans; Aged; Aged, 80 and over; Retina; Macular Degeneration; Algorithms; Tomography, Optical Coherence; Japan; Retinal Drusen
PubMed: 37170011
DOI: 10.1038/s41433-023-02554-4 -
Investigative Ophthalmology & Visual... May 2024To explore the association between the genetics of age-related macular degeneration (AMD) and extramacular drusen (EMD) in patients with and without AMD.
PURPOSE
To explore the association between the genetics of age-related macular degeneration (AMD) and extramacular drusen (EMD) in patients with and without AMD.
METHODS
We included 1753 eyes (912 subjects) with phenotypic characterization regarding AMD and EMD. Genetic sequencing and the genetic risk score (GRS) for AMD were performed according to the EYE-RISK consortium methodology. To test for differences in the GRS from EMD cases, AMD cases, and controls, a clustered Wilcoxon rank-sum test was used. The association of AMD, EMD, and the GRS was evaluated using logistic regression models adjusted for age and sex. Individual associations of common risk variants for AMD with EMD were explored.
RESULTS
EMD were found in 755 eyes: 252 (14.4%) with AMD and 503 (28.7%) without. In total, 122 eyes (7.0%) had only AMD, and 876 (50.0%) were controls. EMD were strongly associated with AMD (odds ratio [OR], 3.333; 95% confidence interval [CI], 2.356-4.623; P < 0.001). The GRS was associated with an increased risk of AMD (OR, 1.416; 95% CI, 1.218-1.646; P < 0.001) but not with EMD. Individually, the common risk variants ARMS2 rs10490924 (P = 0.042), C3 rs2230199 (P = 0.042), and CETP rs5817082 (P = 0.042) were associated with EMD, after adjustment for AMD, sex, and age.
CONCLUSIONS
We found a strong association between EMD and AMD, suggesting a common pathogenesis. The GRS for AMD was not associated with EMD, but a partially overlapping genetic basis was suggested when assessing individual risk variants. We propose that EMD per se do not represent an increase in the global genetic risk for AMD.
Topics: Humans; Female; Male; Macular Degeneration; Retinal Drusen; Aged; Middle Aged; Aged, 80 and over; Genetic Predisposition to Disease; Risk Factors; Polymorphism, Single Nucleotide; Proteins
PubMed: 38776116
DOI: 10.1167/iovs.65.5.35 -
Documenta Ophthalmologica. Advances in... Oct 2023To present electroretinogram findings in extensive macular atrophy with pseudodrusen (EMAP) and describe associated systemic factors.
PURPOSE
To present electroretinogram findings in extensive macular atrophy with pseudodrusen (EMAP) and describe associated systemic factors.
DESIGN
Retrospective case series.
METHODS
Data on medical history, visual symptoms, multimodal imaging findings, and visual field were collected from the medical records of patients with extensive macular atrophy with pseudodrusen who attended a visual electrophysiology laboratory. Electrophysiological tests, including full-field electroretinogram, multifocal electroretinogram and photopic negative response, were performed.
RESULTS
Eighteen patients (10 [56%] females, age 49-66 years) were included. Of these, 17 (94%) had a history of rheumatic fever in childhood and/or adolescence, 7 (39%) had cardiovascular disease, 4 (22%) had autoimmune disease, and 10 (56%) had inflammatory conditions. The primary visual complaints were nyctalopia (95%), followed by visual field loss (67%) and dyschromatopsia (67%). The key retinal findings included retinal pigmented epithelium atrophy in the macular region and subretinal drusenoid deposits. Regarding electrophysiological results, 100% of patients had abnormalities on multifocal electroretinogram, 94% displayed alterations in photopic negative response, and 78% showed changes in the full-field electroretinogram.
CONCLUSIONS
In this cohort, electrophysiologic evaluation demonstrated diffuse retinal dysfunction affecting all layers of the retina in patients with EMAP. The disease is associated with immune-mediated systemic conditions, chiefly rheumatic fever.
Topics: Female; Humans; Middle Aged; Aged; Male; Retrospective Studies; Retinal Drusen; Rheumatic Fever; Electroretinography; Macular Degeneration; Atrophy; Tomography, Optical Coherence
PubMed: 37392267
DOI: 10.1007/s10633-023-09941-y -
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 -
Investigative Ophthalmology & Visual... Sep 2023Progress toward treatment and prevention of age-related macular degeneration (AMD) requires imaging end points that relate to vision. We investigated choriocapillaris...
PURPOSE
Progress toward treatment and prevention of age-related macular degeneration (AMD) requires imaging end points that relate to vision. We investigated choriocapillaris flow signal deficits (FD%) and visual function in eyes of individuals aged ≥60 years, with and without AMD.
METHODS
One eye of each participant in the baseline visit of the Alabama Study on Early Age-Related Macular Degeneration 2 (ALSTAR2; NCT04112667) was studied. AMD presence and severity was determined using the Age-Related Eye Disease Study (AREDS) grading system. FD% was quantified using macular spectral domain optical coherence tomography angiography (OCTA) scans. Vision tests included rod-mediated dark adaptation (RMDA), best-corrected visual acuity, and contrast sensitivity (photopic and mesopic), and microperimetric light sensitivity (scotopic, mesopic, and photopic). Presence of subretinal drusenoid deposits (SDD) was determined using multimodal imaging.
RESULTS
In 410 study eyes of 410 participants (mean [SD] age = 71.7 years [5.9]), FD% was higher in early AMD (mean [SD] = 54.0% [5.5], N = 122) and intermediate AMD (59.8% [7.4], N = 92), compared to normal (52.1% [5.3], N = 196) eyes. Among visual functions evaluated, RMDA showed the strongest association with FD% (r = 0.35, P < 0.0001), followed by contrast sensitivity (r = -0.22, P < 0.0001). Eyes with SDD had worse FD% (58.3% [7.4], N = 87), compared to eyes without SDD (53.4% [6.0], N = 323, P = < 0.0001).
CONCLUSIONS
Choriocapillaris FD% were associated with AMD severity and with impaired vision, especially RMDA. Reduced metabolic transport and exchange across the choriocapillaris-Bruch's membrane retinal pigment epithelium (RPE) complex, a causal factor for high-risk soft drusen formation, also may impair photoreceptor sustenance from the circulation. This includes retinoid resupply, essential to dynamic rod function.
Topics: Humans; Dark Adaptation; Macular Degeneration; Retina; Retinal Drusen; Tomography, Optical Coherence; Choroid
PubMed: 37768273
DOI: 10.1167/iovs.64.12.41 -
Clinical & Experimental Ophthalmology Mar 2024Advanced forms of age-related macular degeneration (AMD), characterised by atrophic and neovascular changes, are a leading cause of vision loss in the elderly population... (Review)
Review
Advanced forms of age-related macular degeneration (AMD), characterised by atrophic and neovascular changes, are a leading cause of vision loss in the elderly population worldwide. Prior to the development of advanced AMD, a myriad of risk factors from the early and intermediate stages of AMD have been published in the scientific literature over the last years. The ability to precisely recognise structural and anatomical changes in the ageing macula, altogether with the understanding of the individual risk implications of each one of them is key for an accurate and personalised diagnostic assessment. The present review aims to summarise updated evidence of the relative risk conferred by diverse macular signs, commonly seen on optical coherence tomography, in terms of progression to geographic atrophy or macular neovascularization. This information may also serve as a basis for tailored follow-up monitoring visits.
Topics: Humans; Aged; Retinal Drusen; Tomography, Optical Coherence; Macular Degeneration; Geographic Atrophy; Biomarkers
PubMed: 38214056
DOI: 10.1111/ceo.14337 -
Diagnostics (Basel, Switzerland) Apr 2024Macular dystrophies (MDs) constitute a collection of hereditary retina disorders leading to notable visual impairment, primarily due to progressive macular atrophy.... (Review)
Review
Macular dystrophies (MDs) constitute a collection of hereditary retina disorders leading to notable visual impairment, primarily due to progressive macular atrophy. These conditions are distinguished by bilateral and relatively symmetrical abnormalities in the macula that significantly impair central visual function. Recent strides in fundus imaging, especially optical coherence tomography (OCT), have enhanced our comprehension and diagnostic capabilities for MD. OCT enables the identification of neurosensory retinal disorganization patterns and the extent of damage to retinal pigment epithelium (RPE) and photoreceptor cells in the dystrophies before visible macular pathology appears on fundus examinations. It not only helps us in diagnostic retinal and choroidal pathologies but also guides us in monitoring the progression of, staging of, and response to treatment. In this review, we summarize the key findings on OCT in some of the most common MD.
PubMed: 38732293
DOI: 10.3390/diagnostics14090878