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BMJ Open Ophthalmology Mar 2024Subretinal drusenoid deposits (SDDs) in age-related macular degeneration (AMD) are associated with systemic vascular diseases that compromise ocular perfusion. We...
PURPOSE
Subretinal drusenoid deposits (SDDs) in age-related macular degeneration (AMD) are associated with systemic vascular diseases that compromise ocular perfusion. We demonstrate that SDDs are associated with decreased ellipsoid zone (EZ) thickness, further evidence of hypoxic damage.
METHODS
Post hoc analysis of a cross-sectional study. 165 AMD subjects (aged 51-100; 61% women). Spectral-domain optical coherence tomography was obtained in both eyes. Masked readers assigned subjects to three groups: drusen only, SDD+drusen (SDD+D) and SDD only. EZ thickness was measured subfoveally and 2000 µm nasally, temporally, superiorly and inferiorly from the fovea. Univariate testing was performed using two-tailed t-tests with Bonferroni correction.
RESULTS
The mean EZ thickness differences between the SDD+D and drusen-only groups were (in μm) 1.10, 0.67, 1.21, 1.10 and 0.50 at the foveal, nasal, temporal, superior and inferior locations, respectively (p=0.08 inferiorly, otherwise p≤0.01); between the SDD-only and drusen-only groups, the differences were 3.48, 2.48, 2.42, 2.08 and 1.42 (p≤0.0002). Differences in EZ thicknesses across all subjects and between groups were not significantly different based on gender, race or age.
CONCLUSION
Subjects with SDDs (±drusen) had thinner EZs than those with drusen only, and the inferior EZ was least affected. EZs were thinnest in SDD-only subjects. This thinning gradation is consistent with progressive destruction of highly oxygen-sensitive mitochondria in the EZ from hypoxia. These findings support the reduced ophthalmic perfusion hypothesis for the formation of SDDs secondary to high-risk systemic vasculopathy.
Topics: Humans; Female; Male; Retinal Drusen; Cross-Sectional Studies; Macular Degeneration; Retina; Tomography, Optical Coherence; Dapsone
PubMed: 38460964
DOI: 10.1136/bmjophth-2023-001622 -
Investigative Ophthalmology & Visual... Feb 2024Subretinal drusenoid deposits (SDDs) in age-related macular degeneration (AMD) are strongly associated with vasculopathies such as myocardial infarction and ischemic...
PURPOSE
Subretinal drusenoid deposits (SDDs) in age-related macular degeneration (AMD) are strongly associated with vasculopathies such as myocardial infarction and ischemic stroke. This study evaluates ischemic stroke subjects for SDDs to determine whether ocular hypoperfusion from internal carotid artery (ICA) stenosis is associated with ipsilateral SDDs.
METHODS
A cross-sectional study at Mount Sinai Hospital recruited 39 subjects with ischemic stroke (aged 52-90; 18 women, 21 men); 28 completed all study procedures. Computed tomography (CT) of the head and neck evaluated 54/56 ICAs for stenosis criteria: none (n = 33), mild (n = 12), moderate (n = 3), severe (n = 3), and complete (n = 3). Spectral-domain optical coherence tomography (SD-OCT) scans were read to consensus by two masked graders for soft drusen, SDDs and choroidal thickness (CTh; choroidal thinning = CTh < 250 µm). Univariate testing was done with Fisher's exact test. Multivariate logistic regression models tested age, gender, and ICA stenosis as covariates.
RESULTS
Moderate or more ICA stenosis (≥50%-69%) was significantly associated with ipsilateral choroidal thinning (P = 0.021) and ipsilateral SDDs (P = 0.005); the latter were present distal to six of nine stenosed ICAs versus five of 33 normal ICAs. Mild ICA stenosis (≥1%-49%) was not significantly associated with ipsilateral SDDs. Multivariate regression found that older age (P = 0.015) and moderate or more ICA stenosis (P = 0.011) remained significant independent risks for ipsilateral SDDs.
CONCLUSIONS
At least moderate ICA stenosis (≥50%-69%) is strongly associated with ipsilateral SDDs and choroidal thinning, supporting downstream ophthalmic artery and choroidal hypoperfusion from ICA stenosis as the mechanism for SDD formation. SDDs may thus serve as sensitive biomarkers for ischemic stroke and other vascular diseases.
Topics: Male; Humans; Female; Carotid Stenosis; Constriction, Pathologic; Cross-Sectional Studies; Choroid; Ischemic Stroke; Dapsone
PubMed: 38407857
DOI: 10.1167/iovs.65.2.37 -
Investigative Ophthalmology & Visual... Feb 2024To examine the effect of reticular pseudodrusen (RPD) on retinal and choroidal vessel perfusion (VP) topography in intermediate age-related macular degeneration (iAMD)...
PURPOSE
To examine the effect of reticular pseudodrusen (RPD) on retinal and choroidal vessel perfusion (VP) topography in intermediate age-related macular degeneration (iAMD) using refined spatial analyses.
METHODS
This was a retrospective cross-sectional study of 120 individuals with 30 iAMDRPD, 60 iAMDno_RPD, and 30 normal eyes, propensity-score matched by age, sex, and presence of cardiovascular-related disease. VP of the superficial and deep retinal and choriocapillaris vascular slabs was assessed from 6 × 6-mm optical coherence tomography angiography (OCTA) scans divided into 126 × 126 grids, with adjustment for various person- and eye-level factors. Grid-wise VP differences (%) among the groups were spatially assessed according to analyses based on the Early Treatment for Diabetic Retinopathy Study (ETDRS), eccentricity (µm), and degree (°).
RESULTS
VP was significantly decreased between iAMDRPD and iAMDno_RPD, across all vascular slabs in various ETDRS sectors (up to -2.16%; 95% confidence interval, -2.99 to -1.34; P < 0.05). Eccentricity analyses revealed more complex patterns: a bisegmented relationship where VP in iAMDRPD eyes decreased linearly toward 1000 µm then returned toward similar values as iAMDno_RPD, plateauing around 2000 µm in the superficial and 3000 µm in the deep retina (R2 = 0.57-0.9; P < 0.001). Degree-based analysis further showed that the greatest VP differences in iAMDRPD eyes were commonly located superiorly and nasally across all vascular slabs (P < 0.05).
CONCLUSIONS
RPD appears to compound the vascular impact of iAMD, displaying complex spatial patterns beyond the ETDRS sectors. This highlights the importance of considering spatial delineations for future work regarding the role of RPD and vascular dysfunction.
Topics: Humans; Cross-Sectional Studies; Retrospective Studies; Perfusion; Retina; Retinal Drusen; Macular Degeneration; Diabetic Retinopathy; Cardiovascular Diseases
PubMed: 38386332
DOI: 10.1167/iovs.65.2.33 -
Bilaterally subluxed diffractive intraocular lenses: big expectations and even bigger comorbidities.Journal of Cataract and Refractive... Mar 2024A 78-year-old woman with an ocular history of cataract surgery with a diffractive intraocular lens (IOL) in each eye has developed fluctuating vision, greater in the...
A 78-year-old woman with an ocular history of cataract surgery with a diffractive intraocular lens (IOL) in each eye has developed fluctuating vision, greater in the right eye than the left eye, after 4 years. She has a history of inactive central serous retinopathy and a vision potential of 20/25 + 2 in the right eye and 20/25 in the left eye. She has well-controlled diabetes, hypertension, and hypercholesterolemia. She has enjoyed her spectacle independence for some time and wishes to have her vision restored. On examination, her uncorrected distance visual acuity (UDVA) was 20/50 in the right eye and 20/25 in the left eye and her uncorrected near visual acuity (UNVA) was J3 in the right eye and J1 in the left eye. Intraocular pressures (IOPs) measured 22 mm Hg in the right eye and 18 mm Hg in the left eye. Pupils had limited reactivity with irregularity in the right eye but no obvious relative afferent pupillary defect. Motility and confrontation visual fields were unremarkable in both eyes. Retinal acuity meter was 20/20 in both eyes, and manifest refraction was plano -1.25 × 105 20/40, J3 in the right eye and +0.50 × 20/25, J1 in the left eye. Pertinent findings on slitlamp examination included temporal iris atrophy and transillumination defects greater in the right eye than the left eye, peripupillary pseudoexfoliative changes in both eyes, significant inferior subluxation of a diffractive 3-piece posterior chamber IOL in the capsular bag with lens-pitting peripherally and few central, moderate pseudophacodonesis, and an open posterior capsule in the right eye. In the left eye, she had mild inferior subluxation of a single-piece acrylic diffractive IOL in the capsular bag with moderate pseudophacodonesis and an open posterior capsule (Figure 1JOURNAL/jcrs/04.03/02158034-202403000-00019/figure1/v/2024-02-20T193212Z/r/image-tiff). All other anterior segment findings were unremarkable. On dilated posterior examination, she had a cup-to-disc ratio of 0.50 in the right eye and 0.65 in the left eye without edema hemorrhage or pallor. There were attenuated vessels in both eyes, posterior vitreous detachment in both eyes, and a few small drusen peripherally in both eyes. There was retinal pigment epithelium irregularity and dropout parafoveal in the right eye and subfoveal in the left eye (Figure 2). There was no evidence of macular edema, subretinal fluid, choroidal thickening, or neovascular membranes. The periphery was unremarkable in both eyes.JOURNAL/jcrs/04.03/02158034-202403000-00019/figure2/v/2024-02-20T193212Z/r/image-tiff What testing would you obtain preoperatively to help guide your decision-making? How would you counsel the patient regarding comorbid conditions and expectations?
Topics: Humans; Female; Aged; Lens Implantation, Intraocular; Motivation; Lenses, Intraocular; Cataract Extraction; Visual Acuity
PubMed: 38381619
DOI: 10.1097/j.jcrs.0000000000001388 -
Frontiers in Genetics 2023Age-related macular degeneration (AMD) is the leading cause of central vision loss in the elderly. One-third of the genetic contribution to this disease remains...
Age-related macular degeneration (AMD) is the leading cause of central vision loss in the elderly. One-third of the genetic contribution to this disease remains unexplained. We analyzed targeted sequencing data from two independent cohorts (4,245 cases, 1,668 controls) which included genomic regions of known AMD loci in 49 genes. At a false discovery rate of <0.01, we identified 11 low-frequency AMD variants (minor allele frequency <0.05). Two of those variants were present in the complement gene, including the replacement of the residues that contribute to the Rodgers-1/Chido-1 blood group antigens: [VDLL1207-1210ADLR (V1207A)] with discovery odds ratio (OR) = 1.7 ( = 3.2 × 10) which was replicated in the UK Biobank dataset (3,294 cases, 200,086 controls, OR = 1.52, = 0.037). A novel variant associated with reduced risk for AMD in our discovery cohort was P1120T, one of the four C4A-isotypic residues. Gene-based tests yielded aggregate effects of nonsynonymous variants in 10 genes including , which were associated with increased risk of AMD. In human eye tissues, immunostaining demonstrated C4A protein accumulation in and around endothelial cells of retinal and choroidal vasculature, and total C4 in soft drusen. Our results indicate that C4A protein in the complement activation pathways may play a role in the pathogenesis of AMD.
PubMed: 38348408
DOI: 10.3389/fgene.2023.1274743 -
Ophthalmology and Therapy Apr 2024
Letter to the Editor Regarding "LIGHTSITE II Randomized Multicenter Trial: Evaluation of Multiwavelength Photobiomodulation in Non-exudative Age-Related Macular Degeneration".
PubMed: 38319554
DOI: 10.1007/s40123-024-00894-2 -
Ophthalmology Science 2024An algorithm developed to obtain drusen area and volume measurements using swept-source OCT angiography (SS-OCTA) scans was tested on spectral-domain OCT angiography...
PURPOSE
An algorithm developed to obtain drusen area and volume measurements using swept-source OCT angiography (SS-OCTA) scans was tested on spectral-domain OCT angiography (SD-OCTA) scans.
DESIGN
Retrospective study.
PARTICIPANTS
Forty pairs of scans from 27 eyes with intermediate age-related macular degeneration and drusen.
METHODS
Patients underwent both SD-OCTA and SS-OCTA imaging at the same visit using the 6 mm × 6 mm OCTA scan patterns. Using the same algorithm, we obtained drusen area and volume measurements within both 3 mm and 5 mm fovea-centered circles. Paired 2-sample -tests were performed along with Pearson's correlation tests.
MAIN OUTCOME MEASURES
Mean square root (sqrt) drusen area and cube root (cbrt) drusen volume within the 3 mm and 5 mm fovea-centered circles.
RESULTS
Mean sqrt drusen area values from SD-OCTA and SS-OCTA scans were 1.57 (standard deviation [SD] 0.57) mm and 1.49 (SD 0.58) mm in the 3 mm circle and 1.88 (SD 0.59) mm and 1.76 (SD 0.58) mm in the 5 mm circle, respectively. Mean cbrt drusen volume measurements were 0.54 (SD 0.19) mm and 0.51 (SD 0.20) mm in the 3 mm circle, and 0.60 (SD 0.17) mm and 0.57 (SD 0.17) mm in the 5 mm circle. Small differences in area and volume measurements were found (all < 0.001); however, the correlations between the instruments were strong (all coefficients > 0.97; all < 0.001).
CONCLUSIONS
An algorithm originally developed for SS-OCTA scans performs well when used to obtain drusen volume and area measurements from SD-OCTA scans; thus, a separate SD-OCT structural scan is unnecessary to obtain measurements of drusen.
FINANCIAL DISCLOSURES
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
PubMed: 38284102
DOI: 10.1016/j.xops.2023.100424 -
Ophthalmology Science 2024Nascent geographic atrophy (nGA) refers to specific features seen on OCT B-scans, which are strongly associated with the future development of geographic atrophy (GA)....
PURPOSE
Nascent geographic atrophy (nGA) refers to specific features seen on OCT B-scans, which are strongly associated with the future development of geographic atrophy (GA). This study sought to develop a deep learning model to screen OCT B-scans for nGA that warrant further manual review (an artificial intelligence [AI]-assisted approach), and to determine the extent of reduction in OCT B-scan load requiring manual review while maintaining near-perfect nGA detection performance.
DESIGN
Development and evaluation of a deep learning model.
PARTICIPANTS
One thousand eight hundred and eighty four OCT volume scans (49 B-scans per volume) without neovascular age-related macular degeneration from 280 eyes of 140 participants with bilateral large drusen at baseline, seen at 6-monthly intervals up to a 36-month period (from which 40 eyes developed nGA).
METHODS
OCT volume and B-scans were labeled for the presence of nGA. Their presence at the volume scan level provided the ground truth for training a deep learning model to identify OCT B-scans that potentially showed nGA requiring manual review. Using a threshold that provided a sensitivity of 0.99, the B-scans identified were assigned the ground truth label with the AI-assisted approach. The performance of this approach for detecting nGA across all visits, or at the visit of nGA onset, was evaluated using fivefold cross-validation.
MAIN OUTCOME MEASURES
Sensitivity for detecting nGA, and proportion of OCT B-scans requiring manual review.
RESULTS
The AI-assisted approach (utilizing outputs from the deep learning model to guide manual review) had a sensitivity of 0.97 (95% confidence interval [CI] = 0.93-1.00) and 0.95 (95% CI = 0.87-1.00) for detecting nGA across all visits and at the visit of nGA onset, respectively, when requiring manual review of only 2.7% and 1.9% of selected OCT B-scans, respectively.
CONCLUSIONS
A deep learning model could be used to enable near-perfect detection of nGA onset while reducing the number of OCT B-scans requiring manual review by over 50-fold. This AI-assisted approach shows promise for substantially reducing the current burden of manual review of OCT B-scans to detect this crucial feature that portends future development of GA.
FINANCIAL DISCLOSURES
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
PubMed: 38284101
DOI: 10.1016/j.xops.2023.100428 -
Serous maculopathy with absence of retinal pigment epithelium (SMARPE) associated with large drusen.International Journal of Retina and... Jan 2024To describe the association of serous maculopathy with absence of retinal pigment epithelium (SMARPE) and large drusen in patients with non-neovascular age-related...
PURPOSE
To describe the association of serous maculopathy with absence of retinal pigment epithelium (SMARPE) and large drusen in patients with non-neovascular age-related macular degeneration (AMD).
METHODS
A retrospective study of ophthalmic examination and multimodal imaging data of individuals with SMARPE and large drusen observed over a period of 12-month was accomplished. SMARPE was defined as subretinal accumulation of fluid within the macular area due to retinal pigment epithelium (RPE) aperture. Large drusen were identified by the presence of sub-RPE deposits using multimodal imaging analysis (color fundus photography, fundus autofluorescence, and spectral-domain optical coherence tomography).
RESULTS
Twelve eyes of 7 white patients with a mean age of 77 years were observed to have SMARPE associated with large drusen. The median visual acuity was 20/100. Bilateral SMARPE lesions were observed in 71% of study patients. All SMARPE lesions were hypoautofluorescent, located in the subretinal space between the RPE and the ellipsoid zone, and presented as complete or incomplete RPE apertures associated with subretinal fluid. The SMARPE in this study had coincident multimodal imaging features as the SMARPE described in other reports in the literature.
CONCLUSIONS
Bilateral SMARPE can occur in association with typical AMD large drusen. Anomalisms resulting in drusen biogenesis or mechanisms that act alongside to these may be related to SMARPE development.
PubMed: 38254230
DOI: 10.1186/s40942-024-00529-5 -
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