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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 -
Graefe's Archive For Clinical and... Feb 2024To define optical coherence tomography (OCT) biomarkers that precede the development of complete retinal pigment epithelium and outer retinal atrophy (cRORA) at that...
PURPOSE
To define optical coherence tomography (OCT) biomarkers that precede the development of complete retinal pigment epithelium and outer retinal atrophy (cRORA) at that location in eyes with age-related macular degeneration (AMD).
METHODS
In this retrospective case-control study, patients with dry AMD who had evidence of cRORA and OCT data available for 4 years (48 ± 4 months) prior to the first visit with evidence of cRORA were included. The visit 4 years prior to the development of cRORA was defined as the baseline visit, and the region on the OCT B-scans of future cRORA development was termed the case region. A region in the same eye at the same distance from the foveal center as the case region that did not progress to cRORA was selected as the control region. OCT B-scans at the baseline visit through both the case and control regions were evaluated for the presence of soft and cuticular drusen, drusen with hyporeflective cores (hcD), drusenoid pigment epithelial detachments (PED), subretinal drusenoid deposits (SDD), thick and thin double-layer signs (DLS), intraretinal hyperreflective foci (IHRF), and acquired vitelliform lesions (AVL).
RESULTS
A total of 57 eyes of 41 patients with dry AMD and evidence of cRORA were included. Mean time from the baseline visit to the first visit with cRORA was 44.7 ± 6.5 months. The presence of soft drusen, drusenoid PED, AVL, thin DLS, and IHRF at the baseline visit was all associated with a significantly increased risk of cRORA at that location. Multivariable logistic regression revealed that IHRF (OR, 8.559; p < 0.001), drusenoid PED (OR, 7.148; p = 0.001), and a thin DLS (OR, 3.483; p = 0.021) were independent predictors of development of cRORA at that location.
CONCLUSIONS
IHRF, drusenoid PED, and thin DLS are all local risk factors for the development of cRORA at that same location. These findings would support the inclusion of these features within a more granular staging system defining specific steps in the progression from early AMD to atrophy.
PubMed: 38300334
DOI: 10.1007/s00417-024-06389-x -
Clinical & Experimental Ophthalmology 2024To examine the association between large choroidal signal hypertransmission ≥250 μm (LHyperT) on optical coherence tomography (OCT) with the risk of developing...
BACKGROUND
To examine the association between large choroidal signal hypertransmission ≥250 μm (LHyperT) on optical coherence tomography (OCT) with the risk of developing geographic atrophy (GA) and compare this risk with those associated with nascent geographic atrophy (nGA).
METHODS
Two hundred and eighty eyes from 140 participants with bilateral large drusen and without late age-related macular degeneration (AMD) or nGA at baseline underwent OCT imaging and colour fundus photography (CFP) at 6-monthly intervals up to 5 years. OCT scans were graded for the presence of LHyperT and nGA, and CFPs were graded for the presence of GA.
RESULTS
The five-year incidence of LHyperT and nGA were 37% and 27% respectively (p = 0.003), and the two-year probability of their progression to GA were 17% and 40%, respectively (p = 0.002). LHyperT and nGA explained 81% and 91% of the variance in the time to develop GA, respectively (p = 0.032), and they were both associated with a significantly higher rate of GA development compared to eyes without these lesions (adjusted hazard ratio = 110.8 and 183.2, respectively; p < 0.001 for both).
CONCLUSIONS
LHyperT and nGA were both high-risk features for GA development, but the latter showed a higher rate of GA progression and explained a significantly greater proportion of the variance in the time to develop GA. As such, nGA may be a more robust surrogate endpoint than LHyperT for the conventional clinical endpoint of CFP-defined GA for intervention trials in the early stages of AMD.
Topics: Humans; Tomography, Optical Coherence; Geographic Atrophy; Female; Male; Aged; Choroid; Disease Progression; Aged, 80 and over; Macular Degeneration; Fluorescein Angiography; Visual Acuity; Retinal Drusen; Follow-Up Studies; Middle Aged; Risk Factors; Prospective Studies; Incidence
PubMed: 38286571
DOI: 10.1111/ceo.14356 -
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 -
Acta Ophthalmologica Jan 2024To test the hypothesis that central drusen location is strongly linked with known Age-related Macular Degeneration (AMD) risk factors and risk of incident late AMD.
PURPOSE
To test the hypothesis that central drusen location is strongly linked with known Age-related Macular Degeneration (AMD) risk factors and risk of incident late AMD.
METHODS
The Alienor study is a prospective population-based cohort study of residents of Bordeaux, France, followed from 2009 to 2017. On retinal photographs, we defined central drusen as at least one soft drusen (>63 μm) within 500 μm from fovea and pericentral drusen as at least one drusen 500-3000 μm from fovea, in the absence of any central drusen. Late AMD (atrophic and/or neovascular) was diagnosed using multimodal imaging. In total, 481 eyes were included in the analysis: 160 central and 321 pericentral. We investigated associations with systemic (age, sex, smoking, medical prescriptions, plasma concentrations of lipids and nutrients, UV exposure, blood pressure), ocular (retinal thickness, cataract extraction) and genetic risk scores (GRS).
RESULTS
In multivariate logistic regression central drusen were associated with smoking (OR, 2.95 for smoking more than 20 pack-years, p = 0.02), HDL-cholesterol (OR, 1.57 for 1 standard deviation (SD) increase, p = 0.0048), pulse pressure (OR, 0.77 for 1 SD increase, p = 0.04), Age-Related Maculopathy Susceptibility 2 (ARMS2) GRS (OR, 1.42; 95% CI, 1.11-1.83) and complement GRS (OR, 1.55; 95% CI, 1.15-2.10). In Cox modelling, the central location of drusen (at baseline or during the follow-up) was associated with a 4.41-fold increased risk (95% CI,1.98-9.81) for an incident late AMD.
CONCLUSION
Central drusen were strongly associated with AMD risk factors and incident late AMD, suggesting that it represents a key marker for AMD progression.
PubMed: 38278777
DOI: 10.1111/aos.16645 -
Progress in Retinal and Eye Research May 2024Inherited retinal diseases (IRD) are a leading cause of blindness in the working age population and in children. The scope of this review is to familiarise clinicians... (Review)
Review
Phenotyping and genotyping inherited retinal diseases: Molecular genetics, clinical and imaging features, and therapeutics of macular dystrophies, cone and cone-rod dystrophies, rod-cone dystrophies, Leber congenital amaurosis, and cone dysfunction syndromes.
Inherited retinal diseases (IRD) are a leading cause of blindness in the working age population and in children. The scope of this review is to familiarise clinicians and scientists with the current landscape of molecular genetics, clinical phenotype, retinal imaging and therapeutic prospects/completed trials in IRD. Herein we present in a comprehensive and concise manner: (i) macular dystrophies (Stargardt disease (ABCA4), X-linked retinoschisis (RS1), Best disease (BEST1), PRPH2-associated pattern dystrophy, Sorsby fundus dystrophy (TIMP3), and autosomal dominant drusen (EFEMP1)), (ii) cone and cone-rod dystrophies (GUCA1A, PRPH2, ABCA4, KCNV2 and RPGR), (iii) predominant rod or rod-cone dystrophies (retinitis pigmentosa, enhanced S-Cone syndrome (NR2E3), Bietti crystalline corneoretinal dystrophy (CYP4V2)), (iv) Leber congenital amaurosis/early-onset severe retinal dystrophy (GUCY2D, CEP290, CRB1, RDH12, RPE65, TULP1, AIPL1 and NMNAT1), (v) cone dysfunction syndromes (achromatopsia (CNGA3, CNGB3, PDE6C, PDE6H, GNAT2, ATF6), X-linked cone dysfunction with myopia and dichromacy (Bornholm Eye disease; OPN1LW/OPN1MW array), oligocone trichromacy, and blue-cone monochromatism (OPN1LW/OPN1MW array)). Whilst we use the aforementioned classical phenotypic groupings, a key feature of IRD is that it is characterised by tremendous heterogeneity and variable expressivity, with several of the above genes associated with a range of phenotypes.
Topics: Humans; Cone-Rod Dystrophies; Eye Diseases, Hereditary; Genotype; Leber Congenital Amaurosis; Molecular Biology; Phenotype; Retinal Diseases
PubMed: 38278208
DOI: 10.1016/j.preteyeres.2024.101244 -
Current Neurology and Neuroscience... Mar 2024Papilledema refers to optic disc swelling caused by raised intracranial pressure. This syndrome arises from numerous potential causes, which may pose varying degrees of... (Review)
Review
PURPOSE OF REVIEW
Papilledema refers to optic disc swelling caused by raised intracranial pressure. This syndrome arises from numerous potential causes, which may pose varying degrees of threat to patients. Manifestations of papilledema range from mild to severe, and early diagnosis is important to prevent vision loss and other deleterious outcomes. The purpose of this review is to highlight the role of optical coherence tomography (OCT) in the diagnosis and management of syndromes of raised intracranial pressure associated with papilledema.
RECENT FINDINGS
Ophthalmoscopy is an unreliable skill for many clinicians. Optical coherence tomography is a non-invasive ocular imaging technique which may fill a current care gap, by facilitating detection of papilledema for those who cannot perform a detailed fundus examination. Optical coherence tomography may help confirm the presence of papilledema, by detecting subclinical peripapillary retinal nerve fiber layer (pRNFL) thickening that might otherwise be missed with ophthalmoscopy. Enhanced depth imaging (EDI) and swept source OCT techniques may identify optic disc drusen as cause of pseudo-papilledema. Macular ganglion cell inner plexiform layer (mGCIPL) values may provide early signs of neuroaxonal injury in patients with papilledema and inform management for patients with syndromes of raised intracranial pressure. There are well-established advantages and disadvantages of OCT that need to be fully understood to best utilize this method for the detection of papilledema. Overall, OCT may complement other existing tools by facilitating detection of papilledema and tracking response to therapies. Moving forward, OCT findings may be included in deep learning models to diagnose papilledema.
Topics: Humans; Papilledema; Optic Disk; Tomography, Optical Coherence; Retinal Ganglion Cells; Nerve Fibers; Intracranial Hypertension
PubMed: 38261144
DOI: 10.1007/s11910-023-01327-6 -
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