Publications by authors named "Robyn H Guymer"

Purpose: To determine local OCT structural correlates of deep visual sensitivity defects (threshold of ≤10 decibels on microperimetry) in early atrophic age-related macular degeneration (AMD).

Design: Prospective observational study.

Participants: Forty eyes from 40 participants, with at least incomplete retinal pigment epithelium (RPE) and outer retinal atrophy (iRORA), or more advanced atrophic lesion(s).

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Purpose: To determine the relationship between structural and functional changes over time in the progression of geographic atrophy (GA) as assessed by defect-mapping microperimetry, an approach optimized to characterize the spatial extent of deep visual sensitivity losses.

Methods: A total of 57 eyes from 50 participants underwent defect-mapping microperimetry testing of the central 8° radius (with a 10-dB stimuli presented once each at 208 locations) over a median of five visits, scheduled at 3-monthly intervals. GA lesion(s) on fundus autofluorescence in the corresponding region tested on microperimetry at each visit were manually annotated.

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Purpose: To investigate neurovascular function in eyes with age-related macular degeneration (AMD).

Methods: Subjects with bilateral large drusen (intermediate AMD) and healthy controls ≥50 years old were recruited. The vasculature within the central 6 × 6-mm retinal area was captured using optical coherence tomography angiography (OCTA) and segmented to return superficial plexus, deep plexus, choriocapillaris, and choroid.

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Age-related macular degeneration (AMD) is a leading cause of vision impairment in people over 50 years of age and has a great impact on quality of life as it affects central vision. Although there have been treatments available for the neovascular form of late AMD for decades, until now there have not been treatments available for the atrophic form of late AMD - geographic atrophy (GA). Recently, treatments acting on the complement pathway have been approved by the United States Food and Drug Administration, with other jurisdictions such as Australia considering their approval.

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Article Synopsis
  • Age-related macular degeneration (AMD) is a complex eye disease influenced by both genetic factors and involves a subtype called reticular pseudodrusen (RPD), which increases the risk of severe vision loss.* -
  • A genome-wide association study compared genetic data from individuals with AMD and/or RPD to controls, finding significant associations specifically on chromosome 10, while chromosome 1 did not show this correlation in RPD cases.* -
  • The chromosome 10 region includes a long non-coding RNA related to retinal health, highlighting its potential role in retinal thickness and influencing the outer segment of photoreceptors.*
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Article Synopsis
  • Reticular pseudodrusen (RPD) are a key factor in vision loss related to age-related macular degeneration (AMD), making their detection essential for effective clinical management.
  • Researchers created a deep learning model that segments RPD from a dataset of 9,800 optical coherence tomography scans, achieving better agreement with retinal specialists compared to their own consensus.
  • The model demonstrated high performance in detecting RPD across multiple test datasets, matching the accuracy of experienced specialists, and is now publicly accessible for use.
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Purpose: To understand the spatial relationship between local rod-mediated visual function and reticular pseudodrusen (RPD) in eyes with large drusen.

Design: Retrospective cross-sectional study.

Participants: One eye with large drusen (>125 μm) each from 91 individuals with intermediate age-related macular degeneration, with and without RPD.

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Objective: Abnormal changes in metabolite levels in serum or plasma have been highlighted in several studies in age-related macular degeneration (AMD), the leading cause of irreversible vision loss. Specific changes in lipid profiles are associated with an increased risk of AMD. Metabolites could thus be used to investigate AMD disease mechanisms or incorporated into AMD risk prediction models.

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Background: Nocturnal hypoxia is common, under-diagnosed and is found in the same demographic at risk of age-related macular degeneration (AMD). The objective of this study was to determine any association between nocturnal hypoxia and AMD, its severity, and the high-risk sub-phenotype of reticular pseudodrusen (RPD).

Methods: This cross-sectional study included participants aged ≥50 years with AMD, or normal controls, exclusive of those on treatment for obstructive sleep apnoea.

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Purpose: To understand the microperimetry response characteristics of regions with a truly nonresponding location, which will be useful when considering criteria for end-stage atrophic age-related macular degeneration (AMD).

Methods: A simulation model was developed using data from 128 participants with bilateral large drusen at baseline seen over 36 months at 6-month intervals. One hundred thousand pairs of real-world microperimetry testing results were simulated separately with and without one truly nonresponding location, where the sensitivity of one randomly selected location for the former group was derived from the distribution of responses from a truly nonresponding location at the optic nerve head from 60 healthy participants.

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Objective: The fragility index (FI) of a meta-analysis evaluates the extent that the statistical significance can be changed by modifying the event status of individuals from included trials. Understanding the FI improves the interpretation of the results of meta-analyses and can help to inform changes to clinical practice. This review determined the fragility of ophthalmology-related meta-analyses.

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Purpose: Investigating the sequence of morphological changes preceding outer plexiform layer (OPL) subsidence, a marker preceding geographic atrophy, in intermediate AMD (iAMD) using high-precision artificial intelligence (AI) quantifications on optical coherence tomography imaging.

Methods: In this longitudinal observational study, individuals with bilateral iAMD participating in a multicenter clinical trial were screened for OPL subsidence and RPE and outer retinal atrophy. OPL subsidence was segmented on an A-scan basis in optical coherence tomography volumes, obtained 6-monthly with 36 months follow-up.

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Purpose: This analysis investigated potential associations between gene variants and clinical end points in the VIEW 1 and 2 randomized clinical trials of intravitreal aflibercept and ranibizumab in neovascular age-related macular degeneration (AMD).

Methods: A genome-wide association analysis was conducted in a subgroup of patients from VIEW 1 and 2 consenting to the optional pharmacogenetic analysis.

Results: Data were pooled from 780 samples from patients representative of the overall VIEW 1 and 2 populations.

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Purpose: The subsidence of the outer plexiform layer (OPL) is an important imaging biomarker on optical coherence tomography (OCT) associated with early outer retinal atrophy and a risk factor for progression to geographic atrophy in patients with intermediate age-related macular degeneration (AMD). Deep neural networks (DNNs) for OCT can support automated detection and localization of this biomarker.

Methods: The method predicts potential OPL subsidence locations on retinal OCTs.

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Background: To examine whether the clinical performance of predicting late age-related macular degeneration (AMD) development is improved through using multimodal imaging (MMI) compared to using colour fundus photography (CFP) alone, and how this compares with a basic prediction model using well-established AMD risk factors.

Methods: Individuals with AMD in this study underwent MMI, including optical coherence tomography (OCT), fundus autofluorescence, near-infrared reflectance and CFP at baseline, and then at 6-monthly intervals for 3-years to determine MMI-defined late AMD development. Four retinal specialists independently assessed the likelihood that each eye at baseline would progress to MMI-defined late AMD over 3-years with CFP, and then with MMI.

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Importance: Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss in old age. There is no proven intervention to prevent AMD and, apart from lifestyle, nutritional, and supplement advice, there is no intervention to delay its progression.

Objective: To determine the impact of long-term low-dose aspirin on the incidence and progression of AMD.

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Article Synopsis
  • Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in older adults, affecting 10-20% of those over 65 in Western countries.
  • AMD causes central vision loss due to the degeneration of critical eye structures and is classified into early, intermediate, and late stages, with late-stage including serious forms like neovascular AMD and geographic atrophy.
  • Treatment options are currently limited, though neovascular AMD is managed with injections; however, a new treatment for geographic atrophy, pegcetacoplan, was recently approved, and there is ongoing research into gene and cell therapies for late-stage AMD.
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Purpose: Obstructive sleep apnoea (OSA) is common, yet often undiagnosed. Self-administered, overnight pulse oximetry (OPO) could screen for OSA in asymptomatic, older populations. However, the inter-night variability of OPO in an asymptomatic, older population is unknown.

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Purpose: There is a need for robust earlier biomarkers of atrophic age-related macular degeneration that could act as surrogate endpoints for geographic atrophy (GA) in early interventional trials. This study sought to examine the risk of progression of complete retinal pigment epithelium and outer retinal atrophy (cRORA) to the traditional atrophic endpoint of GA on color fundus photography. This study also compared the risk of progression for cRORA to that associated with the specific optical coherence tomography features that define nascent GA (nGA), a strong predictor of GA development.

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Purpose: A recent genome-wide association study of age-related macular degeneration (AMD) identified new AMD-associated risk variants. These variants now can be incorporated into an updated polygenic risk score (PRS). This study aimed to assess the performance of an updated PRS, PRS2023, in an independent cohort of older individuals with retinal imaging data and to compare performance with an older PRS, PRS2016.

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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.

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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.

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Purpose: To examine the structure-function relationship in eyes with geographic atrophy (GA) using defect-mapping microperimetry, a testing strategy optimized to quantify the spatial extent of deep visual sensitivity losses.

Methods: Fifty participants with GA underwent defect-mapping microperimetry testing of the central 8°-radius region (208 locations tested once with a 10-decibel stimuli) and fundus autofluorescence imaging in one eye. The GA extent in the corresponding central 8°-radius was derived by manual annotations and image co-registration to examine the global structure-function relationship.

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Purpose: To assess the relationship between choriocapillaris (CC) loss and the development of nascent geographic atrophy (nGA) using optical coherence tomography angiography (OCTA) imaging.

Methods: In total, 105 from 62 participants with bilateral large drusen, without late age-related macular degeneration (AMD) or nGA at baseline, were included in this prospective, longitudinal, observational study. Participants underwent swept-source OCTA imaging at 6-month intervals.

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