Publications by authors named "Usha Chakravarthy"

We investigated whether the effect of lipid-lowering drugs (LLDs) on age-related macular degeneration (AMD) differs according to the main complement genetic variants in Singapore Epidemiology of Eye Diseases (SEED) ( = 5,579) and UK Biobank studies ( = 445,727). The effect of LLD was determined for each stratum of 20 complement genetic variants. In SEED, 484 individuals developed AMD and 216 showed progression over 6 years.

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Purpose: To assess the correlation of lesion growth rate and baseline factors, including foveal involvement and focality, on visual loss as measured by best-corrected visual acuity (BCVA) in patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD).

Design: Retrospective analysis of the lampalizumab phase 3 (NCT02247479 and NCT02247531) and prospective observational (NCT02479386) trials.

Participants: Patients with bilateral GA.

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Geographic atrophy (GA), the non-neovascular advanced form of age-related macular degeneration, remains an important disease area in which treatment needs are currently unmet. Recent clinical trials using drugs that target the complement pathway have shown modest yet consistent reductions in GA expansion but without commensurate changes in measures of visual function. In this review, we summarize information from the wide range of studies describing the characteristics of GA morphology and enumerate the factors influencing the growth rates of lesions and the directionality of expansion.

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The natural history of neovascular age-related macular degeneration (nAMD) leads to scarring and loss of vision. Since the advent of anti-VEGF therapies, which are very effective for controlling exudation, large disciform scars are rarely encountered in the clinic. However long term studies show that smaller and less severe fibrotic scars are not uncommon and develop over time despite optimal treatment.

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Purpose: To explore the contributions of fundus autofluorescence (FAF) topographic imaging features to the performance of convolutional neural network-based deep learning (DL) algorithms in predicting geographic atrophy (GA) growth rate.

Methods: Retrospective study with data from study eyes from three clinical trials (NCT02247479, NCT02247531, NCT02479386) in GA. The algorithm was initially trained with full FAF images, and its performance was considered benchmark.

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Objective: Our objective was to determine the effects of lipids and complement proteins on early and intermediate age-related macular degeneration (AMD) stages using machine learning models by integrating metabolomics and proteomic data.

Design: Nested case-control study.

Subjects And Controls: The analyses were performed in a subset of the Singapore Indian Chinese Cohort (SICC) Eye Study.

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Background: Neovascular age-related macular degeneration (nAMD) is a leading cause of blindness. The first-line therapy is anti-vascular endothelial growth factor (anti-VEGF) agents delivered by intravitreal injection. Ionising radiation mitigates key pathogenic processes underlying nAMD, and therefore has therapeutic potential.

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Article Synopsis
  • The study focuses on diagnosing neovascular age-related macular degeneration (nAMD) using various imaging techniques, assessing their accuracy in clinical practice.
  • It involves 1,067 participants with nAMD symptoms, comparing non-invasive methods like Optical Coherence Tomography (OCT) and Optical Coherence Tomography Angiography (OCTA) against invasive methods like Fundus Fluorescein Angiography (FFA) and Indocyanine-Green Angiography (ICGA).
  • The research aims to determine which combination of imaging techniques is more effective in detecting nAMD, with ethics approval already secured for the study.
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Purpose: In diabetic macular edema (DME), hyper-reflective foci (HRF) has been linked to disease severity and progression. Using an automated approach, we aimed to investigate the baseline distribution of HRF in DME and their co-localization with cystoid intraretinal fluid (IRF).

Methods: Baseline spectral-domain optical coherence tomography (SD-OCT) volume scans (N = 1527) from phase III clinical trials YOSEMITE (NCT03622580) and RHINE (NCT03622593) were segmented using a deep-learning-based algorithm (developed using B-scans from BOULEVARD NCT02699450) to detect HRF.

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Article Synopsis
  • - The GATHER trials aimed to assess how reducing geographic atrophy (GA) lesion growth affects visual acuity, using randomized, double-masked, and sham-controlled methods with participants aged 50 or older.
  • - In these trials, patients were randomized to receive either 2 mg of avacincaptad pegol (ACP) or a sham treatment, with results showing a lower percentage of vision loss in those treated with ACP at 12 months compared to the sham group.
  • - The study concluded that ACP 2 mg treatment effectively delayed the progression of vision loss and maintained eligibility for driving in patients compared to those receiving sham treatment.
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Purpose: To describe the rationale and design of the VOYAGER (NCT05476926) study, which aims to investigate the safety and effectiveness of faricimab and the Port Delivery System with ranibizumab (PDS) for neovascular age-related macular degeneration (nAMD) or diabetic macular edema (DME) in clinical practice. VOYAGER also aims to understand drivers of clinical practice treatment outcomes by gaining novel insight into the intersection of treatment regimens, decisions, anatomic outcomes, and vision.

Design: Primary data collection, noninterventional, prospective, multinational, multicenter clinical practice study.

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Geographic atrophy (GA) is an advanced and irreversible form of age-related macular degeneration (AMD). Chronic low grade inflammation is thought to act as an initiator of this degenerative process, resulting in loss of photoreceptors (PRs), retinal pigment epithelium (RPE) and the underlying choriocapillaris. This review examined the challenges of clinical trials to date which have sought to treat GA, with particular reference to the successful outcome of C3 complement inhibition.

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Importance: Age-related macular degeneration (AMD) affects approximately 20 million people in the US and 196 million people worldwide. AMD is a leading cause of severe vision impairment in older people and is expected to affect approximately 288 million people worldwide by 2040.

Observations: Older age, genetic factors, and environmental factors, such as cigarette smoking, are associated with development of AMD.

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Article Synopsis
  • The study aimed to evaluate visual acuity and structural biomarkers in individuals with neovascular age-related macular degeneration (nAMD) before and 24 months after standard treatment, focusing on both the first and newly affected second eye.
  • Conducted as a prospective observational study across 22 centers, it included older adults with new onset nAMD in their first eye, utilizing various assessments like OCT and quality of life measurements.
  • Results showed that the second eye, diagnosed early, had significantly better visual acuity and lower rates of certain structural issues compared to the first eye, although it experienced a higher prevalence of subretinal fluid after 24.9 months. *
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Purpose: To report the characteristics and correlation of visual acuity in eyes treated for neovascular age-related macular degeneration (nAMD) and developed fibrosis.

Design: Case-control study.

Methods: Three hundred fifty-six treatment-naive nAMD eyes that were treated for 12 months were included.

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Globally age-related macular degeneration (AMD) is a leading cause of blindness with a significant impact on quality of life. Geographic atrophy (GA) is the atrophic late form of AMD and its prevalence increases markedly with age with around 1 in 5 persons aged 85 and above having GA in at least one eye. Bilateral GA leads to severe visual impairment thus posing a significant burden on patients, careers and health providers.

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Purpose: The presences of a double layer sign (DLS) and a shallow irregular retinal pigment epithelium (RPE) elevation (SIRE) were investigated using spectral domain-OCT (SD-OCT) imaging to determine their ability to predict progression to exudative macular neovascularization (eMNV) in the unaffected fellow eyes (study eye) of participants with age-related macular degeneration (AMD) with newly diagnosed unilateral eMNV.

Design: Retrospective, reanalysis of SD-OCT scans of study eyes from the Early Detection of Neovascular AMD (EDNA) study with 3 years follow-up (FU).

Participants: The EDNA study repository of SD-OCT scans was assessed for inclusion.

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Aims/hypothesis: To determine the extent to which diabetic retinopathy severity stage may be classified using machine learning (ML) and commonly used clinical measures of visual function together with age and sex.

Methods: We measured the visual function of 1901 eyes from 1032 participants in the Northern Ireland Sensory Ageing Study, deriving 12 variables from nine visual function tests. Missing values were imputed using chained equations.

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Objective: To describe the spatial and temporal characteristics of hyperreflective material (HRM) on spectral-domain OCT (SD-OCT) in neovascular age-related macular degeneration (nAMD) during antiangiogenic treatment and explore associations with best-corrected visual acuity (BCVA) and macular atrophy (MA).

Design: Retrospective regrading of SD-OCT-images from the multicenter, randomized controlled AVENUE trial (NCT02484690, conducted from August 2015 to September 2017).

Participants: Treatment-naive nAMD patients enrolled from 50 sites in the US.

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