The MACUSTAR consortium has completed a groundbreaking observational study that establishes new standards for clinical trial endpoints in intermediate age-related macular degeneration (iAMD). This comprehensive research effort, spanning up to six years across 20 European centers, represents a significant advancement in AMD research methodology.
Innovative Study Design and Implementation
The study incorporates both cross-sectional and longitudinal components, focusing on developing and validating clinical trial endpoints across multiple assessment domains. Participants aged 55-85 years were evaluated using state-of-the-art imaging technologies, functional assessments, and patient-reported outcomes (PROs).
The research team implemented rigorous quality control measures, including standardized testing protocols and certification requirements for technical staff. Over 128 technicians were certified for imaging procedures, with 93 qualified for visual function assessments, ensuring data consistency across all study sites.
Breakthrough Findings in Visual Function Assessment
Key findings reveal that chart-based and device-based visual function tests achieved high repeatability in multi-center settings. Tests including best-corrected visual acuity, low-luminance visual acuity, and contrast sensitivity demonstrated intra-class correlation coefficients of ≥0.7 in iAMD patients.
Notably, 71% of iAMD patients showed impaired performance in at least one visual function parameter compared to healthy controls, highlighting the prevalence of visual deficits in early disease stages.
Advanced Imaging and Structural Assessments
The study utilized a comprehensive multimodal imaging approach, including:
- Spectral-domain and swept-source optical coherence tomography (OCT)
- OCT angiography
- Fundus autofluorescence
- Multi-wavelength confocal scanning laser ophthalmoscopy
These imaging protocols, managed through a central reading center, enabled precise diagnosis and biomarker categorization.
Patient-Reported Outcomes Innovation
A significant advancement emerged with the validation of the Vision Impairment in Low Luminance (VILL) questionnaire, specifically designed for early AMD stages. The questionnaire demonstrated:
- High repeatability with intra-class correlations ≥0.7
- Significant prognostic value for progression from iAMD to late AMD
- Successful cross-cultural adaptation across multiple European languages
Clinical Trial Implications
The study's findings provide crucial insights for future iAMD clinical trials:
- Validated functional endpoints beyond traditional anatomical markers
- Established reliability of multi-center visual function testing
- Confirmed prognostic value of both structural and functional biomarkers
- Demonstrated feasibility of complex visual function assessments in multi-center settings
Biomarker Development and Future Directions
The research has identified promising biomarkers for disease progression, including reticular pseudodrusen and mesopic microperimetry pattern standard deviation. These findings, combined with ongoing genetic and biobank analyses, are expected to enhance understanding of iAMD subtypes and progression patterns.
The MACUSTAR study continues to generate insights through international collaborations and biobank analyses, positioning itself as a cornerstone for future AMD research and therapeutic development.
