Opera Study In AMD
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Opera Study In AMD

  • Study Overview: The Optos Peripheral Retina (OPERA) Study
    • Ancillary study of Age-Related Eye Disease Study 2 (AREDS2).
    • Longitudinal study assessing peripheral retinal changes in age-related macular degeneration (AMD) over 5 years using ultrawidefield (UWF) imaging.
    • Included 137 participants (265 eyes) with gradable UWF color and fundus autofluorescence (FAF) images at years 5 and 10.
  • AMD Epidemiology and Impact
    • AMD is a leading cause of vision loss, affecting ~20 million people >40 years in the US (2019) and projected to affect 288 million globally by 2040.
    • Established through studies like Beaver Dam Eye Study and Rotterdam Study; AREDS developed the AMD Severity Scale (AMDSS).
  • UWF Imaging and Grading Protocol
    • UWF color and FAF images captured using Optos 200Tx device.
    • 3-zone OPERA grid:
      • Zone 1: Posterior pole (~5.4 mm radius, 3 disc diameters).
      • Zone 2: Mid-periphery (~16.2 mm radius, overlaps vortex veins).
      • Zone 3: Far periphery (anterior to zone 2).
    • Images graded for AMD features (drusen, pigment changes, geographic atrophy [GA], neovascular AMD [nAMD]) and peripheral degenerations (cobblestone, reticular pigmentary changes).
    • AMDSS: 12-step scale (1–8 nonadvanced, 9 noncentral GA, 10 central GA, 11a/b nAMD); progression defined as ≥2-step worsening or development of late AMD.
  • Key Findings in Zone 1 (Macula)
    • AMDSS distribution at year 5: 8% ≤5, 49% 6–8, 15% GA (noncentral/central), 28% nAMD.
    • AMDSS at year 10: 6% ≤5, 30% 6–8, 27% GA, 37% nAMD.
    • Late AMD increased from 43% to 64% over 5 years; nAMD rose from 28% to 37%, GA from 21% to 43% (in eyes without nAMD).
  • Peripheral Findings (Zones 2 and 3)
    • Drusen nearly universal in zone 2 (99% at both time points); increased from 69% to 77% for >1 disc area over 5 years.
    • Pigmentary changes less common: hyperpigmentation (11% both time points), hypopigmentation (4% to 7%) in zone 2.
    • Peripheral degenerations:
      • Cobblestone degeneration: 19% to 30%.
      • Reticular pigmentary changes: 25% to 33%.
    • Reticular pseudodrusen (RPD): 11% (year 5) to 13% (year 10); median area decreased slightly.
    • Late AMD in zone 2: Increased from 14% to 22% (mostly nAMD extensions from macula).
  • Substantial Peripheral Findings
    • Defined as ≥1 disc area of drusen, hyperpigmentation, or hypopigmentation in zones 2/3.
    • Present in 57% of eyes at year 5; more common with higher AMDSS (75% in levels 6–8 vs. 48% in 3–5).
    • No association with increased risk of progression to late AMD; 41% progression rate in eyes with AMDSS 6–8, with or without substantial peripheral findings.
  • Fundus Autofluorescence (FAF) Findings
    • FAF enhances visualization of GA and RPD.
    • GA: 53 eyes (year 5, mean area 3.4 mm²) to 91 eyes (year 10, mean area 7.7 mm²).
    • Reticular autofluorescence pattern: 22% (year 5) to 39% (year 10).
    • Abnormal FAF increased across zones (e.g., 84% to 93% in zone 1).
  • Comparison of UWF vs. Standard Color Photography
    • 95% agreement within 2 AMDSS steps; exact agreement in 60.5%, 1-step difference in 34%.
    • Progression to late AMD: 87% agreement (κ=0.70).
    • UWF and standard imaging not interchangeable due to low exact agreement, but comparable for macular assessments.
  • Clinical Implications
    • AMD is likely a panretinal disease; peripheral drusen correlate with macular AMD severity but do not predict progression to late AMD.
    • Peripheral findings may contribute to symptoms like impaired dark adaptation and low-contrast vision.
    • UWF imaging valuable for comprehensive retinal assessment but requires standardization.
  • Statistical and Methodological Notes
    • Analysis at eye level; gradable images: 99% (zone 2), 46–58% (zone 3).
    • Intergrader agreement: 82% within 1 AMDSS step, 71% for late AMD, 78% for RPD.
    • Participants in OPERA 10-year subset were younger (69.9 vs. 74.0 years) with lower diabetes rates (5.8% vs. 13.0%).

Citation

Froines CP, Pak JW, Agrón E, Chew EY, Peto T, Blodi BA, Domalpally A. Longitudinal Assessment of Age-Related Macular Degeneration Using Ultrawidefield Imaging: The Optos Peripheral Retina Follow-up Study. Ophthalmology. 2025;132(5):569-577. doi:10.1016/j.ophtha.2024.11.024.