Structure function correlation of high resolution retinal imaging in early age-related macular degeneration and physiological aging

• Applicant: Dr. Lukas Goerdt
• Subject Area: Ophthalmology
• Term: from 2023 to 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 531685551

• Final Report Year: 2025

Final Report Abstract

Age-related macular degeneration (AMD) is a leading cause of blindness in high-income countries. Late-stage neovascular AMD is treated with anti-VEGF agents, while atrophic AMD now has complement inhibitors. Oral xanthophylls (Lutein, Zeaxanthin) may slow atrophy progression, but treatments for earlier stages—before irreversible vision loss—are still needed. Identifying at-risk eyes is crucial for understanding AMD and developing trial endpoints. Rod-mediated dark adaptation (RMDA) measures retinoid resupply to rods via the choriocapillaris, Bruch’s membrane, and RPE. Impaired RMDA doubles AMD risk over three years and predicts progression, but testing is time-consuming and strenuous for elderly patients. The ALSTAR2 study explores structural-functional links in aging, AMD onset, and progression. We correlated subretinal drusenoid deposits (SDD), a high-risk AMD feature, with RMDA. SDD first appears near the optic nerve, and is most abundant at 1.5° superior to the fovea, coinciding with the RMDA test target location. SDD extent correlated with RMDA (r=0.27, p<0.01), supporting the role of choriocapillaris impairment in AMD. A key goal was testing fluorescence lifetime imaging ophthalmoscopy (FLIO) long spectral channel (LSC) lifetimes against visual functions. LSC lifetimes were shown to be prolonged in AMD and 25% of healthy eyes. LSC lifetimes of the outer ring of the early treatment of diabetic retinopathy study (ETDRS) grid correlated most strongly with RMDA (r=0.68, p<0.01) compared to any other imaging biomarker for AMD, suggesting that FLIO holds the potential to identify eyes at risk for AMD development and early progression. We also studied macular xanthophyll pigment (MXP), measured as macular pigment optical density (MPOD), using two-wavelength autofluorescence. MXP accumulates around the foveal center and is higher in intermediate vs. early AMD and normal aging. These findings challenge the idea that AMD is MXP-deficient. This raises new questions about xanthophylls’ mechanism in slowing atrophy progression. Finally, we used <3 µm OCT to investigate retinal bands. We identified 28 distinct retinal bands, and matched them to their respective anatomical structures visible in histology, immunofluorescence, and volume electron microscopy. These bands were reliably assessable and reflect age- and disease-related changes of the retinal anatomy. Knowledge of the cellular and subcellular structures underlying retinal bands visible on OCT is key for improving clinical care and the interpretation of research findings.

Publications

• A cell culture system for RPE hypoxia, a physiologic stressor relevant to AMD deposit formation. Eye, 39(4), 611-612.
  Curcio, Christine A. & Goerdt, Lukas
  
• Band Visibility in High-Resolution Optical Coherence Tomography Assessed With a Custom Review Tool and Updated, Histology-Derived Nomenclature. Translational Vision Science & Technology, 13(12), 19.
  Goerdt, Lukas; Swain, Thomas A.; Kar, Deepayan; McGwin, Gerald; Berlin, Andreas; Clark, Mark E.; Owsley, Cynthia; Sloan, Kenneth R. & Curcio, Christine A.
  
• Extent and Topography of Subretinal Drusenoid Deposits Associate With Rod-Mediated Vision in Aging and AMD: ALSTAR2 Baseline. Investigative Ophthalmology & Visual Science, 65(10), 25.
  Goerdt, Lukas; Amjad, Mohymina; Swain, Thomas A.; McGwin, Gerald; Clark, Mark E.; Owsley, Cynthia; Sloan, Kenneth R.; Curcio, Christine A. & Kar, Deepayan
  
• Outer Retinal Thickness Is Associated With Cognitive Function in Normal Aging to Intermediate Age-Related Macular Degeneration. Investigative Ophthalmology & Visual Science, 65(5), 16.
  Owsley, Cynthia; McGwin, Gerald; Swain, Thomas A.; Clark, Mark E.; Thomas, Tracy N.; Goerdt, Lukas; Sloan, Kenneth R.; Trittschuh, Emily H.; Jiang, Yu; Owen, Julia P.; Lee, Cecilia S. & Curcio, Christine A.
  
• Delayed Rod-Mediated Dark Adaptation Is Associated with Incidence and Early Progression of Age-Related Macular Degeneration. Ophthalmology, 132(11), 1273-1283.
  Owsley, Cynthia; McGwin, Gerald; Clark, Mark E.; Gao, Liyan; Gooden, Lindsay; Thomas, Tracy N.; Goerdt, Lukas & Curcio, Christine A.
  
• Fluorescence Lifetime Imaging Ophthalmoscopy, Vision, and Chorioretinal Asymmetries in Aging and Age-Related Macular Degeneration: ALSTAR2. Investigative Ophthalmology & Visual Science, 66(4), 56.
  Goerdt, Lukas; Clark, Mark E.; Thomas, Tracy N.; Gao, Liyan; McGwin, Gerald; Hammer, Martin; Crosson, Jason N.; Sloan, Kenneth R.; Owsley, Cynthia & Curcio, Christine A.
  
• Outer Retinal Thinning is Associated With Brain Atrophy in Early Age-Related Macular Degeneration. American Journal of Ophthalmology, 269, 457-465.
  Jiang, Yu; Swain, Thomas; Gim, Nayoon; Blazes, Marian; Donald, Christine Mac; Rokem, Ariel; Owen, Julia P.; Balu, Niranjan; Clark, Mark E.; Goerdt, Lukas; McGwin, Gerald; Hunt, David; Curcio, Christine A.; Levendovszky, Swati Rane; Trittschuh, Emily H.; Owsley, Cynthia & Lee, Cecilia S.
  
• Topographic Analysis of Two-Wavelength Autofluorescence Supports Higher Macular Xanthophyll Pigment in AMD Than Aging: ALSTAR2 Baseline. Investigative Ophthalmology & Visual Science, 66(3), 61.
  Goerdt, Lukas; Berlin, Andreas; Gao, Liyan; Swain, Thomas A.; Kim, Sarah S.; McGwin, Gerald; Clark, Mark E.; Kar, Deepayan; Owsley, Cynthia; Sloan, Kenneth R. & Curcio, Christine A.