Cláudia Farinha1,2,3, Ana Luísa Silva4, Rita Coimbra5, Sandrina Nunes5, Maria Luz Cachulo5,6,4, João Pedro Marques5,6,4, Isabel Pires5,6,4, José Cunha-Vaz5,4, Rufino Silva5,6,4,7. 1. Association for Innovation and Biomedical Research on Light and Image (AIBILI), Coimbra, Portugal. 10114@chuc.min-saude.pt. 2. Department of Ophthalmology, Centro Hospitalar e Universitário de Coimbra (CHUC), Praceta Mota Pinto, 3000, Coimbra, Portugal. 10114@chuc.min-saude.pt. 3. Faculty of Medicine, University of Coimbra (FMUC), Coimbra, Portugal. 10114@chuc.min-saude.pt. 4. Faculty of Medicine, University of Coimbra (FMUC), Coimbra, Portugal. 5. Association for Innovation and Biomedical Research on Light and Image (AIBILI), Coimbra, Portugal. 6. Department of Ophthalmology, Centro Hospitalar e Universitário de Coimbra (CHUC), Praceta Mota Pinto, 3000, Coimbra, Portugal. 7. Coimbra Institute for Clinical and Biomedical Research, Faculty of Medicine, University of Coimbra (iCBR- FMUC), Coimbra, Portugal.
Abstract
PURPOSE: This study aims to analyze the retinal layers and choroidal thickness in a large set of eyes with early age-related macular degeneration (AMD), in order to detect differences by stage suggestive of early neurodegeneration, and to explore biomarkers of different phenotypes. METHODS: This study is a population-based, cross-sectional study. Patients from the incidence AMD study (NCT02748824) with early AMD (Rotterdam 2a, 2b, 3) were included. All performed spectral-domain optical coherence tomography (SD-OCT) (Spectralis, Heidelberg Engineering, Germany) and automatic segmentation of all retinal layers was obtained with built-in software. Manual correction was performed whenever necessary. The mean thicknesses (ETDRS grid) and volume of each layer were recorded. Subfoveal choroidal thickness was manually measured. Estimates for each layer thickness were calculated with linear mixed models and tested for pairwise differences between stages. Associations between layer thickness and microstructural findings were assessed by multivariate regression analysis. RESULTS: The final cohort comprised 346 eyes (233 patients): 82.66% (n = 286) in stage 2a, 5.49% (n = 19) in stage 2b, and 11.85% (n = 41) in stage 3. A global tendency for lower/inferior thickness of the neuroretinal layers was found comparing stage 3 to 2a: retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), and inner plexiform layer (IPL) were inferior in the inner/outer ETDRS circles and the outer nuclear layer (ONL) and photoreceptors' segments layer in the central circle (p ≤ 0.002). The retinal pigment epithelium-Bruch's membrane (RPE/BrM) layer was thicker in stage 3 (p ≤ 0.001). Subretinal drusenoid deposits (SDD) were associated with thinner neuroretinal layers and choroid (p < 0.05). CONCLUSIONS: Our results showed in a large population-based dataset that several inner and outer neuroretinal layers were thinner with a higher stage in early AMD. These findings support the existence of early and progressive neurodegeneration. Neuronal retinal layer thicknesses might thus be used as quantitative biomarkers of disease progression in AMD. The presence of SDD is possibly associated to more prominent and faster neurodegeneration.
PURPOSE: This study aims to analyze the retinal layers and choroidal thickness in a large set of eyes with early age-related macular degeneration (AMD), in order to detect differences by stage suggestive of early neurodegeneration, and to explore biomarkers of different phenotypes. METHODS: This study is a population-based, cross-sectional study. Patients from the incidence AMD study (NCT02748824) with early AMD (Rotterdam 2a, 2b, 3) were included. All performed spectral-domain optical coherence tomography (SD-OCT) (Spectralis, Heidelberg Engineering, Germany) and automatic segmentation of all retinal layers was obtained with built-in software. Manual correction was performed whenever necessary. The mean thicknesses (ETDRS grid) and volume of each layer were recorded. Subfoveal choroidal thickness was manually measured. Estimates for each layer thickness were calculated with linear mixed models and tested for pairwise differences between stages. Associations between layer thickness and microstructural findings were assessed by multivariate regression analysis. RESULTS: The final cohort comprised 346 eyes (233 patients): 82.66% (n = 286) in stage 2a, 5.49% (n = 19) in stage 2b, and 11.85% (n = 41) in stage 3. A global tendency for lower/inferior thickness of the neuroretinal layers was found comparing stage 3 to 2a: retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), and inner plexiform layer (IPL) were inferior in the inner/outer ETDRS circles and the outer nuclear layer (ONL) and photoreceptors' segments layer in the central circle (p ≤ 0.002). The retinal pigment epithelium-Bruch's membrane (RPE/BrM) layer was thicker in stage 3 (p ≤ 0.001). Subretinal drusenoid deposits (SDD) were associated with thinner neuroretinal layers and choroid (p < 0.05). CONCLUSIONS: Our results showed in a large population-based dataset that several inner and outer neuroretinal layers were thinner with a higher stage in early AMD. These findings support the existence of early and progressive neurodegeneration. Neuronal retinal layer thicknesses might thus be used as quantitative biomarkers of disease progression in AMD. The presence of SDD is possibly associated to more prominent and faster neurodegeneration.
Entities:
Keywords:
Biomarkers of AMD progression; Early age-related macular degeneration; Microstructural spectral-domain optical coherence tomography analysis; Retinal layers and choroidal thicknesses; Subretinal drusenoid deposits
Authors: C C Klaver; J J Assink; R van Leeuwen; R C Wolfs; J R Vingerling; T Stijnen; A Hofman; P T de Jong Journal: Invest Ophthalmol Vis Sci Date: 2001-09 Impact factor: 4.799
Authors: Matt Trinh; Natalie Eshow; David Alonso-Caneiro; Michael Kalloniatis; Lisa Nivison-Smith Journal: Invest Ophthalmol Vis Sci Date: 2022-10-03 Impact factor: 4.925