Progressive Dysmorphia of Retinal Pigment Epithelium in Age-Related Macular Degeneration Investigated by Fluorescence Lifetime Imaging

PURPOSE: The purpose of this study was to observe changes of the retinal pigment epithelium (RPE) on the transition from dysmorphia to atrophy in age-related macular degeneration (AMD) by fluorescence lifetime imaging ophthalmoscopy (FLIO). METHODS: Multimodal imaging including color fundus photography (CFP), optical coherence tomography (OCT), fundus autofluorescence (FAF) imaging, and FLIO was performed in 40 eyes of 37 patients with intermediate AMD and no evidence for geographic atrophy or macular neovascularization (mean age = 74.2 ± 7.0 years). Twenty-three eyes were followed for 28.3 ± 18.3 months. Seven eyes had a second follow-up after 46.6 ± 9.0 months. Thickened RPE on OCT, hyperpigmentation on CFP, hyper-reflective foci (HRF) on OCT, attributed to single or clustered intraretinal RPE, were identified. Fluorescence lifetimes in two spectral channels (short-wavelength spectral channel [SSC] = 500–560 nm, long-wavelength spectral channel [LSC] = 560–720 nm) as well as emission spectrum intensity ratio (ESIR) of the lesions were measured by FLIO. RESULTS: As hyperpigmented areas form and RPE migrates into the retina, FAF lifetimes lengthen and ESRI of RPE cells increase. Thickened RPE showed lifetimes of 256 ± 49 ps (SSC) and 336 ± 35 ps (LSC) and an ESIR of 0.552 ± 0.079. For hyperpigmentation, these values were 317 ± 68 ps (p < 0.001), 377 ± 56 ps (P < 0.001), and 0.609 ± 0.081 (P = 0.001), respectively, and for HRF 337 ± 79 ps (P < 0.001), 414 ± 50 ps (P < 0.001), and 0.654 ± 0.075 (P < 0.001). CONCLUSIONS: In the process of RPE degeneration, comprising different steps of dysmorphia, hyperpigmentation, and migration, lengthening of FAF lifetimes and a hypsochromic shift of emission spectra can be observed by FLIO. Thus, FLIO might provide early biomarkers for AMD progression and contribute to our understanding of RPE pathology.