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Purpose: Hypo-reflective clumps (HRCs) are structures associated with age-related macular degeneration (AMD) that were identified using flood-illumination adaptive optics ophthalmoscopy (FIAO) and hypothesized to be either macrophages that have accumulated melanin through the phagocytosis of retinal pigmented epithelial (RPE) cell organelles or transdifferentiated RPE cells. HRCs may be autofluorescent (AF) in the near infrared (NIR) but clinical NIR autofluorescence imaging lacks the resolution to answer this question definitively. Here, we used near infrared autofluorescence (NIRAF) imaging in fluorescence adaptive optics scanning laser ophthalmoscopy (AOSLO) to determine whether HRCs are AF., Methods: Patients with AMD and HRCs underwent imaging with FIAO, optical coherence tomography (OCT), and multi-modal AOSLO (confocal, NIRAF, and non-confocal multi-offset detection using a fiber bundle). HRCs were segmented on FIAO and images, co-registered across modalities, and HRC morphometry and AF were quantified., Results: Eight patients participated (mean age = 79 years, standard deviation [SD] = 5.7, range = 69-89 years, and 5 female patients). Most HRCs (86%, n = 153/178) were autofluorescent on AOSLO. HRC AF signal varied but most uniformly dark HRCs on FIAO showed corresponding AF on AOSLO, whereas heterogeneous HRCs showed a smaller AF area or no AF., Conclusions: These findings are consistent with the hypothesis that HRCs contain AF RPE organelles. A small proportion of HRCs were not AF; these may represent macrophages that have not yet accumulated enough organelles to become AF. HRCs may have clinical significance but further study is needed to understand the interplay among HRCs, RPE cells, and macrophages, and their relationship to geographic atrophy (GA) progression in AMD.

Purpose: This study aims at linking subtle changes of fixational eye movements (FEM) in controls and in patients with foveal drusen using adaptive optics retinal imaging in order to find anatomo-functional markers for pre-symptomatic age-related macular degeneration (AMD)., Methods: We recruited 7 young controls, 4 older controls, and 16 patients with presymptomatic AMD with foveal drusen from the Silversight Cohort. A high-speed research-grade adaptive optics flood illumination ophthalmoscope (AO-FIO) was used for monocular retinal tracking of fixational eye movements. The system allows for sub-arcminute resolution, and high-speed and distortion-free imaging of the foveal area. Foveal drusen position and size were documented using gaze-dependent imaging on a clinical-grade AO-FIO., Results: FEM were measured with high precision (RMS-S2S = 0.0015 degrees on human eyes) and small foveal drusen (median diameter = 60 µm) were detected with high contrast imaging. Microsaccade amplitude, drift diffusion coefficient, and ISOline area (ISOA) were significantly larger for patients with foveal drusen compared with controls. Among the drusen participants, microsaccade amplitude was correlated to drusen eccentricity from the center of the fovea., Conclusions: A novel high-speed high-precision retinal tracking technique allowed for the characterization of FEM at the microscopic level. Foveal drusen altered fixation stability, resulting in compensatory FEM changes. Particularly, drusen at the foveolar level seemed to have a stronger impact on microsaccade amplitudes and ISOA. The unexpected anatomo-functional link between small foveal drusen and fixation stability opens up a new perspective of detecting oculomotor signatures of eye diseases at the presymptomatic stage.

Purpose: To report the findings of en face adaptive optics (AO) near infrared (NIR) reflectance fundus flood imaging in eyes with geographic atrophy (GA)., Methods: Observational clinical study of AO NIR fundus imaging was performed in 12 eyes of nine patients with GA, and in seven controls using a flood illumination camera operating at 840 nm, in addition to routine clinical examination. To document short term and midterm changes, AO imaging sessions were repeated in four patients (mean interval between sessions 21 days; median follow up 6 months)., Results: As compared with scanning laser ophthalmoscope imaging, AO NIR imaging improved the resolution of the changes affecting the RPE. Multiple hyporeflective clumps were seen within and around GA areas. Time-lapse imaging revealed micrometric-scale details of the emergence and progression of areas of atrophy as well as the complex kinetics of some hyporeflective clumps. Such dynamic changes were observed within as well as outside atrophic areas., Conclusions: in eyes affected by GA, AO nir imaging allows high resolution documentation of the extent of RPE damage. this also revealed that a complex, dynamic process of redistribution of hyporeflective clumps throughout the posterior pole precedes and accompanies the emergence and progression of atrophy. therefore, these clumps are probably also a biomarker of rpe damage. AO NIR imaging may, therefore, be of interest to detect the earliest stages, to document the retinal pathology and to monitor the progression oF GA. (ClinicalTrials.gov number, NCT01546181.).