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Concetta Li Calzi, Michel Paques, Florian Sennlaub, Kiyoko Gocho, Jose Alain Sahel, mustapha benchaboune; Evidence of subretinal migration of melanin-loaded cells during dry age-related macular degeneration. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):5133.
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© ARVO (1962-2015); The Authors (2016-present)
During dry age-related macular degeneration (ARMD), adaptative optics (AO) en face flood imaging improves the resolution of pigmentary changes (Gocho et al, IOVS 2013). This led to the discovery of the presence of numerous migrating hyporeflective clumps within and around atrophic areas. The most likely explanation of these images is taht they are due to the migration of melanin-loaded cells (MLCs).<br /> Here, we explored in more details the kinetics of MLCs.
Observational clinical study.4°x4° AO fundus images were obtained with a commercially available flood imaging AO camera (rtx1; Imagine Eyes, Orsay, France) within an IRB-approved clinical study in eyes with dry AMD (n=4). Care was taken to capture the progression front. The migration of MLCs was documented by time-lapse imaging (mean interval between sessions 26 days; median follow-up 5 months).
Multiple MLCs were seen to migrate within as well at outside of atrophic areas. Approximately 65% of hypereflective clumps were seen to migrate during the observation period. Their mean diameter was 19µm. The density of MLCs ranged from 300 to 800 per mm2. The linear velocity of MLCs peaked at 1um/day. The behaviour of migrating MLCs was somewhat random, with in many adjacent MLCs migrating in opposite directions; however, focal agregations of MLCs were present. Agregation and disaggration of MLCs accounted for the evolution of large pigmentary clumps. The cone mosaic was seen over MLCs in 48% of cases.
During dry ARMD, extensive subretinal migration of MLCs throughout the posterior pole is commonly observed, in atrophic as well as in nonatrophic areas. To our knowledge, this is the first demonstration of such subretinal migration. It is likely that these MLCs correspond to the hypereflective dots reported by optical coherence tomography (Coscas et al, 2013). The nature of these cells and their role in the process of ARMD remains to be clarified; likely candidates are sloughed RPE cells (Curcio et al, IOVS 1998) and macrophages. The subretinal space appears thus as a permissive milieu for the transmission of cellular inputs. The random migration is reminiscent of the behaviour of patrolling, non activated inflammatory cells. We therefore believe that this finding may have important consequences for the understanding and monitoring of dry ARMD, as well as for the validation of experimental models of ARMD.
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