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Christine A Curcio, Jeffrey D Messinger, Yuhua Zhang, David Neely, K Bailey Freund, Richard F Spaide; Histological stages of subretinal drusenoid deposits (SDD) in eyes with age-related macular degeneration (AMD). Invest. Ophthalmol. Vis. Sci. 2016;57(12):No Pagination Specified.
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To guide clinical and laboratory studies of SDD lifecycle we seek correlates for the 3- and 4-stage SDD scales   and for imaging-revealed features of dynamism [3,4], dots-ribbons , outer retinal atrophy , peripapillary SDD [6,7], hyperreflective spots ).
Eyes from 82 white donors with AMD and one eye of a clinically imaged 98-year-old donor with neovascular AMD and abundant SDD  were processed for macula-wide high-resolution sections (http://projectmacula). In fovea and superior perifovea of 32 eyes, 79 examples of SDD attached to photoreceptors were photodocumented and assessed (early AMD, n=15; geographic atrophy; n=10, neovascular AMD, n=8).
The smallest SDD observed were solitary 4 µm-diameter dollops. Bundled retinal pigment epithelium (RPE) apical processes with melanosomes embraced lesions and maintained contact with outer segments. Bundles punctuated confluent lesions and were less visible in extensive lesions. Disintegrated SDD material infiltrated among photoreceptor inner and outer segments, rarely occupying gaps in the outer nuclear layer (ONL). Outer retinal atrophy corresponded to shortened photoreceptors and thinned ONL over RPE with continuous basal laminar deposit. In the previously imaged patient, reflective transdifferentiated RPE in the subretinal space and within the retina associated with SDD. As described , macular SDD were finely granular and distinct from outer segments, RPE lipofuscin, and basal laminar/ linear deposit. SDD with vesicular contents were seen in the peripapillary area only.
Histological observations of SDD reveal an intimate proximity to photoreceptors, particularly as lesions progress. Our current data do not support stage 4 as originally described, because SDD material internal to the ELM was infrequent. Cells participating in SDD clearance could be photoreceptors, RPE, or Müller cells. Importantly other cells with potential clearance capacity like macrophages or microglia were not seen. Association of sloughed RPE with SDD warrants investigation.1. Zweifel. Ophthalmology. 2010;117.2. Querques. IOVS. 2012;53:1264.3. Spaide. Retina. 2013;33:1800.4. Wang. ARVO Meeting Abstracts. 2014;55:3529.5. Suzuki. Retina. 2015;35:859.6. Oak. Retina. 2014;34:825.7. Zarubina. Ophthalmology. in revision.8. Curcio. Am J Ophthalmol. 2015; online.9. Curcio. Retina. 2013;33:265.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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