September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Histological stages of subretinal drusenoid deposits (SDD) in eyes with age-related macular degeneration (AMD)
Author Affiliations & Notes
  • Christine A Curcio
    Ophthalmology, Univ of Alabama at Birmingham, Birmingham, Alabama, United States
  • Jeffrey D Messinger
    Ophthalmology, Univ of Alabama at Birmingham, Birmingham, Alabama, United States
  • Yuhua Zhang
    Ophthalmology, Univ of Alabama at Birmingham, Birmingham, Alabama, United States
  • David Neely
    Ophthalmology, Univ of Alabama at Birmingham, Birmingham, Alabama, United States
  • K Bailey Freund
    Vitreous Retina Macula Consultants of New York, New York, New York, United States
    LuEsther T. Mertz Retinal Research Center, Manhattan Eye, Ear, and Throat Hospital Manhattan Eye, Ear, and Throat Hospital, New York, New York, United States
  • Richard F Spaide
    Vitreous Retina Macula Consultants of New York, New York, New York, United States
    LuEsther T. Mertz Retinal Research Center, Manhattan Eye, Ear, and Throat Hospital Manhattan Eye, Ear, and Throat Hospital, New York, New York, United States
  • Footnotes
    Commercial Relationships   Christine Curcio, Genentech (C), Janssen Cell Therapy (C), Merck (C); Jeffrey Messinger, None; Yuhua Zhang, None; David Neely, None; K Bailey Freund, Genentech (C), Heidelberg Engineering (C), Ohr Pharmaceutical (C), Optos (C), Optovue (C), REGENXBIO (C), ThromboGenics (C); Richard Spaide, Bausch and Lomb (C), Genentech (C), Topcon (C)
  • Footnotes
    Support  2014 von Sallmann Prize; EyeSight Foundation of Alabama; Research to Prevent Blindness; NEI EY06109; NEI P30 EY003039, Edward N. and Della L. Thome Foundation, Beckman Initiative for Macular Research, Macula Foundation
Investigative Ophthalmology & Visual Science September 2016, Vol.57, No Pagination Specified. doi:
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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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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : To guide clinical and laboratory studies of SDD lifecycle we seek correlates for the 3- and 4-stage SDD scales [1] [2] and for imaging-revealed features of dynamism [3,4], dots-ribbons [5], outer retinal atrophy [3], peripapillary SDD [6,7], hyperreflective spots [2]).

Methods : Eyes from 82 white donors with AMD and one eye of a clinically imaged 98-year-old donor with neovascular AMD and abundant SDD [8] 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).

Results : 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 [9], 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.

Conclusions : 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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