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Retinal Thickness Changes throughout the Natural History of Drusen in Age-related Macular Degeneration

Nivison-Smith, Lisa, PhD, BSc, FAAO1,2*; Wang, Henrietta, BSc, BOptom1,2; Assaad, Nagi, MBioMedE, BSc(Med), MBBS2,3; Kalloniatis, Michael, PhD, MScOptom, FAAO1,2

doi: 10.1097/OPX.0000000000001256

SIGNIFICANCE Drusen are associated with retinal thinning in age-related macular degeneration (AMD). These changes, however, have mostly been examined at single time points, ignoring the evolution of drusen from emergence to regression. Understanding the full breadth of retinal changes associated with drusen will improve understanding of disease pathogenesis.

PURPOSE The purpose of this study was to assess how the natural history of drusen affects retinal thickness, focusing on the photoreceptor and retinal pigment epithelium (RPE) layers.

METHODS Spectral domain optical coherence tomography of subjects with intermediate AMD (n = 50) who attended the Centre for Eye Health, Sydney, Australia, for two separate visits (476 ± 16 days between visits) was extracted. Scans were automatically segmented with manufacturer software then assessed for drusen that had emerged, grown, or regressed between visits. For each identified lesion, the thickness of each retinal layer at the drusen peak and at adjacent drusen-free areas (150 μm nasal and temporal to the druse) was compared between visits.

RESULTS Before drusen emergence, the RPE was significantly thicker at the drusen site (14.2 ± 2.6%) compared with neighboring drusen-free areas. There was a 71% sensitivity of RPE thickening predicting drusen emergence. Once drusen emerged, significant thinning of all outer retinal layers was observed, consistent with previous studies. Drusen growth was significantly correlated with thinning of the outer retina (r = −0.38, P < .001). Drusen regression resulted in outer retinal layers returning to thicknesses not significantly different from baseline.

CONCLUSIONS The natural history of drusen is associated with RPE thickening before drusen emergence, thinning of the outer nuclear layer as well as photoreceptor and RPE layers proportional to drusen growth, and return to baseline thickness after drusen regression. These findings have useful clinical applications, providing a potential marker for predicting drusen emergence for AMD prognostic and intervention studies and highlighting that areas of normal retinal thickness in AMD may be former sites of regressed drusen.

1School of Optometry and Vision Science, University of New South Wales, Sydney, New South Wales, Australia

2Centre for Eye Health, University of New South Wales, Sydney, New South Wales, Australia

3Department of Ophthalmology, Prince of Wales Hospital, Randwick, New South Wales, Australia *

Supplemental Digital Content: Appendix Figure A1, (A) Percentage change in thickness of each retinal layer above drusen compared with neighboring drusen-free areas (available at and (B) comparison of these thickness changes to Rogala et al.13 where measurements were made manually for the same lesions (available at Some retinal layers in automated segmentation of (A) analysis were pooled to create the same composite layers used in Rogala et al.13 RPE = retinal pigment epithelium; PR = photoreceptor layer; ONL = outer nuclear layer; OPL = outer plexiform layer; INL = inner nuclear layer; IPL = inner plexiform layer; GCL = ganglion cell layer.

Submitted: January 28, 2018

Accepted: May 7, 2018

Funding/Support: National Health and Medical Research Council of Australia (1033224; to MK); UNSW Sydney (Early Career Research Grant 2015 and 2016; to LN-S); and Guide Dogs NSW/ACT (to MK).

Conflict of Interest Disclosure: None of the authors have reported a financial conflict of interest.

Author Contributions and Acknowledgments: Conceptualization: LN-S; Data Curation: LN-S, HW; Formal Analysis: LN-S, MK; Funding Acquisition: LN-S, MK; Investigation: LN-S, HW, NA; Methodology: LN-S, HW; Project Administration: LN-S; Resources: MK; Supervision: LN-S, MK; Validation: LN-S, NA; Visualization: LN-S; Writing – Original Draft: LN-S; Writing – Review & Editing: LN-S, HW, NA, MK.

The authors thank Adrian Wong, Simone Yip, Sally Vi Hoang, Hung Ton, and Cornelia Zangerl for technical assistance.

Supplemental Digital Content: Direct URL links are provided within the text.

© 2018 American Academy of Optometry