The Life Cycle of Soft Drusen in Age-related Macular Degeneration

Anthony Barrett ¹, Hannah Kamgarpour ¹, Jackson Siskovic ¹, Svetlana Cherepanoff ^{1, 2, 3}
1. The University of Notre Dame Australia, School of Medicine 2 St Vincent’s Hospital Sydney 3 UNSW Sydney

Background:

Age-related macular degeneration (AMD) is the leading cause of blindness in elderly Australians1. Australians in regional and remote areas are less likely to be able to access anti-VEGF treatment for neovascular AMD2. Soft drusen are the hallmark lesions of AMD3, and their presence is a major intraocular risk factor for progression to advanced AMD including neovascular AMD4. However, soft drusen may regress over time5.

Aim:

This project aims to describe the lifecycle of soft drusen by correlating their clinical appearance with their contents on histology, and the severity of AMD.

Methods:

86 eyes (54 patients; 46M/8F) with soft drusen on histology were selected from a clinically and histologically validated archive of over 600 eyes. All study eyes had documented full ophthalmic examination during life. Eyes were excluded if there was other retinal pathology or inadequate fundus visualisation. 71 eyes were prepared for light microscopy (LM) and 15 eyes for transmission electron microscopy (EM) according to published protocols6. Soft drusen contents and clinical fundus appearance were correlated to the thickness and type (early/late) of known AMD histological marker of severity, basal lamina deposit (BLamD).

Results: 

In eyes with thin continuous early-type BLamD, soft drusen contents were pale and washed-out on LM, consisted of lipid rich membranous vesicles on EM, and appeared yellow and indistinct clinically. In eyes with thick continuous early-type  BLamD, soft drusen contents were more likely to have a granular appearance, staining red and blue with picro-Mallory stain on LM, appeared more electron-dense on EM, and were whiter and more distinct clinically. In eyes with thick continuous BLamD and geographic atrophy, soft drusen contents were often lost or replaced with calcification or fibrous tissue. Clinically, these regressed soft drusen may vanish with only calcification remaining visible.    

Conclusion:

Soft drusen undergo a lifecycle of formation and regression. Early soft drusen contain membranous debris. Soft drusen regression is associated with thick continuous and late-type BLamD, and is marked by the presence of granular contents, calcification, collapse, fibrosis and precedes geographic atrophy. Clinically, soft drusen may appear as yellow and indistinct, white and more distinct and can vanish, as their contents change with regression.

Statement of Originality: This study was conceived by Dr. Shirley Sarks, with assistance from Prof. Svetlana Cherepanoff. Data collection and analysis were carried out collaboratively by Anthony Barrett, Hannah Kamgarpour, Jackson Siskovic, Dr. Shirley Sarks, and Prof. Svetlana Cherepanoff.

References:

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