Abstract
Purpose::
To describe the light and electron microscopic appearance of soft drusen in AMD eyes and their relationship to basal laminar deposit (BLamD), retinal pigment epithelial (RPE) abnormalities, subclinical choroidal neovacularisation (CNV), and fundus appearance.
Methods::
Eyes with histopathologically defined soft drusen were selected from a large clinicopathological series. Soft drusen were found in eyes with (i) thin continuous BLamD (31); (ii) thick continuous BLamD (17); (iii) geographic atrophy (22); or (iv) disciform scarring (10). All eyes were examined clinically (best corrected visual acuity, direct fundoscopy and fundus photography) during life, with 0-120 months follow up. Eyes were excluded if the fundus could not be adequately visualised or if other pathology was present. Eighty eyes (50 patients) were included in the study (54 LM, 26 EM) with 8-40 sections examined per eye. Soft drusen size and contents were correlated to BLamD, RPE abnormalities, subclinical CNV and fundus appearance.
Results::
All soft drusen lay within and area 2000µm temporal and 1500µm nasal of the fovea. Soft drusen measured 30-250µm in width (up to 500µm when confluent) and 40-50µm in height. Drusen <65µm were only seen in eyes with thin, continuous BLamD. Intermediate (65-125µm) and large (>125µm) drusen were present in eyes with both thin and thick continuous BLamD. Drusen contents were membranous when early type BLamD was present and became granular in the presence of late type BLamD and increasing histological RPE abnormalities. Clinically, regressing drusen appeared yellower or whiter, with more distinct margins. Associated pigment changes were: a single clump, stippling or a pigment figure. Focal loss of RPE accompanied fading drusen, often leaving foci of calcification. In GA eyes, granular contents were found in all drusen. Many had a collapsed appearance, and contents were often replaced by calcification, cells or avascular fibrous tissue. Subclinical CNV was found in 32% of GA eyes. In disciform scarring, membranous drusen were found in 60% of eyes.
Conclusions::
Soft drusen appear to follow a cycle of formation and regression, first appearing as small, membranous accentuations of BLinD when a continuous layer of BLamD is present. Drusen regression, marked by the presence of granular contents, collapse, calcification and replacement by cells, is associated with production of late type BLamD and RPE failure. Clinically, this is seen initially as regressing drusen with pigment changes and later as fading drusen with focal RPE loss.
Keywords: age-related macular degeneration • pathology: human • clinical (human) or epidemiologic studies: natural history