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Br J Ophthalmol. 1999 March; 83(3): 358–368.
PMCID: PMC1722952

Early drusen formation in the normal and aging eye and their relation to age related maculopathy: a clinicopathological study

Abstract

AIM—To describe the early formation of drusen and their relation to normal aging changes at the macula and to the development of age related maculopathy (ARM).
METHOD—Histopathological features of 353 eyes without histological evidence of ARM are described and correlated with the clinical appearance. In addition, 45 of these eyes were examined by transmission electron microscopy.
RESULTS—Drusen were detected histopathologically in 177 (50%) eyes but were seen clinically in only 34% of these. Drusen were mainly small hard drusen with an occasional soft distinct drusen: no soft indistinct drusen were seen. Only those drusen deposits larger than 25-30 µm in diameter were detectable clinically. Preclinical drusen in eyes with only an occasional drusen were seen on electron microscopy as entrapment sites of coated membrane bound bodies which formed adjacent to the inner collagenous zone of Bruch's membrane. In contrast, preclinical drusen deposits in eyes with many drusen were seen as accumulations of amorphous material which appeared hyalinised by light microscopy. A distinct feature were rows of dense hyalinised microdrusen (1-2 µm in diameter), over which larger globular hyalinised drusen formed.
CONCLUSION—Histological and ultrastructural examination can recognise and distinguish the earliest drusen formed as a result of normal aging from those associated with ARM. In eyes without diffuse deposits, histologically all drusen were of the hard hyalinised variety or their derivatives; no soft drusen composed of membranous debris were found. These findings support and explain those of other authors who do not consider the presence of a few small hard drusen to be a risk factor for the development of ARM.

Keywords: aging; macular degeneration; retinal drusen; entrapment

Figure 1
Basal lamina deposit over drusen of mixed composition. (A) Earliest BLD from a group 2 eye consisting of irregular nodules of fibrillar material (arrow) continuous with the RPE basement membrane; there is no membranous debris. (B) In comparison, ...
Figure 2
Electron lucent droplets forming a layer three to four rows deep beneath the RPE basement membrane (white arrow) and also beneath and over the apex of a small clinical drusen composed of amorphous material. 79 year old man with normal fundal ...
Figure 3
Preclinical hyalinised drusen formation in eyes with normal fundal appearance. (A) Left arrow shows row of three drusen, all less than half the height of an RPE cell. Right arrow shows single drusen one RPE cell high; (B) note the "root-like" extension ...
Figure 4
Preclinical small globular drusen and microdrusen. Microdrusen each around 1-2 µm in size forming a row (between arrows) of around 125-150 µm. Open arrow marks a cluster of two small preclinical drusen. A 74 year old man with ...
Figure 5
Preclinical drusen composed of entrapment sites, (A) and (B) only detectable on EM. (A) Intact (left) and ruptured (right) coated membrane bound bodies (CMBB) situated between the inner collagenous zone (icz) and basement membrane of the RPE (arrow). ...
Figure 6
Preclinical drusen, entrapment site. This drusen appeared hyalinised on light microscopy (inset A) but EM (B) shows that it is an entrapment site composed of coated membrane bound bodies. A 50 year old man with normal fundal appearance, vision ...
Figure 7
Preclinical drusen of mixed composition. EM shows an entrapment site of coated membrane bound bodies (asterisk) which has enlarged by the addition of amorphous material (a). This drusen would stain heterogeneously on LM with picro-Mallory. A 58 year ...
Figure 8
Smallest drusen detectable clinically. (A) Colour fundus photograph showing small hard drusen near the fovea (arrow). (B) LM section through fovea showing hyalinised drusen (arrow); (C) high power LM. The drusen measures 30 µm in diameter. ...
Figure 9
Clinical drusen measuring 60 µm in diameter. Note that the hyalinised drusen has formed over a row of dense microdrusen (arrow) which continues beyond the drusen margin to the right. Compare with the normal Bruch's membrane on the left ...
Figure 10
Dispersal of hyalinised clinical drusen. (A) The contents of this cluster of two drusen appear paler, beginning from the base. Note the row of dense microdrusen lying beneath the drusen. (B) On EM there is dispersal of the amorphous contents giving a ...
Figure 11
Degenerative changes in a clinical drusen. (A) LM shows outpouching from the smooth globular surface and pigment granules within the drusen; (B) low; and (C) high magnification EM showing dark and condensed RPE cells overlying the drusen (open arrow). ...
Figure 12
Drusen regression and disappearance. (A) The drusen contents have become coarsely granular. The overlying RPE is degenerate; note the large hyperpigmented cell (asterisk) next to an area of RPE attenuation and cell loss (arrow). (B) The RPE basement ...

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