Sub-retinal drusenoid deposits in human retina: Organization and composition

Abstract

We demonstrate histologically sub-retinal drusenoid debris in three aged human eyes, two of them affected by age-related maculopathy. By postmortem fundus examination, the lesions appeared drusen-like, i.e., they were pale spots apparently at the level of the retinal pigment epithelium (RPE). Light and electron microscopy revealed aggregations of membranous debris, the principal constituent of soft drusen, in the sub-retinal space. Immunohistochemistry and confocal microscopy confirmed the presence of molecules typically associated with drusen (positive for unesterified cholesterol, apoE, complement factor H, and vitronectin) without evidence for molecules associated with photoreceptors (lectins and opsins), Müller cells (glial fibrillary acid protein and cellular retinal binding protein, CRALPB), or RPE (CRALPB). The fact that a drusenoid material, sharing some markers with conventional drusen, can occur on opposite faces of the RPE, suggests deranged polarity of normally highly vectorial processes for basolateral secretion from RPE, and that overproduction of secreted materials and direction of secretion are independently specified processes. In the future, drusenoid sub-retinal debris might be more frequently revealed by emerging high-resolution imaging techniques.

Differentiating drusen: Drusen and drusen-like appearances associated with ageing, age-related macular degeneration, inherited eye disease and other pathological processes

“…RPD however do differ from drusen in some constituents, and have low levels of apoB, apoA-I, and esterified cholesterol, thought to represent components of an RPEproduced lipoprotein (Li et al, 2006). RPD were also thought to lack immunoreactivity for photoreceptor, Müller cell, and RPE marker proteins (Rudolf et al, 2008b). However Sarks et al have identified components of disorganized and undigested photoreceptor outer segment in the same specimens as RPD (Sarks et al, 2011).…”

“…These include the presence of membranous vesicles, membrane-bounded particles with neutral lipid interiors, unesterified cholesterol (UC), apolipoprotein E (apoE), complement factor H, and vitronectin (Rudolf et al, 2008b). The same material has also been identified enclosed within RPE intracellular vacuoles and so it has been suggested that these vacuoles eventually release their contents, forming conventional drusen at the basolateral RPE surface or RPD if released from the apical surface (Curcio et al, 2013;Curcio and Millican, 1999;Curcio et al, 2005;Sarks et al, 1988;Sarks et al, 2007).…”

Acquired Vitelliform Detachment in Patients With Subretinal Drusenoid Deposits (Reticular Pseudodrusen)

“…4 Recently, it was shown by spectral-domain optical coherence tomography (SD-OCT) and histopathology that reticular pseudodrusen are accumulations of material that are above the RPE, in the subretinal space, and therefore were named subretinal drusenoid deposits. 5,6 However, subretinal drusenoid deposits can look similar in color fundus photography to cuticular drusen and might be mistaken for cuticular drusen. Through the development of enhanced imaging modalities, especially the advent of SD-OCT, ideas about drusen [4][5][6][7] This report describes the association of vitelliform detachment in adults with subretinal drusenoid deposits using multimodal imaging.…”

“…5,6 However, subretinal drusenoid deposits can look similar in color fundus photography to cuticular drusen and might be mistaken for cuticular drusen. Through the development of enhanced imaging modalities, especially the advent of SD-OCT, ideas about drusen [4][5][6][7] This report describes the association of vitelliform detachment in adults with subretinal drusenoid deposits using multimodal imaging. In each patient, 31 to 37 B-scans were obtained within a 20°x 25°or 30°x 25°rectangle to encompass the macula, including the area between the temporal arcades.…”

“…5 The presence of basal laminar drusen was based on finding small densely packed drusen causing a starrysky appearance by fluorescein angiography. Soft drusen were determined from color fundus photographs and confirmed by SD-OCT. Acquired vitelliform lesions were considered to be present if there were subretinal accumulations of yellow material in the macular region.…”