Original Articles
Location, substructure, and composition of basal laminar drusen compared with drusen associated with aging and age-related macular degeneration

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Abstract

PURPOSE:

To determine whether basal laminar drusen differ in their location, ultrastructure, or composition from drusen associated with aging and age-related macular degeneration.

METHODS:

A paraffin-embedded block from an eye of a patient with basal laminar drusen was obtained. Sections were examined immunohistochemically using a battery of antibodies and lectins directed against drusen-associated proteins and glycoconjugates, respectively. Thin sections were examined by electron microscopy and compared with eyes with age-related macular degeneration.

RESULTS:

Drusen in the eye with basal laminar drusen are located between the basal lamina of the retinal pigment epithelium and the inner collagenous layer of Bruch membrane, just as they are in age-related macular degeneration. Two distinct ultrastructural phenotypes are observed in the eye with basal laminar drusen; their substructure is indistinguishable from drusen phenotypes in age-related macular degeneration. Both basal laminar drusen and drusen associated with age-related macular degeneration are bound by the lectins Ricinis communis agglutinin and Arachis hypogea agglutinin (after neuraminidase digestion) and by antivitronectin, anti–HLA-DR, anti–serum amyloid P, and anti-C5 antibodies, but not by antibodies directed against basement membrane–associated heparan sulfate proteoglycan, laminin, fibrinogen, or collagen type IV.

CONCLUSIONS:

These data support the notion that cuticular or basal laminar drusen are similar to, and perhaps indistinguishable from, drusen associated with age-related macular degeneration and are not nodular or diffuse thickenings of Bruch membrane, as previously suggested. Thus, we suggest basal laminar drusen is a misnomer. This clinical phenotype should be identified as “early adult onset, grouped drusen” or by the eponym “Gass syndrome.” Features of basal laminar drusen, such as uniform drusen size, clustered distribution, and angiographic features, do not appear to be related to differences in drusen location, composition, or substructure.

Section snippets

Methods

Antibodies directed against amyloid P component, complement C5, fibrinogen, and HLA-DR were obtained from Dako (Carpinteria, California); antibodies directed against fibronectin and laminin were obtained from Chemicon International (Temecula, California), and antilaminin and antifibronectin antibodies were purchased from Telios (San Diego, California). Clostridium perfringens neuraminidase and antibodies directed against transthyretin were obtained from Boehringer-Mannheim (Indianapolis,

Results

Conventional periodic acid Schiff and hemotoxylin- and eosin-stained sections confirm that the deposits in the “basal laminar” phenotype are located between the retinal pigment epithelium and Bruch membrane, a location consistent with the use of the term drusen. Basal laminar drusen show amorphous or finely granular material deposited in discrete nodules or mounded deposits, which may be fused along their lateral borders. Like drusen associated with age-related macular degeneration, these

Discussion

In this study, we sought to examine the substructural and compositional characteristics of basal laminar drusen, a drusen phenotype associated with an early adult onset form of macular degeneration. Basal laminar drusen are located between the basal lamina of the retinal pigment epithelium and the inner collagenous layer of Bruch membrane, thus warranting the moniker of drusen.4 In contrast to previous interpretations, we provide evidence that basal laminar drusen share common topographic,

Acknowledgements

The authors wish to thank Dr J. Donald M. Gass for his insightful discussion and help in specimen acquisition. In addition, we wish to thank Lynn Gardner, Heidi Hoopes, Robert Folberg, MD, and Cory Speth for their assistance.

References (18)

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This study was supported in part by National Institutes of Health grants EY06463/(Dr Hageman), EY11515/(Dr Hageman), and an unrestricted grant to the Department of Ophthalmology and Visual Sciences, The University of Iowa, from Research to Prevent Blindness, Inc. Dr. Hageman is the recipient of a Research to Prevent Blindness Lew R. Wasserman Merit Award.

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