Drusen and pachydrusen: the definition, pathogenesis, and clinical significance.

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The pachychoroid disease spectrum encompasses seven major retinal conditions including central serous chorioretinopathy (CSC), polypoidal choroidal vasculopathy (PCV), and pachychoroid neovasculopathy or type I macular neovascularisation (MNV) secondary to chronic persistent thickening and dysfunction of the choroidal vasculature. Drusen are focal yellow-white deposits of extracellular debris, which consist of complement proteins, esterified and nonesterified cholesterol, apolipoproteins, carbohydrates, and trace elements, above the retinal pigment epithelium (RPE) or between the RPE and Bruch’s membrane. Although drusen are an essential disease precursor of advanced age-related macular degeneration (AMD), a new entity “pachydrusen” has been identified to be associated with some of the enitites that constitute the pachychoroid spectrum. It remains to be determined what the exact differences are between soft drusen, pseudodrusen, and pachydrusen in terms of phenotype, genotype, and pathogenesis. Improving our knowledge in these areas will inevitably improve our understanding of their clinical significance especially as in disease prediction in AMD and the pachychroid spectrum disorders. It remains controversial whether PCV is a subtype of AMD. Understanding the pathogenesis of different types of drusen may also help in addressing if phenotype and/or genotype of type 1 MNV associated with pachychoroid are similar to type 1 MNV related to AMD. Furthermore, because pachydrusen links two pachychoroid diseases, CSC and PCV, it is also of great interest to investigate if CSC is an early stage or a predictor of PCV in future research. In this review, we share our experience in clinical practice and the latest published evidence-based literature to emphasize the differences and similarities in morphology, pathogenesis, and clinical significance of drusen and pachydrusen, a new member of the pachychoroid spectrum disorders.

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