Clinical and genetic characteristics of pachydrusen in patients with exudative age-related macular degeneration

Abstract

We investigated the clinical and genetic characteristics of patients with unilateral exudative age-related macular degeneration (AMD), including typical AMD, polypoidal choroidal vasculopathy, and retinal angiomatous proliferation, in whom pachydrusen was seen. Patients with unilateral exudative AMD with at least a 12-month follow-up period were included. According to the fellow eye condition, 327 consecutive patients were classified into 4 groups: Group 0: no drusen (42.8%), Group 1: pachydrusen (12.2%), Group 2: soft drusen (30.3%), Group 3: pseudodrusen with or without soft drusen (14.7%). Development of exudative AMD in the fellow eye was retrospectively studied for a 60-month period and this inter-group comparisons were performed. Genotyping was performed for ARMS2 A69S and CFH I62V. The thickness of the choroid in the fellow eyes increased significantly in Group 1 than in other groups (all P < 1.0 × 10 −7 ). The development of exudative AMD in the fellow eye was significantly less frequent in Group 1 than in Groups 2 or 3 (P = 0.022 and 0.0015, respectively). Risk allele frequency of ARMS2 A69S was significantly lower in Group 1 than in Group 2 and 3 (all P < 1.0 × 10 −4 ). Patients with pachydrusen have genetic and clinical characteristics distinct from those of soft drusen and pseudodrusen.

Five-year outcomes of photodynamic therapy combined with intravitreal injection of ranibizumab or aflibercept for polypoidal choroidal vasculopathy

“…The genotyping of ARMS2 A69S (rs10490924) and CFH I62V (rs800292) was performed for all participants using TaqMan assays on ABI7300/7500 Real Time PCR System (Applied Biosystems, Foster City, US) as we recently described. [15]…”

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

“…Pachydrusen are found to be associated with thick subfoveal choroid by SS-OCT, further confirming that pachydrusen are a new entity distinct from soft drusen [1]. Subsequently the predictive role of pachydruen in disease progression has been established from nine publications from 2018 to 2020, confirming that pachydrusen are a precursor of PCV [24][25][26][27][28][29][30][31][32] and seven with CSC [27,30,[33][34][35][36]. Pachydrusen are included as member of PCD spectrum because they are associated with common PCD features including reduced choroidal vascular markings in fundus and small pigment epithelium detachments due to the drusenoid RPE changes.…”

“…The protein associated with oxidative damage, carboxymethyllysine (confirmed activation of downstream VEGF expression [93]), and advanced glycosylation end products is also found in human [91]. To date, there is no histochemistry and pathological evidence to show if the component of pachydrusen is same or similar to that of soft drusen [32].…”

“…The pathogenesis of pachydrusen has not been fully elucidated, however, recent genetic studies have provided evidence that PCD is different from drusen-driven AMD. Some genetic studies showed that the risk frequency of ARMS2 A69S is significantly lower in AMD patients with pachychoid drusen than those patients with soft and pseudodrusen [32,99]. Furthermore, the risk allele in ARMS2 A69S is also found less commonly in AMD patients with GA, which was diagnosed in 23% of the total study cohort than in the patients with conventional GA, implying AMD patients with pachychoid may have different clincial outcome in comparison with those with normal thickness of choroid [113].…”

Genetic factors associated with response to as-needed aflibercept therapy for typical neovascular age-related macular degeneration and polypoidal choroidal vasculopathy

“…Prior to the treatment, all patients had undergone comprehensive ophthalmic examinations including best-corrected visual acuity (BCVA) measurement using Landolt C chart, intraocular pressure measurement, slit-lamp biomicroscopy with 78 diopter contact lens, fundus color photography, spectral-domain optical coherence tomography(OCT) using Spectralis version 5.4 HRA + OCT (Heidelberg Engineering, Dossenheim, Germany) and fluorescein angiography(FA) and indocyanine green angiography(ICGA) using a confocal laser scanning system (HRA-2;Heidelberg Engineering, Dossenheim, Germany). The fellow eye condition was classified into 5 groups;1) no drusen,2) pachydrusen,3)soft drusen,4)pseudodrusen with or without soft drusen,5)exudative AMD/scarring based on the criteria as we previously described 23 .…”