The association of polypoidal choroidal vasculopathy clinical phenotypes with previously reported genetic markers

Mingyue Luo,Jingyuan Yang,Youxin Chen,Xinyu Zhao

doi:10.1007/s00417-020-04702-y

Abstract

PurposeGenetic studies have identified the association of some single-nucleotide polymorphisms (SNPs) with polypoidal choroidal vasculopathy (PCV), but little is known about whether these SNPs are related to PCV clinical features as well. We performed this study to examine the association of 12 SNPs with PCV clinical phenotypes.MethodsSixty-nine PCV eyes of 69 patients were included. Genomic DNA was extracted from peripheral blood. Agilent SureSelect Human ALL Exon V6 was used to sequence the 12 SNPs previously reported to associate with PCV. Baseline best-corrected visual acuity (BCVA), sub-foveal choroidal thickness (SFCT), choroid maximum vascular diameter (MVD), choroidal vascular hyperpermeability (CVH), and greatest linear dimension (GLD) of entire lesion were measured and compared between patients of different genotypes. Fisher’s exact test and Mann-Whitney U test were mainly used to compare categorical variables and continuous variables respectively.ResultsHTRA1 rs2293870 was a protective factor of PCV or AMD in the fellow eye (P = 0.040) and was related with greater SFCT in PCV eye after multiple linear regression (P = 0.043). C3 rs17030 was associated with smaller GLD (P = 0.033). CFH rs2274700 was related to lower MVD (P = 0.043) and was a protective factor for CVH (P = 0.034).ConclusionMultiple PCV-associated SNPs are associated with PCV clinical phenotypes. The involvement of several synonymous SNPs calls for further research on the role of transcriptional alterations and trans-regulation of distant signaling pathways in PCV pathogenesis.

Highlights

Polypoidal choroidal vasculopathy (PCV), first described by Yannuzzi et al in the 1980s [1], is characterized by orange-red lesions on fundus examination and recurrent serosanguineous pigmented epithelium detachment (PED) [2]
Inclusion criteria were as follows: (1) clear diagnosis of PCV based on hyperfluorescent dilated polypoidal lesions (“polyps”) and/or BVN lesions on ICGA, especially within the first 6 min [10]; (2) treatment-naïve or a treatment-free period for at least 6 months; (3) patients who underwent comprehensive ophthalmic examination, including best-corrected visual acuity (BCVA), slit-lamp examination, fundus photography, fluorescein angiography (FA), ICGA, and enhanced depth imaging (EDI) spectral-domain optical coherence tomography (SD-OCT)
We found that subjects with variants of HTRA1 rs2293870 were more likely to develop unilateral PCV

Summary

Introduction

Polypoidal choroidal vasculopathy (PCV), first described by Yannuzzi et al in the 1980s [1], is characterized by orange-red lesions on fundus examination and recurrent serosanguineous pigmented epithelium detachment (PED) [2]. While it remains controversial whether PCV is a subtype of neovascular agerelated macular degeneration (nAMD) or a separate clinical. The dissection of PCV into various clinical phenotypes helps predict disease course, treatment response, and prognosis, the variety of classification methods, the unpredictable transition between subtypes, and the inevitable impact of personal experience in imaging interpretation call for a more objective and subtle classification

Methods

Results

Conclusion