Idiopathic Multifocal Choroiditis and Punctate Inner Choroidopathy – Evaluation of Risk Factors for Increased Relapse Rate: A 2-Year Prospective Observational Cohort Study

Abstract

Introduction The aim of this study is to describe the course of disease in patients with idiopathic multifocal choroiditis (MFC) and punctate inner choroidopathy (PIC) and to identify risk factors associated with an increased relapse rate of disease activity. Methods In this prospective observational cohort study, demographical and clinical data were collected concerning the relapses rate of disease activity, the conclusions of the multimodal imaging results, treatment, complications and self-reported quality of life. Disease activity was defined as new inflammatory lesions or active inflammation in pre-existing chorioretinal lesions either with or without active choroidal neovascularization (CNV). Linear regression analysis was performed to identify risk factors associated with an increased relapse rate. Results In total 122 eyes of 82 patients (93% females) were included with a median age (IQR) of 45 (37-54) years. A history of secondary CNV was present in 66% of the eyes. During follow-up the best-corrected visual acuity remained stable despite a median relapse rate (IQR) of 1.0 (0.25-3). Cycles of oral corticosteroids was given in 59% of the patients, 72% were treated at baseline or started treatment during follow-up with a disease-modifying antirheumatic drug (DMARD) and 35% with a biological agent in addition to the DMARD. Both a history of secondary CNV (B=1.2, 95% CI 0.7-1.7, P=3.6×10-5) and high myopia (<-6 diopters) (B=0.6, 95% CI 0.1-1.1, P=0.02) independently increased the relapse rate of disease activity. Discussion/Conclusion A history of secondary CNV and high myopia were associated with an increased relapse rate of disease activity. Moreover, the results of this study emphasize the challenging character of treating patients with MFC/PIC.

The Pleiotropy of Complement Factor H

“…The effect size at this locus (ie, the odds of carrying the G allele if diagnosed with MFC) is so high that even a small sample size is enough, much like the original AMD GWAS cohorts, which had even fewer individuals with AMD and control individuals but discovered this same region (albeit at an even higher effect size) . Likely because of the lack of statistical power, de Groot et al did not find other genetic associations.…”

“…Discovery in complex trait genetics has skyrocketed in the last 18 years since then, but this CFH discovery continues to stand out as one of the most important complex trait associations. Though the exact mechanism through which genetic variants in the region of CFH exert their effect is not fully understood, it likely involves dysregulation of the complement system leading to a state of chronic inflammation and maladaptive healing, slowly driving select tissues toward atrophy and disease . Interestingly, several of the same variants within CFH are significantly associated with and decrease risk of central serous chorioretinopathy (CSR), and associations have also been shown between genotypes at variants in this region and choroidal thickness in healthy individuals …”

“…First, it is important to note that common variant associations found through GWAS identify regions of the genome that are associated with disease and are not necessarily the causal variant. Thus, the result reported by de Groot et al means that a causal variant is somewhere in the region of CFH but could theoretically be affecting a neighboring gene, such as one of the complement-related proteins they found to be elevated in the serumlike CFHR-2 . Regardless, these results are a sign that the CFH variants are pleiotropic, not just in terms of diseases to which they contribute but also in the sense that in addition to the retinal pigment epithelium (RPE), the choroid is likely affected by complement dysregulation, given that CFH is now implicated in MFC, CSR, and choroidal thickness.…”

“…de Groot et al report the first GWAS systematic review and meta-analysis for idiopathic MFC. With a strict phenotypic definition that used Standardization of Uveitis Nomenclature (SUN) criteria and excluded any cases caused by possible infection, they analyzed 8.5 million common genetic variants between a total of 205 individuals with MFC and 4267 control individuals drawn from 2 independent Dutch cohorts, and they followed up results with analysis of patient serum samples.…”