Drusenoid Pigment Epithelial Detachment: Genetic and Clinical Characteristics

Few studies report drusenoid pigment epithelial detachment (DPED) in Asians. In this multicenter study, we report the clinical and genetic characteristics of 76 patients with DPED, and, for comparison, 861 patients with exudative age-related macular degeneration (AMD) were included. On the initial presentation, the mean best-corrected visual acuity was 0.087 ± 0.17 (logMAR unit), and mean DPED height and width were 210 ± 132 and 1633 ± 1114 µm, respectively. Fifty-one (67%) patients showed macular neovascularization in the contralateral eye. The risk allele frequency of both ARMS2 A69S and CFH I62V was significantly higher in DPED than in typical AMD and polypoidal choroidal vasculopathy (PCV) (ARMS2 A69S risk allele frequency: DPED 77% vs. typical AMD 66% vs. PCV 57%, CFH I62V risk allele frequency: DPED 87% vs. typical AMD 73% vs. PCV 73%), although the risk allele frequency of both genes was similar between the DPED group and retinal angiomatous proliferation (RAP) group (ARMS2 A69S: p = 0.32, CFH I62V, p = 0.11). The prevalence of reticular pseudodrusen (RPD) was highest in RAP (60%), followed by DPED (22%), typical AMD (20%), and PCV (2%). Although the prevalence of RPD differs between DPED and RAP, these entities share a similar genetic background in terms of ARMS2 and CFH genes.

CFH Y402H and ARMS2 A69S Genes Polymorphism Role in Susceptibility to Rhegmatogenous Retinal Detachment and its Complications

Background: Rhegmatogenous retinal detachment (RRD) is the most common type of retinal detachment. Purpose of this study is to evaluate the possible association of ARMS2 A69S and CFH Y402H polymorphisms with RRD and its postoperative complications. Materials and Methods: Polymerase chain reaction for DNA replication followed by restriction fragment length polymorphism for enzyme digestion. RRD patients (102 cases) and healthy controls (150 individuals for ARMS2 and 94 individuals for CFH). The two polymorphisms were genotyped by Polymerase Chain Reaction (PCR) – Restriction Fragment Length Polymorphism (RFLP) in a case-control study of 102 RRD patients and 150 controls to evaluate the possible association of ARMS2 A69S and CFH Y402H polymorphism with RRD susceptibility.Results: The genotypes frequencies for ARMS2 A69S and CFH Y402H found to be significantly different between RRD and normal controls (ARMS2 A69S 42.1%vs 32.7%, OR =1.69, p< 0.036 for GT and, CFH Y402H 10.8% vs 6.4%, OR=4.17, p=0.01 for CC genotype and 67.6% vs 40.4%, OR=4.13, p< 0.0001 for CT genotype). The ARMS2 A69S GT genotype showed significant association with postoperative cystoid macular edema (CME) (OR=3.11, P = 0.0039).Conclusions: ARMS2 A69S and CFH Y402H showed significant association with RRD. The ARMS2 A69S GT genotype was also associated with postoperative cystoid macular edema.

Genetic Variants Affecting Anti-VEGF Drug Response in Polypoidal Choroidal Vasculopathy Patients: A Systematic Review and Meta-Analysis

Polypoidal choroidal vasculopathy (PCV) is usually regarded as a subtype of choroidal neovascularization (CNV) that is secondary to age-related macular degeneration (AMD) characterized by choroidal vessel branching, ending in polypoidal lesions. Despite their close association, PCV and neovascular AMD have shown differences, especially regarding patients’ treatment response. Currently, antivascular endothelial growth factor (anti-VEGF) drugs, such as ranibizumab, bevacizumab and aflibercept, have demonstrated their efficacy in CNV patients. However, in PCV, anti-VEGF treatments have shown inconclusive results. Many genetic polymorphisms have been associated with a variable response in exudative/wet AMD patients. Thus, the aim of this study is to explore the genetic variants affecting anti-VEGF drug response in PCV patients. In this regard, we performed a systematic review and meta-analysis. We found four variants (CFH I62V, CFH Y402H, ARMS2 A69S, and HTRA1-62A/G) that have been significantly related to response. Among them, the ARMS2 A69S variant is assessed in our meta-analysis. In conclusion, in order to implement anti-VEGF pharmacogenetics in clinical routines, further studies should be performed, distinguishing physio-pathogenic circumstances between PCV and exudative AMD and the combined effect on treatment response of different genetic variants.

Meta-analysis of the pharmacogenetics of ARMS2 A69S polymorphism and the response to advanced age-related macular degeneration

Background Age-related macular degeneration (AMD) causes irreversible vision loss, and targeted anti-vascular endothelial growth factor (VEGF) therapy is now the most common and effective treatment. The aim of this meta-analysis is to discuss whether genetic polymorphism of ARMS2 A69S could confer susceptibility to advanced AMD with the response to anti-VEGF treatment.Methods We performed a meta-analysis of relevant published studies selected through electronic databases. A total of 21 preferred studies regarding the association between ARMS2 gene and anti-VEGF treatment response in advanced AMD were generally included in the meta-analysis.Results The pooled results demonstrated that the carriage of G allele for ARMS2 A69S presented a better clinical prognosis for advanced AMD treated with anti-VEGF drugs (OR=1.38, 95% CI=1.13-1.69, P=0.002). Additionally, in the subgroup analysis based on ethnicity, ARMS2 polymorphisms were more likely to be a positive responder for East Asian patients (OR=1.67, 95% CI=1.29-2.16, P<0.001).Conclusion This meta-analysis through a series of rigorous methodology data demonstrated a significant association between ARMS2 A69S polymorphism and the anti-VEGF treatment response in advanced AMD, especially among East Asian population. Numerous well-designed, randomized, multicenter clinical trials with large sample size are required to validate the association.