Background Age-related macular degeneration (AMD) has considerable global burden, being a major cause of vision loss. Subsequently, genetic predisposition holds a role in this case by contributing to disease susceptibility. Polymorphisms in genes such as Complement Factor H (CFH) and Age-Related Maculopathy Susceptibility 2 (ARMS2) play a key role as risk factors for AMD. This systematic review and meta-analysis synthesizes existing evidence to investigate and quantify the association between these polymorphisms and the actual risk of AMD. Additionally, the paper sets to unravel the prevalence of high- and low-risk genotypes among AMD patients. Methods In accordance with PRISMA guidelines, we conducted a systematic search of PubMed, Scopus, Web of Science, EMBASE, and the Cochrane Library databases to identify relevant studies. We included primary studies that involved patients diagnosed with AMD and assessed genetic polymorphisms of CFH (Y402H, rs1061170), ARMS2 (A69S, rs10490924), and we included studies evaluating CFH Y402H and ARMS2 A69S in relation to AMD susceptibility and extracted any available data on anti VEGF treatment response for narrative synthesis. The analytical series considered random effects models to perform the associated meta-analyses. Study heterogeneity was assessed using the I² statistic measure as a standard assessment within the studies. The odds ratio (OR) with 95% confidence intervals (CI) was used as the effect measure. Results The literature search obtained 1,420 studies from which 10 satisfied the eligibility criterion. The meta-analysis utilized eight studies. The association between CFH Y402H polymorphism and AMD risk indicated that the risk of AMD among risk allele carriers was OR 2.25 (95% CI: 1.27–4.00, p = 0.006). ARMS2 polymorphisms demonstrated a strong genetic association to the risk of AMD with an OR of 4.05 (95% CI: 1.79–9.16, p < 0.001). In the second meta-analysis evaluating genotype prevalence, the random-effects model showed an OR of 1.439 (95% CI: 0.929–2.231, p = 0.103), suggesting a variable but moderate prevalence of high-risk genotypes among AMD patients (I² = 95.7%, p < 0.001). Conclusions This meta-analysis confirms the significant association between CFH and ARMS2 polymorphisms and AMD susceptibility, emphasizing their role in disease pathogenesis. The findings highlight the potential for genetic screening in AMD risk assessment and personalized treatment strategies. However, substantial heterogeneity across studies underscores the need for standardized methodologies and further research into gene-environment interactions. Integrating genetic risk assessment into clinical practice may improve early detection and targeted interventions for AMD.

How do genetic polymorphisms influence the efficacy of age-related macular degeneration treatments? A systematic review and meta-analysis

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发表日期：

2026年2月5日

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Kai-Yang Chen,
Hoi-Chun Chan,
Chi-Ming Chan

摘要

Background

Age-related macular degeneration (AMD) has considerable global burden, being a major cause of vision loss. Subsequently, genetic predisposition holds a role in this case by contributing to disease susceptibility. Polymorphisms in genes such as Complement Factor H (CFH) and Age-Related Maculopathy Susceptibility 2 (ARMS2) play a key role as risk factors for AMD. This systematic review and meta-analysis synthesizes existing evidence to investigate and quantify the association between these polymorphisms and the actual risk of AMD. Additionally, the paper sets to unravel the prevalence of high- and low-risk genotypes among AMD patients.

Methods

In accordance with PRISMA guidelines, we conducted a systematic search of PubMed, Scopus, Web of Science, EMBASE, and the Cochrane Library databases to identify relevant studies. We included primary studies that involved patients diagnosed with AMD and assessed genetic polymorphisms of CFH (Y402H, rs1061170), ARMS2 (A69S, rs10490924), and we included studies evaluating CFH Y402H and ARMS2 A69S in relation to AMD susceptibility and extracted any available data on anti VEGF treatment response for narrative synthesis. The analytical series considered random effects models to perform the associated meta-analyses. Study heterogeneity was assessed using the I² statistic measure as a standard assessment within the studies. The odds ratio (OR) with 95% confidence intervals (CI) was used as the effect measure.

Results

The literature search obtained 1,420 studies from which 10 satisfied the eligibility criterion. The meta-analysis utilized eight studies. The association between CFH Y402H polymorphism and AMD risk indicated that the risk of AMD among risk allele carriers was OR 2.25 (95% CI: 1.27–4.00, p = 0.006). ARMS2 polymorphisms demonstrated a strong genetic association to the risk of AMD with an OR of 4.05 (95% CI: 1.79–9.16, p < 0.001). In the second meta-analysis evaluating genotype prevalence, the random-effects model showed an OR of 1.439 (95% CI: 0.929–2.231, p = 0.103), suggesting a variable but moderate prevalence of high-risk genotypes among AMD patients (I² = 95.7%, p < 0.001).

Conclusions

This meta-analysis confirms the significant association between CFH and ARMS2 polymorphisms and AMD susceptibility, emphasizing their role in disease pathogenesis. The findings highlight the potential for genetic screening in AMD risk assessment and personalized treatment strategies. However, substantial heterogeneity across studies underscores the need for standardized methodologies and further research into gene-environment interactions. Integrating genetic risk assessment into clinical practice may improve early detection and targeted interventions for AMD.