Systemic Dyslipidemia in Age-related Macular Degeneration: An Updated Systematic Review and Meta-analysis

Abstract

Topic: Though lipid and cholesterol dyshomeostasis is thought to contribute to the pathogenesis of age-related macular degeneration (AMD), there is no consensus regarding which elements of systemic lipid homeostasis are perturbed in AMD. In this systematic review and meta-analysis, an update to that performed by Wang et al in 2016, we characterized serum lipoprotein profiles in patients with AMD and its various stages.

Clinical relevance: These findings may identify novel therapeutic approaches for AMD, a leading cause of blindness among older adults in the industrialized world.

Methods: We used MEDLINE, Embase, and Web of Science to identify articles from database inception to May 2022 that reported blood/serum levels of lipid subspecies (triglycerides [TGs], total cholesterol [TC], low-density lipoprotein [LDL], and high-density lipoprotein [HDL]) in patients with AMD compared with controls. We meta-analyzed the data by generating multilevel random-effects models using restricted maximum likelihood estimation.

Results: Our updated meta-analysis included 56 studies, almost 3 times as many studies as the 2016 meta-analysis with a total of 308 188 participants. There were no significant differences in serum TG, TC, LDL, or HDL between patients with AMD and non-AMD controls. Given significant heterogeneity, we performed subanalyses specifically in patients with early to intermediate nonexudative AMD, advanced nonexudative AMD, and advanced exudative AMD. Compared with non-AMD controls, patients with early to intermediate nonexudative AMD had significantly lower serum TG (standardized mean difference [SMD]: -0.03; 95% confidence interval [95% CI]: -0.06 to -0.01) and higher serum HDL (SMD: 0.07; 95% CI: 0.04-0.11). Patients with advanced exudative AMD had significantly higher serum LDL (SMD: 0.33; 95% CI: 0.04-0.62) compared with non-AMD controls. There were no other significant differences identified.

Conclusion: We found that there is significant heterogeneity in systemic lipoproteins in patients with AMD compared with non-AMD controls. The specific pattern of lipid dyshomeostasis appeared to be distinct based on AMD stage. These findings highlight both the underlying heterogeneity of AMD as well as the presence of distinct pathophysiological mechanisms involved at different stages or subtypes of AMD and may inform the development of novel therapeutic approaches.

Financial disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Keywords: Age-related macular degeneration; Cholesterol; Lipids; Meta-analysis.

Figure 1

Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram showing citations identified, screened, included, and excluded. AMD = age-related macular degeneration.

Figure 2

Forest plot for systemic triglycerides (TG) in patients with age-related macular degeneration (AMD) versus non-AMD controls. Blue diamonds denote the 95% confidence interval (95% CI); dashed lines denote the 95% prediction interval. SMD = standardized mean difference.

Figure 3

Forest plot for systemic total cholesterol (TC) in patients with age-related macular degeneration (AMD) versus non-AMD controls. Blue diamonds denote the 95% confidence interval (95% CI); dashed lines denote the 95% prediction interval. SMD = standardized mean difference.

Figure 4

Forest plot for systemic low-density lipoprotein (LDL) in patients with age-related macular degeneration (AMD) versus non-AMD controls. Blue diamonds denote the 95% confidence interval (95% CI); dashed lines denote the 95% prediction interval. SMD = standardized mean difference.

Figure 5

Forest plot for systemic high-density lipoprotein (HDL) in patients with age-related macular degeneration (AMD) versus non-AMD controls. Blue diamonds denote the 95% confidence interval (95% CI); dashed lines denote the 95% prediction interval. SMD = standardized mean difference.