Age-Related Macular Degeneration: From Epigenetics to Therapeutic Implications

Farkas, Michael H.; DeAngelis, Margaret M.

doi:10.1007/978-3-030-66014-7_9

Cited by 4 publications

(2 citation statements)

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“…Second, because AMD is associated with cardiovascular disease [ 38 , 39 , 40 , 41 , 42 , 43 , 44 ], renal disease [ 38 , 45 , 46 , 47 ], periodontal disease [ 48 , 49 , 50 , 51 , 52 , 53 ] and Alzheimer’s disease [ 54 , 55 , 56 ], prevention of AMD may also reduce the burden of these common diseases. This would remarkably amplify the clinical significance following the prevention of AMD after metformin use.…”

Section: Discussionmentioning

confidence: 99%

The Risk of Age-Related Macular Degeneration Is Reduced in Type 2 Diabetes Patients Who Use Metformin

Tseng

2023

Pharmaceuticals

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Background: Whether metformin may reduce the risk of age-related macular degeneration (AMD) requires confirmation. This study compared the risk of AMD between ever users and never users of metformin matched on propensity score (PS) in Taiwanese patients with type 2 diabetes mellitus. Methods: We enrolled study subjects from Taiwan’s National Health Insurance. A total of 423,949 patients with new onset diabetes from 1999 to 2005 were identified. After excluding ineligible patients and enrolling only patients aged between 50 and 79 years, we created 13,303 pairs of ever users and never users of metformin matched on PS. The patients were followed from 1 January 2006 to 31 December 2011. We estimated hazard ratios by Cox regression. Results: AMD was newly diagnosed in 506 ever users and 639 never users. The respective incidence rates (per 100,000 person-years) were 778.72 and 1016.62. The hazard ratio (HR) and 95% confidence interval (CI) for ever versus never users was 0.756 (0.673–0.850). While ever users were categorized by tertiles of cumulative duration (<31.8, 31.8–63.9 and >63.9 months) and cumulative dose (<947.1, 947.1–2193.5 and >2193.5 g) of metformin, a dose–response pattern was observed. For the respective tertiles of cumulative duration, the HRs (95% CIs) were 1.131 (0.961–1.330), 0.821 (0.697–0.967) and 0.464 (0.384–0.561), while compared to never users. For the respective tertiles of cumulative dose, the HRs (95% CIs) were 1.131 (0.962–1.329), 0.739 (0.624–0.876) and 0.525 (0.438–0.629). A risk reduction among ever users was observed for all tertiles of defined daily dose but was most remarkable for the third tertile with a defined daily dose of >0.64. Subgroup analyses suggested that the benefit of metformin could be similarly observed among men and women and for age subgroups of 50–64 and 65–79 years. However, patients with diabetic retinopathy would not be significantly benefited and metformin did not seem to be preventive for exudative AMD. Conclusion: In general, metformin significantly reduces the risk of AMD.

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Section: Discussionmentioning

confidence: 99%

The Risk of Age-Related Macular Degeneration Is Reduced in Type 2 Diabetes Patients Who Use Metformin

Tseng

2023

Pharmaceuticals

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“…An overall important consideration in study design is that similar to RNA, non-coding RNAs are tissue and cell specific [ 24 , 77 , 78 , 79 , 80 , 81 , 82 ]. Given that it is still unknown if pathogenic changes in AMD are localized to specific ocular tissues or systemic, one must take into consideration that potential biomarkers identified in the peripheral blood as “disease associated” may not reflect the disease mechanism occurring in the neural retina and/or RPE.…”

Section: Introductionmentioning

confidence: 99%

AMD Genomics: Non-Coding RNAs as Biomarkers and Therapeutic Targets

Zhang

Owen

Lillvis

et al. 2022

JCM

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Age-related macular degeneration (AMD) is a progressive neurodegenerative disease that is the world’s leading cause of blindness in the aging population. Although the clinical stages and forms of AMD have been elucidated, more specific prognostic tools are required to determine when patients with early and intermediate AMD will progress into the advanced stages of AMD. Another challenge in the field has been the appropriate development of therapies for intermediate AMD and advanced atrophic AMD. After numerous negative clinical trials, an anti-C5 agent and anti-C3 agent have recently shown promising results in phase 3 clinical trials, in terms of slowing the growth of geographic atrophy, an advanced form of AMD. Interestingly, both drugs appear to be associated with an increased incidence of wet AMD, another advanced form of the disease, and will require frequent intravitreal injections. Certainly, there remains a need for other therapeutic agents with the potential to prevent progression to advanced stages of the disease. Investigation of the role and clinical utility of non-coding RNAs (ncRNAs) is a major advancement in biology that has only been minimally applied to AMD. In the following review, we discuss the clinical relevance of ncRNAs in AMD as both biomarkers and therapeutic targets.

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