Association between high-risk disease loci and response to anti-vascular endothelial growth factor treatment for wet age-related macular degeneration
Open accessAbstract
PURPOSE: To investigate whether there is an association between known age-related macular degeneration genetic risk variants in the CFH, ARMS2, and HTRA1 genes and response to anti-vascular endothelial growth factor (VEGF) (ranibizumab or bevacizumab) treatment for wet age-related macular degeneration. METHODS: A retrospective review of 150 patients with documented wet age-related macular degeneration based on clinical examination and fluorescein angiogram was performed. Patients received anti-VEGF therapy with ranibizumab and/or bevacizumab. Patients were genotyped for the single-nucleotide polymorphism rs1061170, rs10490924, rs3750848, rs3793917, rs11200638, and rs932275 and for the indel del443ins54 spanning the CFH, ARMS2, and HTRA1 genes. RESULTS: There were 57 patients who were characterized as negative responders to anti-VEGF therapy, and 93 patients who were characterized as positive responders. There was no significant difference in mean baseline visual acuity between the groups. Negative responders were followed for a mean duration of 24.0 months, while positive responders were followed for a mean duration of 22.0 months. Although the frequency of the at-risk alleles was higher in the positive responders when compared with the negative responder, this did not reach statistical significance. Additionally, there was no significant association between genotype and the number of injections or absolute change in visual acuity in both groups of responders. CONCLUSION: In our patient cohort, there was no statistically significant association between response to anti-VEGF therapy and the genotype in both positive-responder and negative-responder groups. Larger studies with more power are necessary to further determine whether a pharmacogenetic association exists between wet age-related macular degeneration and anti-VEGF therapy.
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Results for ARMS2 A69S and HTRA1 promoter polymorphisms are conflicting, and no definitive conclusions can be drawn.
“Results from studies evaluating the ARMS2 A69S and HTRA1 promoter polymorphisms are also conflicting with regard to treatment response and no definitive conclusions can be drawn.9–11”
From Pharmacogenetics for Genes Associated with Age-related Macular Degeneration in the Comparison of AMD Treatments Trials (CATT) (2013) · cites this paper as [9]
The Discussion (page unavailable) reports no significant association between the tested ARMS2/HTRA1 variants and anti-VEGF response and calls for a larger study, supporting the lack of a definitive conclusion. But the paper does not establish conflicting results from studies of both named polymorphisms: it says there were no previously published reports assessing HTRA1’s influence on treatment response. (LLM, conf=0.84)
Experimental — accuracy not yet measuredOther studies report no association between the CFH risk genotype and treatment response.
“However, other studies report no association with the risk genotype.9,10”
From Pharmacogenetics for Genes Associated with Age-related Macular Degeneration in the Comparison of AMD Treatments Trials (CATT) (2013) · cites this paper as [9]
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- Authors
- Orlin, A., Hadley, D., Chang, W., Ho, A. C., Brown, G., Kaiser, R. S., Regillo, C. D., Godshalk, A. N., Lier, A., Kaderli, B., & Stambolian, D.
- Affiliations
- University of Pennsylvania (US)
- Yeungnam University College (KR)
- Thomas Jefferson University (US)
- Corresponding author
- Orlin, Anton
- Hadley, Dexter
- Stambolian, Dwight
- Venue
- Retina
- Published
- 2012-01
- Volume
- 32
- Issue
- 1
- Pages
- 4-9
- ISSN
- 0275-004X (ISSN-L)
- PMC
- PMC7440363
- OpenAlex
- W2072352093
- Cited by
- 60
- References
- 29
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 2 · 2023: 1 · 2022: 1 · 2020: 4 · 2019: 3 · 2018: 2 · 2017: 7 · 2016: 6 · 2015: 7 · 2014: 7 · 2013: 11 · 2012: 5
- FWCI
- 6.89
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Retina (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Human Genome Research Institute (U01HG008684)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (L40 HD070451)
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Health Sciences › Medicine › Ophthalmology › Ocular Diseases and Behçet’s Syndrome
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Retinal Imaging and Analysis
- Keywords
- neovascular age-related macular degeneration, anti-VEGF therapy, ranibizumab, bevacizumab, CFH gene, genetic risk variants, treatment response, pharmacogenetics, single nucleotide polymorphisms, visual acuity
- MeSH terms
- Bevacizumab, Ranibizumab, High-Temperature Requirement A Serine Peptidase 1, Aged, Aged, 80 and over, Drug Administration Schedule, Humans, Macular Degeneration, Proteins, Retrospective Studies, Risk Factors, Serine Endopeptidases, Visual Acuity, Treatment Outcome, Complement Factor H, Angiogenesis Inhibitors, Polymorphism, Single Nucleotide, Vascular Endothelial Growth Factor A, Antibodies, Monoclonal, Humanized
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