Genetic testing for age-related macular degeneration: progress and perspectives

Abstract

Validated prediction models estimate an individual’s likelihood of progression to advanced age-related macular degeneration. In several studies, inclusion of selected genotype improves accuracy beyond that achievable with phenotype alone. Identification of patients at increased genetic risk may provide opportunity to alter monitoring strategies and physician recommendations. Advancements in genetic testing can provide results that could refine and guide medical management and inform efforts to drive development and validation of genotype-directed therapies. Testing for age-related macular degeneration may be useful to physicians and select patients in specific clinical scenarios, and, as with all emerging diagnostic or therapeutic innovations, an awareness regarding the limitations of testing, the need for additional data, and need for appropriate patient selection, counseling and education are vital.

Keywords:

• age related macular degeneration
• genetic testing
• genotype
• phenotype
• prediction models

Financial & competing interests disclosure

This meeting was supported by an unrestricted educational grant from Nicox SA. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Age-related macular degeneration (AMD) is an example of an age-related disease caused by a complicated interplay of genetic and lifestyle factors.

• Very strong associations have been observed between common genetic variants and AMD susceptibility, with the most influential genes located within two major genetic regions (loci at chromosome 1q32 and 10q26).

• Current commercially available prognostic tests apply validated prediction models, assessing variants within or near CFH, ARMS2/HTRA1, C3, and other susceptibility genes combined with assessment of phenotypic features to estimate the risk of progression from early or intermediate disease to advanced AMD.

• The findings tend to support that incorporation of genotype assessment improves accuracy of CNV prediction beyond that achievable with grading of clinical severity alone.

• Test results for AMD risk are probabilistic and patients cannot be provided definitive results of whether or not they will progress to advanced AMD.

• Adherence to ethical practice is paramount and time must be taken to ensure that patients are well informed and rights are protected.

• Careful consideration of patient selection for testing is essential.

• Increased genetic risk of AMD is influenced by age, and the upper age limit of testing is narrowed by testing those patients in which the results will still have clinical value.