AMD_LifeGene: Can the Risk for AMD be Modulated?
Study Details
Study Description
Brief Summary
The goal of this Cross-sectional, interventional study is to learn about whether different risk factors, as Mediterranean diet, lifestyle and concomitant medication can modulate the risk imprinted by genetics in Age-related macular degeneration (AMD). The main question it aims to answer is: How the genetic risk interacts with environmental and lifestyle factors, especially Mediterranean diet and chronic medication, in order to assess how this interplay protects or presents higher risk for the establishment or the progression of AMD.
Participants:
Vital Signs will be measured; Medical History, Demographics, Nutritional/lifestyle habits and Family History of AMD will be recorded; Ophthalmological Examination will be performed Genetic analysis will be performed.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Detailed Description
Age-related macular degeneration (AMD) is the major cause of vision loss in people over 55 years in western countries. By 2040, AMD prevalence is estimated to reach 288 million. Age-related macular degeneration is a multifactorial disease, implying genetic and demographic/environmental risk factors. Several worldwide epidemiologic studies characterized AMD from an epidemiologic standpoint, identifying risk factors for the disease, such as age and smoking habits, the two most widely accepted, besides genetics. Most of these studies have evaluated the different risk factors from a single-way point of view, not assessing gene-lifestyle/nutrition/medication interplay. A few studies stepped forward on this matter by studying the difference between the genetic risk conferred by specific and associated single nucleotide polymorphisms (SNPs), alone or in combination with other risk factors. Our group conducted the epidemiologic Coimbra Eye Study (NCT01298674) and assessed the prevalence of AMD in two cohorts (from an inland population - Lousã, and a costal one - Mira), and AMD incidence in the coastal cohort. AMD prevalence in Mira was inferior to that in Lousã, emphasizing that this population may have specific environmental, lifestyle or genetic characteristics.
Differences in major allele frequencies were already identified in the coastal population in the AMD incidence study (NCT02748824) that might explain previous findings in both prevalence and incidence in the Mira population, and it was found that rare variants conferred high risk of disease in this coastal cohort. Increasing the sample and analysis of another geographic population by focusing now on the incidence and genetic data from the inland population of Lousã will further contribute to the disease genetic knowledge in Europe, and by extension will deepen the knowledge on genetic interplay with environment and lifestyle, under the concept of personalized medicine.
AMD_LifeGene is a cross-sectional, interventional study, with a single visit. The study intervention consists of a blood draw, that is not considered part of AMD routine care.
The General practitioner (GP) physicians from the health care unit of Lousã will refer participants who have already participated in the first study to determine the prevalence of AMD (NCT01298674).
This study will have as primary endpoints: assessment of risk factors including demographics, medical history, ophthalmic history, family history of AMD, systemic co-morbidities and medication, environmental, nutritional and lifestyle habits, together with a complete phenotypic characterization of AMD on multimodal imaging evaluation, and association with the genetic background. Secondary endpoints will be epidemiological characterization of this larger population in terms of incidence and disease progression.
After signing the informed consent form, participants will be submitted to a single visit approximately ten years after the participant's participation in the Epidemiologic Coimbra Eye Study (NCT01298674). Data on participants' demographics, height and weight, medical history (general and ophthalmic), analytical systemic parameters, family history of AMD, current medication, nutrition/lifestyle will be collected. For those who give consent, a blood sample will be collected for molecular and genetic analysis.
Ophthalmologic examination will be performed including visual acuity, tonometry, and multimodal imaging with Colour Fundus Photography (CFP), Spectral-Domain Optical Coherence Tomography (SD-OCT), OCT Angiography (OCTA), Fundus Autofluorescence (FAF), Infrared imaging (IR) and Ultra-Widefield Fundus Imaging (UWF-FI).
Ophthalmological examinations performed will be analyzed at AIBILI Coimbra Ophthalmology Reading Centre (AIBILI-CORC).
All imaging data collected will be exported to AIBILI's Reading Centre (CORC) for centralized reading and grading, performed according to pre-specified grading protocols by certified ophthalmologist graders. The grading will be performed in two steps:
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General grading: disease/no disease staging.
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AMD phenotypic and stage grading: this assessment will be applicable to those eyes that were graded as AMD in the previous step.
Grading will be carried out by classifying the signs of AMD into 5 exclusive stages (stage 0-4) using the Rotterdam staging system, and additionally, with the Beckman classification system. The grading will be performed in both eyes. However, AMD staging, for an individual participant, will be based on the eye that presents a more severe status, if both eyes are gradable. If only one eye is gradable, the grading will be based only on it.
Genetic analysis will be performed by the International Age-Related Macular Degeneration Gene Consortium (IAMDGC).
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Other: Epidemiologic study This is an epidemiologic study. No arms are considered. |
Other: Blood draw
The study intervention consists of a blood draw for genetic analysis.
|
Outcome Measures
Primary Outcome Measures
- Development of AMD [18 months]
Assessment of the presence or absence of AMD.
Secondary Outcome Measures
- Genetically characterize the population and the presence of common and rare variants associated with AMD. [18 months]
To genetically characterize the inland population of Lousã and assess the presence of common and rare variants associated with AMD.
- The 10-year incidence of AMD in the inland population. [18 months]
To determine the 10-year incidence of AMD in the inland population, and compare it and analyze together with the coastal population cohort 5-year incidence.
- Identify genotypic-phenotypic correlations. [18 months]
To establish genotypic-phenotypic correlations (both rare and common variants) in either cohort and for the total population.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Adult subjects (none of whom are vulnerable) who participated in the Epidemiologic Coimbra Eye Study (NCT01298674);
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Subjects capable of understanding the information about the study and to give their written informed consent to enter the study;
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Subjects willing and able to comply with the study procedures
Exclusion Criteria:
- No exclusion criteria apply.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | AIBILI-CEC (AIBILI- Clinical Trials Centre) | Coimbra | Portugal | 3000-548 |
Sponsors and Collaborators
- Association for Innovation and Biomedical Research on Light and Image
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 4C-2022-11