Age-related macular degeneration (AMD) is the most common cause of blindness in people over 50 years in the UK. 90% of vision loss in AMD is due to wet AMD. Wet AMD is treated by frequent injections into the eye; while effective, these are expensive and painful.
Parkinson’s disease is a progressive disease affecting the nervous system, causing symptoms such as tremors, rigidity, uncontrollable movements and sleep issues. Around 1 in 500 people in the UK have Parkinson’s disease.
AMD and Parkinson’s disease are degenerative disorders, and the risk of both diseases increases as people get older. Some studies have shown an increased risk of developing Parkinson’s disease among people with AMD. However, there is no large study exploring whether people with Parkinson’s disease have an increased risk of developing AMD.
Levodopa is a medication commonly prescribed to treat Parkinson’s disease. Recent evidence suggests that levodopa may improve outcomes for people with wet AMD and reduce how often they need to have injections in their eye, or even delay the development of AMD. However, the association between levodopa and prevention of AMD has not been explored in a large UK dataset.
The aims of our study are to explore the associations between:
1. Parkinson’s disease
2. levodopa
and the risk of developing AMD.
If our study provides evidence of a protective effect of levodopa, the medication would be a candidate for further evaluation in clinical trials for prevention of AMD, particularly in patient groups at high risk of developing AMD.
Aims:
To explore the association between 1. Parkinson’s disease, 2. Parkinson’s disease medications (levodopa) and development of AMD.
Study design:
Cohort 1 comparing people with and without Parkinson’s disease: A matched retrospective open cohort study to explore the association between Parkinson’s disease and development of AMD. Exposed and unexposed participants will be matched in a 1:2 ratio by age (±1 year), sex, and general practice on the index date.
Cohort 2 comparing people with Parkinson’s disease prescribed levodopa to those not prescribed levodopa: A retrospective open cohort study with levodopa drug prescriptions as a time-varying exposure variable.
Study period is 01/01/1995 to 01/07/2021.
Population:
Cohort 1: Adults aged ≥40 years.
Cohort 2: Adults aged ≥40 years with a diagnosis of Parkinson’s disease.
Exposures:
Cohort 1: Parkinson’s disease.
Cohort 2: Levodopa prescription.
Outcome:
Age-related macular degeneration.
Covariates:
We will include the following covariates in the adjusted models: sociodemographic characteristics (sex, age at index, ethnicity), smoking status, body mass index (BMI), comorbidities (hypertension, myocardial infarction, stroke, heart failure, diabetes, arthritis, diabetic retinopathy, glaucoma, cataract) and lipid-lowering drugs.
Analysis:
Cohort 1: A Cox proportional hazards model will be used to estimate hazard ratios with 95% confidence intervals for development of AMD in those with Parkinson’s disease compared to those without, adjusting for the above covariates.
Cohort 2: An extended Cox proportional hazards model will be used to estimate hazard ratios for the development of AMD in patients with Parkinson’s disease prescribed levodopa compared to those not prescribed levodopa, adjusting for the above covariates.
The proportional hazards assumption will be checked using log-log plots and the Schoenfeld residuals test.
Public health benefits: If our study provides evidence of a protective effect, levodopa would be a candidate for evaluation in clinical trials for prevention of AMD, particularly in patients at high risk of developing AMD.
In both Cohorts 1 and 2, outcome is age-related macular degeneration (AMD).
Nicola Adderley - Chief Investigator - University of Birmingham
Nicola Adderley - Corresponding Applicant - University of Birmingham
Jingya Wang - Collaborator - University of Birmingham
Krishnarajah Nirantharakumar - Collaborator - University of Birmingham
Rasiah Thayakaran - Collaborator - University of Birmingham