A recent study found that retinal age gap, defined as chronological age subtracted from retinal age, is a potential indicator of Parkinson disease development.
A study published in Age and Ageing found that retinal age could be used to identify the likelihood of Parkinson disease (PD) in older patients. The aim of the study was to investigate the association between the retinal age gap, defined as one’s retinal age minus their chronological age, and incident PD using a large-scale population-based sample.
The study used data from UK Biobank, a population-based cohort of more than 500,000 UK residents aged between 40 and 69 years. The data included information about the residents’ lifestyle, environment, medical history, and demographic characteristics. Comprehensive physical and functional measurements, including ophthalmic examinations, were performed at baseline.
Ophthalmic examinations included the logarithm of the minimum angle of resolution visual acuity, autorefraction, and keratometry; intraocular pressure; and paired retinal fundus and optical coherence tomography imaging. The researchers collected 131,238 images from 66,500 participants in the UK Biobank data set; after image quality checks, 80,170 images from 46,970 participants were used.
Among the 80,169 images, 19,200 fundus images of 11,052 participants who reported no previous disease were used to train the model for age prediction. Of the remaining 35,917 participants, 83 had a history of PD prior to the baseline examination, which left 35,834 participants who were eligible for the analysis. Diagnosis of PD was identified through hospital administration data, national death register data, and self-reported data.
The investigators adjusted for covariates including age, gender, ethnicity, smoking status, drinking status, obesity, physical activity, history of diabetes, hypertension, stroke, and the use of psychotropic medication, as they were considered potential confounding factors.
A total of 35,834 participants were included in the analysis. The participants had a mean (SD) age of 56.7 (8.04) years and 55.7% were female. During the median (IQR) follow up period of 5.83 (5.74-5.97) years, 63 PD cases were identified.
A positive retinal age gap suggested that the retina appears older than the patient’s age, whereas a negative retinal age gap suggested that the retina appears younger.
After adjusting for confounding factors, each 1-year increase in retinal age gap was associated with a 10% increase in the risk of future PD (HR, 1.10; 95% CI, 1.01-1.20). The risk of PD in participants with retinal age gap in the third (HR, 2.66; 95% CI, 1.13-6.22) or fourth (HR, 4.86; 95% CI 1.59-14.8) quartiles was higher than that of participants in the lowest quartile. The risk of PD in the second quartile was similar to the lowest quartile.
After further adjustment for age, the association between retinal age gap and PD remained significant. The authors presented receiver operator characteristic curves of using retinal age and established risk factors, including age, gender, and smoking status, as predictors of 5-year PD risk. The predictive values of the retinal age–based model (area under the curve [AUC], 0.708; 95% CI, 0.638-0.778) and the risk factor–based model (AUC, 0.717; 95% CI, 0.633-0.802) were similar.
There were some limitations to this study. The UK Biobank study included healthier and younger participants than the general population, which may lead to bias. The limited number of PD cases prevented the researchers from performing further subgroup analyses. Due to lack of follow-up data on fundus images, the researchers could not investigate the association between dynamic changes of retinal age gap and incident PD. The possibility of residual confounders could not be excluded.
The researchers concluded that the study showed that retinal age gap was associated with the risk of PD. “The retinal age gap may be considered a biological aging marker that may be applied for the identification of preclinical PD patients,” the authors wrote.
Further studies were recommended in order to investigate the association between dynamic changes of retinal age gaps over time and the risks of PD to further validate the findings in the study.
Hu W, Wang W, Wang Y, et al. Retinal age gap as a predictive biomarker of future risk of Parkinson’s disease. Age Ageing. 2022;51(3):afac062. doi:10.1093/ageing/afac062