Researchers at the Institute of Ophthalmology, University College London and Moorfields Eye Hospital have reported that biomarkers, analysed by OCT scans, have shown reduced thickness of the INL (inner nuclear layer) and GCIPL (ganglion cell-inner plexiform layer) of the retina with Parkinson’s disease (PD) patients. Their UK research results showed an association between the thinning of the GCIPL (and to a lesser extent, the INL) with a higher risk of PD. The researchers’ findings were conducted over 10 years with a large dataset and the lead author of the study, Dr. Siegfried Wagner, commented that, “collectively, these findings strengthen the argument that neurodegenerative pathology in Parkinson disease involves the GCIPL and INL and that these retinal layers may have prognostic clinical relevance”.
The research was conducted in collaboration between the NIHR (National Institute of Health and Social Care) Biomedical Research Centres at Moorfields Eye Hospital, University Hospital Birmingham, Great Ormond Street Hospital (GOSH), Oxford University Hospital, University College Hospital London and the UCL Great Ormond Street Institute of Child Health. The analysis of the study used two datasets, one, “AlzEye”, a retinal imaging database with individual-level ophthalmic data linked with hospital admissions across England for patients and, data from the UKBB (UK Biobank) holding an estimated 500,000 participants in the UK and registered with the National Health Service. The results of their research showed that in the AlzEye cohort, there were 700 individuals with prevalent PD and 105,770 controls (mean age 65.5 ± 13.5 years, 51.7% female). Individuals with prevalent PD had thinner GCIPL (-2.12 μm, 95% CI: -3.17, -1.07, p = 8.2 × 10-5) and INL (-0.99 μm, 95% CI: -1.52, -0.47, p = 2.1 × 10-4). The UK Biobank included 50,405 participants (mean age 56.1 ± 8.2 years, 54.7% female), of whom 53 developed PD at a mean of 2,653 ± 851 days. Analysing the data showed thinner GCIPL (hazard ratio: 0.62 per st.dev increase, 95% CI: 0.46, 0.84, p=0.002) and thinner INL (hazard ratio: 0.70, 95% CI: 0.51, 0.96, p=0.026) were also associated with incident PD.
In terms of the implications of the report, the authors suggested that inner retinal accumulation of toxic protein aggregates may provide a potential explanation for reduced INL thickness. On a molecular level, the authors surmised that, “toxic protein aggregates lead to increase of free radicals and oxidative stress, mitochondrial damage, and dysfunction, Ca2+ influx all of which lead to energy deficiency and neurodegeneration”. Consequently, “a biologically plausible explanation for our finding could be a primary inner retinal Parkinson disease-related dopaminergic degeneration manifesting as INL thinning on OCT. In terms of next steps, one of the senior authors, Professor Alastair Denniston, consultant ophthalmologist at University Hospitals Birmingham said that, “this work demonstrates the potential for eye data, harnessed by the technology to pick up signs and changes too subtle for humans to see. We can now detect very early signs of Parkinson’s, opening up new possibilities for treatment.”