A potential biomarker located in the eye for a debilitating complication of diabetes could be the key to future development of a new point-of-care screening device.
Dr Maria Markoulli, an optometrist and senior lecturer at the University of New South Wales, was the senior investigator on the first study to demonstrate that signs of diabetic peripheral neuropathy can be traced in tear film.
The research, recently published in the journal The Ocular Surface, found people with type 1 diabetic peripheral neuropathy – a complication that can result in recurring foot ulcers and in extreme cases amputation– have reduced levels of a protein known as ‘substance P’ in the tear film.
Markoulli said the research could form the basis of a new point-of-care tear test, similar to devices used for the diagnosis of dry eye disease.
“What we’re proposing with this method is something that will be done quickly, non-invasively, and potentially could be done by an optometrist, chemist, GP or at the diabetes centre, who could then refer to the endocrinologist or neurologist,” she said.
“Peripheral nerve damage in diabetes can be really debilitating, so it’s important to be able to detect it early and, while you can’t reverse it, at least you can limit its progress by better managing the diabetes.”
Markoulli said the tear test would be a viable alternative to current diagnostic methods that are either invasive, such as a skin biopsy, subjective or unreliable.
“Something more ideal is required. Corneal confocal microscopy has also been recommended in the past and, while I agree it would be a great tool to have, it’s just not that available in private practice, and it also does take some time.”
Markoulli joined the study’s lead investigator, PhD candidate Mr Shyam Tummanapalli, and collaborated with the Prince of Wales Hospital Diabetes Centre on the project.
Involving almost 100 participants, the researchers tested the concentration of two proteins – substance P and calcitonin gene-related peptide – in the tear film of people with both type 1 and type 2 diabetes and compared the findings with control groups. It built on the findings of a smaller 2017 study that established an association between the number of corneal nerves and the level of substance P in the tear film.
Markoulli said while the latest findings fit with the original study for the type 1 group, she was interested to discover there was no difference in neuropeptides in type 2 diabetics when compared with the control group.
“This tells us something we already know; type 1 and type 2 diabetes are quite different, with type one being autoimmune-related and type 2 part of metabolic disease.
“Possibly the type 2 group we were looking at is older, and so already show less substance P in the tear film, making it harder to see a reduction. Another factor is that in type 2 diabetes there are other associated complications – they tend to have dry eye disease, they tend to have other systemic conditions as well that could potentially contribute, it’s a harder condition to analyse.”
Markoulli said the next phase of the study could focus on explaining the difference shown in type 2 diabetics, while in type 1 patients they may investigate the impact on lifestyle and/or drug interventions on substance P levels.
Image: (From left to right) The study’s lead author PdD candidate Mr Shyam Tummanapalli with Arun Krishnan, Maria Markoulli, Aumy Yan and Tushar Issar.