Dry eye, Feature, Report, Therapies

Taking advantage of the ocular surface to diagnose other forms of disease

In Part 3 of Insight’s dry eye series, academic and author Dr Maria Markoulli shares her interest in the impact of ocular and systemic disease on the tear film and how eyecare professionals can better use this to diagnose and manage these conditions.

Dr Maria Markoulli, a senior lecturer and postgraduate research coordinator at the School of Optometry and Vision Science at UNSW, says collaboration between researchers, clinicians and industry is key to helping solve the dry eye equation.

While a large proportion of research and development has targeted methods to diagnose and treat the disease, Markoulli is interested in discovering what else the tear film can reveal about a person’s health.

Her current research focussing on the ocular surface to diagnose systemic disease has seen her lead a team of researchers to develop a non-invasive test to detect people at risk of peripheral neuropathy, a diabetes complication.

One of Markoulli’s postgraduate students, now a postdoctoral fellow, Dr Shyam Tummanapalli, conducted the study.

“Shyam’s work found people with type 1 diabetic peripheral neuropathy – a complication that can result in recurring foot ulcers and amputation in extreme cases – have reduced levels of a protein known as ‘substance P’ in the tear film,” she says.

“This could form the basis of a new point-of-care tear test, similar to devices used for the diagnosis of dry eye disease. 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 says current diagnostic methods for peripheral neuropathy are either invasive, or subjective and unreliable, whereas this method of collecting and analysing tears is accessible, non invasive, quick and objective.

The emergence of such research perhaps demonstrates why the tear film should not be underrated. For example, Markoulli says homeostasis of the tear film is a key contributor to ocular comfort; anything that impacts this equilibrium will have a downstream effect on tear film quality and, consequently, ocular surface integrity and comfort.

Local disease such as meibomian gland dysfunction (MGD), or systemic disease such as diabetes, or systemic medications like Roaccutane can affect this equilibrium.

“It is therefore incumbent on us as clinicians to conduct a thorough medical history in order to identify risk factor of dry eye disease, gauge the level of symptoms, and assess the tear film, ocular surface and adnexa, putting measures into place to minimise progression or exacerbation of symptoms in the future,” she says.

Markoulli, a global ambassador for the Tear Film and Ocular Surface Society (TFOS) and deputy editor for Clinical and Experimental Optometry, anticipates optometrists are likely to see an increase in dry eye prevalence, especially with continuing use of personal devices.

She also foresees an expansion of in-practice devices and therapeutics for MGD management.

“I am hoping in Australia we will gain more access to ocular therapeutic drugs such as the secretagogue diquafosol, so that we can better manage aqueous deficiency. I think that the management of dry eye disease will become even more personalised than it is now.”

Alongside this, Markoulli says clinical practice has seen an influx in devices that differentiate between the different subcategories of dry eye disease.

“For example, this includes the measurement of lipid layer thickness, the objective measurement of tear break-up time, the measurement of tear film inflammatory mediators and tear film osmolarity,” she says.

“Industry has really come on board to help clinical practice with making progress in diagnosis. Similarly, with the understanding that MGD is the greatest cause of dry eye disease, more so in some populations than others, we have also seen an influx in tools to help us manage these conditions, both in-office and take-home therapy.”

While stronger ties are forming between industry and clinical practice, Markoulli notes this has evolved alongside an explosion in research.

She cites the publication of the 2017 TFOS DEWS II report, which has provided clearer guidance into the disease’s definition. It’s also shown that while a patient may present with either the aqueous deficient or the evaporative form, they may also have a hybrid of the two, requiring a modified response from the practitioner.

In terms of the treatment market, Markoulli says there has been significant growth in artificial tears, with more companies offering ‘non-preserved’ products. Other innovations are also emerging.

“IPL and low-level light therapy, longer-lasting artificial tears, and more anti-inflammatories that minimise the adverse effects that actively inhibit T cell migration are potential options for treatment,” she says.

Dr Maria Markoulli is a senior lecturer and postgrad research coordinator at UNSW SOVS, deputy editor of Clinical and Experimental Optometry and TFOS ambassador.

“Other possibilities include the use of biologics, for example, the use of DNase – which is currently being tested – this clears up debris such as DNA released by neutrophils which propagate inflammation, and the use of dietary modifications and supplements – such as fish oil and potentially probiotics.”

Nasal neurostimulation and nasal sprays that harness the trigeminal parasympathetic pathway to improve tear film production, and the use of mucin secretagogues are further areas of potential treatment, she says.

NEXT: Optimel secures its niche