Research projects – Ocular Surface Research (inc. dry eye and contact lenses)

Research in this emerging field fits within existing areas of expertise in ocular surface, which have already received ARC funding. In Australia, 500,000 people suffer from dry eye disease due to aging. Allergies to the eye are also a very common complaint and one of the leading reasons for people to visit their eye doctor. We are researching and developing methods to understand the mechanisms of disease. The increasing prevalence of diabetes means clinicians will have to deal with complications relating to the underlying disease process. To predict nerve damage earlier, we are studying biochemical changes in the tear film as they relate to corneal structural changes in diabetes. ARC Linkage has granted fundign to investigate the use of tears as a fluid to assess breast cancer progression and treatment. Collaborators include Schepens Eye Institute, Boston, St. George Hospital, Sydney and international ophthalmic industries. Markoulli, Willcox, Jalbert, Golebiowski, Madigan, Stapleton

Details to come.

Research in this area focuses on the development of antimicrobial contact lenses and ways to control microbial colonisation of contact lens cases during use to prevent keratitis during lens wear. In order for the contact lens market to grow, infections that occur during wear, as well as comfort for the wearer must be addressed. The main national collaborators include the School of Chemistry (UNSW) and Warm Contact Pty Ltd. International collaborators include the LV Prasad Eye Institute, Hyderabad, India. These projects also involve collaborations with international industry.

Many countries are developing contact lenses as a means of correcting myopia, presbyopia, slowing the progression of myopia, as a drug delivery device, and as sensors for monitoring diabetes control, among other things. Several issues need to be addressesed for current and new contact lenses to be effective.

Two main objectives are to reduce the incidence of keratitis associated with contact lens wear (see Development of novel surface-bound antimicrobials) and to improve the comfort of lenses during wear.

We are addressing the following research questions related to contact lens comfort:

1. What is the role of the tear film lipid layer in contact lens discomfort?
2. How does the use of multipurpose disinfecting solutions affect ocular comfort?
3. Is there a relationship between corneal sensitivity and tear film parameters during contact lens wear?

Techniques include clinical trials of contact lenses, lipidomic, proteomic and glycomic analysis of the tear film, and analysis of biochemical changes to ocular surface cells.

These studies are conducted in collaboration with A/Prof Todd Mitchell, Dr Mike Kelso and Dr Simon Brown (University of Wollongong), and Prof Tom Millar (University of Western Sydney).

Microbes can colonise the surface of biomaterials, forming biofilms and leading to acute and chronic infections in many areas of the body. Contact lenses as well as other medical devices such as cochlear and orthopaedics implants and replacement organs are susceptible to microbial colonisation. We have been studying the effect of coating materials with antimicrobial substances such as the cationic peptide melimine, quorum-sensing inhibitors and nitric oxide producing surfaces on biofilm formation. We are the first group to test antimicrobial surfaces on contact lenses in clinical trials. We are addressing the following research questions:

1. Can surfaces be modified to prevent microbial colonisation as well as non-specific protein/lipid deposition?
2. Can surfaces be modified to prevent microbial adhesion but encourage mammalian cell attachment so that the “race-to-the-surface” is won by mammalian cells?
3. Do antimicrobial contact lenses reduce the incidence of keratitis during contact lens wear?

Techniques include microscopic analysis of microbial biofilm formation (confocal, AFM, electron), clinical trials, models of biomaterial infection. These studies are conducted in collaboration with Prof Naresh Kumar (UNSW Chemistry - Bioactive Molecules Group), the LV Prasad Eye Institute, Hyderabad, India and industrial sponsors.

Approximately 70% of people with diabetes experience nerve damage related to their diabetes, which imposes a significant burden on them, their families, and the community as a whole. Early detection can prevent ulcers of the feet, amputations and reduced quality of life. Currently, detection methods are invasive or subjective. The goal of this research is to characterise the neuropeptide changes in the tear film that accompany corneal neuropathy in order to predict nerve damage before its onset. Markoulli, Willcox, Jalbert, Golebiowski.

Dry eye is increasingly common in an aging population, and affects 500,000 individuals in Australia. Various factors can cause symptoms of dry eye, which are especially common in post-menopausal women and contact lens wearers. Other factors that may impact health include, allergies, LASIK surgery and obesity. Research will help us to understand the mechanisms of dry eye disease, specifically through the exploration of ocular surface innervation, meibomium gland disease, neuropeptides, sex hormones and dietary supplementation in the modulation of dry eye. Golebiowski, Stapleton, Jalbert, Markoulli, Hui.

Research in this area is focused on daily contact lens wear and the identification of changes in the tear film proteome and lipidome. It also looks at the application of therapies to improve ocular comfort. National collaborators include the Illawara Health and Medical Research Institute and the Schools of Health Sciences and Chemistry, University of Wollongong, and the School of Health and Science, University of Western Sydney. This research also involves collaboration with international ophthalmic industries. Willcox, Stapleton, Kumar, Markoulli.

The ocular surface is a unique mucosal site. The cornea is an avascular tissue, and its immunological responses are different to other areas of the body. Inflammation of the cornea can be devastating, leading to scarring and vision loss. Our team investigates the role of inflammation and corneal defences during infection, particularly with Pseudomonas aeruginosa and Staphylococcus aureus.

We are addressing the following research questions:

1. What are the different responses to infection with the Gram-negative bacterium P. aeruginosa compared to the Gram-positive bacterium S. aureus?
2. What is the role of inflammasomes in microbial keratitis?
3. What is the role of regulatory T-cells and their role in autoimmune and inflammatory eye disorders?

Techniques include the use of gene knock-out models of infection, and antibodies to control the inflammatory response.

These studies are conducted in collaboration with Prof Matt Cooper (University of Queensland)

Orthokeratology (OK) is a contact lens-based corneal reshaping technology for temporary correction of refractive error. This world-leading group has investigated the corneal mechanisms underlying the procedure, its safety, and the use of OK to inhibit myopia progression in children. We are currently exploring the influence of OK on binocular vision, in addition to investigating the impact of corneal biomechanical properties on the stability and efficacy of OK. Swarbrick, Kang, Maseedupally

Our research focuses on discovering whether the ocular surface harbours a unique microbiome, or whether microbes are transient colonisers from the surrounding skin. We have established that the culturable microbiota of the ocular surface is sparse and consists of low levels of coagulase-negative staphylococci and Proprionibacterium sp. When the ocular surface is swabbed, it can be isolated 50% of the time.We are addressing the following research questions:

1. Whether any ocular microbiome changes during contact lens wear.
2. Whether any ocular microbiome is protective from colonisation by potential pathogens.
3. What is the microbiome of contact lenses, and contact lens cases and how does this change over time?

Techniques we are using include standard microbial culture and 16s rDNA sequencing.

These studies are conducted in collaboration with Prof Ian Paulsen (Macquarie University, Sydney) and Prof Minas Coroneo (Ophthalmology, UNSW).

Tears can be collected non-invasively and without trauma to the eye. Changes in tears that occur during ocular, and non-ocular diseases, allow us to use tears as a source of biomarkers for disease. We are currently examining changes to the biochemistry of tears to determine whether these can be used to diagnose and/or monitor dry-eye, keratoconus, and breast and prostate cancer.

We are addressing the following research questions:

1. Do tears contain markers that allow for their use in diagnosing disease?
2. How do we monitor disease progression?
3. How do we determine the effects of therapies?

Techniques include mass spectrometric analysis of the tear lipidome, proteome and glycome, as well as antibody-based biomarker discovery.

These studies are conducted in collaboration with A/Prof Todd Mitchell, Dr Simon Brown (University of Wollongong), Dr Brad Walsh (Minomic International), Dr Valerie Wasinger (BMSF, UNSW), and A/Prof Yong Li (St. George Hospital, Sydney).