- Biomarkers in ocular surface disease
- Climate change, air pollution, bushfires: effects on the ocular surface
- Dry eye, obesity and nutrition
- Eye discomfort during smartphone use
- Ocular allergy – signs, symptoms and innervation
- Ocular surface inflammation in youth
- Ocular symptoms innervation and ocular pain in dry eye and contact lens wear
- Optometry patients’ use of alternative and complementary medicines
- Post LASIK dry eye
- Sex hormones and dry eye
- Tear film biochemistry
Biomarkers in ocular surface and other diseases
This emergent field fits with existing areas of expertise in ocular surface, which have already received funding from the ARC. Dry eye is increasingly common in the aging population, affecting 500,000 individuals in Australia. Ocular Allergy is also a very common complaint and one of the leading causes of people attending eye examinations. We are researching and developing methods to understand mechanisms of disease. The increasing prevalence of diabetes means that clinicians will be increasingly faced with the challenge of treating the complications relating to the underlying disease process. We are researching the biochemical changes in the tear film in relationship to the corneal structural changes in diabetes so as to be able to predict nerve damage earlier. The use of tears as a fluid to assess breast cancer progression and treatment has been funded by ARC Linkage applications. Collaborators include Schepens Eye Institute, Boston, St. George Hospital, Sydney and international ophthalmic industries. Markoulli, Willcox, Jalbert, Golebiowski, Madigan, Stapleton
Climate change, air pollution, bushfires: effects on the ocular surface
details to follow
This research focuses on the development of antimicrobial contact lenses and ways of controlling 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, and comfort for the wearer must be addressed. Main national collaborators include the School of Chemistry (UNSW), Warm Contact Pty Ltd; international collaborators include the LV Prasad Eye Institute, Hyderabad, India. These projects also involve collaborations with international industry.
Contact lenses and care systems
Contact lenses provide an excellent form of vision correction, and are being developed in many places to correct mypoia, presbyopia, to reduce the progression of myopia, as drug delivery devices and as sensors (e.g. for monitoring diabetes control). In order for current and new contact lenses to achieve maximum effect several issues need to be addressed. These include reducing the incidence of keratitis associated with contact lens wear (see Development of novel surface-bound antimicrobials), and improving the comfort of lenses during wear.
Research questions that we are addressing in regard to contact lens comfort include: (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 sensitivty 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 in collaboration with A/Prof Todd Mitchell, Dr Mike Kelso and Dr Simon Brown (University of Wollongong), Prof Tom Millar (University of Western Sydney).
Development of novel surface-bound antimicrobials to combat biofilm infections
Microbes can colonise the surface of biomaterials, forming biofilms, and leading to acute and chronic infections in many areas of the body. Contact lenses are susceptible to microbial colonisation as are other medical devices such as contact lens cases, cochlear implants, catheters, implants for orthopaedics, and replacement organs. 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 in clinical trials antimicrobial surfaces on contact lenses.
Research questions that we are addressing include: (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 indicence of keratitis during contact lens wear?
Techniques include microscopic analysis of microbial biofilm formation (confocal, AFM, electron etc), clinical trials, models of biomaterial infection.
These studies are in collaboration with Prof Naresh Kumar (UNSW Chemistry - Bioactive Molecules Group), the LV Prasad Eye Institute, Hyderabad, India and industrial sponsors.
Diabetes and the Ocular Surface
Diabetes-related nerve damage affects up to 70% of people with diabetes and imposes a significant burden on them, their families and the community. Early detection is needed to prevent ulcers of the feet, amputation and reduced quality of life. Current detection methods are invasive or subjective in their nature. The goal of this research is to characterise the neuropeptide changes in the tear film that accompany corneal neuropathy so as to predict nerve damage before its onset. Markoulli, Willcox, Jalbert, Golebiowski
Dry eye is increasingly common in the aging population, affecting 500,000 individuals in Australia. Various factors influence the occurrence of symptoms of dry eye, which are especially common in post-menopausal women and contact lens wearers. Allergy, LASIK surgery and obesity may also be relevant. Research in these areas is being carried out to understand the mechanisms of dry eye disease, specifically through the exploration of the roles of ocular surface innervation, meibomium gland disease, neuropeptides, sex hormones and dietary supplementation in the modulation of dry eye. Golebiowski, Stapleton, Jalbert, Markoulli, Hui,
Ocular Homeostasis, the tear film and ocular comfort
This research has focused on identification of changes in the tear film proteome and lipidome during the day, during contact lens wear and during application of therapies to improve ocular comfort. National collaborators are the Illawara Health and Medical Research Institute and 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. Indeed, 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.
Research questions that we are addressing include: (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 in collaboration with Prof Matt Cooper (University of Queensland)
Research in Orthokeratology
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. Furthermore, we are investigating the impact of corneal biomechanical properties on the stability and efficacy of OK. Swarbrick, Kang, Maseedupally
The ocular surface microbiome
We are interested in 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. that can be isolated 50% of times the ocular surface is swabbed.
Research questions that we are addressing include: (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 this changes over time?
Techniques we are using include standard microbial culture and 16s rDNA sequencing.
These studies are in collaboration with Prof Ian Paulsen (Macquarie University, Sydney) and Prof Minas Coroneo (Ophthalmology, UNSW).
The use of tears as a source of biomarkers for disease
Tears can be collected without trauma to the eye and non-invasively. Changes in tears that occur during ocular, and even non-ocular diseases, may 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.
Research questions include that we are addressing in these studies include: (1) do tears contain markers that allow for their use in diagnosing disease, (2) monitoring disease progression, (3) or determining 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 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).