Maria Markoulli

• PhD, BOptom(Hons)
• Professor (Associate) at UNSW Sydney

To determine the types of microorganisms and their frequency of isolation on the external ocular surface in children wearing soft contact lenses on a daily wear schedule. Children aged 8 to 14 years were fitted with commercially available, soft contact lenses which were worn on a daily wear basis. The upper bulbar conjunctiva and the lower lid marg...

To identify a rapid and effective tear collection method providing sufficient tear volume and total protein content (TPC) for analysis of individual proteins in cats. Domestic adult short-haired cats (12-37 months; 2.7-6.6 kg) were used in the study. Basal tears without stimulation and eye-flush tears after instillation of saline (10 μl) were colle...

To validate the more easily applicable "flush" tear collection technique as a viable alternative to basal and reflex tear collection. Total protein content (TPC) and immunoglobulin A (IgA) concentrations were determined in the basal, reflex, and flush tears of 16 healthy non-contact lens wearers. The overall protein profile was established using so...

To study the histopathology of paralimbal bulbar conjunctival flaps occurring secondary to soft contact lens wear. Slit-lamp biomicroscopy using sodium fluorescein, cobalt blue light, and a Wratten filter was used to observe the presence, location, and dimensions of bulbar conjunctival flaps presenting in a cohort of contact lens wearers. Two subje...

Matrix metalloproteinases (MMPs) are degrading enzymes which maintain and remodel tissue architecture. Upregulation of MMP-9 has been associated with corneal erosions and ulceration. As these conditions are often exacerbated on waking, suggesting that degrading activity is upregulated overnight, this study set out to determine the diurnal variation...

Background To identify evidence on the use of topical CsA for ocular surface diseases (OSD). Methods A literature search was conducted following the preferred reporting items for systematic reviews and meta‐analyses (PRISMA) through June 2023 via Cochrane Central Registries, Clinical Trials Registry, Grey literature and citation searching. Randomi...

Aims/hypothesis Diabetic peripheral neuropathy is a debilitating microvascular complication of diabetes mellitus, with limited disease-modifying therapies to date. This study aimed to assess the effect of metformin on the corneal sub-basal nerve plexus as a peripheral neuropathy outcome measure in people with type 2 diabetes. Methods A cohort of 3...

SIGNIFICANCE Significant associations in the epidemiologic and clinical features between migraine and dry eye syndrome suggest that both conditions are comorbid. A potentially overlapping pathophysiological mechanism further indicates a connection between the two conditions. This study highlights the clinical implications of treating dry eye diseas...

SIGNIFICANCE In an aging population, the number of people living with neurodegenerative disease is projected to increase. It is vital to develop reliable, noninvasive biomarkers to detect disease onset and monitor progression, and there is a growing body of research into the ocular surface as a potential source of such biomarkers. BACKGROUND This...

SIGNIFICANCE This study establishes an increased risk of developing dry eye disease (DED) in patients with diabetic peripheral neuropathy using validated diagnostic criteria for both conditions. PURPOSE The disruption of ocular surface homeostasis has been associated with diabetes. However, it remains unclear if this association is independently i...

Purpose: This study aims to determine the effects of SGLT2 inhibitors on corneal dendritic cell density and corneal nerve measures in type 2 diabetes. Methods: Corneal dendritic cell densities and nerve parameters were measured in people with type 2 diabetes treated with SGLT2 inhibitors (T2DM-SGLT2i) [n = 23] and those not treated with SGLT2 in...

The Tear Film & Ocular Surface Society (TFOS) Workshop entitled 'A Lifestyle Epidemic: Ocular Surface Disease' was a global initiative undertaken to establish the direct and indirect impacts of everyday lifestyle choices and challenges on ocular surface health. This article presents an Executive Summary of the evidence-based conclusions and recomme...

Purpose: The study aimed to ascertain the potential effects of chronic kidney disease (CKD) on substance P concentration in the tear film of people with type 2 diabetes. Methods: Participants were classified into two groups: type 2 diabetes with concurrent chronic kidney disease (T2DM-CKD (n = 25)) and type 2 diabetes without chronic kidney dise...

In-vivo corneal confocal microscopy is a powerful imaging technique which provides clinicians and researcher with the capabilities to observe microstructures at the ocular surfaces in significant detail. In this Mini Review, the optics and image analysis methods with the use of corneal confocal microscopy are discussed. While novel insights of neur...

Nutrients, required by human bodies to perform life-sustaining functions, are obtained from the diet. They are broadly classified into: macronutrients (carbohydrates, lipids, and proteins), micronutrients (vitamins and minerals) and water. All nutrients serve as a source of energy, provide structural support to the body and/or regulate the chemical...

In this report the use of eye cosmetic products and procedures and how this represents a lifestyle challenge that may exacerbate or promote the development of ocular surface and adnexal disease is discussed. Multiple aspects of eye cosmetics are addressed, including their history and market value, psychological and social impacts, possible problems...

This poster explored the impact of chronic corneal nerve loss on the ocular surface in type 2 diabetes with and without chronic kidney disease.

The conjunctival microcirculation is an accessible complex network of micro vessels whose quantitative assessment can reveal microvascular haemodynamic properties. Currently, algorithms for the measurement of conjunctival haemodynamics use either manual or semi-automated systems, which may provide insight into overall conjunctival health, as well a...

Aim: To determine the impact of chronic kidney disease on corneal nerve measures and dendritic cell counts in type 2 diabetes. Methods: In vivo corneal confocal microscopy images were used to estimate corneal nerve parameters and compared in people with type 2 diabetes with chronic kidney disease (T2DM-CKD) (n = 29) and those with type 2 diabete...

Significance: There is a reduction in corneal nerve fiber density and length in type 2 diabetes with chronic kidney disease compared to type 2 diabetes alone; however, this difference does not result in worse ocular surface discomfort or dry eye disease. Purpose: This study aimed to determine the clinical impact of corneal nerve loss on ocular s...

Purpose: The aim of this study was to investigate the reliability of subbasal corneal nerve plexus parameters of the inferior whorl compared with the central cornea with in vivo corneal confocal microscopy and to investigate the impact of inferior whorl pattern complexity on reproducibility. Methods: Subbasal corneal nerves of healthy controls (...

Dry eye is considered an inflammatory disease. Gut microbiota are important in the regulation of low-grade chronic inflammation, including in the eye. Probiotics and prebiotics are increasingly used to regulate chronic-disease-associated gut dysbiosis. Therefore, this double-masked, randomized controlled clinical trial aimed to explore the potentia...

Purpose To examine the effect of hydroxypropyl-guar nanoemulsion (HP-Guar nanoemulsion, Alcon Laboratories Ltd, Fort Worth, TX, USA) versus saline (0.9% sodium chloride; Pfizer Inc., Bentley WA Australia) on the comfort and tear film properties of people with dry eye disease both in the short-term (up to 2 h post-drop instillation) and longer-term...

Purpose: To measure variation in corneal dendritic cell density, and percentage of mature to total dendritic cells, in healthy individuals during the sleep/wake cycle. Methods: Using in vivo confocal microscopy, images of the subbasal nerve plexus were captured from 19 healthy, noncontact lens wearing participants. The central cornea and inferior w...

Peripheral nerve disorders are caused by a range of different aetiologies. The range of causes include metabolic conditions such as diabetes, obesity and chronic kidney disease. Diabetic neuropathy may be associated with severe weakness and the loss of sensation, leading to gangrene and amputation in advanced cases. Recent studies have indicated a...

Purpose: Substance P is a sensory neuropeptide increasingly used as a biomarker for ocular and systemic neuropathic conditions. Due to the limited studies on tear storage conditions compared to other bodily fluids including blood and urine, the aim of this study was to investigate whether different storage durations at 4 °C can impact on substance...

Ocular surface neuropeptides are vital molecules primarily involved in maintaining ocular surface integrity and homeostasis. They also serve as communication channels between the nervous system and the immune system, maintaining the homeostasis of the ocular surface. Tear film and ocular surface neuropeptides have a role in disease often due to abn...

Immune cell infiltration has been implicated in neurotoxic chemotherapy for cancer treatment. However, our understanding of immune processes is still incomplete and current methods of observing immune cells are time consuming or invasive. Corneal dendritic cells are potent antigen-presenting cells and can be imaged with in-vivo corneal confocal mic...

Purpose To determine the repeatability of TearLab and I-PEN osmometers in vivo and their accuracy in vitro. Design Prospective, single-visit study. Methods The tear osmolarity of 28 participants was evaluated with TearLab and I-PEN on two occasions in random order, over a 2-h period. Both eyes were measured in a randomised order. Coefficients of...

The tear film is a thin, moist layer covering the ocular surface and is laden with proteins, peptides, lipids, mucins, electrolytes and cellular debris which function to maintain the healthy status of the ocular surface. In many cases of ocular or systemic disease, the integrity of this layer is changed and/or the balance of its constituents is dis...

Objectives Many chronic eye conditions are managed within public hospital ophthalmology clinics resulting in encumbered wait lists. Integrated care schemes can increase system capacity. In order to direct implementation of a public hospital-based integrated eye care model, this study aims to evaluate the quality of referrals for new patients throug...

Multiple sclerosis (MS) is a neurological inflammatory disorder known to attack the heavily myelinated regions of the nervous system including the optic nerves, cerebellum, brainstem and spinal cord. This review will discuss the clinical manifestations and investigations for MS and other similar neurological inflammatory disorders affecting vision,...

Clinical relevance: There is potential benefit in analysing corneal nerve tortuosity as a marker for assessment and progression of systemic diabetic neuropathy. Background: The aim of this work was to determine whether tortuosity significantly differs in participants with type 1 (T1DM) and type 2 (T2DM) diabetes compared to controls and whether...

Aim: To investigate the expression of the keratinization-related protein, filaggrin, in the lid margin epithelium of contact lens (CL) wearers compared with nonwearers. Methods: This was a cross-sectional study of 100 individuals with different exposures to CL wear: short, moderate, and long experience; previous CL wearers; and nonwearers as con...

Survival rates of cancer has improved with the development of anticancer drugs including systemic chemotherapeutic agents. However, long-lasting side effects could impact treated patients. Neurotoxic anticancer drugs are specific agents which cause chemotherapy-induced peripheral neuropathy (CIPN), a debilitating condition that severely deteriorate...

Background There is a strong association between the metabolic syndrome in diabetes and the development of peripheral neuropathy, however the pathophysiological mechanisms remain unknown. Methods Participants with type 2 diabetes and metabolic syndrome (T2DM/MetS, n = 89) and type 2 diabetes alone (T2DM, n = 59) underwent median nerve ultrasound a...

Dry eye disease is one of the most common, chief-complaints presenting in clinical practice, with a prevalence of up to 50%. Evaporative dry eye, as a result of meibomian gland dysfunction, is thought to be the biggest component factor. Treatments for meibomian gland dysfunction aim to restore tear film homoeostasis and include warm compress therap...

Ocular surface dysfunction is common in patients receiving anti-cancer drug treatment. The effects of paclitaxel, a neurotoxic chemotherapeutic drug, on ocular surface discomfort associated with dry eye disease was investigated. Patients with cancer who had completed paclitaxel treatment between 3 and 24 months prior to assessment (n = 29) and age-...

Purpose: Sub-basal corneal nerves have been shown to change during neurotoxic chemotherapy treatment. This cross-sectional study investigated corneal nerve morphology in patients who have completed neurotoxic chemotherapy well after treatment cessation and its association with peripheral nerve function. Methods: Central corneal nerve fiber lengt...

Clinical relevance: Diagnosis and monitoring of keratoconus is increasingly being conducted with the aid of imaging equipment such as corneal aberrometry. There is a need to also know the confidence with which ocular aberration measurements can be made. Background: To assess the repeatability of lower- and higher-order aberration measurements in...

Cancer is a global health problem and is one of the leading causes of death worldwide. Pleasingly, the rate of survival has improved and continues in an upward trend mainly due to better diagnosis and treatment modalities. In particular, the development of anticancer drugs including cytotoxic chemotherapy, hormonal agents and targeted therapies hav...

Aim To examine the associations between of continuous overlapping net glycaemic action (CONGA), percentage time in hyperglycaemia (%HG) or normoglycaemia (%NG) and peripheral nerve structure and function in type 1 diabetes. Methods Twenty‐seven participants with type 1 diabetes underwent continuous glucose monitoring followed by corneal confocal m...

Measurement of corneal nerve tortuosity is associated with dry eye disease, diabetic retinopathy, and a range of other conditions. However, clinicians measure tortuosity on very different grading scales that are inherently subjective. Using in vivo confocal microscopy, 253 images of corneal nerves were captured and manually labelled by two research...

Significance: This study set out to explore the relationship between the ocular surface immune and nervous systems by exploring corneal nerve structure and the presence of inflammatory mediators and neuropeptides in the tear film. Purpose: The purpose of this study was to determine the association between corneal nerve morphology and tear film i...

Aims: To determine the utility of corneal confocal microscopy and tear neuromediator analysis in the diagnosis of diabetic peripheral neuropathy (DPN) as a result of type 1 and type 2 diabetes. Methods: Seventy individuals with either type 1 diabetes or type 2 diabetes (T1D/T2D) underwent corneal confocal microscopy to assess the corneal nerve mo...

Objective Corneal confocal microscopy (CCM) has been identified as a non-invasive technique to assess corneal nerve fiber morphology. It is not known how corneal nerve changes relate to measures of peripheral nerve function in diabetic peripheral neuropathy (DPN). The present study investigates the relationship between nerve structure and function...

Purpose: To evaluate the effect of age, gender and body mass index (BMI) on the levels of tear film neuromediators and corneal nerve parameters in healthy individuals. Methods: Twenty-six healthy subjects were screened for any neurological deficits. The concentration of substance P and calcitonin gene-related peptide (CGRP) in tears was measured b...

Purpose: To investigate the association between levels of MMP-9, a common marker of inflammation in tears, and changes to the meibomian glands accompanying soft contact lens (CL) wear. Methods: Flush tears were collected from: (1) three groups of CL wearers who had worn CLs on a daily basis for different durations (Short: 2 ± 1 years, Moderate:...

Purpose: To investigate the effect of soft contact lens (CL) wear on the morphology of the epithelial-lamina propria junction as well as the possible association with symptoms of discomfort. Methods: Ninety-two subjects were recruited, including 60 soft CL wearers, 16 previous wearers, and 16 non-wearers. Additionally, subjects were classified a...

Objective: To explore the changes that occur in the concentrations of substance P (SP) and calcitonin gene-related peptide (CGRP) in tears as a result of corneal denervation and its association with diabetic peripheral neuropathy (DPN). Methods: Sixty-three individuals with type 1 diabetes/type 2 diabetes (T1D/T2D) and 34 age-matched healthy con...

Objective: To investigate the association between the concentration of tear film substance P and diabetic peripheral neuropathy (DPN) in type1 and type 2 diabetes. Conclusions: The concentration of substance P in tears is reduced in type 1 with DPN only, although corneal nerve physiology is changed with type1 and type 2 DPN. This may indicate a dif...

Purpose: To determine the repeatability of tear ferning (TF) grading analysed by subjective and objective techniques, and its correlation with lipid layer thickness (LLT), non-invasive keratograph break-up time (NIKBUT), and ocular surface disease index (OSDI) comfort scores with and without ocular lubricants. Methods: A prospective, randomised,...

PURPOSE. To determine the association between corneal dendritic cell (DC) density and corneal nerve morphology and tear film inflammatory mediators and neuromediators in healthy individuals. METHODS. Flush tears were collected from 21 healthy participants aged 39.7 ± 9.9 years and analyzed for total protein content (TPC), substance P, matrix-metall...

Aims To investigate changes in corneal nerve morphology in Type 2 diabetes and to establish relationships between in vivo corneal confocal microscopy and markers of peripheral nerve structure and function. Participants and methods We recruited 57 participants with Type 2 diabetes and 26 healthy controls of similar age and sex distribution. We also...

AIMS: To investigate changes in corneal nerve morphology in Type 2 diabetes and to establish relationships between in vivo corneal confocal microscopy and markers of peripheral nerve structure and function. PARTICIPANTS AND METHODS: We recruited 57 participants with Type 2 diabetes and 26 healthy controls of similar age and sex distribution. We al...

The underlying mechanisms of dry eye are thought to be part of a vicious circle involving a hyperosmolarity-triggered inflammatory cascade, resulting in loss of goblet cells and glycocalyx mucin and observed corneal and conjunctival epithelial cell damage. This damage leads to increased tear film instability, further hyperosmolarity and hence perpe...

Background: Patients with chronic kidney disease (CKD) in type 2 diabetes (T2DM) typically manifest with severe neuropathy. Corneal confocal microscopy (CCM) and axonal excitability are novel techniques that serve as biomarkers for the structure and function of peripheral nerves. Aim: This study aimed to investigate the relationship between CCM, a...

Abstract Purpose : To examine the ability of corneal nerve fibre assessment and axonal ion-channel function to diagnose diabetic peripheral neuropathy (DPN). Methods : A total of 36 subjects with type 1 diabetes and 10 age-matched controls underwent confocal microscopy to assess corneal nerve fibre length, density area, width, branch density, and...

Purpose: To investigate the influence of blinking on tear film parameters, ocular surface characteristics, and dry eye symptomology. Methods: A total of 154 participants were recruited in an age, gender and ethnicity-matched cross-sectional study, of which 77 exhibited clinically detectable incomplete blinking, and 77 did not. Blink rate, dry ey...

Significance: This cross-sectional study presented a link between contact lens wear and changes on the cellular morphology characteristics of the lid wiper (LW) epithelium, which was not visible by LW staining. Purpose: The aim of this study was to establish if the duration of contact lens (CL) wear affects the cellular morphology of the LW epit...

Purpose: To evaluate the impact of Optive (Allergan, Irvine, CA) and Optive Advanced (Allergan, Irvine, CA) on tear film stability and quality during a one-hour observation period when compared to saline (Pfizer, Perth, WA). Methods: This was a double-masked, cross-over study. Twenty participants attended three visits, randomly receiving either Opt...

To investigate the relationship between corneal nerve structure and axonal ion-channel function in patients with and without DPN.

Purpose. To compare non-invasive break-up time (NIBUT) when measured with the Tearscope-Plus™ and the Oculus® Keratograph 5M, and to compare lipid layer thicknesses (LLT) when measured with the Tearscope-Plus™ and the LipiView®. This study also set out to establish the repeatability of these methods. Methods. The following measurements were taken f...

Diabetes mellitus is a chronic disease that results from inadequate insulin production or ineffective insulin utilization. It is one of the most common systemic diseases worldwide with increasing prevalence. Diabetes mellitus is associated with premature mortality, macrovascular complications such as cardiovascular disease, and microvascular compli...

Interest has grown over the past decade in using in vivo confocal microscopy to analyse the morphology of corneal nerves and their changes over time. Advances in computational modelling techniques have been applied to automate the estimation of sub-basal nerve structure. These objective methods have the potential to quantify nerve density (and leng...

Purpose: This work aims to characterize the relationship between tear film neuropeptide substance P and the structural integrity of the sub-basal nerve plexus in diabetes. Methods: Seventeen healthy control participants and nine participants with diabetes were recruited in this cross-sectional study. Total protein content and substance P concent...

The TFOS DEWS II Pathophysiology Subcommittee reviewed the mechanisms involved in the initiation and perpetuation of dry eye disease. Its central mechanism is evaporative water loss leading to hyperosmolar tissue damage. Research in human disease and in animal models has shown that this, either directly or by inducing inflammation, causes a loss of...

The number of contact lens wearers worldwide has remained relatively stable over the past decade, despite the investment that has gone into contact lens technology. This is largely because 10%–50% of wearers dropout of contact lens wear within 3 years of commencement; the most common reason cited being contact lens discomfort (CLD). Of the symptoms...

Purpose: To determine the repeatability of the flush tear collection technique and the Schirmer strip for Substance P tear analysis. Methods: The tears of 10 healthy non-contact-lens wearers were collected via Schirmer strip and microcapillary following instillation of either 20 μL (F-20) or 60 μL (F-60) of saline. Each technique was conducted o...

Purpose: To observe the emission intensity profile of sodium fluorescein in the human tear film as a function of time and concentration. Methods: Twenty-two participants with no dry eye signs or symptoms were randomly allocated to receive 1 μL of either a 2 or 10% concentration of fluorescein to one eye. Images of the inferior tear meniscus were...

Purpose: The aim of the study was to understand natural changes of meibomian glands (MG) that occur with aging in the absence of any ocular pathology or ocular discomfort symptoms, to differentiate between "age normal" and pathologic or dysfunctional changes of the MG. Methods: A total of 185 subjects (109 females) with no pre-existing ocular an...

When a single light cue is given in the visual field, our eyes orient towards it with an average latency of 200 ms. If a second cue is presented at or around the time of the response to the first, a secondary eye movement occurs that represents a re-orientation to the new target. While studies have shown that eye movement latencies to ‘single-step’...

Purpose: To investigate the effects of the duration of contact lens (CL) wear on the meibomian glands (MGs), eyelid and tear film. Methods: This was a cross-sectional study of CL wearers and non-wearers (NWs) aged between 18 and 35 years. The sample comprised of: (i) Three groups of CL wearers of different duration profiles (short, moderate and...

Purpose: We sought to determine the relative lipase production of a range of ocular bacterial isolates and to assess the efficacy of glycerol monolaurate (GML) in inhibiting this lipase production in high lipase-producing bacteria without affecting bacterial cell growth. Methods: Staphylococcus aureus,Staphylococcus epidermidis,Propionibacterium...

Background and aim: When a sole light cue is presented in the visual field, gaze automatically orients to the target. The illumination of a second light target during this response induces another gaze shift, involving the correction of the initial reactive response. When seated, both types of saccadic eye-movements are delayed in the elderly, comp...

Efron, N., Jones, L., Bron, A. J., Knop, E., Arita, R., Barabino, S., … Markoulli, M. (2013). The TFOS International Workshop on Contact Lens Discomfort: Report of the Contact Lens Interactions With the Ocular Surface and Adnexa Subcommittee. Investigative Opthalmology & Visual Science, 54(11), TFOS98. https://doi.org/10.1167/iovs.13-13187

Purpose: This study set out to determine how contact lens wear affects the profile of matrix metalloproteinase 9 (MMP-9) in the tear film. Methods: Flush tears were collected from 47 healthy neophytes before lens wear, during the first day of lens wear, and after 1 month adaptation. Participants were randomized to either Acuvue Oasys or O2OPTIX...

Background: Rabbits have a longer inter-blink time (approximately 10 minutes) compared with humans (five to eight seconds), suggesting that rabbits have a much more stable tear film. Using fluorescein, the tear break-up time of rabbits has been reported to be similar to that of humans. This study set out to measure the tear break-up time in rabbit...

This study evaluates the use of differential gel electrophoresis (DIGE) for tear analysis and applies this technique to establish the effect of extended contact lens wear on the tear proteome. Flush tears were collected from nine healthy non-contact lens wearers at baseline, during the first day, and after 1 month of contact lens wear. Participants...

Reduced tear film stability is reported to contribute to dry eye. Rabbits are known to have a more stable tear film than humans. Thus, we sought to examine the tears of rabbits and humans for metal cations, and to test how they influence tear film stability. Tears were collected from 10 healthy humans and 6 rabbits. Tear osmolality was measured by...