Publications by authors named "Maria Markoulli"

55 Publications

Filaggrin Expression in the Lid Margin During Contact Lens Wear.

Eye Contact Lens 2021 Jun 22. Epub 2021 Jun 22.

Department of Optometry (W.A.), College of Applied Medical Science, Qassim University, Qassim, Saudi Arabia; and School of Optometry & Vision Science (W.A., M.M., E.P.), University of New South Wales, Sydney, Australia.

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 controls. Impression cytology samples were collected from the lid wiper (LW) area of the central upper lid margin. After fixing, an equal, random sample was selected from each group (n=13) for immunocytochemistry analysis using antihuman primary anybody (mouse filaggrin), then stained with secondary antibody (fluorescein isothiocyanate-conjugated donkey anti-mouse immunoglobulin G horseradish peroxidase) to detect filaggrin. Imaging was performed with the 3i-Vivo 2-photon microscope equipped with a Zeiss 20×-objective and SlideBook-reader software.

Results: Sixty-five samples from 65 participants (37 women; mean age±SD: 25.1±4.1 years) were collected. Filaggrin was detected in all 65 randomly selected immunostained marginal epithelium samples. All samples were similar in showing patchy areas of filaggrin immunostaining, regardless of CL wear, symptoms or epithelium morphology. Because the filaggrin immunostaining showed similar patterns across almost all the observed samples, comparison between subject groups was impractical. The presence of filaggrin in the healthy LW was additionally confirmed by an independent laboratory.

Conclusion: Filaggrin expression seems to be a normal part of epithelial cell differentiation in the lid margin and may not be a useful keratinization/stress biomarker in the marginal epithelium. Investigating other keratinization biomarkers that are not detected in the normal mucocutaneous junction/LW may help to understand the keratinization nature of LW epithelium changes in CL wearers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/ICL.0000000000000805DOI Listing
June 2021

Corneal nerve changes following treatment with neurotoxic anticancer drugs.

Ocul Surf 2021 Jun 16;21:221-237. Epub 2021 Jun 16.

School of Optometry & Vision Science, Faculty of Medicine and Health, University of New South Wales, Sydney, Australia.

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 deteriorates quality of life of cancer patients and survivors. The ocular surface is also prone to neurotoxicity but investigation into the effects of neurotoxic chemotherapy on the ocular surface has been more limited compared to other systemic etiologies such as diabetes. There is also no standardized protocol for CIPN diagnosis with an absence of a reliable, objective method of observing nerve damage structurally. As the cornea is the most densely innervated region of the body, researchers have started to focus on corneal neuropathic changes that are associated with neurotoxic chemotherapy treatment. In-vivo corneal confocal microscopy enables rapid and objective structural imaging of ocular surface microscopic structures such as corneal nerves, while esthesiometers provide means of functional assessment by examining corneal sensitivity. The current article explores the current guidelines and gaps in our knowledge of CIPN diagnosis and the potential role of in-vivo corneal confocal microscopy as a diagnostic or prognostic tool. Corneal neuropathic changes with neurotoxic anticancer drugs from animal research progressing through to human clinical studies are also discussed, with a focus on how these data inform our understanding of CIPN.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jtos.2021.06.007DOI Listing
June 2021

Photobiomodulation (low-level light therapy) and dry eye disease.

Clin Exp Optom 2021 Jul 27;104(5):561-566. Epub 2021 Feb 27.

School of Optometry & Vision Science, University of New South Wales, Sydney, Australia.

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 therapy, eyelid hygiene, in-office meibomian gland expression and lipid-containing, artificial tears. A recent introduction to the in-office treatments available for meibomian gland dysfunction has been low-level light therapy, also known as photobiomodulation. The technique involves applying red, or near infra-red, radiation using low-power light sources and is suggested to promote tissue repair, decrease inflammation, and relieve pain. This work aims to review the available literature on the efficacy and safety of photobiomodulation in meibomian gland dysfunction and dry eye disease, as well as what is currently known about its mechanism of action.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/08164622.2021.1878866DOI Listing
July 2021

The multi-faceted approach to dry eye disease.

Clin Exp Optom 2021 Apr 11;104(3):417-420. Epub 2021 Feb 11.

School of Optometry & Vision Science, University of New South Wales, Sydney, Australia.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/08164622.2021.1877534DOI Listing
April 2021

Impact of the metabolic syndrome on peripheral nerve structure and function in type 2 diabetes.

Eur J Neurol 2021 Jun 21;28(6):2074-2082. Epub 2021 Mar 21.

Prince of Wales Clinical School, UNSW Sydney, Sydney, NSW, Australia.

Background And Purpose: 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 and excitability studies to assess peripheral nerve structure and function. A subset of T2DM/MetS (n = 24) and T2DM (n = 22) participants underwent confocal microscopy to assess central and inferior whorl corneal nerve structure. Neuropathy severity was assessed using the modified Toronto Clinical Neuropathy Score (mTCNS). Diabetes groups were similar for age, sex distribution, diabetes duration, hemoglobin A , insulin treatment, and renal function. Sixty healthy controls similar for age and sex distribution were recruited for comparison.

Results: Participants with T2DM/MetS manifested with a greater mTCNS compared to T2DM (p < 0.05). Median nerve cross-sectional area was larger in the T2DM/MetS group compared to the T2DM cohort (p < 0.05). Participants with T2DM/MetS had reductions in central (all p < 0.01) and inferior whorl (all p < 0.05) nerve measures. Compared to T2DM, the T2DM/MetS group demonstrated more severe changes in nerve excitability measures, which was due to reduced sodium channel permeability and sodium-potassium pump function. In comparison, only sodium channel permeability was reduced in the T2DM group.

Conclusions: Compared to participants with type 2 diabetes alone, those with diabetes and metabolic syndrome manifested greater alterations in peripheral nerve structure and function, which may be due to reduced function of the sodium-potassium pump.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ene.14805DOI Listing
June 2021

A Cross-Sectional Study of Sub-Basal Corneal Nerve Reduction Following Neurotoxic Chemotherapy.

Transl Vis Sci Technol 2021 01 12;10(1):24. Epub 2021 Jan 12.

School of Optometry & Vision Science, University of New South Wales, Sydney, Australia.

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 length (CNFL) and inferior whorl length (IWL), average nerve fiber length (ANFL), corneal nerve fiber density (CNFD) and corneal nerve branch density (CNBD), and nerve fiber area (CNFA) were examined using in vivo corneal confocal microscopy in patients with cancer who had completed treatment with either paclitaxel or oxaliplatin between 3 and 24 months prior to assessment in comparison with 2 separate groups of healthy controls. Neurological assessments were conducted including clinician- and patient-reported outcomes, and neurological grading scales.

Results: Both paclitaxel- ( = 40) and oxaliplatin-treated ( = 30) groups had reduced IWL and ANFL compared to the respective healthy control groups ( = 15 in each group) (paclitaxel: IWL = = 0.02, ANFL = = 0.009; and oxaliplatin: IWL = = 0.008, ANFL = 0.02). CNFL and CNFD reduction were observed only in the paclitaxel-treated group compared with healthy controls ( = 0.008 and = 0.02, respectively), whereas CNFA was reduced in the oxaliplatin-treated group ( = 0.04). IWL reduction correlated with worse fine hand dexterity in chemotherapy-treated patients ( = -0.33, = 0.007).

Conclusions: There is evidence of corneal nerve loss in patients with cancer who have been treated with paclitaxel and oxaliplatin well after treatment cessation associated with worse upper limb function.

Translational Relevance: Sub-basal corneal nerve reduction is evident even after cessation of neurotoxic treatment. In vivo corneal confocal microscopy may be useful in the monitoring of nerve function in patients receiving chemotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1167/tvst.10.1.24DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7804570PMC
January 2021

A cross-sectional study of ocular surface discomfort and corneal nerve dysfunction after paclitaxel treatment for cancer.

Sci Rep 2021 Jan 19;11(1):1786. Epub 2021 Jan 19.

School of Optometry and Vision Science, University of New South Wales Sydney, Sydney, Australia.

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- and sex-matched healthy control subjects (n = 29) were recruited and assessed with the Ocular Surface Disease Index (OSDI) to measure ocular surface discomfort. In-vivo corneal confocal microscopy was used to evaluate corneal nerve parameters in the right eye. Peripheral neurotoxicity was assessed using patient-reported outcomes and clinical grading scales. The paclitaxel group had significantly worse OSDI total scores compared with controls (Median, Md = 19.3 and Md = 0, p = 0.007, respectively). Corneal nerve fiber and inferior whorl lengths were reduced in the paclitaxel group compared with controls (14.2 ± 4.0 and 14.4 ± 4.0 mm/mm vs. 16.4 ± 4.0 and 16.9 ± 4.9 mm/mm, respectively, p = 0.04). When analyzed by presence of peripheral neuropathy, paclitaxel-treated patients with neuropathy showed worse OSDI total scores compared to those without peripheral neuropathy post-treatment (p = 0.001) and healthy controls (p < 0.001). More severe ocular discomfort and worse visual function was associated with greater peripheral neurotoxicity symptoms (r = 0.60, p = 0.001) and neuropathy severity (r = 0.49, p = 0.008), respectively. Patients who have been treated with paclitaxel have a higher risk of ocular surface discomfort associated with dry eye disease, particularly those with peripheral neuropathy. Future longitudinal studies should investigate the clinical impact of corneal nerve reduction in dry eye disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-81398-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815840PMC
January 2021

Sodium-glucose co-transporter-2 inhibition and ocular outcomes in patients with type 2 diabetes: A systematic review and meta-analysis.

Diabetes Obes Metab 2021 01 13;23(1):252-257. Epub 2020 Oct 13.

George Institute for Global Health, UNSW Sydney, Sydney, Australia.

Sodium-glucose co-transporter-2 (SGLT2) inhibitors are effective for the treatment of macrovascular complications and nephropathy in type 2 diabetes, but effects on microvascular eye outcomes are unclear. We conducted a systematic review and meta-analysis of randomized placebo-controlled trials to evaluate the effect of SGLT2 inhibition on total ocular events and retinopathy in patients with type 2 diabetes. We searched MEDLINE and Embase for the period from database inception date to October 11, 2019. Two reviewers working independently extracted relevant data. Random-effects models with inverse variance weighting were selected to estimate summary risk ratios (RRs) and 95% confidence intervals (CIs). We included nine studies, involving 39 982 patients with a mean follow-up of 2.8 years. There were 1414 total ocular events, of which 624 were retinopathy events. SGLT2 inhibition was not associated with a change in the risk of total ocular events (RR 0.97, 95% CI 0.85, 1.11) or retinopathy (RR 0.98, 95% CI 0.84, 1.16), with consistent effects across studies (P for heterogeneity = 0.35 and 0.45, respectively). The effects of SGLT2 inhibition on eye disease in individuals with type 2 diabetes are probably null, although the available data cannot exclude small to moderate benefits or harms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/dom.14197DOI Listing
January 2021

Clinical utility of irx3 in keratoconus.

Clin Exp Optom 2021 Jan;104(1):107-114

School of Optometry and Vision Science, The University of New South Wales , Sydney, Australia.

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 patients with keratoconus using the irx3 wavefront aberrometer (Imagine Eyes, Orsay, France) and evaluate correlations with corneal curvature.

Methods: The irx3 wavefront aberrometer was used to measure bilateral lower- and higher-order ocular aberrations on 33 participants with keratoconus. Three measurements were taken from each eye to determine the repeatability of lower-order aberrations (quantified as sphere and cylinder in dioptres) and higher-order aberration co-efficients (up to eighth order in micrometres), coma, trefoil and total higher-order aberration root mean square (in micrometres). Corneal curvature was measured using the Pentacam HR system (OCULUS, Wetzlar, Germany).

Results: Repeat measurements for lower-order aberrations resulted in larger co-efficients of repeatability than higher-order aberrations. Similarly, larger co-efficients of repeatability between repeated measures across all Zernike co-efficients were observed in eyes with severe keratoconus (that is, corneal curvature > 52-D) compared to eyes with flatter corneas. The difference between repeated measures tended to be significant for the lower-order aberrations regardless of corneal curvature. The highest correlations with corneal curvature for right and left eyes respectively, were identified for total higher-order aberration root mean square (r = 0.92, p < 0.001 and r = 0.91, p < 0.001), followed closely by coma (r = -0.93, p < 0.001 and r = -0.86, p < 0.001) and the Z (3, -1) co-efficient (r = -0.92, p < 0.001 and r = -0.86, p < 0.001 for right and left eyes, respectively).

Conclusions: Lower-order aberrations tended to be less repeatable, indicating that instrument variability must be considered when monitoring progression. Total higher-order aberration root mean square and third-order aberrations, in particular the vertical coma Z (3, -1) co-efficient, demonstrated a stronger correlation with corneal curvature than the lower-order aberrations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cxo.13133DOI Listing
January 2021

Scientia Professor Fiona Stapleton: leading academic and world-renowned epidemiologist of contact lens-related eye disease.

Clin Exp Optom 2020 07 7;103(4):552-554. Epub 2020 May 7.

School of Optometry and Vision Science, The University of New South Wales, Sydney, Australia.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cxo.13085DOI Listing
July 2020

The impact of anticancer drugs on the ocular surface.

Ocul Surf 2020 07 25;18(3):403-417. Epub 2020 Apr 25.

Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia.

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 have provided the most effective treatment options in combatting cancerous cells. However, the antineoplastic mechanisms of these drugs can also lead to undesirable systemic and ocular side effects resulting from cytotoxicity, inflammation and neurotoxicity. While survival rates are projected to increase with time, the number of patients presenting with these side effects that can substantially impact quality of life will also rise. The current paper reviews the ocular surface and adnexal side effects of anticancer drugs, the appropriate management and possible interactions between drugs for ocular surface pathology treatment and the anticancer drugs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jtos.2020.03.008DOI Listing
July 2020

The Relationship between Corneal Nerve Morphology and Inflammatory Mediators and Neuropeptides in Healthy Individuals.

Optom Vis Sci 2020 03;97(3):145-153

School of Optometry and Vision Science, Queensland University of Technology, Brisbane, Queensland, Australia.

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 inflammatory mediators and a neuropeptide in healthy individuals.

Methods: Flush tears were collected from both eyes of 21 healthy participants aged 39.7 ± 9.9 years (10 females, 11 males) and analyzed for substance P, matrix metalloproteinase-9, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), tumor necrosis factor α, and interleukin 6. In vivo central corneal confocal microscopy was performed on the right eye, and eight images were captured. Variables measured were corneal nerve fiber length (CNFL), corneal nerve density (CNFD), corneal nerve branch density, fiber total branch density, corneal nerve fiber area, corneal nerve fiber width (CNFW), and corneal nerve fractal dimension (CNFrac). For each eye, the average across the images and the maximum and minimum values were determined for each variable. Pearson correlation analysis was performed to test for associations.

Results: Substance P correlated with CNFrac (max) (r = -0.48, P = .03) and CNFW (min) (r = -0.52, P = .02). TIMP-1 correlated with CNFD (average) (r = -0.53, P = .03), CNFL (average) (r = -0.49, P = .05), CNFrac (max) (r = -0.49, P = .05), and CNFD (min) (r = -0.55, P = .02). Interleukin 6 correlated with CNFW (average) (r = -0.49, P = .05), the standard deviation of CNFL (r = -0.51, P = .04), CNFL (max) (r = -0.50, P = .04), CNFrac (max) (r = -0.50, P = .04), and CNFW (min) (r = -0.55, P = .02). Tumor necrosis factor α, matrix metalloproteinase-9, and its ratio with TIMP-1 did not correlate with any corneal nerve parameters.

Conclusions: Both inflammatory mediators and neuropeptides correlated with measures of corneal nerve morphology, supporting the link between the inflammatory and nervous systems.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/OPX.0000000000001484DOI Listing
March 2020

Women in optometry and vision science.

Authors:
Maria Markoulli

Clin Exp Optom 2020 03;103(2):131-132

School of Optometry and Vision Science, The University of New South Wales, Sydney, Australia.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cxo.13052DOI Listing
March 2020

A Comparative Study on the Diagnostic Utility of Corneal Confocal Microscopy and Tear Neuromediator Levels in Diabetic Peripheral Neuropathy.

Curr Eye Res 2020 08 26;45(8):921-930. Epub 2019 Dec 26.

School of Optometry & Vision Science, University of New South Wales , Sydney, Australia.

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 morphology. The concentration of substance P and calcitonin gene-related peptide (CGRP) in tears was measured by enzyme-linked immunosorbent assay. Motor excitability studies were conducted on the median nerve to assess axonal ion channel function. Based on total neuropathy score (TNS), participants were stratified into DPN (DPN+ve; TNS ≥ 2; T1D, n = 19; T2D, n = 16) and without DPN (DPN-ve; TNS ≤ 1; T1D, n = 19; T2D, n = 16). Areas under the receiver operating characteristic curves (AUCs) were calculated to obtain specificity and sensitivity of the measures to diagnose DPN.

Results: In T1D, the concentration of substance P and confocal microscopy measures were significantly reduced ( < .010) in DPN+ve. Also, for the nerve excitability measures, mean peak response, percentage of threshold electrotonus at peak and after 90-100 ms, superexcitability and subexcitability were significantly reduced ( < .050) in DPN+ve. In T2D, except for inferior whorl length ( = .190), all other corneal confocal microscopy measures were significantly reduced ( < .010) in DPN+ve, but there was no difference in substance P concentration. For the diagnosis of DPN in T1D, the AUC for inferior whorl length (0.910), mean peak response (0.800) and concentration of substance P (0.770) were high and in T2D, the AUC for corneal nerve fiber length (0.809) and nerve fractal dimension (0.777) were high.

Conclusion: Corneal confocal microscopy parameters provide a better diagnostic ability to detect DPN in T1D and T2D than nerve excitability measures or concentrations of tear neuromediators. The concentration of substance P could also be useful in diagnosing DPN but for T1D only.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/02713683.2019.1705984DOI Listing
August 2020

Corneal nerve fiber loss in diabetes with chronic kidney disease.

Ocul Surf 2020 01 23;18(1):178-185. Epub 2019 Nov 23.

School of Optometry & Vision Science, University of New South Wales, Australia.

Aims: Patients with chronic kidney disease (CKD) in type 2 diabetes typically manifest with severe peripheral neuropathy. Corneal confocal microscopy is a novel technique that may serve as a marker of nerve injury in peripheral neuropathy. This study examines the changes that occur in corneal nerve morphology as a result of peripheral neuropathy due to renal dysfunction in people with type 2 diabetes.

Methods: Sixty-two participants (mean age, 62 ± 12 years) with type 2 diabetes and 25 age-matched healthy controls underwent a comprehensive assessment of neuropathy using the total neuropathy score (TNS). The corneal sub-basal nerve plexus was imaged using corneal confocal microscopy. Corneal nerve fiber length, fiber density, branch density, total branch density, nerve fractal dimension, inferior whorl length and inferior whorl nerve fractal dimension were quantified. Based on the eGFR, participants were classified into those with diabetic CKD (eGFR < 60; n = 22) and those without CKD (eGFR ≥ 60; n = 40).

Results: Participants with diabetic CKD had significantly lower corneal nerve fiber density (P = 0.037), length (P = 0.036) and nerve fractal dimension (P = 0.036) compared to those without CKD. Multiple linear regression analysis revealed that reduced corneal nerve fiber density (ß coefficient = 0.098, P = 0.017), length (ß coefficient = 0.006, P = 0.008) and nerve fractal dimension (ß coefficient = 0.001, P = 0.007) was associated with low eGFR levels when adjusted for age, duration of diabetes and severity of neuropathy.

Conclusion: Corneal confocal microscopy detects corneal nerve loss in patients with diabetic CKD and reduction in corneal nerve parameters is associated with the decline of kidney function.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jtos.2019.11.010DOI Listing
January 2020

Association of corneal nerve loss with markers of axonal ion channel dysfunction in type 1 diabetes.

Clin Neurophysiol 2020 01 11;131(1):145-154. Epub 2019 Nov 11.

School of Optometry & Vision Science, University of New South Wales, Australia.

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 in DPN.

Methods: Fifty participants with type 1 diabetes (T1DM) and 29 healthy controls underwent CCM to assess corneal nerve fiber density (CNFD), branch density (CNBD), fiber length (CNFL), total branch density (CTBD), nerve fractal dimension (CNFrD) and inferior whorl length (IWL). The severity of DPN was assessed as Total Neuropathy Score (TNS). Motor nerve axonal excitability tests were conducted to assess axonal function.

Results: Significant correlations were noted between CNFD (rho = -0.783; P < 0.01) or superexcitability (rho = 0.435; P < 0.01) and TNS. CNFrD was significantly correlated with peak response to stimulus (r = 0.414; P < 0.01) and superexcitability (r = -0.467; P < 0.01) measurements.

Conclusion: Corneal nerve loss demonstrates a significant association with axonal ion channel dysfunction in T1DM.

Significance: Detection of altered corneal nerve morphology may lead to the earlier diagnosis of DPN.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clinph.2019.09.029DOI Listing
January 2020

The Effect of Age, Gender and Body Mass Index on Tear Film Neuromediators and Corneal Nerves.

Curr Eye Res 2020 04 18;45(4):411-418. Epub 2019 Sep 18.

School of Optometry & Vision Science, University of New South Wales, Sydney, Australia.

: 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.: 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 by enzyme-linked immunosorbent assay. Corneal nerve fibers were imaged using confocal microscopy and assessed by automated image analysis software. Associations between the clinical variables were analyzed using Pearson or Spearman correlation. Univariate general linear regression was performed to examine the independent relationship between age, BMI and gender of the subjects with concentrations of substance P, CGRP and corneal nerve fiber parameters.: Fifteen (58%) of the study participants were male. The mean age of the study cohort was 36 ± 12 years (range, 21-59) with an average BMI of 25 ± 4 kg/m. The median [IQR] concentrations of substance P and CGRP was 715 [372-1463] pg/mL and 38 [15-74] ng/mL respectively. Moderate but significant positive correlations were found between the concentration of substance P and corneal nerve fiber density (r = 0.467, = .016), nerve fiber length (r = 0.528, = .006) and nerve fractal dimension (r = 0.614, = .002). There was a significant age-dependent reduction in the concentration of substance P (-6% pg/mL per year, = .001) and CGRP (-8% ng/ml per year, < .001). Corneal nerve fiber density (-0.171 no./mm per year, = .029) and nerve fractal dimension (-0.001 per year, = .021) showed reductions with advancing age. Gender and BMI did not influence any of the measurements.: The concentrations of substance P and CGRP in tears, as well as corneal nerve fiber density and nerve fractal dimension, are significantly reduced with advancing age. Age should be considered when evaluating patients for diagnosis and follow-up of corneal neuropathy or ocular surface disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/02713683.2019.1666998DOI Listing
April 2020

Tear film substance P: A potential biomarker for diabetic peripheral neuropathy.

Ocul Surf 2019 10 30;17(4):690-698. Epub 2019 Aug 30.

School of Optometry & Vision Science, University of New South Wales, Australia.

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 controls underwent a detailed assessment of neuropathy using the Total Neuropathy Score (TNS). The concentration of SP and CGRP in tears was measured by enzyme-linked immunosorbent assay. The corneal sub-basal nerve plexus was imaged using corneal confocal microscopy. Corneal nerve fibre length, fibre density, branch density, total branch density, nerve fractal dimension and inferior whorl length were quantified.

Results: In T1D, the median [IQR] concentration of SP in tears was significantly reduced in those with DPN, (130 [61-692]pg/mL) compared to both control subjects (763 [405-1555]pg/mL, P < 0.01) and in those without DPN (914 [339-1832]pg/mL, P = 0.01); the concentration of CGRP was not changed. In T2D, there was no difference in neuropeptides between participants with diabetes and controls, regardless of neuropathic status. In T1D and T2D, corneal nerve parameters were significantly different between those with DPN or without DPN and controls. A significant correlation was noted between the concentration of tear film SP and TNS in T1D (r = -0.49; P < 0.001) and corneal nerve fibre density (r = 0.45; P < 0.001). The concentration of tear film CGRP was correlated significantly with the reduction of corneal nerve fibre density (r = 0.41; P = 0.01) in T1D.

Conclusion: Tear film SP may provide a potential non-invasive biomarker for assessing neuropathy in T1D.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jtos.2019.08.010DOI Listing
October 2019

Changes in the tarsal conjunctiva viewed by in vivo confocal microscopy are associated with ocular symptoms and contact lens wear.

Ophthalmic Physiol Opt 2019 09 28;39(5):328-336. Epub 2019 Aug 28.

School of Optometry & Vision Science, University of New South Wales, Sydney, Australia.

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 as symptomatic or asymptomatic using the Contact Lens Dry Eye Questionnaire 8 for the CL wearers (a score ≥ 12 was considered symptomatic) and the Dry Eye Questionnaire 5 for the previous wearers and non-wearers (a score ≥ 5 was considered symptomatic). In vivo confocal microscopy of the tarsal conjunctiva was performed on a single occasion. Papillae density, shortest diameter, longest diameter, area, circularity, lumen/wall brightness ratio, irregularity, reflectivity, inhomogeneous appearance of wall and inhomogeneous appearance of rete ridges were evaluated. Effects of CL wear, symptoms and their interaction were analysed using two-way analysis of variance. Correlations were investigated using Spearman's coefficient. Data are presented as mean (standard deviation) or median [interquartile range].

Results: Contact lens wearers, compared to previous wearers and non-wearers, showed higher circularity [0.65 (0.08) vs 0.59 (0.10) vs 0.57 (0.11), p = 0.003]. Subjects with symptoms, compared to asymptomatic participants, showed higher circularity [0.64 (0.08) vs 0.61 (0.10), p < 0.001] and lower irregularity (1.0 [0.7-2.0] vs 1.3 [1.0-2.3], p = 0.009). For previous wearers, those with symptoms showed greater density (135.4 [107.3-183.3] vs 87.5 [85.4-116.7], p = 0.013) and circularity [0.64 (0.07) vs 0.54 (0.10), p = 0.016]. For non-wearers, those with symptoms showed higher circularity [0.65 (0.08) vs 0.50 (0.08), p < 0.001]. DEQ-5 correlated with circularity (ρ = 0.55, p = 0.001).

Conclusions: Soft CL wear modifies papillae of the epithelial-lamina propria junction into a more rounded shape; however, CL cessation appears to resolve this alteration. Additionally, a more rounded papillae shape is associated with ocular symptoms in subjects not actively wearing CLs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/opo.12638DOI Listing
September 2019

The relationship between tear film MMP-9 and meibomian gland changes during soft contact lens wear.

Cont Lens Anterior Eye 2020 04 6;43(2):154-158. Epub 2019 Aug 6.

School of Optometry & Vision Science, University of New South Wales, Sydney, Australia.

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: 5 ± 1 years and Long experience: 10 ± 2 years); (2) a group of previous CL wearers (PWs) who had ceased wear for at least 6 months; and (3) healthy non-wearers (NW) as a control group. Total MMP-9 and its inhibitor, tissue inhibitor of MMPs-1 (TIMP-1) concentration were established using sandwich enzyme-linked immunosorbent assay. The MMP-9: TIMP-1 ratio was calculated for every individual, and then the average of all ratios for each group were compared. The non-parametric statistical Kruskal Wallis one-way analysis of variance was used for comparison, with Dunn's testing post-hoc.

Results: Tear samples from 100 participants (51 females; mean age ± SD: 25.4 ± 4.1 years) were analysed. MMP-9 concentrations and MMP-9:TIMP-1 ratio were significantly different between groups (Kruskal Wallis p = 0.001 and p < 0.001 respectively), while the concentration of TIMP-1 did not vary statistically between study groups (Kruskal Wallis, p = 0.32). Post hoc analysis indicated that only CL wearers with short experience had MMP-9 concentrations that were significantly high compared to NWs (23.1 ± 17.9 ng/mL and 4.1 ± 4.1 ng/mL, respectively, Dunn p < 0.001). Additionally, the ratio of MMP-9 to TIMP-1 concentration was only significantly greater in CL wearers with short experience (mean ratio ± SD = 1.15 ± 0.76) when compared to NWs (0.19 ± 0.29, Dunn P < 0.001), CL wearers with moderate experience (0.37 ± 0.41; P = 0.01) and PWs (0.38 ± 0.36; P = 0.02).

Conclusions: The early years of CL wear appear to be associated with increased expression of MMP-9 relative to its inhibitor TIMP-1. This may be indicative of low-level inflammation during this phase of wear. The role this plays in propagating dry eye disease and MGD in CL wear requires further exploration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clae.2019.07.007DOI Listing
April 2020

Professor Mark Willcox: the 2017 H Barry Collin Research Medallist.

Authors:
Maria Markoulli

Clin Exp Optom 2019 07;102(4):349

School of Optometry and Vision Science, The University of New South Wales, Sydney, New South Wales, Australia.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cxo.12925DOI Listing
July 2019

The repeatability of subjective and objective tear ferning assessment and its association with lipid layer thickness, non-invasive tear break-up time and comfort.

Cont Lens Anterior Eye 2019 08 24;42(4):420-427. Epub 2019 Apr 24.

School of Optometry and Vision Science, University of New South Wales, Australia.

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, controlled clinical study was conducted. Eighteen healthy non-contact lens wearers aged between 18 to 45 years attended a total of three visits. They were randomly allocated to receive no drops on two occasions to examine method repeatability (visits A and B) or a 60 μL drop of Refresh® (visit C). At each visit, LLT and NIKBUT were assessed followed by basal tear collection. The TF pattern was established by pipetting one μL volume of tears onto a glass slide that was allowed to air-dry and imaged under a microscope. The resulting tear ferning pattern was determined using subjective grading and a novel computerized objective analysis technique that measured the local contrast of ferning contours.

Results: Paired t-tests found that all measurements collected between eyes, on different days for visit A and B were not significantly different (p >0.05). Eyes and days were averaged and compared to visit C. Paired t-tests between the averaged baseline visits and visit C for LLT, NIKBUT including subjective and objective TF scores showed no significant difference (p>0.05). No significant correlation was shown between the TF scoring and OSDI, LLT or NITBUT (p>0.05). There was however a high significant correlation and agreement between the subjective and objective analysis techniques for TF grading.

Conclusions: TF grade, LLT and NITBUT are repeatable. As with other ocular surface assessments, subjective and objective TF gradings did not significantly correlate with the measures of tear film stability or comfort. Lubricants had no effect on TF grade, LLT or NITBUT. The novel objective analysis technique is a promising candidate for a repeatable and unbiased assessment of tear ferning.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clae.2019.04.003DOI Listing
August 2019

The Relationship Between Corneal Dendritic Cells, Corneal Nerve Morphology and Tear Inflammatory Mediators and Neuropeptides in Healthy Individuals.

Curr Eye Res 2019 08 15;44(8):840-848. Epub 2019 Apr 15.

a Institute of Health and Biomedical Innovation, School of Optometry and Vision Science, Queensland University of Technology , Brisbane , Australia.

: To determine the association between corneal dendritic cell (DC) density and corneal nerve morphology and tear film inflammatory mediators and neuromediators in healthy individuals. : Flush tears were collected from 21 healthy participants aged 39.7 ± 9.9 years and analyzed for total protein content (TPC), substance P, matrix-metalloproteinase-9 (MMP-9), tissue inhibitor of MMPs-1 (TIMP-1), tumor necrosis factor-a (TNF-α) and interleukin-6 (IL-6). confocal microscopy was used to assess DC density and corneal nerve morphology. Corneal nerve variables measured were corneal nerve fiber length (CNFL), fiber density (CNFD), branch density (CNBD), fiber total branch density (CTBD), fiber area (CNFA), fiber width (CNFW) and fractal dimension (CNFrac). : Participants with DC density over 50 cells/mm correlated with CNBD-average (r = 0.7, p = 0.02), CNBD-high (r = 0.6, p = 0.02), CNBD-low (r = 0.6, p = 0.02) CTBD-average (r = 0.7, p = 0.01), CTBD-high (r = 0.6, p = 0.03), CTBD-low (r = 0.7, p = 0.01), CNFA-average (r = 0.7, p = 0.00), CNFA-high (r = 0.7, p = 0.01), CNFA-low (r = 0.8, p < 0.001), CNFrac-SD (r = -0.6, p = 0.04), CNFrac-low (r = 0.6, p = 0.04) and CNFL-low (r = 0.7, p = 0.02). The percentage of MMP-9 correlated with DC density in the entire cohort (r = 0.47, p = 0.03). : Corneal nerve measures showed a strong correlation with higher DC density, suggesting that the number of cells maybe be modulated by the corneal nerves in the central cornea. MMP-9 also showed a moderate correlation with DC, supporting an inflammatory role.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/02713683.2019.1600196DOI Listing
August 2019

Emerging targets of inflammation and tear secretion in dry eye disease.

Drug Discov Today 2019 08 22;24(8):1427-1432. Epub 2019 Feb 22.

School of Optometry & Vision Science, University of New South Wales, Sydney, Australia.

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 perpetuating of a vicious circle. The aim of dry eye management is to restore the homeostasis of the tear film and break the perpetuation of this vicious circle. Despite the plethora of treatment options available, many of these are largely palliative, short-lived and require repeated instillations. Two emerging areas in dry eye therapy aim to promote tear secretion and to safely manage dry eye-associated inflammation and are the focus of this review.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.drudis.2019.02.006DOI Listing
August 2019

Impact of blinking on ocular surface and tear film parameters.

Ocul Surf 2018 10 5;16(4):424-429. Epub 2018 Jun 5.

Department of Ophthalmology, New Zealand National Eye Centre, The University of Auckland, New Zealand. Electronic address:

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 eye symptomology, tear film parameters, and ocular surface characteristics were assessed in a single clinical session.

Results: Overall, a higher proportion of participants exhibiting incomplete blinking fulfilled the TFOS DEWS II dry eye diagnostic criteria (64% versus 44%, p = 0.02), with an odds ratio (95% CI) of 2.2 (1.2-4.2) times. Participants exhibiting incomplete blinking had higher Ocular Surface Disease Index scores (18 ± 13 versus 12 ± 9, p = 0.01), and greater levels of meibomian gland dropout (41.3 ± 15.7% versus 27.5 ± 14.1%, p < 0.001). Furthermore, poorer tear film lipid layer thickness, non-invasive tear film stability, expressed meibum quality, eyelid notching, and anterior blepharitis grades were also observed in those exhibiting incomplete blinking (all p < 0.05). Blink frequency did not correlate significantly with any ocular surface parameters (all p > 0.05).

Conclusions: Incomplete blinking was associated with a two-fold increased risk of dry eye disease. The greater levels of meibomian gland dropout, as well as poorer expressed meibum quality and tear film lipid layer thickness, observed would suggest that incomplete blinking may predispose towards the development of evaporative dry eye.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jtos.2018.06.001DOI Listing
October 2018

The Effect of Contact Lens Wear on the Cellular Morphology of the Lid Wiper Area.

Optom Vis Sci 2018 06;95(6):491-497

School of Optometry & Vision Science, University of New South Wales, Sydney, New South Wales, Australia.

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 epithelium.

Methods: This was a cross-sectional study of 100 individuals with different exposures to CL wear: short, moderate, and long experience of CL wear; previous CL wearers; and nonwearers (NWs) as controls. Impression cytology samples were collected from the central upper lid margin (LW area). After fixing, samples were stained with periodic acid-Schiff and haematoxylin for cell morphology analysis and subsequently graded according to the Nelson 0- to 3-point scale. Lid wiper staining was assessed with the aid of lissamine green and graded using the Korb (0- to 3-point) scale. One-way Kruskal-Wallis analysis followed by the Dunn multiple-comparisons test was used for statistical comparison.

Results: The Nelson grade for LW epithelium morphology was significantly different between groups (P = .003). Abnormal epithelial morphology as defined by grade 2 or 3 was evident in 66.7% of CL wearers with short experience and 76.5% of CL wearers with moderate experience. This was significantly higher than NWs of whom only 21.5% showed greater than grade 1 (P = .02 and .005, respectively). There was no significant difference between NWs and other groups. Lid wiper staining did not significantly differ between groups (P = .50) or correlate with the Nelson grade (Spearman r = 0.02, P = .08).

Conclusions: Metaplasia of the LW epithelium was significantly greater in the early to moderate stages of CL. This supports the view that mechanical irritation is responsible for LW changes in CL wear. Ceasing CL wear seems to lead to recovery. Lid wiper staining did not reflect the underlying morphological changes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/OPX.0000000000001224DOI Listing
June 2018

The Effect of Optive and Optive Advanced Artificial Tears on the Healthy Tear Film.

Curr Eye Res 2018 05 1;43(5):588-594. Epub 2018 Feb 1.

c Department of Ophthalmology, Prince of Wales Clinical School, Faculty of Medicine , UNSW Sydney , Sydney , Australia.

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 Optive, Optive Advanced or saline. Oculus Keratograph 5M (Oculus, Arlington, WA, USA), non-invasive keratograph break-up time (NIKBUT), Lipiview (TearScience Inc, Morrisville, NC, USA), lipid layer thickness (LLT) and comfort were measured prior to and 5, 15 and 60 min after drop instillation.

Results: Optive Advanced demonstrated a significant increase in LLT between baseline (57.5 ± 12.3 nm) and both 5 min (67.5 ± 18.8 nm, p = 0.04) and 15 min (68.9 ± 17.3 nm, p = 0.04) but not 60 min (61.6 ± 14.3 nm, p = 0.47). Optive and saline were not different between timepoints for LLT (p > 0.05). There was no difference between timepoints for any of the drops for NIKBUT (p = 0.75). Comfort was significantly better at 5 min compared to baseline for Optive (8.3 ± 1.2 and 7.3 ± 1.4, respectively, p = 0.03) but not different for Optive Advance or saline (p > 0.05).

Conclusions: Optive Advanced increased LLT for 15 min following instillation, returning to baseline within one hour. This did not however, translate into an improvement in tear film stability over this time period. Only Optive demonstrated an improvement in comfort.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/02713683.2018.1433860DOI Listing
May 2018

Automatic analysis of corneal nerves imaged using in vivo confocal microscopy.

Clin Exp Optom 2018 03 28;101(2):147-161. Epub 2017 Nov 28.

School of Optometry and Vision Science, The University of New South Wales, Sydney, New South Wales, Australia.

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 length), tortuosity, variations in nerve thickness, as well as temporal changes in nerve fibres such as migration patterns. Different approaches to automated nerve analysis, methods proposed and how they were validated in previous literature are reviewed. Improved understanding of these approaches and their limitations will help improve the diagnostic leverage of emerging developments for monitoring the onset and progression of a broad class of systemic diseases, including diabetes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cxo.12640DOI Listing
March 2018