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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).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.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.Tear film SP may provide a potential non-invasive biomarker for assessing neuropathy in T1D.

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.

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

Using recent advances in science mapping, this article systematically reviews the Human Resource Management (HRM) field. We analyze 12,157 HRM research articles published over 23 years to reveal the topic content and intellectual structure of HRM scholarship. A downloadable, searchable HRM topic map is provided ( http://bit.ly/HR-Map ) that reveals: a) 1702 HRM article topics, b) the number of articles on each topic, c) topic relations, trends, and impact, and d) five major HRM topic clusters. We discuss the overall intellectual structure of HRM scholarship and review the five topic clusters. Next, the topic content of HRM scholarship is compared to that of 6114 articles from the practitioner-oriented outlet HR Magazine . We identify 100 topics emphasized to a much greater degree in the practitioner-oriented literature. Seven key themes for future research that could help align HRM scholarship with the interests of HR practitioners are identified and discussed.

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 reported, sensation of dry eye is the most common. Given the outcome of reduced wearing time, increased chair time, and ultimate contact lens discontinuation, the challenge is to identify the warning signs of CLD early on. Clinically detectable changes such as conjunctival staining, conjunctival indentation, conjunctival epithelial flap formation, lid wiper epitheliopathy, Demodex blepharitis, and meibomian gland dysfunction have been linked to CLD, highlighting the need to perform regular aftercare visits to identify these changes. At a cellular level, conjunctival metaplasia and reduced goblet cell density have been linked to CLD, leading to a downstream effect on the tear film breakup time of contact lens wearers. These factors suggest a strong link between CLD and friction, raising the need to target this as a means of minimizing CLD. The purpose of this review is to identify the clinical signs that relate to CLD as a means of earlier detection and management in order to combat contact lens dropout.

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.

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).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.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).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.

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 both epithelial and goblet cells. The consequent decrease in surface wettability leads to early tear film breakup and amplifies hyperosmolarity via a Vicious Circle. Pain in dry eye is caused by tear hyperosmolarity, loss of lubrication, inflammatory mediators and neurosensory factors, while visual symptoms arise from tear and ocular surface irregularity. Increased friction targets damage to the lids and ocular surface, resulting in characteristic punctate epithelial keratitis, superior limbic keratoconjunctivitis, filamentary keratitis, lid parallel conjunctival folds, and lid wiper epitheliopathy. Hybrid dry eye disease, with features of both aqueous deficiency and increased evaporation, is common and efforts should be made to determine the relative contribution of each form to the total picture. To this end, practical methods are needed to measure tear evaporation in the clinic, and similarly, methods are needed to measure osmolarity at the tissue level across the ocular surface, to better determine the severity of dry eye. Areas for future research include the role of genetic mechanisms in non-Sjogren syndrome dry eye, the targeting of the terminal duct in meibomian gland disease and the influence of gaze dynamics and the closed eye state on tear stability and ocular surface inflammation.

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 complications, including nephropathy leading to kidney failure, potentially blinding diabetic retinopathy, and diabetic neuropathy. While the retinal complications of diabetes are well recognized by eye care professionals, the effects on the ocular surface are poorly understood. Recent studies have reported on the association between peripheral neuropathy and corneal neuropathy, showing the latter to be of predictive value for the systemic disease. Corneal neuropathy can lead to loss of corneal sensation and can ultimately result in neurotrophic ulcers and significant visual morbidity. The epithelial fragility and poor wound healing that result from reduced epithelial adhesion to the underlying basement membrane in diabetes, together with corneal neuropathy, are thought to increase the susceptibility to persistent corneal erosions and infection, as well as to increase the risk of post-surgical complications. The aim of this article is to review the impact of diabetes on corneal nerve morphology and ocular surface integrity. Changes in the tear film and ocular surface microbiome are highlighted in discussion of the mechanisms that underpin ocular surface changes that increase the susceptibility to corneal erosion and infection.

To determine the repeatability of the flush tear collection technique and the Schirmer strip for Substance P tear analysis.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 on two occasions and in a randomized order. Total protein content (TPC) and Substance P concentrations were determined. The overall protein separation profile of each type of tears was examined using one-dimensional gel electrophoresis (1DGE).Collection rates were significantly faster for the F-60 compared to F-20 (17.3 ± 6.9 μL/min and 11.9 ± 5.3 μL/min, respectively, P.001), with an average Schirmer strip length of 1.5 ± 2.1 mm/min. The coefficient of repeatability between days and eyes was greatest for the Schirmer strip, with eyes and days being significantly different (P = .03 and P = .03, respectively) for Schirmer strip Substance P. TPC was 3.8 ± 2.6 mg/mL, 3.3 ± 1.8 mg/mL, and 3.6 ± 3.0 mg/mL for F-20, F-60, and Schirmer strip techniques, respectively, with no significant difference between techniques (P = .85). Substance P concentration was 13.1 ± 14.8 ng/mL, 9.1 ± 6.1 ng/mL, and 14.9 ± 10.6 ng/mL for F-20, F-60, and Schirmer strip tears, respectively, with no significant difference between techniques (P = .57). 1DGE profile showed similar electrophoresis patterns among F-20, F-60, and basal tears.The F-60 method allows faster collection than F-20, but the latter results in better repeatability than both the F-60 and Schirmer sampling techniques. All three techniques return the same concentrations of TPC and Substance P. This indicates that tear collection using the F-20 may be more appropriate when conducting comparative analysis, whereas the F-60 may be more appropriate when more volume is required.

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 captured at regular intervals over 30 minutes and the process repeated for the other eye with the alternate concentration. Fluorescence intensity was quantified on the basis of the grayscale pixel values in the tear meniscus images. The fluorescein-decay profile over time and between concentrations was determined. Results Peak fluorescence intensity was reached in 3.9 ± 3.0 and 8.7 ± 4.4 minutes after instillation for the 2 and 10% concentrations, respectively. The 10% concentration of fluorescein maintained its peak fluorescence intensity longer than the 2% concentration (about 9 and 2 minutes, respectively). The peak fluorescence intensity was not significantly different between the higher and lower concentrations (44 ± 37 vs. 38 ± 32 units, P = .22). For both concentrations, the observed intensity did not return to baseline levels by the end of the 30-minute observation time. Conclusions The fluorescence intensity of fluorescein in a clinical setting varies with time such that both the onset and duration of maximum brightness are concentration dependent. At low concentration (2%), maximum brightness occurs almost immediately after instillation and lasts about 2 minutes. With a higher concentration (10%), the effective working window is delayed for about 7 to 8 minutes. Irrespective of initial concentration, observable fluorescence remains in the tear film beyond 30 minutes post-instillation.

This issue of Clinical and Experimental Optometry includes the 2017 H Barry Collin Research Medal Lecture. The H Barry Collin Research Medal was established in 1977 to recognise the pioneering rese...

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 with the choice of extended (EW) or daily wear (DW). Each time, tears were collected at midday, before sleep, and on waking and analyzed for concentrations of total protein, MMP-9, and its regulators TIMP-1 (tissue inhibitor of metalloproteinases 1) and NGAL (neutrophil gelatinase-associated lipocalin). Results: Initial extended contact lens wear resulted in significantly elevated MMP-9 levels on waking (3598.7 ± 3229.1 ng/mL) compared with the same time point at baseline (2123.3 ± 1762.8; p = 0.02), whereas DW remained unchanged (2373.0 ± 2091.6 ng/mL; p = 0.61). After 1 month of EW, the levels on awakening were no longer different to those of baseline (2408.2 ± 1376.1 ng/mL; p = 0.63). The MMP:TIMP ratio during EW was greater after the first night (18.6 ± 19.9) than both no wear (13.2 ± 13.4) and 1 month (10.4 ± 7.7), but only the latter was significant (p = 0.048). The profile of NGAL did not differ from baseline (p = 0.055). Conclusions: In the neophyte, the initial period of overnight lens wear seems to disturb the tear film homeostasis, as indicated by a significant increase in MMP-9 on awakening. The return to baseline by 1 month suggests that an adaptive process takes place. No comparable changes are seen in DW. © 2013 American Academy of Optometry.

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 rabbits using non-invasive methods and to establish the pattern of tear break-up compared to humans. Methods The tear break-up time was measured and the pattern of tear break-up was observed in six New Zealand White rabbits on two separate occasions using both the Keeler Tearscope-plusTM and a slitlamp biomicroscope. Results The mean rabbit tear break-up time was 29.8 ± 3.4 (SD) minutes. This contrasts with the reports of human tear break-up time of eight to 30 seconds. The tear breaking spread very slowly and was often restricted to the area of the initial break. Conclusion Rabbit tears have a significantly higher tear break-up time than humans and this aligns with previously demonstrated differences in inter-blink time between rabbits and humans. Understanding the underlying mechanisms of tear stability may lead to novel ways of increasing human tear film stability.

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 and systemic abnormalities were recruited and divided into four age groups: 25 to 34, 35 to 44, 45 to 54, and 55 to 66 years. At a single visit, the following MG measures were collected: meibum quality (MQ) and MG expressibility (MGE) of the lower lid, and MG drop-out score (meiboscale) using infrared meibography of the upper and lower lids. Assessments of anterior eye, tear function variables, noninvasive and invasive tear breakup time (TBUT), corneal integrity, and lid wiper epitheliopathy were also performed during the visit. An Ocular Surface Disease Index (OSDI) questionnaire was used to record dry eye symptoms. Meibum lipids samples were collected and analyzed. RESULTS A majority of the study population (61%) was asymptomatic. There was a significant worsening in the MQ (P< 0.048), MGE (P < 0.03), and meiboscale (P < 0.01) with increasing age. Significant increase was observed in anterior blepharitis (P < 0.001) and telangiectasia (P< 0.02) with aging. Interestingly, tear osmolarity decreased significantly (P < 0.001), while tear meniscus height (P < 0.001) and invasive TBUT (P = 0.02) increased with increase in age. There was no significant association between MG variables and sex, ocular discomfort symptoms, or meibum lipids classes. CONCLUSIONS Progressive MG loss occurs normally with age accompanied by reduced quality and quantity of the meibum produced. However, clinical presentation of ocular discomfort symptoms is stalled without corresponding disruption to tear function.

Purpose. 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. Methods. 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 wore AIR OPTIX on an extended wear (EW) schedule. Tears were collected at mid-day and upon waking and analyzed for concentrations of total protein using the bicinchoninic acid assay method. DIGE was then performed to detect biomarkers likely to be affected by contact lens wear. Technique variability, physiological variability, and the effect of EW were established. Proteins with significantly changed abundance during lens wear were cut and identified with mass spectrometry. Results. Both Cy3 and Cy5 identified the same proteins relative to Cy2 with the highest fold difference of 4.4. The proteome varied by 3% at the same time point, with a significant increase in protein spots found between mid-day (257) and upon awakening (298). With EW, of the 311 proteins spots identified upon awakening, 15 differed significantly. Of the five differences between baseline and the first night of EW, all were greater at baseline. Of the differences between baseline and 1 month, six were greater at 1 month and four were greater at baseline. Conclusions. DIGE is a repeatable proteomic technique capable of determining differences in the tear proteome. The extent of the participants' experience with lens wear is an important factor to consider when analyzing the tears from lens wearers, as neophytes appear to differ from those with experience. © 2012 American Academy of Optometry.

Contact lens wear continues to be the highest single risk factor for microbial keratitis, particularly when worn in the extended wear modality. For microbial keratitis to occur, the presence of at least a bacterial load as well as a break in the corneal surface is required. One such break occurs in the case of a corneal erosion. These well-circumscribed areas of full thickness epithelial loss can occur both with and without contact lens wear, however the risk of infection is greater in the presence of a lens due to its capacity to provide a vector for the entry of bacterial pathogens. While erosions in non-contact lens wearers are thought to result from defective epithelial basement membrane anchoring, the underlying causes during contact lens wear are yet unknown. This article sets out to review corneal erosions associated with contact lens wear, their associated risk factors such as extended wear, the mechanisms that may be responsible for their formation and the factors that differentiate them from other contact lens related adverse events. Appropriate diagnosis and understanding of the relevant pathophysiology is important to the effective treatment and an understanding of the aetiological factors responsible for erosions is critical to the development of preventative strategies and effective clinical care.

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 long experience of CL wear); (ii) a group of previous CL wearers (PWs) who had ceased wear for at least 6 months prior to the present study; (iii) healthy non-wearers as a control group. Study procedures were conducted in the order from least invasive to most invasive as follows: symptom assessment, lipid assessment, non-invasive break-up time, tear meniscus area, tear osmolarity and evaporation, Phenol red thread, MG expressibility, ocular surface and eyelid assessments, meibography, Marx line and lid wiper assessment using lissamine green. For statistical comparison of continuous data, one-way analysis of variance was used with Bonferroni post-hoc correction, where appropriate. Kruskal–Wallis test and Pearson Chi-Square respectively were used for ordinal and categorical variables. Results A total of 100 participants (49 males and 51 females; mean age ± SD: 25.4 ± 4.1) were enrolled across the five groups, such that each was composed of 20 age/sex matched individuals. Significant differences between the study groups were found for MG expressibility (p

This article provides a structural review of the Human Resource Management (HRM) field from articles published between 1992 and 2013, through the utilization of bibliometric mapping and clustering techniques. By applying a transparent, replicable, and inductive approach to the analysis of the HRM literature, this paper presents a rigorously developed field classification system in the form of a scientometric term map (bit.ly/HRMMap). This classification system visualizes five key prevailing subfields of HRM research – i.e., Functional HRM, International HRM, Strategic HRM, Industrial Relations, and the HRM Process Approach – and reveals associations between these topics. We briefly review each of these five clusters, providing a bird’s eye view of the HRM field. In addition, we describe how the HRM Map can be used as a "theory creation tool", allowing HRM academics to go beyond their specialization and engage in research that bridges subfields. Implications for future research are discussed.

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 acnes, and Corynebacterium spp. were inoculated at a density of 10 6 /mL in varying concentrations of GML up to 25 lg/mL for 24 hours at 378C with constant shaking. Bacterial suspensions were centrifuged, bacterial cell density was determined, and production of bacterial lipase was quantified using a commercial lipase assay kit. RESULTS. Staphylococcus spp. produced high levels of lipase activity compared with P. acnes and Corynebacterium spp. GML inhibited lipase production by Staphylococcal spp. in a dose- dependent manner, with S. epidermidis lipase production consistently more sensitive to GML than S. aureus. Glycerol monolaurate showed significant (P < 0.05) lipase inhibition above concentrations of 15 lg/mL in S. aureus and was not cytotoxic up to 25 lg/mL. For S. epidermidis, GML showed significant (P < 0.05) lipase inhibition above 7.5 lg/mL. CONCLUSIONS. Lipase activity varied between species and between strains. Staphylococcal spp. produced higher lipase activity compared with P. acnes and Corynebacterium spp. Glycerol monolaurate inhibited lipase production by S. aureus and S. epidermidis at concentrations that did not adversely affect bacterial cell growth. GML can be used to inhibit ocular bacterial lipase production without proving detrimental to commensal bacteria viability.

Purpose: To study the histopathology of paralimbal bulbar conjunctival flaps occurring secondary to soft contact lens wear. Methods: 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 subjects who exhibited such flaps agreed to undergo conjunctival biopsy. Tissue samples, obtained from the region of the flap, and an adjacent unaffected area were processed by standard histopathological methods. Results: In the first subject, analysis of the flap tissue showed even collagen distribution and overall normal histology. The flap of the second subject displayed a mild focal increase in collagen and mild degeneration of collagen, but no increase in elastic tissue. Conjunctival epithelium was normal in both cases. Conclusions: In these 2 subjects, conjunctival flap tissue either was normal or showed only minimal abnormality. There is insufficient evidence for significant pathological change on the time scale of this study. Copyright © 2011 by Lippincott Williams & Wilkins.

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 sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and mass spectrometry (MS).Collection-rates were 4.6 ± 6.7 μl/min, 13.9 ± 11.1 μl/min, and 25.7 ± 12.4 μl/min for the basal, reflex, and flush tears, respectively. TPC was 7.14 ± 2.22 mg/mL, 6.01 ± 2.11 mg/mL, and 3.79 ± 1.51 mg/ mL for basal, reflex, and flush tears, respectively, with flush tears being significantly less concentrated than basal (p = 0.001) and reflex (p = 0.008). IgA concentration was 1.04 ± 0.29 mg/ mL, 0.64 ± 0.26 mg/mL, and 0.65 ± 0.23 mg/mL for basal, reflex, and flush tears, respectively, with basal tears being significantly more concentrated (p 0.001). As a percentage of TPC, IgA represented 19.8 ± 14.9%, 11.4 ± 3.9%, and 19.8 ± 8.7% for basal, reflex, and flush, respectively. The flush was not significantly different to basal (p = 1.00) but significantly greater than reflex (p = 0.02). SDS-PAGE showed the same tear profiles for basal and flush tears. MS identified the most abundant proteins in all tear types.The flush method allows much faster collection than basal secretion sampling but returns essentially the same spectrum of proteins in similar proportions. This behavior is confirmation that the flush technique has utility as a more convenient alternative to basal tear sampling in studies involving composition analysis.

Acta Ophthalmol. 2011: 89: e75–e81 Abstract. Purpose: 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. Methods: 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 collected using microcapillary tubes from animal eyes either unwounded control or wounded with 9-mm central epithelial debridement giving four groups with n = 3. Tear comparisons were based on total time and rate for tear collection, TPC using micro bicinchoninic acid (BCA), tear immunoglobulin A (IgA), total matrix-metalloproteinase (MMP)-9 concentration using sandwich enzyme-linked immunosorbent assay (ELISA) and MMP-9 activity. Results: Eye-flush tears were collected significantly faster than basal tears in wounded eyes with higher rates for tear collection in unwounded control and wounded eyes. TPC was significantly lower in eye-flush tears compared to basal tears. The relative proportion of tear IgA normalized to TPC (% IgA of TPC) was not significantly different between basal and eye-flush tears. In unwounded control eyes, MMP-9 was slightly higher in eye-flush than in basal tears; activity of MMP-9 in both tear types was similar. In wounded eyes, eye-flush tears showed highest MMP-9 levels and activity on Day 1, which subsequently decreased to Day 7. MMP-9 activity in basal tears from wounded eyes did not display changes in expression. Conclusions: Eye-flush tears can be collected rapidly providing sufficient tear volume and TPC. This study also indicates that eye-flush tears may be more suitable than basal tears for the analysis of MMPs following corneal wounding.

Purpose. 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. Methods. 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 margins of each eye were swabbed at baseline and then at 6-monthly intervals for 2 years during lens wear. Swabs were processed, cultured and microorganisms identified using standard microbiological techniques. Results. At baseline, 36% of the upper bulbar conjunctivae and 53% of the lower lid margins were contaminated with predominantly gram-positive bacteria. Recovery of samples with positive growth from the upper bulbar conjunctivae decreased during lens wear and ranged from 27 to 14%. The difference was statistically significant at the 12-month visit (14%, p = 0.011). The lower lid margins generally showed similar levels of contamination as at baseline except for less contamination at the 12-month visit (33%) (p = 0.05). Staphylococcus epidermidis and Propionibacterium sp. were the predominant microorganisms isolated from both the sites with and without lens wear. Gram-negative bacteria were infrequent and when isolated, the numbers of colonies were few. Fungus was isolated in a small percent (ranging from 0 to 4.8%) of eyes at various time points. Conclusions. The external ocular surface of children is contaminated with gram-positive bacteria that are resident micro biota. During lens wear, there was a trend for lesser recovery of organisms from the upper bulbar conjunctival samples, but there was no change in the type of microorganisms isolated. At all times, lower lid margins showed consistently greater colonization and is a source of potential contamination of the conjunctival surface.

Purpose: To investigate (i) the effect of probe position on the lid when using the Proview Eye Pressure Monitor (Proview) and (ii) the accuracy of the Proview and its agreement with the Goldmann applanation tonometer (GAT) in a normal population. Methods: Intraocular pressure (IOP) measurements were performed on 107 control subjects (mean 25 years) using the Proview and the GAT. The Proview probe was applied to two locations on the eyelid (superior nasal and superior temporal). The IOPs measured with both instruments were compared. Results: A total of 4.6% of young normal eyes could not perceive the phosphene. The mean Proview reading using the recommended nasal lid position was significantly higher (+2.5 mmHg) than that measured using the GAT. The position of the probe application was significant, with temporal lid application giving statistically significantly higher IOP readings than the recommended nasal lid application. The repeatability of Proview measurements was lower than the GAT (coefficients of repeatability of GAT and Proview nasal were 0.96 and 4.21 mmHg respectively). The limit of agreement between the GAT and the Proview nasal was low at ±7.95 mmHg. Conclusion: This study shows that the position of probe application can influence the measurements taken using the Proview. Application of the probe to the nasal superior lid (as recommended) gives the more repeatable and accurate results. Overall however the data indicate that the Proview is neither sufficiently accurate nor repeatable to be used in the detection and management of glaucoma. More work is needed in developing this interesting product.

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 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 of MMP-9, Tissue Inhibitor of Metalloproteinase (TIMP)-1, and Neutrophil Gelatinase-Associated Lipocalin (NGAL). METHODS Flush tears were collected from 46 healthy, non-contact lens wearers at midday, before sleep, and immediately on waking. Total protein content (TPC) was measured using the bicinchoninic acid method, and MMP-9, TIMP-1, and NGAL concentrations were measured using sandwich enzyme-linked immunoassay. Statistical analysis was performed using repeated measures analysis of variance. RESULTS TPC was 3.4 ± 1.5 mg/mL, 5.0 ± 3.7 mg/mL and 15.5 ± 8.4 mg/mL for midday, before sleep, and on waking respectively, the latter being significantly greater than the other two (P < 0.001). MMP-9 concentrations at the corresponding time points were 9.8 ± 14.3 ng/mL, 8.5 ± 11.7 ng/mL, and 2000.7 ± 1950.7 ng/mL. Again, the value on waking was significantly greater than the previous two visits (P < 0.001). TIMP-1 concentrations exceeded those of MMP-9 at midday but the ratio of the two reversed on awakening. CONCLUSIONS Concentrations of MMP-9 are negligible during the day and completely inhibited by TIMP-1. On awakening, MMP-9 increases 200-fold, an increase that is not completely inhibited by TIMP-1. This diurnal change, along with the presence of NGAL which protects MMP-9 from degradation, suggests that the closed eye is an environment conducive to extracellular matrix remodeling.

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’ targets may or may not be lengthened with age, secondary eye-movements (during ‘double-step’ displacements) are significantly delayed with increasing age. The aim of this study was to investigate if the postural challenge posed simply by standing (as opposed to sitting) results in significantly longer eye movement latencies in older adults compared to the young. Ten young (65 years) participated in the study. They were required to fixate upon a central target and move their eyes in response to 2 types of stimuli: 1) a single-step perturbation of target position either 15º to the right or left, and 2) a double-step target displacement incorporating an initial target jump to the right or left by 15º, followed after 200 ms, by a shift of target position to the opposite side (e.g., +15º then -15º). All target displacement conditions were executed in sit and stand positions with the participant at the same distance from the targets. Eye movements were recorded using electro-oculography. Older adults did not show significantly longer eye movement latencies than the younger adults for single-step target displacements, and postural configuration (stand compared to sit) had no effect upon latencies for either group. We categorised double-step trials into those during which the second light changed after or before the onset of the eye shift to the first light. For the former category, young participants showed faster secondary eye shifts to the second light in the standing position, while the older adults did not. For the latter category of double-step trial, young participants showed no significant difference between sit and stand secondary eye movement latencies, but older adults were significantly longer standing compared to sitting. The older adults were significantly longer than the younger adults across both postural conditions, regardless of when the second light change occurred during the eye shift to the first light. We suggest that older adults require greater time and perhaps attentional processes to execute eye movements to unexpected changes of target position when faced with the need to maintain standing balance. Keywords: Balance, Ageing, Gaze, Electro-oculography, Target perturbations.