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Purpose: Wildfire occurrence is increasing worldwide, putting firefighters and general public at increased risk of eye injuries from smoke exposure. This study explored ocular symptoms and use of protective eyewear amongst wildland firefighters in Australia., Methods: Australian wildland firefighters were invited to complete an online survey about the occurrence of eye irritation, use of protective eyewear and behaviours associated with occupational smoke exposure. Responses were analysed using logistic regression and qualitative inductive content analysis., Results: 338 wildland firefighters completed the survey. Eye irritation was reported by 90 % of firefighters at least sometimes during work and by 70 % after work. Frequency of eye irritation was greater amongst females than males (OR 2.01, CI 1.22-3.31, p < 0.001). Protective eyewear was used often or always by 67 % of firefighters on the fireground, however 55 % had to remove their protective eyewear due to sweat, fogging or another reason. Goggles were more likely to be removed compared to sunglasses and safety glasses (OR 4.28, CI 2.75-6.68, p < 0.001). Firefighters reported that, at times smoke exposure necessitated eye closure and impaired vision on the fireground. Firefighters also reported that protective eyewear helped to reduce eye symptoms, but its consistent use on the fireground was difficult. The severity and recovery from eye symptoms varied between participants., Conclusion: Australian wildland firefighters frequently experience eye irritation from smoke exposure, and this can affect operational capabilities. These findings can support the development of evidence-based strategies to help protect and aid recovery of the eye surface following smoke exposure., Competing Interests: Declaration of competing interest None of the authors have any conflicts of interest or funding disclosures to report., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Sex hormones impact inflammatory and immune-mediated diseases. During IVF (in vitro fertilisation) treatment, circulating estrogen levels increase dramatically (10-50x) alongside changes in other hormones. This study examined changes in dry eye with IVF and its relationship with sex hormones., Methods: A two visit study was conducted on first day of menstruation when estrogen levels are lowest (baseline visit), and on day 9-11 (peak estrogen visit (PO)) of IVF. Symptoms of dry eye and ocular pain and signs of dry eye were examined. Serum hormone levels were assessed using mass spectrometry and immunoassay. Changes in signs and symptoms and associations were explored. Hierarchical multiple regression analysis assessed factors contributing to signs and symptoms., Results: 40 women (36.2 ± 4.0 years) completed the study. Baseline and PO oestradiol (E2) levels were 28.9 pg/ml (20) (median (IQR)); 1360 pg/ml (1276) respectively. Ocular pain and dry eye symptoms worsened (p = 0.02 and p < 0.01) and tear break up and tear secretion values decreased (p = 0.005 and 0.01) at PO. Higher E2 and lower luteinizing hormone (LH) were associated with worsening of dry eye symptoms (ρ = 0.34 p = 0.03, ρ = -0.49 p = 0.001). Reduction in LH and increase in progesterone (P4) were associated with increased ocular pain (ρ = 0.45, p = 0.004 and ρ = 0.39, p = 0.01). Dry eye symptoms were predicted by LH and tear break up (p = 0.02; R 2  = 0.18)., Conclusions: IVF treatment resulted in significantly increased ocular symptoms and tear film alterations although these changes were not clinically significant. Dry eye signs and symptoms were poorly predicted by hormone levels., Competing Interests: Disclosure/conflict of interest statement The authors declare that there are no financial disclosures or conflict of interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The widely used immortalised human meibomian gland epithelia cell (iHMGEC) line has made possible extensive studies of the biology and pathophysiology of meibomian glands (MG). Tissue culture protocols for iHMGEC have been revised and modified to optimise the growth conditions for cell differentiation and lipid accumulation. iHMGEC proliferate in serum-free medium but require serum or other appropriate exogenous factors to differentiate. Several supplements can enhance differentiation and neutral lipid accumulation in iHMGEC grown in serum-containing medium. In serum-free medium, rosiglitazone, a peroxisome proliferator activator receptor-γ (PPARγ) agonist, is reported to induce iHMGEC differentiation, neutral lipid accumulation and expression of key biomarkers of differentiation. iHMGEC cultured in serum-containing medium under hypoxia or with azithromycin increases DNAse 2 activity, a biomarker of terminal differentiation in sebocytes. The production of lipids with composition similar to meibum has not been observed in vitro and this remains a major challenge for iHMGEC culture. Innovative methodologies such as 3D ex vivo culture of MG and generation of MG organoids from stem cells are important for further developing a model that more closely mimics the in vivo biology of human MG and to facilitate the next generation of studies of MG disease and dry eye., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: Aromatase inhibitors (AIs) limit the synthesis of oestrogen in peripheral tissues thus lowering levels of oestrogen. The primary aim was to evaluate whether women treated with AIs have altered dry eye symptoms and signs. A sub-aim was to investigate whether symptoms of dry eye in postmenopausal women were associated with symptoms of non-eye pain, ocular pain and self-rated pain perception., Methods: This cross-sectional, observational, single visit study recruited 56 postmenopausal women (mean age 64.1 + 7.9 years) and 52 undergoing AI treatment (mean age 66.6 + 9.0). Ocular symptoms (OSDI, MGD14) and pain questionnaires (PSQ, OPAS) were administered and signs of dry eye and meibomian gland dysfunction were evaluated., Results: Almost half of each group reported dry eye symptoms, defined as OSDI>12 (48% control, 46% AI). The PSQ score was significantly higher in the AI group (p = 0.04). Neither frequency or severity of dry eye (or MGD) symptoms scores were significantly different between groups. In the AI group, meibomian gland expressibility score was worse (p = 0.003); there were no differences in any other signs. Higher OSDI scores were associated with higher OPAS eye-pain scores (r = 0.49, p < 0.001), but not OPAS non-eye pain (r = 0.09, p = 0.35). Pain perception (PSQ) showed a moderate positive association with OPAS eye-pain (r = 0.30, p = 0.003)., Conclusions: In this study elevated ocular symptoms were observed in both the AI treated and the untreated groups, with no difference between the groups. Women undergoing AI treatment for early stage breast cancer had worse meibum expressibility score and increased pain perception compared to an untreated group of women., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: Women are more prone to ocular surface symptoms and circulating estrogen levels have been implicated. Fluctuations in estrogen during the menstrual cycle may influence ocular symptoms but existing research is incomplete and conflicting, partly due to paucity of validated questionnaires to assess daily ocular symptoms. This study aimed to evaluate daily fluctuations in ocular symptoms across a complete menstrual cycle and to compare symptoms in normally menstruating women and women using the combined oral contraceptive pill (OCP)., Methods: To do this, a short online tool to assess daily symptoms was developed. 36 normally menstruating women and 36 women using the combined OCP were recruited. A two-item questionnaire, the Instant Ocular Symptoms Survey (IOSS) was developed and administered on a smartphone platform every day for 40 days. Linear mixed model analysis was used to examine differences in symptom scores over time and between groups., Results: The IOSS was found to be effective for measuring instantaneous symptoms, exhibiting good diagnostic abilities and repeatability. (AUC ± SE = 0.80 ± 0.07 and ICC = 0.75). Daily ocular symptoms showed a cyclic fluctuation across the cycle (p = 0.004) and highest symptoms were recorded on day 2 of the cycle when estrogen levels are lowest. Symptom scores were significantly higher in the OCP group (p = 0.02)., Conclusions: Effects of menstrual phase and OCP use should be considered in the interpretation of ocular symptoms in clinical practice. These findings enhance the current understandings of ocular surface and systemic pain during menstrual cycle., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: Numerous studies have reported a wide range of corneal epithelial dendritic cells (CEDC) density using in-vivo confocal microscopy in healthy participants. It is necessary to establish normal CEDC values for healthy corneas to enable differentiation from pathological corneas. This meta-analysis aimed to establish CEDC density and distribution and examine their relationship with age and sex., Methods: A systematic review of the literature of studies using the Heidelberg Retinal Tomograph with Rostock Corneal Module and reporting CEDC density in healthy subjects up to December 2018 was conducted via Medline, Google Scholar, Scopus, PubMed, Embase and Cochrane library. A random effect modeling approach was used to obtain the results of meta-analysis and meta-regression was conducted to estimate the effect of age and sex., Results: 38 studies reported central and 9 reported peripheral inferior CEDC density of 1203 participants (mean age 46.0 ± 12.2, range 18-81 years). CEDC density in the central and peripheral inferior cornea was 26.4 ± 13.6 cells/mm 2 (95% CI:22.5-26.8) and 74.9 ± 22.7 cells/mm 2 (95%CI:59.8-90.0), respectively. No effect of age was found on central CEDC density (p = 0.63); whereas peripheral CEDC density decreased with increasing age (p = 0.02). CEDC density was not influenced by sex at either location (p > 0.48)., Conclusion: This study established that the density at the peripheral inferior cornea is three-fold higher than at the central cornea. Peripheral but not central CEDC density decreased with increasing age. There are limited studies in youth (<18 years), precluding a more detailed analysis. Sex does not appear to be a significant factor in CEDC density., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: A review of ocular surface and meta-analysis of tear stability (tear break up time, TBUT) and tear secretion (Schirmer test) values in healthy children was conducted., Methods: Articles published between 1996 and 2017 indexed on MEDLINE, PubMed, Embase, Scopus and Google Scholar were retrieved using defined search terms. Statistical analysis (including sensitivity analysis and meta-regression) was performed., Results: 23 studies were summarised (5,291 participants; neonates (0-29 days), infants (1 month - 1 year) or children (1-18 years) and a meta-analysis conducted using 15 eligible studies (1,077 participants). The combined mean TBUT in children was 14.64 seconds (s) (95% CI, 11.64, 17.64) and 21.76 s (95% CI, 20.43, 23.09) for sodium fluorescein TBUT and non-invasive TBUT respectively (NIBUT). The combined mean NIBUT was 32.5 s (95% CI, 31.78-33.22) in neonates. The combined mean Schirmer I with and without anesthesia were 16.26 mm/5 min (95% CI, 13.17, 19.36) and 29.30 mm/5 min (95% CI, 27.65, 30.96) in children and 9.36 mm/5 min (95% CI, 6.54, 12.18) and 17.63 mm/5 min (95% CI, 12.03, 23.23) in neonates. Meta-regression showed a significantly lower TBUT in children from studies conducted in Asia (p = 0.004)., Conclusion: There is paucity of data on ocular surface variables in healthy children, making it difficult to draw valid comparisons with adult values., (Copyright © 2018 Elsevier Inc. All rights reserved.)

One of the most compelling features of dry eye disease (DED) is that it occurs more frequently in women than men. In fact, the female sex is a significant risk factor for the development of DED. This sex-related difference in DED prevalence is attributed in large part to the effects of sex steroids (e.g. androgens, estrogens), hypothalamic-pituitary hormones, glucocorticoids, insulin, insulin-like growth factor 1 and thyroid hormones, as well as to the sex chromosome complement, sex-specific autosomal factors and epigenetics (e.g. microRNAs). In addition to sex, gender also appears to be a risk factor for DED. "Gender" and "sex" are words that are often used interchangeably, but they have distinct meanings. "Gender" refers to a person's self-representation as a man or woman, whereas "sex" distinguishes males and females based on their biological characteristics. Both gender and sex affect DED risk, presentation of the disease, immune responses, pain, care-seeking behaviors, service utilization, and myriad other facets of eye health. Overall, sex, gender and hormones play a major role in the regulation of ocular surface and adnexal tissues, and in the difference in DED prevalence between women and men. The purpose of this Subcommittee report is to review and critique the nature of this role, as well as to recommend areas for future research to advance our understanding of the interrelationships between sex, gender, hormones and DED., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: To investigate the recovery of orthokeratology (OK)-induced changes in corneal nerve morphology and sensitivity following lens wear discontinuation, over a 3-month period., Methods: Sixteen myopic subjects who wore OK lenses during sleep for 3 months discontinued lens wear for 3 months. Corneal nerve morphology and sensitivity were assessed on the right eye only 3 h after waking at the pre-lens wear baseline and after lens wear discontinuation. Corneal nerve fiber density (NFD) and global nerve fiber orientation (GNFO) were assessed by sampling a 1 mm 2 area of the subbasal nerve plexus at the corneal apex and temporal mid-periphery using in vivo confocal microscopy. Corneal sensitivity was measured using the Cochet-Bonnet aesthesiometer at similar corneal locations., Results: Significant changes in corneal sensitivity, NFD, and GNFO were observed at various corneal locations during the lens wear discontinuation period. In the central cornea, NFD and corneal sensitivity increased during the 3-month non-lens wear period (p < 0.01); no significant changes in NFD or corneal sensitivity were noted in the mid-peripheral cornea. Central corneal sensitivity recovered to pre-lens wear levels after 1 month of non-lens wear. Central NFD appeared to remain slightly decreased after 3 months of non-lens wear compared to pre-lens wear levels, but this difference did not reach statistical significance (p = 0.09). GNFO did not change significantly at the central cornea during the 3-month non-lens wear period, but altered in a counter-clockwise rotational direction (reversal of OK-induced change) at the mid-peripheral cornea (p < 0.05), although it did not appear to fully recover to pre-lens wear orientation (p = 0.05)., Conclusions: OK lens-induced reduction in corneal sensitivity recovers with cessation of lens wear, returning to pre-lens wear levels shortly after lens wear discontinuation. Changes to nerve morphology induced by OK lens wear, however, appear to recover more slowly towards pre-lens wear levels. This requires confirmation in a longer non-lens wear period., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: To investigate changes in corneal subbasal nerve fiber density and orientation during a 3-month orthokeratology (OK) lens wear period and their relationship with concurrent changes in corneal sensitivity., Methods: Sixteen subjects wore overnight OK lenses for 90 days and were assessed at baseline, Day 30, and Day 90. Nerve images at the corneal apex and temporal mid-periphery were captured from the right eye only using in vivo confocal microscopy and analyzed to calculate nerve fiber density (NFD) and global nerve fiber orientation (GNFO). Corneal sensitivity was measured using the Cochet-Bonnet aesthesiometer at similar corneal locations. Control groups of non-lens (NL) wearing and conventional rigid gas-permeable (GP) lens-wearing subjects were also examined., Results: Significant changes in NFD, GNFO and corneal sensitivity were observed during OK lens wear over the study period. In the central cornea, both NFD and corneal sensitivity decreased by Day 30, with further reductions at Day 90. Reduced NFD was associated with reduced corneal sensitivity. In the mid-peripheral cornea only, GNFO was rotated in a clockwise direction at Day 30, with further rotation at Day 90. Corneal sensitivity reduction plateaued by Day 30. In the GP lens-wearing subjects, only corneal sensitivity decreased by Day 30 at both corneal locations. No changes were observed in the NL control subjects., Conclusions: Alterations in corneal nerve morphology occur rapidly with commencement of OK lens wear and appear to underpin functional sensitivity loss. Nerve fiber orientation can provide a useful index for changes in corneal nerve morphology., (Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.)

Almost half the patients who undergo laser in situ keratomileusis (LASIK) experience dry eye following the procedure. However, the etiology of LASIK-induced dry eye is unclear. The purpose of this review is to examine and summarize the current evidence for the etiology of LASIK-induced dry eye, with a focus on ocular surface sensitivity and corneal innervation. Evidence suggests that the alteration of corneal nerves after LASIK is the most likely cause of the subjective symptoms of LASIK-induced dry eye, even though corneal sensitivity and the clinical indicators of dry eye return to apparently normal values within a year due to the partial recovery of the corneal nerve plexus. The hypothesis is explored that dry eye symptoms following LASIK may result from abnormal sensation due to LASIK-induced corneal neuropathy. Other factors, such as alterations in conjunctival goblet cell density, might also contribute to the symptoms and signs of LASIK-induced dry eye. Inter-relationships between nerve morphology, tear neuropeptide levels and dry eye require further investigation. A better understanding of this phenomenon may result in improved management of post-LASIK dry eye., (Copyright © 2014 Elsevier Inc. All rights reserved.)