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Purpose: Fibroblast growth factor receptor 2 (Fgfr2) is crucial for the homeostasis of meibomian gland (MG). However, the role of Fgfr2 in MG ductal epithelial progenitors remains to be delineated. Herein, we created a new transgenic mouse model with conditional deletion of Fgfr2 from MG ductal progenitors and investigated the cell-specific role in the pathogenesis of obstructive meibomian gland dysfunction., Methods: Peritoneal injection of tamoxifen (TAM) at 50 µg/gm for three consecutive days was performed to induce conditional deletion of Fgfr2 in two-month-old Krt5Fgfr2CKO or Krt5Fgfr2CKO-mTmG mice. Phenotypes of MG after Fgfr2 deletion were monitored by meibography, lipid staining, and immunostaining against keratin-6a in MG whole mounts. Lineage tracing of the Krt5+ progenitors of MG and biomarkers for ductal differentiation and proliferation were also examined by immunostainings., Results: The Krt5Fgfr2CKO mice developed extensive ductal occlusion and acinar atrophy at day 10 after TAM administration. Robust thickening of ductal epithelium with abnormal differentiation and proliferation of ductal basal meibocytes were observed in the MGs of Krt5Fgfr2CKO mice. In Krt5Fgfr2CKO-mTmG mice, the Krt5+ progenitors and its progeny were labeled by EGFP after Fgfr2 depletion by TAM with evident expansion of the suprabasal and superficial layers of MG ductal epithelium when compared with the controls., Conclusions: Our results substantiated the crucial role of Fgfr2 in homeostasis of the MG ductal epithelium. Deletion of Fgfr2 affects the MG ductal basal progenitors by impacting the differentiation of ductal meibocytes and the maintenance of acinar meibocytes, which are likely the underlying pathogenesis of obstructive MGD.

One of the most common causes of blindness on a global scale is glaucoma. There is a strong association between glaucoma and increased intraocular pressure (IOP). Because of this, adequate IOP-lowering is the most important treatment strategy, mostly through topical eyedrops. Well-functioning meibomian glands are paramount for maintaining a stable tear film, and their dysfunction is the most common cause of dry eye disease. There is a growing concern that both topical glaucoma medications themselves and their added preservatives damage the meibomian glands, and consequently, the ocular surface. Preserved topical glaucoma medications appear to cause dysfunction and atrophy of the meibomian glands. Upon comparison, preserved formulations caused more symptoms of dry eye, tear film instability, inflammatory changes and meibomian gland dropout than the preservative-free counterpart. However, although seemingly less detrimental, unpreserved alternatives may diminish glandular efficacy, and, depending on the active ingredient, lead to glandular death. This negatively impacts quality of life, adherence to treatment regimens and prognosis. In this review, we explore the available evidence regarding the effects of IOP-lowering eye drops on the meibomian glands., (© 2024 The Author(s). Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Purpose: The objective of this study was to illustrate the changes in ocular findings, meibography, and tear break-up time (TBUT) values in pediatric patients with ocular rosacea following a standardized treatment., Methods: The study included consecutive patients diagnosed with ocular rosacea, referred to a tertiary hospital between 2021 and 2023. Each patient underwent biomicroscopic examinations, non-invasive TBUT assessments, corneal fluorescein staining (evaluated using the Oxford scoring system), and meibography. The standard treatment protocol involved warm compresses, eyelid hygiene, preservative-free sodium hyaluronate eye drops (administered four times daily), topical azithromycin 1.5% (twice daily for 3 days), topical steroids (loteprednol 0.5%, four times daily for 2 weeks), and either doxycycline 100 mg/day for 14 days or oral suspension of azithromycin 10 mg/kg for 3 days followed by an additional three-day course of treatment administered 10 days later (for patients above and below 14 years of age, respectively)., Results: The study included 18 patients, with 10 (55.5%) being female and 8 (44.4%) being male, with a mean age of 9.7 ± 4.5 years (range: 3-18). Four patients displayed cutaneous involvement. The treatments resulted in significant improvements in the Oxford scores, reduction in corneal neovascularization, and increased TBUT ( p  < 0.001, p  = 0.016, p  < 0.001, respectively). Meibomian gland loss area also significantly improved post-treatment (27.4 ± 6.7% vs 39.2 ± 13.4%, p  = 0.001)., Conclusion: This study demonstrated that pediatric ocular rosacea patients may exhibit improved meibomian gland function, regression of corneal neovascularization, and enhanced tear film parameters following a standardized treatment protocol that includes both topical and systemic approaches.

Ethnopharmacological Relevance: Meibomian gland dysfunction (MGD), complicated by type 2 diabetes, is associated with a high incidence of ocular surface disease, and no effective drug treatment exists. Diabetes mellitus (DM) MGD shows a notable disturbance in lipid metabolism. Er-Dong-Xiao-Ke decoction (EDXKD) has important functions in nourishing yin, clearing heat, and removing blood stasis, which are effective in the treatment of DM MGD., Aim of the Study: To observe the therapeutic effect of EDXKD on DM MGD and its underlying molecular mechanism., Materials and Methods: After establishing a type 2 DM (T2DM)-induced MGD rat model, different doses of EDXKD and T0070907 were administered. The chemical constituents of EDXKD were identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and the molecular mechanism of EDXKD in treating DM MGD was predicted using network pharmacology. Lipid metabolism in DM meibomian glands (MGs) was analyzed using LC-MS/MS, and lipid biomarkers were screened and identified. Histological changes and lipid accumulation in MGs were detected by staining, and Peroxisome proliferator-activated receptor gamma (PPARG) expression in MG acinar cells was detected by immunofluorescence. The expression of lipid metabolism-related factors was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) or western blotting., Results: EDXKD reduced lipid accumulation in the MGs and improved the ocular surface index in DM MGD rats. The main active components of EDXKD had advantages in lipid regulation. Additionally, the PPARG signaling pathway was the key pathway of EDXKD in the treatment of DM MGD. Twelve lipid metabolites were biomarkers of EDXKD in the treatment of DM MGD, and glycerophospholipid metabolism was the main pathway of lipid regulation. Moreover, EDXKD improved lipid deposition in the acini and upregulated the expression of PPARG. Further, EDXKD regulated the PPARG-mediated UCP2/AMPK signaling network, inhibited lipid production, and promoted lipid transport., Conclusion: EDXKD is an effective treatment for MGD in patients with T2DM. EDXKD can regulate lipids by regulating the PPARG-mediated UCP2/AMPK signaling network, as it reduced lipid accumulation in the MGs of DM MGD rats, promoted lipid metabolism, and improved MG function and ocular surface indices., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: To evaluate the effects of serial intravitreal injections (IVI) on the ocular surface and meibomian glands in patients with neovascular age-related macular degeneration (nAMD)., Methods: Patients receiving anti-vascular endothelial growth factor (anti-VEGF) agent injections for unilateral nAMD were included. Untreated fellow eyes served as the control group. All participants followed a pre-IVI asepsis protocol with povidone-iodine (PI). Ocular surface diseases index (OSDI) questionnaire scores, first and average non-invasive tear break-up time (fNITBUT and avgNITBUT), Schirmer-1 test results, corneal staining score (according to Oxford scale), meibomian gland (MG) loss rates of lower and upper eyelids were recorded four weeks after the last IVI., Results: Forty-two nAMD patients with a mean age of 63.3 ± 19.4 were included in the study. The mean OSDI score was 20.3 and the median of IVI number was 9 (6-22). There were no statistically significant difference between treated and untreated fellow eyes regarding fNITBUT (5.6 vs. 4.5, p = 0.872), avgNITBUT (6.2 vs. 7.2, p = 0.968), Shirmer-1 results (7 vs. 7, p = 0.854), corneal staining (0.3 vs. 0.2, p = 0.341), lower and upper MG loss rate (29.3 vs. 28.4, p = 0.162, and 27.1 vs. 26.9, p = 0.476, respectively). Only significant correlation was observed between age with lower and upper MG loss rate (r:0.396, p = 0.042, and r:0.365, p = 0.047)., Conclusion: The results of the present study demonstrated that serial IVI of anti-VEGF agents with PI asepsis is well tolerated by nAMD patients in terms of ocular surface, MG loss and DED measurements., (© 2024. The Author(s).)

Purpose: The purpose of this study was to investigate the effects of artificial tears (AT) on the sublayers of the tear film assessed by a novel tear film imaging (TFI) device., Methods: The mucoaqueous layer thickness (MALT) and lipid layer thickness (LLT) of 198 images from 11 healthy participants, 9 of whom had meibomian gland disease, were prospectively measured before and after exposure to 3 different AT preparations (Refresh Plus; Retaine [RTA]; Systane Complete PF [SYS]), using a novel nanometer resolution TFI device (AdOM, Israel). Participants were assessed at baseline and at 1, 5, 10, 30, and 60 minutes after instilling 1 drop of AT during 3 sessions on separate days. Repeated-measures analysis of variances were used for comparisons with P < 0.05 considered significant., Results: For all ATs, the mean MALT was greatest 1 minute after drop instillation, with an increase of 67%, 55%, and 11% above the baseline for SYS, Refresh Plus, and RTA, respectively. The SYS formulation demonstrated the highest percentage increases in mean MALT and LLT at most postdrop time points. The MALT differences were significantly higher in the SYS than in the RTA ( P = 0.014). After 60 minutes, no AT group demonstrated statistically significant changes in MALT or LLT compared with baseline., Conclusions: We report, for the first time, the effects of AT on MALT and LLT using a high-resolution TFI. A substantial acute mean MALT increase occurs 1 minute after AT instillation with all agents tested, but there were clear differences in response and durability, suggesting the benefits of choosing specific AT according to the needs of each patient., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To investigate the effectiveness and safety of Jiejing Runmu decoction in relieving the clinical manifestations of dry eye disease (DED)., Design and Interventions: This single-arm prospective intervention study was conducted at the Peking University Third Hospital and People's Hospital of Yongqing. Of the 211 patients recruited, 200 completing the follow-up were included in the analysis. Patients received Jiejing Runmu decoction once a day for 4 weeks continuously, without any change in eye care habits. Individuals were evaluated at four time points: pretreatment (baseline), 2 weeks, 1 month, and 3 months (2 months after completion of treatment), using the Ocular Surface Disease Index (OSDI), tear film breakup time (TBUT), corneal fluorescein staining, Schirmer test I and meibomian gland assessments. Adverse effects were evaluated at each follow-up visit and systematic examinations were performed during the first and last visits., Results: OSDI, TBUT, corneal fluorescein staining, Schirmer test I, meibomian gland expressibility, and quality of secretions improved at 2 weeks, 1 month and 3 months compared to baseline (P < 0.0001). No significant differences were found between the sexes. Patients above 45 years showed worse subjective symptoms and objective signs, and greater improvements in corneal fluorescein staining, meibomian gland expressibility, and quality of secretions were observed in this group. No obvious adverse effects were detected during any follow-up visit., Conclusion: Jiejing Runmu decoction significantly improved both the subjective symptoms and objective signs of DED, with favorable tolerance., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: To assess the effects of 1% azithromycin ophthalmic solution (AZM) in patients with bacterial blepharitis accompanied by meibomian gland dysfunction (MGD)., Study Design: A multicenter, single arm, prospective interventional study., Methods: AZM was administered to the affected eyes twice daily for the first 2 days and once daily for the subsequent 12 days. Lid margin hyperaemia/redness, collarette at the root of the eyelashes, conjunctival hyperaemia, foreign body sensation, and epiphora were assessed on Days 1, 14, and 28. The Dry Eye-related Quality of Life Score (DEQS) and objectives related to MGD, including lid vascularity, lid margin irregularity, foaming, lid plugging, keratoconjunctival disorders, Marx line, meibum grade, and tear breakup time, were also assessed. Bacterial culture of the conjunctival sac and meibum was performed on Days 1 and 14., Results: Twenty-four eyes of 24 patients (10 men/14 women, mean age 72.3 ± 13.2) were included. On Days 14 and 28, the total score, lid vascularity, lid plugging, and meibum grade showed significant improvement (p < 0.05). On Day 1, 71 strains were isolated from 22 of the 24 eyes (91.7%). Cutibacterium acnes, Corynebacterium spp., and Staphylococci were detected at high frequencies. The overall disappearance rates of the bacteria in the conjunctival sac and meibum at the end of treatment were 65.7% and 58.3%, respectively. No serious ocular or systemic adverse events were observed., Conclusion: Fourteen-day treatment with AZM was effective in patients with blepharitis accompanied by MGD, and the efficacy of AZM persisted for a period after the treatment., (© 2024. The Author(s).)

Purpose: The study aims to investigate changes in tear function, meibomian glands and corneal endothelium in patients receiving systemic isotretinoin therapy., Materials and Methods: This prospective study included 38 eyes from 38 patients (23 females and 15 males) treated with systemic isotretinoin (0.5-1 mg/kg/day) following the diagnosis of acne vulgaris. All patients underwent a comprehensive ophthalmologic examination at baseline, 1st month, and third month of treatment. Subjective complaints were assessed using the Ocular Surface Disease Index (OSDI). Tear functions were evaluated through non-invasive tear break up time (NIBUT) and Schirmer I test. Meibomian gland (MG) changes were examined using meibography. Corneal parameters, including endothelial cell density (ECD), coefficient of variation (CV), the number of cells with a hexagonal shape (6A), average cell area (AVG), and central corneal thickness (CCT) were assessed using non-contact specular microscopy., Results: The mean age of the patients was 19.29 ± 2.83 years. Ocular surface-related discomfort, measured with OSDI scores, significantly worsened at the third month measurements compared to the pre-treatment values ( p  < 0.001). In the 1st month of treatment, there was a significant decrease in NIBUT ( p  < 0.05). No statistically significant difference was found in the Schirmer test results at each visit. According to the 1st and third-month analysis, there was a significant increase in MG loss compared to the pre-treatment period ( p  < 0.001). ECD, CV, 6 A, AVG measurements at the first and third months showed a significant change compared to the pre-treatment values ( p  < 0.001). No significant difference was observed in the CCT measurements during the treatment., Conclusion: Systemic isotretinoin disrupted tear stability, caused MG loss, deterioration in corneal endothelium, and led to symptomatic complaints in patients.

Purpose: To develop a simple, subjective, and reliable grading scale for isotretinoin-induced meibography changes., Methods: After analyzing meibography images obtained from systemic isotretinoin users, a grading scale was proposed and named "meibography health score." The score ranged from 1 to 3, with decreasing gland reflectivity and identifiable margins. A total of 11 medical professionals were asked to grade 10 meibography images obtained from isotretinoin users using the proposed scale and were divided into three groups: (A) ophthalmologists with experience with meibography, (B) ophthalmologists with no experience with meibography, and (C) radiologists. The kappa statistic was determined to test interrater reliability., Results: The overall kappa was approximately 0.64. The kappa scores for Groups A, B, and C were 0.78, 0.59, and 0.90, respectively. Grade 2 had the lowest kappa scores (0.62, 0.35, and 0.82 for A, B, and C, respectively) and grade 3 the highest (0.78, 0.90, and 1.0 for A, B and C, respectively). Furthermore, Group C had the highest kappa scores and Group B the lowest., Conclusion: The meibography health score exhibited good interrater reliability, particularly in severe cases.

Exposure to particulate matters in air pollution of 2.5 μm or less (PM 2.5 ) was associated with loss of meibomian glands. The aim of this study was to verify that PM 2.5 could directly impact meibomian gland epithelial cells and damage their function. To investigate the impact of PM 2.5 on meibomian gland, immortalized human meibomian gland epithelial cells were treated with various concentrations of PM 2.5 in vitro. Meibomian gland cell microstructure, cell viability, expression of proliferating cell nuclear antigen and IL-1β, and intracellular accumulation of acidic vesicles were measured by transmission electron microscopy, cell counting, Western blot and LysoTracker staining, respectively. To further study the effect of PM 2.5 in vivo, male C57BL/6J mice were treated with 5 mg/ml PM 2.5 or vehicle for 3 months. Corneal fluorescein staining and ocular examinations were done before and after the treatment. Eyelids tissues were processed for morphological studies, immunostaining and Oil Red O staining. Our data suggest that exposure to PM 2.5 caused significant meibomian gland dropout, clogged gland orifice and increased corneal fluorescein staining that were consistent with the clinical presentations of meibomian gland dysfunction. Prominent changes in the morphology and ultrastructure of meibomian glands was observed with PM 2.5 treatment. PM 2.5 promoted ductal keratinization, inhibited cell proliferation, induced cell apoptosis and increased Interleukin-1β production in meibomian gland epithelial cells. This study may explain the association between PM 2.5 exposure and meibomian gland dropout observed in clinic. PM 2.5 resuspension instillation could be used to induce a meibomian gland dysfunction animal model., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier Ltd.)

To investigate the changes in meibomian gland dysfunction (MGD) and tear matrix metalloproteinase-9 (MMP-9) levels in patients with moderate-to-severe MGD after combined treatment with intense pulsed light (IPL) therapy and cyclosporine 0.05%. Thirty-six patients concurrently treated with IPL and cyclosporine 0.05% ophthalmic drops were retrospectively enrolled. Tear break up time (TBUT), corneal and conjunctival staining scores, Schirmer test, and ocular surface disease index (OSDI) questionnaire responses were recorded. Meibum quality, consistency, and eyelid margin telangiectasia were evaluated. MMP-9 levels were examined by the positivity and signal intensity of red lines (scored 0-4). IPL was performed four times with a vascular filter at 2-week intervals, followed by a 1-month follow-up after treatment cessation. Immediately after each IPL treatment, gentle meibomian gland expression was performed in both the upper and lower eyelids using meibomian gland expressor forceps. TBUT (1.88 ± 1.02 s to 3.12 ± 1.08 s, p < 0.001), corneal and conjunctival staining (6.19 ± 2.11 to 3.12 ± 1.89, p < 0.001), Oxford staining grade (2.66 ± 0.89 to 1.35 ± 0.76, p < 0.001), and OSDI (52.97 ± 21.86 to 36.36 ± 22.45, p < 0.001) scores significantly improved after the combined treatment. Meibum quality, consistency and lid margin telangiectasia showed significant post-treatment improvement in both the upper and lower eyelids. MMP-9 positivity showed a significant decrease (97-69%, p = 0.026) with a reduction in signal intensity (2.72 ± 0.87 to 2.09 ± 0.95, p = 0.011). The combination of IPL therapy and 0.05% cyclosporine eye drops effectively treats moderate-to-severe MGD by reducing symptoms and signs of MGD and by decreasing ocular surface MMP-9-associated inflammation., (© 2024. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Purpose: To compare the efficacy of a 0.15% HA with that of 0.1% HA eye drops for DES after cataract surgery., Methods: This study was double blinded, randomized and prospective study, and conducted in 69 participants (70 eyes) from Pusan National University Yangsan Hospital and executed from February 1, 2022 to November 30, 2022. Participants were adult cataract patients with normal lid position, not suffering from any other ocular disease and not meet the exclusion cirteria of clinical trial. Participants were randomly divided into two groups: 35 participants (17 males and 18 females) in the 0.1% HA group and 34 participants (19 males and 15 females) in the 0.15% HA group, receiving treatment six times daily for 6 weeks following cataract surgery. Subjective and objective assessments were performed at preoperative and postoperative visits, including ocular surface disease index score, tear break up time, corneal staining score, Schirmer's I test score, lipid layer thickness), meiboscore, and biochemical analysis of the eye drops., Results: Throughout the study, the postoperative ocular surface disease index score was significantly lower in the group receiving 0.15% hyaluronic acid than in the group receiving 0.1% hyaluronic acid. Additionally, the postoperative ocular surface disease index score showed a significant positive correlation with the postoperative use of 0.15% hyaluronic acid and the preoperative Schirmer's I test score. In multivariate analysis, treatment with 0.15% hyaluronic acid and the preoperative ocular surface disease index score were significant independent parameters affecting the postoperative ocular surface disease index score., Conclusion: The use of 0.15% hyaluronic acid is recommended for its potential advantages in alleviating symptoms following cataract surgery, making it a viable alternative to traditional 0.1% hyaluronic acid treatment., Trial Registration: ISRCTN95830348., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Yang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: The aim of this study was to assess the long-term effects of topical azithromycin on signs, symptoms and self-management of meibomian gland dysfunction (MGD)., Methods: Forty participants were assessed for MGD and its effect on the fluorescein tear break-up time (FTBUT). Participants were treated with topical azithromycin twice daily for 2 weeks and then once daily for a further 2 weeks. One year after treatment, 31 participants completed a survey assessing pre- and post-treatment effect on symptoms, lifestyle and self-treatment methods., Results: Following treatment, there was a significant reduction in MGD grading from a median of grade 2 to grade 0 (z = 4.40, p < 0.0001) and an increase in FTBUT from a median of 3-8 s (z = 4.75, p < 0.0001). One year afterwards, the survey showed a significant improvement in symptoms (sensitivity to light, grittiness, burning, blurred vision, all p < 0.03) and reduction in required self-treatments (lid wipes, tear substitutes, both p < 0.03). There was also a reduced impact on lifestyle (reading, night driving, computer use and watching television, all p < 0.0001) and in all environmental conditions (all p < 0.0001)., Conclusions: This study confirms the positive effect of topical azithromycin on MGD and shows it has a long-term impact on symptoms, self-treatment methods and lifestyle. This has implications for both chair time and healthcare costs when managing patients with MGD. Pending further clinical trials in a larger population with different demographics, topical azithromycin should be considered by all eyecare practitioners as a viable pharmacological treatment when managing MGD., (© 2024 College of Optometrists.)

Importance: Taking ω-3 supplements has been associated with a reduction in symptoms of dry eye disease (DED) associated with meibomian gland dysfunction (MGD). However, a recent relatively large clinical trial concluded that treating DED with ω-3 consumption was ineffective, potentially warranting additional investigations., Objectives: To investigate the effect of re-esterified triglyceride (rTG) ω-3 fatty acid supplementation on DED associated with MGD., Design, Setting, and Participants: This double-masked, parallel-group, randomized clinical trial was conducted at 7 institutions from September 2020 to January 2023. Patients with DED associated with MGD were included and randomly assigned to the ω-3 group (received 1680 mg of eicosapentaenoic acid and 560 mg of docosahexaenoic acid), whereas those in the grape-seed group received 3000 mg of grape-seed oil daily., Interventions: rTG ω-3 Fatty acid supplementation vs grape-seed oil., Main Outcome Measures: The primary end point was the Ocular Surface Disease Index (OSDI) from baseline to 6 and 12 weeks. The safety parameters were visual acuity and intraocular pressure change., Results: A total of 132 patients (mean [SD] age, 50.6 [13.8] years; 103 female [78.0%]) were included in this study. The mean (SD) baseline OSDI scores of the ω-3 and grape-seed groups were 43.5 (16.5) and 44.1 (16.6), respectively. A total of 58 patients (87.9%) and 57 patients (86.4%) in the ω-3 and grape-seed groups, respectively, completed 12 weeks of follow-up. There were no differences in compliance with the dietary supplement intake between groups (ω-3, 95.8% and grape-seed, 95.4%). The OSDI (SD) change from baseline to 6 and 12 weeks was -20.5 (16.0) and -22.7 (15.7), respectively, in the ω-3 group and -15.1 (20.2) and -18.8 (21.7), respectively, in the grape-seed control group (difference at 6 weeks = -5.4; 95% CI, -12.15 to 1.33; P = .12 and at 12 weeks = -3.9; 95% CI, -10.90 to 3.13; P = .28). There were no changes in safety parameters or adverse events related to taking the dietary supplement in either group., Conclusions and Relevance: This randomized clinical trial did not show a benefit of the rTG form of ω-3 for ameliorating symptoms of DED associated with MGD, although fewer than 60 participants were evaluated in each group. Any secondary outcomes from this study should be considered for hypothesis generation of future evaluations of the effect of the rTG form of ω-3 on DED associated with MGD., Trial Registration: CRIS Identifier: KCT0004927.

Objectives: The objective of the study was to evaluate whether a twice-daily instillation of 0.45% preservative-free ketorolac tromethamine (FKT) or 0.4% benzalkonium chloride-preserved ketorolac tromethamine (BACKT), every 12 h for 30 days may affect tear film parameters and the meibography in healthy dogs. Additionally, we assessed whether the same treatments irritated the ocular surface, affected goblet cell density (GCD), and the levels of oxidative stress biomarkers (OSB) in the conjunctiva of the same dogs., Procedures: Experimental and masked comparison study. In 11 healthy dogs baseline values of the lipid layer thickness, tear meniscus height, non-invasive tear breakup time (NI-TFBT), and the meibomian gland (MG) loss were assessed by OSAvet®. For each dog, one eye received 40 μL of BACKT, while the other received 40 μL FKT, every 12 h for 30 consecutive days. Tear parameters and meibography were repeated 15, 30, and 60 days post-treatments. Conjunctival hyperemia and blepharospasm were monitored at the same time points. At baseline and Day 30, a conjunctival biopsy was collected for GCD and OSB determination., Results: Conjunctival hyperemia and blepharospasm were not observed. At Day 15, the MG loss increased only in FKT-treated eyes (p < .001). On Day 30, both treatment groups showed increased MG loss, shortened NI-TFBT, and reduced GCD and catalase (p < .05). At Day 30, BACKT-treated eyes showed lower levels of superoxide dismutase (SOD) (p = .006) and higher levels of malondialdehyde (MDA) (p = .02). Differences between treatments were not observed for any parameter at any time point (p > .05). 60 days after treatment, OSAvet® parameters tended to return to values assessed at baseline; however, significant differences remained for MG loss (p < .05)., Conclusions: Twice-daily instillation of KT, containing or not BAC, for 30 consecutive days shortened NI-TFBT, decreased GCD, and increased the MG loss in healthy dogs. KT should be used with caution when prescribed for long periods, particularly in patients with tear film abnormalities. However, future controlled studies using KT, BAC, and other topical NSAIDs are indicated to further support this finding., (© 2023 American College of Veterinary Ophthalmologists.)

Age-related meibomian gland dysfunction (MGD) is the main cause of evaporative dry eye disease in an aging population. Decreased meibocyte cell renewal and lipid synthesis are associated with age-related MGD. Here, we found an obvious decline of Ki67, ΔNp63, and Na + /K + ATPase expression in aged meibomian glands. Potential Na + /K + ATPase agonist periplocin, a naturally occurring compound extracted from the traditional herbal medicine cortex periplocae, could promote the proliferation and stem cell activity of meibocyte cells in vitro. Moreover, we observed that periplocin treatment effectively increased the expression of Na+ /K+ ATPase, accompanied with the enhanced expression of Ki67 and ΔNp63 in aged meibomian glands, indicating that periplocin may accelerate meibocyte cell renewal in aged mice. LipidTox staining showed increased lipid accumulation after periplocin treatment in cultured meibomian gland cells and aged meibomian glands. Furthermore, we demonstrated that the SRC pathway was inhibited in aged meibomian glands; however, it was activated by periplocin. Accordingly, the inhibition of the SRC signaling pathway by saracatinib blocked periplocin-induced proliferation and lipid accumulation in meibomian gland cells. In sum, we suggest periplocin-ameliorated meibocyte cell renewal and lipid synthesis in aged meibomian glands via the SRC pathway, which could be a promising candidate for age-related MGD., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Purpose: To assess the impact of intravitreal injections (IVTI) on ocular surface of patients treated with multiple injections., Methods: Prospective, tricentric study conducted in patients treated with unilateral IVTI. An asepsis protocol with povidone-iodine was used for all patients during IVTI. The primary endpoint was the difference between the pre-IVTI Ocular Surface Disease Index (OSDI 1) score and that measured on day one (D1) post-IVTI (OSDI 2). Secondary endpoints were the evaluation of predictive factors for OSDI scores, pain assessment on D1, and the Lacrydiag® analysis of tears from the injected eye versus contralateral eye before IVTI., Results: Two hundred and nineteen patients with a mean age of 75.9 ± 10 years were included. The mean OSDI2-OSDI1 difference was 19.2 ± 20.6 (p < 0.001). The mean noninvasive tear break-up time was 6.41 ± 4.59 seconds in the injected eye versus 7.36 ± 4.36 seconds in the contralateral eye (p < 0.001). In the multivariate analysis, the factors significantly associated with the OSDI 2 score were the OSDI 1 score (p < 0.001), the pain score on D1 (p < 0.001) the number of instilled glaucoma eye drop (p = 0.01) and a centre effect (centres 2 and 3 versus centre 1, p < 0.001)., Conclusion: Our results confirm the impairment of the ocular surface and quality of life immediately after an IVTI. These results suggest 3 levels of action to improve the immediate tolerance: improving the basal status of the ocular surface, reducing the contact time with povidone-iodine that might be toxic to the surface, and improving immediate post-IVTI treatment., (© 2021 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Background: To investigate the association of long-term androgen deprivation therapy (ADT) with ocular surface characteristics in prostate cancer patients., Methods: A total of 30 male prostate cancer patients who received ADT were selected. All candidates were scored using the Ocular Surface Disease Index (OSDI) and subsequently divided into two groups containing 9 symptomatic patients (scores >12) and 21 asymptomatic patients (scores ≤ 12). Another 20 healthy age-matched males were selected as the control group. Each candidate was assessed with respect to eyelid margin abnormality, tear film break-up time (NI-BUT), tear meniscus height (TMH), meiboscore, meibum expressibility, and demodex infection., Results: The NI-BUT in the ADT group was significantly shorter than that in the control group. The scores for OSDI, eyelid margin abnormality, meibum expressibility, and meiboscores were significantly higher in the ADT group ( P < 0.05). Moreover, the NI-BUT in the symptomatic ADT group was significantly shorter than that in the asymptomatic ADT group ( P < 0.05). The meiboscores and meibum expressibility score in the symptomatic ADT group were significantly higher than those in the asymptomatic ADT group ( P < 0.05). The presence of demodex in the symptomatic ADT group was also higher than that in the asymptomatic ADT group ( P < 0.05).The length of time that patients had been taking ADT was positively correlated with meiboscores and negatively correlated with NI-BUT., Conclusion: Androgen levels were associated with significant changes in relative meibomian gland function. Subjective symptoms, such as dryness and foreign body sensation, were more obvious in prostate cancer patients receiving ADT, which may be caused by MGD and demodex infection. It's recommended that more attention be paid to the ocular surface in prostate cancer patients taking ADT by performing examination of NI-BUT and meibomian gland morphology and function with a view to providing more comprehensive prevention and treatment protocols., Competing Interests: The authors declare that there is no potential conflict of interest relevant to the publication of this article., (Copyright © 2021 Weina Li et al.)

Two spectrophotometric microplate assays with dual staining for either fluorescent Nile red (NR) plus 4,6-diamidino-2-phenylindole (DAPI) or non-fluorescent Oil red O (ORO) plus Crystal violet (CV) were applied and optimised to evaluate the lipid producing capacity of immortalised human meibomian gland epithelial cells (iHMGEC). Cells were treated with rosiglitazone (Rosi, 10-50 μM), a known lipid producing inducer for iHMGEC, and were analysed for lipids using the NR-DAPI and ORO-CV microplate assays. The lipid producing capacity of iHMGEC after each treatment was determined by normalising lipid quantity (measured with NR or ORO) to cell number (measured with DAPI or CV). The dye concentrations of NR 1 μg/mL, DAPI 5 μg/mL, ORO 0.3% (v/v) and CV 0.5% (v/v), provided optimal linearity and coverage of signals over a range of cell densities (corresponding to 10-100% cell confluence). Both NR-DAPI and ORO-CV showed a dose-dependent effect of Rosi on lipid production in iHMGEC, consistent with the results reported previously using traditional microscopic imaging methods. The microplate assays offer a rapid, high throughput and objective measurement of the amount of lipids in iHMGEC (and potentially other lipid-producing cells) and can be used for screening the effects of biological agents or incubation changes on lipid production in cells in future studies., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Exocrine Meibomian glands (MG) play a central role in the ocular surface physiology by producing meibum - a lipid secretion composed of cholesteryl esters (CE), cholesterol (Chl), triacylgycerols (TAG), waxes and other types of lipids. MG were previously shown to synthesize Meibomian lipids (ML) in situ via a complex array of reactions termed meibogenesis. However, questions remain about the role of dietary lipids in meibogenesis. To establish if dietary Chl (DC) and TAG (DT) can participate in meibogenesis, we studied mice whose diet was supplemented with trace amounts of deuterated Chl ( 2 H-Chl) and 13 C-labeled triolein ( 13 C-TO), and the products of their biosynthetic transformations were analyzed using LC/MS. We demonstrated that 2 H-Chl, but not 13 C-TO, could be directly incorporated into meibum. Furthermore, 2 H-Chl was esterified into MG-specific ultra long 2 H-CE, which were vastly different from plasma CE and 2 H-CE. The measured 2 H-Chl/Chl and 2 H-CE/CE ratios in meibum increased in a time-dependent manner reaching ∼5% and ∼1.2 %, respectively. The 2 H-Chl/ 2 H-CE ratio was about 3.5x higher than that for endogenous unlabeled Chl and CE, indicating accumulation of 2 H-Chl in meibum. The elongation pattern of Meibomian 2 H-CE closely replicated that of unlabeled CE. On the other hand, 13 C-TO was not detected in any of the ML samples as an intact lipid or its metabolized/hydrolyzed products. We conclude that DC can be directly esterified into MG-specific CE, while DT undergo extensive catabolic transformations before reaching MG. These findings demonstrate that DC can have a direct impact on MG and ocular surface lipid homeostasis and pathophysiology., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Preliminary work has shown that select triacylglycerols (TAGs) are upregulated in a preclinical model of MGD, suggesting that TAGs may be an important outcome variable in research involving human meibomian gland epithelial cells (HMGECs). The purpose of this study was to explore the HMGEC TAG lipidome in culture conditions known to influence differentiation. HMGECs were differentiated in DMEM/F12 with 10 ng/ml EGF, FBS (2% or 10%), and rosiglitazone (0, 20, or 50 μM) for two or five days. Following culture, lipids were extracted, processed, and directly infused into a Triple TOF 5600 mass spectrometer (SCIEX, Framingham, MA) with electrospray ionization. MS and MS/MS ALL spectra were acquired in the positive ion mode and performed with the SWATH technology. Only the TAGs that were present in all 48 samples were included in the analysis. Multiple regression techniques were utilized to assess the effects of each factor (FBS, rosiglitazone, and culture duration) on each expressed TAG. The HMGEC TAG lipidome consisted of 115 TAGs with 42-62 carbons and zero to 10 double bonds. Fatty acyl chains had 14 to 26 carbons and zero to five double bonds. C18:1 (oleic acid, 25/115, 21.7%) and C16:0 (palmitic acid, 16/115, 13.9%) were the most common fatty acids. FBS, rosiglitazone, and culture duration were significant predictors for 93 TAGs (80.9%) with R 2 values ranging from 0.20 to 0.77 (p < 0.05). FBS and rosiglitazone achieved significance (p < 0.05) for 80 (69.6%) and 67 TAGs (58.3%), respectively. Rosiglitazone demonstrated a selective upregulation of TAGs containing 16 or 18 carbons. Culture duration reached significance (p < 0.05) for only 36 TAGs (31.3%). When comparing the 10 most abundant C18:1-containing TAGs in meibum, FBS was a negative predictor for five TAGs (mean standardized coefficient [SC] = -0.58, p < 0.001), rosiglitazone was a positive predictor for six TAGs (mean SC = 0.41, p ≤ 0.03), and culture duration weakly influenced one TAG (SC = 0.27, p = 0.008). FBS and rosiglitazone, unlike culture duration, are powerful modulators of the TAG profile. Rosiglitazone induces changes that could be consistent with fatty acid synthesis, suggesting that quantifying the TAG lipidome could be an indirect measure of lipogenesis. Though both have been described as differentiating agents, FBS and rosiglitazone induce opposing effects on meibum-relevant TAGs. Culturing with rosiglitazone is associated with a TAG profile that is more consistent with the expected outcome of lipogenesis and with the profile observed in normal human meibum., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: To quantitatively evaluate the effects of 0.05% cyclosporine A (CsA) on lipid layer thickness (LLT) and meibomian glands after cataract surgery using the LipiView® ocular surface interferometer., Methods: This study was a prospective randomized double-masked clinical trial conducted by Pusan National University Yangsan Hospital between April 04, 2019, and November 31, 2019. Sixty-two participants were recruited, and 12 of them were not enrolled because they had undergone previous treatments for ocular surface diseases. The participants were adult patients with cataract, exhibiting normal lid position; they did not present any other ocular disease and did not meet the exclusion criteria of the clinical trial. Fifty subjects were enrolled in the study. The randomized subjects received treatment with 0.05% CsA (group A) or 0.5% carboxymethyl cellulose (CMC) (group B) over the 3 months following the cataract surgery. Subjective and objective assessments were performed at preoperative and postoperative visits. Ocular Surface Disease Index (OSDI), tear breakup time (TBUT), and Schirmer's I test were performed by the same surgeon, and LLT and meiboscore were determined using the LipiView® interferometer., Results: Fifty subjects subjects enrolled consisted of men (50%) and women (50%), with a mean (SD) age of 65.94 (10.35) years. Four subjects in group A and five in group B were excluded from the analysis as they were lost to follow-up within 1 month after cataract surgery. Thus, the study comprised 41 eyes of 41 subjects; 21 subjects were treated with CsA and 20 subjects with CMC. Comparing the clinical measurements between groups A and B taken at the last visit, while controlling the effects of the preoperative values, TBUT and LLT showed significant differences (p = 0.035 and p = 0.047, respectively, by ANCOVA). The TBUT between the subjects using CsA and those using CMC after cataract surgery showed a significant difference during follow up (p = 0.003 by repeated measures ANOVA). In the multivariate analysis, preoperative LLT and the use of CsA were found to be independent parameters for postoperative LLT (R2 = 0.303; p = 0.008 and p = 0.045, respectively), whereas the follow-up duration exhibited a positive correlation with the difference between the preoperative and postoperative values of LLT in the group treated with CsA (R2 = 0.738 and p < 0.001)., Conclusion: Treatment with 0.05% CsA following cataract surgery is effective in improving TBUT and LLT in comparison with 0.5% CMC. A higher preoperative value of LLT and the postoperative use of CsA could be significant determinants of a higher postoperative LLT value., Trial Registration: ISRCTN registry with ISRCTN 10173448., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Infestation with demodex mites has been linked to the development of chalazion, meibomian gland dysfunction, and blepharitis. An effective treatment is the eyelid application of terpinen-4-ol (T4O), a tea tree oil component. However, T4O is also known to be toxic to nonocular epithelial cells. We hypothesize that T4O toxicity also extends to human meibomian gland epithelial cells (HMGECs)., Methods: Immortalized (I) HMGECs were cultured with varying concentrations (1.0%-0.001%) of T4O under proliferating or differentiating conditions up to 5 days. Experimental procedures included analyses of cell appearance, survival, P-Akt signaling, lysosome accumulation, and neutral lipid content., Results: Our findings show that T4O causes a dose- and time-dependent decrease in the cell survival of IHMGECs. After 15 minutes of exposure to 1% T4O, IHMGECs exhibited rounding, atrophy, and poor adherence. Within 90 minutes of such treatment, almost all cells died. Reducing the T4O concentration to 0.1% also led to a marked decrease in P-Akt signaling and cell survival of IHMGECs. Decreasing the T4O amount to 0.01% caused a slight, but significant, reduction in the IHMGEC number after 5 days of culture and did not influence the ability of these cells to differentiate., Conclusions: T4O, even at levels 10-fold to 100-fold lower than demodicidal concentrations, is toxic to HMGECs in vitro.

Purpose: Previous studies have suggested an association between dyslipidemia and meibomian gland dysfunction (MGD). The aim of this prospective, nonrandomized clinical study is to evaluate the possible association of dyslipidemia and its treatment with meibomian gland (MG) morphologic changes by standardized meibography., Design: Prospective, nonrandomized clinical study., Methods: Two groups of participants were enrolled: group 1, comprised of patients under regular 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitor (statin) treatment for dyslipidemia, and group 2, those with newly diagnosed dyslipidemia who were under lifestyle interventions. Meibography was performed at baseline and at both the 6- and 12-month visits and were graded by meiboscores. Participants underwent slit lamp examination for signs of changes in meibum quality and MG lid morphologic features. The Ocular Surface Disease Index questionnaire was given to measure subjective symptoms of ocular surface disease. Dry eye parameters including tear meniscus height, noninvasive first and average tear film break-up time, and Schirmer test results were also recorded., Results: Ninety-eight participants completed this longitudinal study over 12 months. There were statistically significant changes in total meiboscores (P = .01) and upper eyelid meiboscores (P = .012), lid margin abnormality scores (P = .0059), and meibum quality (P = .0002) in the statin group during follow-up visits. Similar changes of upper eyelid meiboscores (P = .046) and meibum quality (P = .046) were noted in the nonstatin group., Conclusion: Meibomian gland atrophy and deterioration of meibum quality continued in the long term among participants with dyslipidemia even under statin usage., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Recently, we discovered that the cosmetic preservatives, benzalkonium chloride and formaldehyde, are especially toxic to human meibomian gland epithelial cells (HMGECs). Exposure to these agents, at concentrations approved for human use, leads within hours to cellular atrophy and death. We hypothesize that these effects are not unique, and that other cosmetic preservatives also exert adverse effects on HMGECs. Such compounds include parabens, phenoxyethanol and chlorphenesin, which have been reported to be toxic to corneal and conjunctival epithelial cells, the liver and kidney, as well as to irritate the eye. To test our hypothesis, we examined the influence of parabens, phenoxyethanol and chlorphenesin on the morphology, signaling, survival, proliferation and lipid expression of immortalized (I) HMGECs. These cells were cultured under proliferating or differentiating conditions with varying concentrations of methylparaben, ethylparaben, phenoxyethanol and chlorphenesin for up to 5 days. We monitored the signaling ability, appearance, number and neutral lipid content of the IHMGECs, as well as their lysosome accumulation. Our findings show that a 30-min exposure of IHMGECs to these preservatives results in a significant reduction in the activity of the Akt pathway. This effect is dose-dependent and occurs at concentrations equal to (chlorphenesin) and less than (all others) those dosages approved for human use. Further, a 24-h treatment of the IHMGECs with concentrations of methylparaben, ethylparaben, phenoxyethanol and chlorphenesin close to, or at, the approved human dose induces cellular atrophy and death. At all concentrations tested, no preservative stimulated IHMGEC proliferation. Of particular interest, it was not possible to evaluate the influence of these preservatives, at close to human approved dosages, on IHMGEC differentiation, because the cells did not survive the treatment. In summary, our results support our hypothesis and show that methylparaben, ethylparaben, phenoxyethanol and chlorphenesin are toxic to IHMGECs., Competing Interests: Declaration of competing interest The authors have no conflict of interests., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Purpose: To evaluate ocular side effects associated with systemic isotretinoin histopathologically., Methods: In this multicenter study, a total of 15 male and 15 female rats were randomly divided into 3 equal groups according to the oral dose of isotretinoin they were administered: 0 mg/kg/d (group A), 7.5 mg/kg/d (group B), and 15 mg/kg/d (group C). Biopsy specimens were taken from the globe conjunctiva, cornea, and eyelid conjunctiva. Expression levels of human beta-defensin-1, human beta-defensin-2, toll-like receptor (TLR)-2, and TLR-4 were evaluated by immunohistochemical methods., Results: The number of goblet cells in eyelid conjunctiva was significantly lower in group B than that in group A and group C (P = 0.002). The sizes of meibomian gland acini were significantly smaller in group B and group C than those in group A (P < 0.001). Fibrosis of eyelid conjunctiva was significantly higher in group C and group B than that in group A (P = 0.002). The levels of staining of TLR-4 in the cornea with group B were significantly lower compared with group C (P = 0.035)., Conclusions: Our study suggests that isotretinoin in the early period affects eyelid conjunctiva and meibomian glands without affecting the globe conjunctiva and cornea. Occurrence of the initial symptoms of isotretinoin on the eyelids, especially on the meibomian glands, suggests that the symptoms of patients occur because of evaporative dry eye.

Purpose: To compare the degree of tear film instability and severity of meibomian gland dysfunction between subjects who use eyeliner and those who do not use eyeliner., Methods: This cross-sectional study included 42 healthy volunteer women who had no dry eye symptoms (Ocular Surface Disease Index score < 13) and aged between 18 and 40 years. The subjects were classified into 2 groups: an eyeliner-use group (EL: regularly used eyeliner ≥3 d/wk and continuously used ≥6 mo) and a noneyeliner-use group as controls. A questionnaire for ocular surface symptoms using a visual analog scale was administered. Then, a number of eye tests were performed [grading of conjunctival inflammation, fluorescein tear breakup time, ocular surface fluorescein staining, Schirmer I, evaluation of meibomian gland (MG) function, detection of eyelid margin abnormalities, and Demodex detection]., Results: Tear breakup time was significantly lower in the EL group compared with controls (3.0 ± 1.9 vs. 5.8 ± 2.1 s, P < 0.001). MG grading was significantly higher in the EL group than in controls (P = 0.004); higher grade (grades 2-3) was found in 85.7% of EL and 47.6% of controls. Meiboscore was also higher in EL than in controls (P = 0.001). Regarding the morphological changes in lid margin, only telangiectasia was detected significantly more in EL (28.6%) compared with controls (4.8%) (P = 0.041). Conjunctival inflammation was observed 4 times more in EL (66.7%) than in controls (14.3%), P = 0.001. Other outcomes included ocular surface symptoms and fluorescein staining scores, and Schirmer I and Demodex detection were not significantly different between both groups., Conclusions: The regular use of eyeliner induces tear film instability and MG dysfunction.

Purpose: We recently discovered that a hypoxic environment is beneficial for meibomian gland (MG) function. The mechanisms underlying this effect are unknown, but we hypothesize that it is due to an increase in the levels of hypoxia-inducible factor 1α (HIF1α). In other tissues, HIF1α is the primary regulator of cellular responses to hypoxia, and HIF1α expression can be induced by multiple stimuli, including hypoxia and hypoxia-mimetic agents. The objective of this study was to test our hypothesis., Methods: Human eyelid tissues were stained for HIF1α. Immortalized human MG epithelial cells (IHMGECs) were cultured for varying time periods under normoxic (21% O2) or hypoxic (1% O2) conditions, in the presence or absence of the hypoxia-mimetic agent roxadustat (Roxa). IHMGECs were then processed for the analysis of cell number, HIF1α expression, lipid-containing vesicles, neutral and polar lipid content, DNase II activity, and intracellular pH., Results: Our results show that HIF1α protein is present in human MG acinar epithelial cells in vivo. Our findings also demonstrate that exposure to 1% O2 or to Roxa increases the expression of HIF1α, the number of lipid-containing vesicles, the content of neutral lipids, and the activity of DNase II and decreases the pH in IHMGECs in vitro., Conclusions: Our data support our hypothesis that the beneficial effect of hypoxia on the MG is mediated through an increased expression of HIF1α.

Purpose: To compare the impact of ocular changes between systemic treatment with doxycycline and low-dose oral isotretinoin in patients with moderate-to-severe papulopustular rosacea., Methods: Patients were randomized to receive either isotretinoin 0.3-0.4 mg/kg (group A) or doxycycline 100 mg/day (group B) for 16 weeks. Ocular symptoms were searched and evaluated, including best-corrected visual acuity (BCVA), Schirmer test, breakup time, rose bengal staining score, and meibomian gland dysfunction grading. The patients were retested at the end of treatment., Results: The present study included 39 patients (30 females and 9 males). Best-corrected visual acuity was > 20/30 in >90% of patients in both groups and did not change after treatment. After treatment, improvement in ocular symptoms and meibomian gland dysfunction was more pronounced in group B (p<0.05); the other parameters did not reach statistical significance., Conclusion: Doxycycline improved meibomian gland dysfunction, ocular symptoms, and ocular surface in patients with rosacea. Even though some patients experienced worsening meibomian gland dysfunction and symptoms, no subject experienced any serious complications after administration of low-dose isotretinoin.

Purpose: The efficacy of topical azithromycin (AZ) supplementation to systemic AZ has not been studied. This study evaluates the efficacy of topical AZ supplementation to systemic AZ, warm compresses, artificial tears, and lid scrubs for the treatment of meibomian gland dysfunction (MGD)., Methods: Eighty-five patients with stage 4 MGD were enrolled in the study. The patients enrolled into the study were divided into 2 groups. Group 1 comprised 55 patients who received preservative-free topical 1.5% AZ administered as a unit dose, and group 2 comprised 30 patients who did not receive topical AZ. Both groups were prescribed artificial tear eye drops and systemic AZ. Fluorescein tear film breakup time (TBUT), corneal staining, Ocular Surface Disease Index (OSDI) symptom scores, and meibum quality were evaluated at baseline and after 1 and 3 months., Results: The mean age of patients in group 1 was 48.3 ± 13.4 years (25 men and 30 women) and in group 2 was 50.7 ± 10.2 years (12 men and 18 women). After treatment at the first and third month, group 1 showed significant improvement in mean TBUT, mean corneal staining score, meibum quality, and mean OSDI scores compared with baseline (P < 0.05). In group 2, only the OSDI score and meibum quality improved significantly after treatment compared with baseline (P < 0.05)., Conclusions: These results demonstrate clinically and statistically greater improvement in MGD-associated signs and symptoms with the addition of topical AZ to the systemic treatment.

Purpose: A follow-up experimental study on the exposure of animal tarsal plate to ultraviolet-A radiation aimed at establishing an optimum range for safe irradiation conditions., Methods: Sheep tarsus specimens were excised postmortem and then subjected to irradiation with ultraviolet-A rays (wavelength 365 nm) at higher irradiances than those reported in an initial study, using a laboratory radiation source. The mechanical properties (tensile strength and Young's modulus) of irradiated and nonirradiated samples were evaluated in a mechanical tester. The test and control specimens were examined histologically with an aim to assess the effects of radiation upon the meibomian glands and tarsal collagen networks, and to establish a safe range for the exposure irradiance level., Results: As expected, irradiation induced both stiffening and strengthening of the tarsal plate specimens. At an irradiance of 50 mW/cm for 3-minute exposure, these effects were at their maximum level, after which a decline in mechanical characteristics were observed. No destruction of the tarsal connective tissue or the meibomian glands were noticed up to an irradiance of 125 mW/cm for 3-minute exposure, corresponding to a fluence of 22.5 J/cm. Histology revealed that the collagen network surrounding the glands were packed more compactly following irradiation. At a fluence of 45 J/cm, massive destruction of periglandular collagen-rich network and meibocytes were demonstrated histologically., Conclusions: The study indicates that irradiation of tarsal collagen leading to tissue stiffening shall be carried out at levels of fluence between 10 and 15 J/cm, a region that is deemed safe. The exposure time can be adjusted according to the surgeon's decision.Safe irradiation conditions are established for the exposure of ex vivo ovine tarsus to ultraviolet-A radiation as a potentially effective treatment for eyelid laxity in human patients.

Dry eye disease (DED) after cataract surgery has become a critical concern, and various therapeutic options have been developed. Recently, preservative-free diquafosol ophthalmic solution has been introduced; however, its therapeutic effect on DED after cataract surgery has not been reported. We investigated the efficacy of preservative-free diquafosol in patients with pre-existing DED after cataract surgery. We divided subjects who were diagnosed with DED and scheduled to undergo cataract surgery, into 3 groups (preservative-free diquafosol, group 1; preservative-containing diquafosol, group 2; preservative-free hyaluronate, group 3), and each eye drops was administered 6 times daily after surgery. Tear break up time (TBUT), Ocular Surface Disease Index (OSDI), corneal staining score, lid margin abnormality, and meibum quality improved over time in group 1. Groups 1 and 2 had significantly superior TBUT, meibomian gland dysfunction grade, and meibomian gland expressibility throughout the study period than group 3. Meibum quality of group 1 was significantly better than group 2 at 1 and 3 months after surgery. Preservative-free diquafosol showed better efficacy in treating DED after cataract surgery than preservative-containing diquafosol or preservative-free hyaluronate. Preservative-free diquafosol may serve as a reliable option for the management of patients with pre-existing DED after phacoemulsification.

Age-related meibomian gland (MG) atrophy, characterized by decreased meibocyte proliferation, is one of the causes of meibomian gland dysfunction (MGD), which leads to dry eye disease. Currently, there is no available treatment effectively preventing or reversing the decreased cell proliferation and acinar tissue atrophy. In this study, we investigated the therapeutic effects of a pigment epithelium-derived factor (PEDF) peptide in treating this condition. We found abundant expression of PEDF in the nucleus of acinar basal cells, but not in mature meibocytes, and that the expression levels were significantly decreased in the aged mice. We next treated the aged mice (15-month old) with atrophic MGs using a synthetic PEDF-derived peptide 29-mer (residues 93-121). We found that 29-mer effectively stimulated acinar basal cell proliferation and the following mature meibocyte proliferation in the atrophied MGs. In addition, the treatment increased ΔNp63 and Lrig1 expressions in acinar basal cells. Finally, the aged mice receiving the treatment showed MG growth and improved tear film break-up time. In conclusion, the 29-mer treatment is effective in promoting MG acinar basal cell proliferation and enlarging the acinar size of MG, as well as improving MG function in aged mice, suggesting a therapeutic potential of the PEDF-derived short peptide in ameliorating age-related MGD., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Purpose: To investigate the usefulness of meibomian gland (MG) dropout rate in the evaluation of MG morphological change associated with the use of prostaglandin for glaucoma treatment through the association between MG and the ocular surface parameters and medication duration and presence of preservative., Methods: This cross-sectional study was conducted on 88 eyes of 88 patients who were diagnosed with glaucoma and used only Tafluprost as treatment. The patients were divided into four "user" groups: 1) 23 patients used preservative-free (PF) Tafluprost for 6 months; 2) 21 patients used preservative-containing (PC) Tafluprost for 6 months; 3) 23 patients used PF-Tafluprost for 24 months; 4) 21 patients used PC-Tafluprost for 24 months. Ocular surface parameters and the MG condition, including MG dropout rate and meiboscale, were evaluated. Multiple regression was used to identify associations., Results: There were significant differences in age (p = 0.003), tear breakup time (p = 0.016), lid margin abnormality (p = 0.016), expressibility (p = 0.039), meiboscale (p<0.001), and MG dropout rate (p<0.001) among the 4 groups. MG dropout rate and meiboscale showed significant differences in all post hoc analyses, except for the comparison between the PF-Tafluprost and PC-Tafluprost 6-month user groups. Medication duration, preservative status, and meiboscale were significantly correlated with MG dropout rate (p<0.001, p = 0.024, p<0.001, respectively). In the 6-month user group, preservative status significantly correlated with MG dropout rate (p = 0.015). However, in the 24-month user group, meiboscale was the only parameter significantly associated with MG dropout rate (p<0.001)., Conclusion: MG dropout rate in patients using Tafluprost showed a significant correlation with medication duration and preservative status. This result indicates MG dropout rate reflects MG morphologic change associated with prostaglandin., Competing Interests: The authors have declared that no competing interests exist.

Purpose: To determine the efficacy of azithromycin 1.5% eyedrops compared with oral doxycycline in patients with moderate to severe meibomian gland dysfunction (MGD)., Methods: This prospective randomized trial included 169 participants with newly diagnosed moderate to severe MGD. Participants were randomly assigned to treatment with azithromycin 1.5% eyedrops (n = 85) twice daily for 2 days then once daily until 4 weeks or oral doxycycline (n = 84) 100 mg twice daily for 4 weeks. Signs and symptoms of MGD were evaluated at baseline and 4 weeks later. The percentages of participants with improvement in meibum quality were assessed as a primary outcome. Secondary outcomes were MGD-related symptoms, meibum expressibility, Oxford ocular surface staining score, tear film break up time (TBUT), and drug side effects., Results: Although there were significant improvements in all outcomes in both groups, there was no between-group differences in the percentages of participants with improved meibum quality (P = 0.80), MGD-related symptoms (P > 0.05), meibum expressibility (P = 0.92), Oxford ocular surface staining score (P = 0.59), and TBUT (P = 0.99). Five (5.88%) participants in azithromycin group and four (4.76%) participants in doxycycline group discontinued medications due to drug side effects (P = 0.75)., Conclusions: Both azithromycin 1.5% eyedrops and oral doxycycline significantly improved signs and symptoms in patients with moderate to severe MGD. Both azithromycin 1.5% eyedrops and oral doxycycline showed no difference in term of improved signs and symptoms of MGD as well as drug side effects that lead to discontinuation of medication.

Purpose: Benzalkonium chloride is the most widely used preservative in ophthalmic topical solutions. The aim of this study was to investigate the influence of BAC as a single substance or as a component of several commercially available ophthalmic solutions on meibomian gland epithelial cells in vitro., Materials and Methods: An immortalized human meibomian gland epithelial cell line (HMGEC) was used and cells were cultured in the absence or presence of fetal bovine serum to assess cell morphology, cell proliferation, cell viability (MTS assay) and impedance sensing (ECIS) after stimulation with BAC. Further, the viability of HMGECs stimulated with BAC-containing and BAC-free bimatoprost, travoprost and latanoprost was evaluated using the MTS assay. Real-time PCR analysis for hyperkeratinization associated genes (cornulin, involucrin) was performed., Results: In the absence of serum, the proliferation rate of HMGECs decreased starting with 0.1μg/ml BAC. At concentrations of 50μg/ml BAC and higher, cell viability was reduced after 10min exposure with a corresponding change in cell morphology. Toxicity of BAC-containing ophthalmic solutions was greater than that of BAC alone, whereas BAC-free alternative products did not significantly influence cell viability. Confluence, cell-cell contacts and serum-containing medium appeared to facilitate HMGECs survival. Expression rate of involucrin and cornulin declined after exposure to preserved bimatoprost and BAC., Conclusions: BAC showed cytotoxic effects on HMGECs starting with a concentration of 0.1μg/ml. The combination of BAC and prostaglandin-analogs might have a synergistic effect which results in higher toxicity than BAC alone. Unpreserved eye drops and eye drops preserved with Polyquaternium-1 are less damaging to HMGECs., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

Purpose: To investigate changes in higher order ocular aberrations (HOA) induced by the administration of 0.15% sodium hyaluronate tear enhancer (TE) and meibomian gland expression (ME) on the tear film of normal subjects., Methods: HOA values were obtained from the corneal surface (CS) and whole eye (WE), using a corneal topographer and Shack-Hartmann aberrometer, from both eyes of 50 subjects (25 females, mean age±sd 32.5±11.0 years, and 25 males, 33.88±11.2 years) for two pupil sizes (3 and 6mm) in a dark environment. One drop of Blink Contacts™ (Abbott Medical Optics) was instilled into the right eye and HOA measurements repeated after 30s. After 1h, the meibomian glands of the left lower eyelid were gently squeezed and HOA measurements repeated after 30s., Results: There was no significant difference for CS and WE root mean square (RMS) HOAs between right and left eyes before (both pupil sizes) and after TE use or ME (3mm pupil). For 6mm pupil, TE use significantly reduced the WE RMS HOA (p<0.05, mean±sd) for Z 4 0 (0.297±0.136 to 0.053±0.069), and Z 5 5 (0.221±0.372 to 0.098±0.121) while ME significantly increased CS RMS HOA (p<0.05, mean±sd) for Z 3 -3 (0.799±1.178 to 1.302±1.991) and Z 4 4 (0.594±1.184 to 0.988±1.463). In general, the change in HOA was significantly correlated with the initial value before TE use or ME (p<0.05)., Conclusion: There were no detectable differences between right and left eyes. For the 6mm pupil, the tear enhancer tended to improve optical performance of the WE and meibomian gland expression tended to reduce the optical performance at the CS., (Copyright © 2018 Spanish General Council of Optometry. All rights reserved.)

Purpose: The Meibomian gland (MG) produces the lipid layer of the tear film, and changes to the MG that lead to a decrease or alteration in lipid quality/content may lead to MG dysfunction, a major cause of evaporative dry eye disease with prevalence ranging from 39% to 50%. Little is known about the developmental cues that regulate MG morphogenesis and homeostasis. Our study investigates the role of hyaluronan (HA), a major extracellular matrix component, in eyelid formation and MG development and function., Methods: Hyaluronan synthase (Has) knockout mice were used to determine the role of HA in the eyelid and MG. Eyelids were obtained during different developmental stages and MG morphology was analyzed. Tet-off H2B-GFP/K5tTA mice and 5-ethynyl-2'-deoxyurdine (EdU) incorporation were used to determine the role of HA in maintaining slow-cycling and proliferating cells within the MG, respectively. Data were confirmed using an in vitro proliferation assay, differentiation assay and spheroid cultures., Results: Has knockout mice present precocious MG development, and adult mice present MG hyperplasia and dysmorphic MGs and eyelids, with hyperplastic growths arising from the palpebral conjunctiva. Our data show that a highly organized HA network encompasses the MG, and basal cells are embedded within this HA matrix, which supports the proliferating cells. Spheroid cultures showed that HA promotes acini formation., Conclusions: HA plays an important role in MG and eyelid development. Our findings suggest that Has knockout mice have abnormal HA synthesis, which in turn leads to precocious and exacerbated MG morphogenesis culminating in dysmorphic eyelids and MGs.

Purpose: Lipopolysaccharide (LPS), a bacterial endotoxin, is known to stimulate leuokotriene B4 (LTB4) secretion by human corneal (HCECs), conjunctival (HConjECs) and meibomian gland (HMGECs) epithelial cells. We hypothesize that this LTB4 effect represents an overall induction of proinflammatory gene expression in these cells. Our objective was to test this hypothesis., Methods: Immortalized HCECs, HConjECs and HMGECs were cultured in the presence or absence of LPS (15 μg/ml) and ligand binding protein (LBP; 150 ng/ml). Cells were then processed for RNA isolation and the analysis of gene expression by using Illumina BeadChips, background subtraction, cubic spline normalization and GeneSifter software., Results: Our findings show that LPS induces a striking increase in proinflammatory gene expression in HCECs and HConjECs. These cellular reactions are associated with a significant up-regulation of genes associated with inflammatory and immune responses (e.g. IL-1β, IL-8, and tumor necrosis factor), including those related to chemokine and Toll-like receptor signaling pathways, cytokine-cytokine receptor interactions, and chemotaxis. In contrast, with the exception of Toll-like signaling and associated innate immunity pathways, almost no proinflammatory ontologies were upregulated by LPS in HMGECs., Conclusions: Our results support our hypothesis that LPS stimulates proinflammatory gene expression in HCECs and HConjECs. However, our findings also show that LPS does not elicit such proinflammatory responses in HMGECs., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: We previously discovered that azithromycin (AZM) acts directly on immortalized human meibomian gland epithelial cells (IHMGECs) to stimulate their lipid and lysosome accumulation and overall differentiation. We hypothesize that this phospholipidosis-like effect is due to AZM's cationic amphiphilic drug (CAD) nature. If our hypothesis is correct, then other CADs (e.g., solithromycin [SOL]) should be able to duplicate AZM's action on IHMGECs. Our purpose was to test this hypothesis., Materials and Methods: IHMGECs were cultured in the presence of vehicle or SOL (2, 10, or 20 µg/ml) for up to 7 days under proliferating or differentiating conditions. Positive (epidermal growth factor and bovine pituitary extract for proliferation; AZM for differentiation) and negative (vehicle) controls were included with the experiments. IHMGECs were evaluated for cell number, neutral lipid content, and lysosome accumulation., Results: Our results demonstrate that SOL induces a rapid and dose-dependent increase in the accumulation of neutral lipids and lysosomes in HMGECs. The lysosomal effects were most prominent with the 10 and 20 µg/ml doses, and occurred earlier (i.e., 1 day) with SOL than with the AZM (10 µg/ml) control. The effects of SOL and AZM on IHMGEC differentiation were essentially the same after 3 days of culture. SOL did not influence the proliferation of HMGECs during a 7-day time period., Conclusions: Our results support our hypothesis that SOL, a CAD, is able to reproduce AZM's impact on lysosome and lipid accumulation, as well as the differentiation, of HMGECs. The effect of SOL on lysosome appearance was faster than that of AZM.

Purpose: To investigate the efficacy of a novel treatment - intra-meibomian gland (MG) injection of the anti-VEGF agent bevacizumab - for MG dysfunction (MGD) with eyelid-margin vascularity., Methods: A total of 26 eyes from 13 patients diagnosed with MGD and eyelid-margin vascularity were included in our study. Patients received intra-meibomian gland injections of bevacizumab (150 μL, 2.5 mg/0.1 mL) at multiple sites with a 29 G needle where telangiectasia was severe. The Ocular Surface Disease Index (OSDI), tear film, tear-breakup time (TBUT), eyelid-margin features, MG features, conjunctiva, and corneal staining were assessed at 1 day before injection and 1 week, 1 month, and 3 months after injection. Blood pressure, best-corrected visual acuity, intraocular pressure, and slit lamp examinations were performed to assure the safety of patients at 1 day before and 1 day, 1 week, 1 month, and 3 months after injection., Results: Lid-margin vascularity, conjunctival injection, expressed secretion quality, expressivity of the MG, TBUT, corneal staining, and OSDI were significantly improved 1 week, 1 month, and 3 months after injection compared to baseline values. Lid-margin vascularity, conjunctival injection, meibomian gland expressivity, TBUT, and OSDI continued to improve; the greatest improvements were observed at 1 month and sustained for 3 months. Spearman's correlation analysis indicated that age and sex significantly influenced TBUT improvement. Females and older patients tended to have shorter baseline TBUT that followed a different trend from that of males and younger patients during postinjection visits, revealed by subgroup analysis. No local or systemic side effects were observed at follow-up visits., Conclusion: This study is the first to explore a novel therapy for MGD - intra-MG injection of the anti-VEGF agent bevacizumab - and it demonstrates that the treatment is effective and safe in eliminating eyelid-margin vascularity, improving MG function and relieving clinical signs and symptoms of MGD., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

We recently discovered that the anti-glaucoma pharmaceuticals timolol, a β adrenergic antagonist, and pilocarpine, a cholinergic compound, negatively influence the morphology, proliferative capacity and survival of human meibomian gland epithelial cells (HMGECs). We hypothesize that another class of anti-glaucoma drugs, the α2 adrenergic agonists, also acts directly on HMGECs to affect their structure and function. We tested this hypothesis. Immortalized (i) HMGECs were cultured with brimonidine, as well as clonidine (α2 agonist), phenylephrine (α1 agonist), RX821002 (inverse α2 agonist) and MK912 (neutral α2 agonist) for up to 7 days. Cells were counted with a hemocytometer, and evaluated for morphology, signaling pathway activity, protein biomarker expression, and the accumulation of neutral lipids, phospholipids and lysosomes. Our findings demonstrate that brimondine treatment induces a dose-dependent decrease in Akt signaling and proliferation of iHMGECs. In contrast, brimonidine also promotes a dose-dependent differentiation of iHMGECs, including an increase in neutral lipid, phospholipid and lysosome levels. These effects were paralleled by an inhibition of p38 signaling, and duplicated by cellular exposure to clonidine, but not phenylephrine. Brimonidine also enhanced the cellular content of sterol regulatory binding protein-1, a master regulator of lipid synthesis. Of particular interest, the putative α2 antagonists, RX821002 and MK912, did not interfere with brimonidine action, but rather stimulated IHMGEC differentiation. Our results support our hypothesis and demonstrate that α2 adrenergic agonists act directly on iHMGECs. However, these compounds do not elicit an overall negative effect. Rather, the α2 agonists promote the differentiation of iHMGECs., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Purpose: To investigate, using in vivo confocal microscopy (IVCM), the Meibomian gland (MG) features and conjunctival goblet cell density (GCD) in glaucomatous patients controlled with prostaglandin/timolol fixed combinations (PTFCs)., Materials and Methods: In this cross-sectional study, 60 white patients were treated with PTFCs, 15 with latanoprost+timolol (L+T) unfixed combination, and 15 controls were enrolled. Patients underwent the Ocular Surface Disease Index questionnaire, tear film breakup time, corneal staining, Schirmer test I, and IVCM of MGs and goblet cells. The main outcome measures were: mean Meibomian acinar density (MMAD) and area (MMAA), inhomogeneity of glandular interstice (InI) and acinar wall (InAW), and GCD., Results: PTFCs were: latanoprost/timolol (LTFC, 15 eyes), travoprost/timolol (TTFC, 15), bimatoprost/timolol (BTFC, 15), and preservative-free bimatoprost/timolol (PF-BTFC, 15) fixed combinations. Mean time on therapy did not differ among treatments. IVCM documented lower GCD, MMAD, and MMAA (P<0.001), and greater InI and InAW (P<0.05) in glaucoma patients compared with controls. L+T showed worse values compared with PTFCs and PF-BTFC (P<0.05). Preserved PTFCs showed lower MMAD, MMAA, GCD, and greater InI and InAW compared with PF-BTFC (P<0.05) and controls (P<0.001). Differences were not found among PTFCs. InI and InAW significantly correlated with Ocular Surface Disease Index and breakup time (P<0.001), corneal staining (P<0.05), and GCD (P<0.001); GCD correlated with MMAD (P<0.05)., Conclusions: PTFCs were less toxic towards MGs and goblet cells compared with the L+T unfixed combination, with PF-BTFC presenting the most tolerated profile. These findings should be carefully considered given the role of these structures in the induction of the glaucoma-related ocular surface disease.

Purpose: The purpose of the study is to investigate the effect of 3% diquafosol sodium eye drops on meibomian gland and ocular surface alterations in the superoxide dismutase-1 (Sod1 -/- ) mice in comparison to the wild-type mouse., Methods: Three percent diquafosol sodium eye drop was instilled to 20 eyes of 10 50-week-old male Sod1 -/- mice and 22 eyes of 11 C57BL/6 strain 50-week-old wild-type (WT) male mice six times a day for 2 weeks. Aqueous tear secretion quantity was measured with phenol red-impregnated cotton threads without anesthesia. Tear film stability and corneal epithelial damage were assessed by fluorescein and lissamine green staining. We also performed oil red O (ORO) lipid staining to evaluate the lipid changes in the meibomian glands. Meibomian gland specimens underwent hematoxylin and eosin staining to examine histopathological changes and meibomian gland acinar unit density after sacrifice. Immunohistochemistry staining was performed using cytokeratin 4, cytokeratin 13, and transglutaminase-1 antibodies. Quantitative real-time polymerase chain reaction for cytokeratin 4, cytokeratin 13, and transglutaminase-1 mRNA expression was also performed., Results: The aqueous tear quantity, the mean tear film breakup time, and the number of lipid droplets significantly improved in the Sod1 -/- mice with treatment. The mean meibomian acinar unit density did not change in the Sod1 -/- mice and WT mice after treatment. Application of 3% diquafosol sodium eye drop significantly decreased the corneal fluorescein and lissamine green staining scores in the Sod1 -/- mice after 2 weeks. We showed a notable increase in cytokeratin 4, cytokeratin 13 immunohistochemistry staining, and cytokeratin 4, cytokeratin 13 mRNA expressions with a marked decrease in immunohistochemistry staining and significant decline in mRNA expression of transglutaminase-1 after 3% diquafosol sodium treatment., Conclusion: Topical application of 3% diquafosol sodium eye drop improved the number of lipid droplets, tear stability, and tear production which in turn appeared to have a favorable effect on the ocular surface epithelium. Three percent diquafosol sodium eye drop may be a potential treatment for age-related meibomian gland and dry eye disease based on the observations of the current study.

PurposeTo assess tear cytokine levels and clinical outcomes in meibomian gland dysfunction (MGD) in the blind eye of patients wearing an ocular prosthesis after 2 months of treatment with topical loteprednol etabonate and eyelid scrubs with warm compresses.Patients and methodsThis study included patients with MGD wearing a unilateral ocular prosthesis for more than 1 year. All patients topically received 0.5% loteprednol etabonate and were instructed to scrub their eyelids with warm compresses on the prosthetic eye for 2 months. We evaluated tear cytokine levels using Multiplex Bead Immunoassays, performed biomicroscopic examination of the lid margins and meibomian gland, conducted meibography imaging, and assessed MGD-related ocular symptoms using a questionnaire for the prosthetic eye before and 2 months after treatment.ResultsThirty consecutive patients were included. There were significant reductions in the levels of interleukin (IL)-6, interferon-γ, monocyte chemotactic protein-1, IL-8, tumor necrosis factor-α, and IL-1β (P<0.001 for each cytokine). Moreover, there were improvements in ocular symptoms (P=0.001), lid margin abnormalities (P<0.001), meibomian gland expressibility (P<0.001) and meibography findings (P=0.037).ConclusionTopical loteprednol etabonate in conjunction with eyelid scrubs and warm compresses were effective in treating MGD in prosthetic eye wearers. Furthermore, tear cytokine measurements may serve as an additional approach for evaluating the efficacy of anti-inflammatory treatment for MGD in prosthetic eye wearers.

Purpose: The aim of this study was to investigate the association between tear film and meibomian gland parameters in patients with normal tension glaucoma (NTG), who underwent topical prostaglandin analog (PGA) monotherapy, and medication compliance., Methods: Ocular surface disease index (OSDI), Schirmer's test, tear film break-up time (TBUT), keratoepitheliopathy (KEP) score with fluorescein, and meibomian gland parameters were assessed in 45 eyes of 45 patients with NTG (NTG group), who received topical PGA monotherapy for more than 1 year. The results were compared to those of 40 eyes of 40 normal subjects (control group). Medication compliance was assessed by an 8-item Morisky Medication Adherence Scale (MMAS-8). Multiple logistic regression analysis was used to identify the factors associated with medication compliance., Results: There was a significant difference in OSDI (P = 0.043), Schirmer's test (P < 0.001), TBUT (P < 0.001), KEP score (P = 0.015) and all meibomian gland parameters (all P < 0.001) between two groups. When the NTG group was divided into compliant and non-compliant groups based on the scores of MMAS-8, 30 (75%) patients were classified into the compliant group. Multiple logistic regression analysis revealed that the lid margin score (OR, 0.256; 95% CI, 0.072-0.908, P = 0.035), meibum score (OR, 0.144; 95% CI, 0.023-0.915, P = 0.04), and meibo score (OR, 0.344; 95% CI, 0.140-0.845, P = 0.02) were significant factors associated with compliance in patients with NTG. The meibomian gland parameters showed a negative correlation with medication compliance (all P < 0.005)., Conclusions: Malfunction of the meibomian glands can be an important clinical finding associated with compliance of PGA monotherapy in patients with NTG.

Objective: To investigate the bacterial profile in the conjunctiva and meibomian glands in patients before penetrating ocular surgeries, and to compare the anti-bacterial efficacy of 0.5% levofloxacin and its combination with meibomian gland massage., Design: Hospital-based, case-control study., Participants: Two hundred and twenty-six eyes from 226 patients with non-infective ocular diseases and scheduled for penetrating ocular surgeries., Methods: Tested eyes were administered topical 0.5% levofloxacin (4 times daily) for 2 days. Among them, 91 eyes received meibomian gland massage before levofloxacin application. Samples from the conjunctival sac and meibomian glands were collected for aerobic and anaerobic cultures., Main Outcome Measures: Culture-positivity and bacterial strains., Results: Before treatment, aerobes and anaerobes were cultured from 38.5% and 11.0% of the conjunctival samples respectively, compared with 38.5% and 8.8% in the meibomian secretions respectively. Staphylococcus epidermidis and Propionibacterium acnes were the commonest isolated aerobe and anaerobe. Two-day application of levofloxacin reduced aerobic growth to 29.6% in the conjunctiva and 19.3% in the meibomian glands. It had no effect on the anaerobes in these regions (13.3% in the conjunctiva and 10.4% in the meibomian glands). Combined levofloxacin with meibomian gland massage further reduced aerobic growth to 19.8% in the conjunctiva and 11.0% in the meibomian glands. It also drastically decreased anaerobic growth in the meibomian glands (1.1%)., Conclusions: Meibomian glands carrying considerable bacteria should be considered as a potential source of contamination in ocular surgery. Meibomian gland massage shows additional anti-bacterial effects to topical levofloxacin and could be recommended as a complementary preoperative prophylaxis., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: The aim was to evaluate the clinical efficacy of topical azithromycin 1.5 per cent ophthalmic solution in treatment of the clinical signs and symptoms associated with meibomian gland dysfunction (MGD)., Methods: In this retrospective study, 35 patients with MGD were treated with topical azithromycin 1.5 per cent ophthalmic solution for 30 days. Topical azithromycin 1.5 per cent ophthalmic solution was prescribed twice daily for two days and then once daily for a total of 30 days. Daily lid hygiene with dilute baby shampoo was instructed for all patients. Patient total symptom score, meibomian gland grading score, Schirmer score with anaesthetic, tear film break-up time (TFBUT) and corneal fluorescein staining score were evaluated at baseline and after one and three months., Results: Patient total symptom score, meibomian gland grading score, Schirmer score with anaesthetic, TFBUT and corneal staining score reduced significantly from the baseline to the first month (p < 0.05, for each); however, at the third month, there was no significant difference from baseline in the meibomian gland grading score, Schirmer score with anaesthetic, TFBUT and corneal fluorescein staining score (p > 0.05, for each)., Conclusion: These results demonstrate that topical azithromycin 1.5 per cent ophthalmic solution appears effective in the short-term treatment of the clinical signs and symptoms associated with MGD., (© 2017 Optometry Australia.)

Purpose: This prospective, randomized, double-blind interventional case series was designed to evaluate the short-term efficacy of 0.03% tacrolimus ointment as a new therapeutic approach for refractory cases of posterior blepharitis., Methods: Forty eyes (20 patients) with posterior blepharitis refractory to previous treatment were randomized. Eighteen eyes (9 patients) were treated with 0.03% tacrolimus ointment and 20 eyes (10 patients) with placebo ointment twice daily. Patients were evaluated with a questionnaire and slit-lamp examination 14 days and 28 days after treatment, and symptoms and signs of blepharitis were compared to those observed at baseline., Results: We could observe statistical difference in the outcome measurements of meibomian gland secretion, conjunctival hyperemia, telangiectasia of inferior lid, Rose Bengal, and fluorescein scoring for the study group. As for the symptoms score, we observed statistical difference in the symptoms scoring for pruritus and dry eye sensation in the tacrolimus group., Conclusion: This study suggests that topical administration of 0.03% tacrolimus ointment can improve some symptoms and some ocular surface status in patients with refractory posterior blepharitis.