Efficacy and safety of topical azithromycin therapy in patients with blepharitis and meibomian gland dysfunction.

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.

Er-Dong-Xiao-Ke decoction regulates lipid metabolism via PPARG-mediated UCP2/AMPK signaling to alleviate diabetic meibomian gland dysfunction.

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.

The topical azithromycin meibomian gland dysfunction survey: The effect of topical azithromycin on signs and symptoms of meibomian gland dysfunction.

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.

Re-Esterified Triglyceride ω-3 Fatty Acids in Dry Eye Disease With Meibomian Gland Dysfunction: A Randomized Clinical Trial.

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.

Recent United States Developments in the Pharmacological Treatment of Dry Eye Disease.

Dry eye disease (DED) can arise from a variety of factors, including inflammation, meibomian gland dysfunction (MGD), and neurosensory abnormalities. Individuals with DED may exhibit a range of clinical signs, including tear instability, reduced tear production, and epithelial disruption, that are driven by different pathophysiological contributors. Those affected often report a spectrum of pain and visual symptoms that can impact physical and mental aspects of health, placing an overall burden on an individual's well-being. This cumulative impact of DED on an individual's activities and on society underscores the importance of finding diverse and effective management strategies. Such management strategies necessitate an understanding of the underlying pathophysiological mechanisms that contribute to DED in the individual patient. Presently, the majority of approved therapies for DED address T cell-mediated inflammation, with their tolerability and effectiveness varying across different studies. However, there is an emergence of treatments that target additional aspects of the disease, including novel inflammatory pathways, abnormalities of the eyelid margin, and neuronal function. These developments may allow for a more nuanced and precise management strategy for DED. This review highlights the recent pharmacological advancements in DED therapy in the United States. It discusses the mechanisms of action of these new treatments, presents key findings from clinical trials, discusses their current stage of development, and explores their potential applicability to different sub-types of DED. By providing a comprehensive overview of products in development, this review aims to contribute valuable insights to the ongoing efforts in enhancing the therapeutic options available to individuals suffering from DED.

Systemic antibiotic treatment for meibomian gland dysfunction-A systematic review and meta-analysis.

PURPOSE: To review the efficacy and safety of oral doxycycline antibiotics versus macrolides in the treatment of meibomian gland dysfunction (MGD). DESIGN: Systematic review and meta-analysis. METHODS: We performed a systematic search of electronic databases for all peer-reviewed published studies which included clinical outcomes of oral antibiotic MGD treatment. Individual study data were extracted and evaluated in a weighted pooled analysis, including total sign and symptom scores, meibomian gland secretion score, tear break-up time (TBUT), fluorescein staining score and rate of complications. RESULTS: Two thousand nine hundred and thirty-three studies were found, of which 54 were eligible for the systematic review, and six prospective studies were ultimately included for analysis, reporting on 563 cases from three countries. Age of affected patients ranged between 12 and 90 years. Overall, both treatment methods induced improvement in MGD signs and symptoms. In pooled analysis, macrolides were significantly superior in the total signs score (pooled standardized mean difference (SMD) -0.51, 95% confidence interval (CI): -0.99 to -0.03), meibomian gland secretion score (pooled SMD -0.25, 95%CI: [-0.48, -0.03]), TBUT (SMD -0.31, 95%CI: [-0.50, -0.13]) and fluorescein staining score (SMD -1.01, 95%CI: [-1.72, -0.29]). Moreover, while no severe complications were reported for both treatments, the macrolide group exhibited significantly less adverse events (pooled odds ratio 0.24 with a 95% CI of 0.16 to 0.34). CONCLUSIONS: Both macrolides and tetracyclines are effective treatments for MGD. In this study, macrolides exhibited better efficacy and safety profile compared to tetracyclines.

Relationship between ocular surface temperature and 0.1% cyclosporine a in dry eye syndrome with meibomian gland dysfunction.

To determine the relationship between ocular surface temperature (OST) and 0.1% cyclosporine A in patients with dry eye syndrome and meibomian gland dysfunction (MGD). This study retrospectively analyzed 35 eyes from 18 patients with dry eye disease (DED) and MGD, who were divided into two groups. Group 1 was treated with artificial tears, and eyelid margin scrubs without anti-inflammatory eye drops, while group 2 received the same treatment as group 1 along with 0.1% cyclosporine A. The ocular surface disease index (OSDI), tear meniscus height (TMH), noninvasive tear breakup time (NIBUT), lipid layer thickness (LLT), meibum quality score (MQS), and OST were measured at baseline and 1 month later. Nineteen and 16 eyes were included in groups 1 and 2, respectively. Both groups showed a significant decrease in OSDI and OST; however, the decrease was more significant in group 2. No other significant differences in TMH, NIBUT, and LLT were observed; however, MQS significantly differed in group 2. This study found that 0.1% CsA administration can relieve symptoms in patients with DED and MGD although there were no definite keratitis clues, such as epithelial erosion. In addition, the conjunctival temperature showed a correlation with symptom improvement.

Dry eye disease due to meibomian gland dysfunction treated with Pinggan Yuyin Qingre formula: a stratified randomized controlled trial.

OBJECTIVE: To observe the clinical efficacy on improving the quality of meibum in patients suffer from dry eye disease (DED) due to meibomian gland dysfunction (MGD) with hyperactivity ofdue todeficiency pattern after being treated with Pinggan Yuyin Qingre formula (, PGYYQR). METHODS: Totally 120 patients who met the inclusion criteria were included and stratified into three levels according to the level of MGD (1-3), and patients in each level was randomly allocated into the treatment group and control group according to a 1∶1 ratio. Both groups were treated with sodium hyaluronate eye drops, and the treatment group was also given PGYYQR granules. Both groups were treated continuously for eight weeks. The score of the properties of meibomian gland (MG) secretion, the score of the palpebral margins, the average noninvasive tear breakup time (NITBUTav), lipid layer thickness (LLT), and Traditional Chinese Medicine (TCM) syndrome efficacy were compared between the two groups after treatment. RESULTS: A total of 116 cases were included in the statistical analysis. The differences were statistically significant in the score of the properties of MG secretion, the score of the palpebral margins, and NITBUTav between the two groups after treatment, the treatment group was superior to the control group; there was no evidence of a difference in LLT. In terms of TCM syndrome efficacy, the total effective rate was 84.7% in the treatment group and 50.9% in the control group, with the statistically significant difference. None of the included cases had adverse reactions. CONCLUSIONS: PGYYQR is effective in improving the quality of meibum, and the tear film stability which thereby relieving the ocular symptoms in MGD-related DED patients with hyperactivity ofdue todeficiency pattern.

Effect of Treatment with Topical Azithromycin or Oral Doxycycline on Tear Film Thickness in Patients with Meibomian Gland Dysfunction: A Randomized Controlled Trial.

Purpose: This prospective, randomized, observer-masked, parallel-group study aimed to compare the effect of topical azithromycin and oral doxycycline on tear film thickness (TFT) and signs and symptoms of ocular surface disease (OSD) in patients with meibomian gland dysfunction (MGD). Methods: Patients were randomized to either receive topical azithromycin or oral doxycycline. After a baseline visit, three follow-up visits at intervals of 2 weeks were scheduled. Main outcome of the study was change in TFT as measured with ultrahigh resolution optical coherence tomography. Results: Twenty patients were included in the analysis. TFT significantly increased in both groups (P = 0.028 vs. baseline) with no difference between the groups (P = 0.096). As secondary outcomes, ocular surface disease index (OSDI) score and composite signs of OSD significantly decreased in both groups (P = 0.023 for OSDI and P = 0.016 for OSD signs vs. baseline). While eye-related adverse events (AEs) occurred more frequently in the azithromycin group, systemic AEs were more common in the doxycycline group. Conclusions: Both treatments improved signs and symptoms of OSD in patients with MGD with no difference between the groups. Due to the higher frequency of systemic side effects of doxycycline, azithromycin eye drops seem to be an alternative with comparable efficacy. Clinical Trial Registration number: NCT03162497.

Comparative study evaluating the efficacy of topical azithromycin versus oral doxycycline in the treatment of meibomian gland dysfunction.

Objective: To assess the efficacy of topical azithromycin drops versus oral doxycycline therapy in meibomian gland dysfunction. METHODS: The prospective randomised trial was conducted from December 2019 to June 2020 at the Qazi Hussain Ahmad Medical Complex, Nowshera, Pakistan, and comprised patients of either gender aged 26-42 years having long-standing posterior blepharitis / meibomian gland dysfunction. The subjects were randomised into two equal groups. Both the groups were advised to do warm compresses and lid massage three times a day for 5 min. each for 4 weeks. In addition, group A received azithromycin 1% drops 2 times/day for 1 week, followed by once a day for 3 weeks, while group B received oral doxycycline 100mg once a day for 4 weeks. Baseline, midstream at 2 weeks and post-intervention status, including subjective symptoms, were compared. RESULTS: Of the 60 subjects enrolled, there were 30(50%) in each of the two groups; 32(53.3%) males and 28(46.4%) females. While all 30(100%) the participants in group A completed the trial without any adverse reaction to medication, 8(26.7%) in group B quit midstream owing to anorexia/nausea and gastrointestinal discomfort. Compared to baseline, reduction in both subjective and objective features of the disease in both groups were noted regardless of gender (p=0.08). No significant difference was evident in symptoms healing rate and improvement in foreign body sensation between the groups (p>0.05). Group A treatment improved eye redness, while group B proved better in respect of meibomian glands obstruction healing and corneal staining p<0.05). Conclusion: Both topical azithromycin and oral doxycycline were effective and had their own edge as far as symptomatic improvement was concerned in the treatment of meibomian gland dysfunction.

Pulsed Oral Azithromycin vs 6-Week Oral Doxycycline for Moderate to Severe Meibomian Gland Dysfunction: A Randomized Clinical Trial.

Importance: The treatment of moderate to severe meibomian gland dysfunction (MGD) with oral doxycycline requires a 6-week course of treatment and has frequent adverse effects (AEs), which may be associated with poor compliance. Objective: To determine if the AEs of a 3-week course of oral azithromycin were equivalent to the AEs of a 6-week course of oral doxycycline. Design, Setting, and Participants: This double-masked randomized clinical trial was conducted at a referral center in Thailand from September 2018 to May 2022. Participants with moderate to severe MGD judged unresponsive to conservative management were included. Interventions: Patients were randomized 1:1 to receive oral azithromycin (1 g once per week for 3 weeks) or oral doxycycline (200 mg daily for 6 weeks). Main Outcomes and Measures: After initiating therapy, the study team assessed the total MGD score and Ocular Surface Disease Index (OSDI) score at the initial visit, at 6 weeks, and at 8 weeks, and assessed AEs at 6 weeks and 8 weeks. The prespecified equivalence margins for MGD score and OSDI score were set at ±2 and ±9, respectively. Results: A total of 137 eyes from 137 patients were randomized into groups, 68 eyes in the azithromycin group and 69 eyes in the doxycycline group (female, 66.4%; mean age, 62.0 [SD, 15.1] years). The adjusted mean difference of total MGD scores between groups at week 6 and week 8 were -0.33 (95% CI, -1.70 to 1.03; P for equivalence = .01) and 0.13 (95% CI, -1.59 to 1.84; P for equivalence = .02), respectively. The adjusted mean difference of OSDI between groups score at week 6 and week 8 was -1.20 (95% CI, -5.31 to 2.91; P for equivalence < .001) and -1.59 (95% CI, -5.73 to 2.55; P for equivalence < .001), respectively. In addition, patients treated with azithromycin had fewer gastrointestinal AEs (4.4% vs 15.9%; risk difference, 11.5%; 95% CI 1.6%-21.4%; P = .03). Conclusions and Relevance: These data support an equivalency of effects of azithromycin as compared with doxycycline for MGD score and OSDI score at both follow-up times. The study did not show more gastrointestinal AEs in the azithromycin group. The reduced dosing and potentially fewer gastrointestinal AEs associated with azithromycin support its use as an alternative to doxycycline for at least 6 weeks. Trial Registration: ThaiClinicalTrials.org Identifier: TCTR20180810001.

Perfluorohexyloctane Eye Drops for Dry Eye Disease Associated With Meibomian Gland Dysfunction in Chinese Patients: A Randomized Clinical Trial.

Importance: Meibomian gland dysfunction (MGD) is a leading cause of evaporative dry eye disease (DED). Medical and surgical management for DED is limited; therefore, new treatment options are sought. Objective: To evaluate the efficacy and safety of SHR8058 (perfluorohexyloctane) eye drops in Chinese patients with DED associated with MGD through 57 days. Design, Setting, and Participants: This was a randomized, multicenter, double-masked, saline-controlled, phase 3 clinical trial conducted from February 4, 2021, to September 7, 2022. Patients were recruited from the departments of ophthalmology in 15 hospitals in China. Patients with DED associated with MGD were enrolled between February 4 and July 1, 2021. The diagnosis was based on patient complaint of DED symptoms, an ocular surface disease index of 25 or higher, tear film break-up time of 5 seconds or less, Schirmer I test without anesthesia results of 5 mm or more at 5 minutes, total corneal fluorescein staining (tCFS) score of 4 to 11, and an MGD score of 3 or higher. Interventions: Eligible participants were randomly assigned 1:1 to receive perfluorohexyloctane eye drops or 0.6% sodium chloride [NaCl]) 4 times per day. Main Outcomes and Measures: The primary end points were the changes from baseline in tCFS and eye dryness scores at day 57. Results: A total of 312 participants were included in the analysis: 156 (mean [SD] age, 45.4 [15.2] years; 118 female [75.6%]) in the perfluorohexyloctane group and 156 (mean [SD] age, 43.7 [15.1] years; 127 female [81.4%]) in the NaCl group. Both primary end points were achieved, ie, changes from baseline at day 57 of tCFS score (mean [SD], -3.8 [2.7] vs -2.7 [2.8]) and eye dryness score (mean [SD], -38.6 [21.9] vs -28.3 [20.8]) in the perfluorohexyloctane group were superior to the control group, with estimated mean differences of -1.14 (95% CI, -1.70 to -0.57; P < .001) and -12.74 (95% CI, -17.20 to -8.28, P < .001), respectively. Improvements on both end points appeared to be noted on day 29 and day 15, respectively, and maintained through day 57. Compared with the control, perfluorohexyloctane eye drops also alleviated symptoms including pain (mean [SD] tCFS score, 26.7 [23.7] vs -18.7 [22.5]; P = .003), awareness of DED symptoms (mean [SD] tCFS score, -38.1 [25.1] vs -23.7 [27.6]; P < .001), and frequency of dryness (mean [SD] tCFS score, -43.3 [23.8] vs -29.1 [24.8]; P < .001). Treatment-emergent adverse events occurred in 34 participants (21.8%) and 40 participants (25.6%) in the perfluorohexyloctane and control groups, respectively. Conclusions and Relevance: Results of this randomized clinical trial demonstrate that perfluorohexyloctane eye drops significantly ameliorated the signs and symptoms of DED associated with MGD with a rapid efficacy as well as satisfactory tolerability and safety through 57 days. Findings support the use of these eye drops if results can be confirmed independently and over longer time periods. Trial Registration: ClinicalTrials.gov Identifier: NCT05515471.

Randomised assessor-masked trial evaluating topical manuka honey (Optimel) in treatment of meibomian gland dysfunction.

PURPOSE: To evaluate the effects of manuka honey eye-drops in the treatment of meibomian gland dysfunction. METHODS: This is an assessor-masked (single-blind), randomised controlled trial comparing conventional treatment group with interventional group using Optimel 16% manuka honey topical eye-drops. 59 patients were recruited to the study and randomised into two groups: one given regular lubricants and the other given Optimel 16% manuka honey eye-drops. The Standard Patient Evaluation of Eye Dryness (SPEED) score was measured at baseline and on follow-up. 4 patients were lost to follow-up. Multiple ocular surface parameters were graded from slit lamp examination by a masked assessor. Results were compared from baseline to follow-up date 3 weeks later. RESULTS: Patients in the conventional treatment group demonstrated minimal difference in SPEED score at 3-week follow-up (mean difference 1.087, p=0.183), which was not statistically significant. However, measurements of tear film break-up time, corneal surface stain (Oxford), lid margin, conjunctival redness, as well as meibum quality and expressibility showed significant improvements at 3 weeks (p<0.01). Patients in the manuka honey eye-drops group showed significant difference after 3 weeks in SPEED score (mean difference 2.53, p=0.006), as well as in lid margin redness, conjunctival redness, corneal surface stain (Oxford), and meibum quality and expressibility (p=0.000). CONCLUSIONS: Optimel 16% manuka honey eye-drops showed significant improvement in symptoms and objective signs in meibomian gland dysfunction and are an effective alternative treatment for meibomian gland dysfunction. TRIAL REGISTRATION NUMBER: NCT04457648.

Periplocin ameliorates mouse age-related meibomian gland dysfunction through up-regulation of Na/K-ATPase via SRC pathway.

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.

Efficacy of Topical Ivermectin for the Treatment of Cutaneous and Ocular Rosacea.

Purpose: To investigate the efficacy of once-daily topical treatment of ocular and cutaneous rosacea with ivermectin 1% cream (Soolantra®, Galderma).Methods: Ten patients with rosacea were evaluated in a retrospective monocentric pilot study. Subjective symptoms (measured with the Ocular Surface Disease Index), skin findings, and ocular changes (blepharitis with telangiectasia and meibomian gland dysfunction, conjunctival redness, tear breakup time (TBUT), and fluorescein staining of the cornea) were evaluated. The follow-up was 8 months (range: 5-12 months).Results: The OSDI score decreased in the 8th week of treatment (38.5 ± 21.7, P = .004). After 16 weeks, blepharitis (P = .004), and conjunctival redness (P = .008) had strongly improved, and grade 1 was seen in all patients until the end of follow-up. Fluorescein staining of the cornea (P = .001) and TBUT (P = .016) showed significant improvement until the last follow-up visit. No side effects were observed. Conclusion: Topical ivermectin cream 1% given daily is an effective and safe therapy against rosacea.

Ocular surface changes in the treatment of rosacea: comparison between low-dose oral isotretinoin and doxycycline / Alterações da superfície ocular no tratamento da Rosácea: comparação entre isotretinoína oral em baixa dosagem e doxiciclina

ABSTRACT 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.

RESUMO Objetivos: Comparar o impacto das alterações oculares entre o tratamento sistêmico de doxiciclina e isotretinoína em baixa dosagem em pacientes com rosácea papulopustulosa moderada a grave. Métodos: Os pacientes form randomizados para receber isotretinoína 0,3 a 0,4 mg/kg (grupo A) ou doxiciclina 100mg/dia (grupo B) por 16 semanas. Os sintomas oculares foram pesquisados e avaliados, incluindo melhor acuidade visual corrigida, teste de Schirmer, tempo de ruptura do filme lacrimal, coloração de rosa bengala e graduação da disfunção de glândula de Meibomius. Os pacientes foram novamente testados no final do tratamento. Resultados: O presente estudo incluiu 39 pacientes (30 mulheres e 9 homens). A melhor acuidade visual corrigida foi >20/30 em >90% dos pacientes em ambos os grupos e não se alterou após o tratamento. A melhora dos sintomas oculares e da disfunção de glândula de Meibomius foi mais pronunciada no grupo B (p<0,05) após o tratamento; as demais variáveis não atingiram significância estatística. Conclusão: A doxiciclina melhorou a disfunção de glândula de Meibomius, os sintomas oculares e a superfície ocular de pa cientes com rosácea. Mesmo que alguns pacientes tenham piorado a disfunção e os sintomas da glândula de Meibomius, nenhum indivíduo apresentou complicações graves após a admi nistração de baixas doses de isotretinoína.

Ocular surface changes in the treatment of rosacea: comparison between low-dose oral isotretinoin and doxycycline.

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.

The Role of Topical Azithromycin in the Treatment of Meibomian Gland Dysfunction.

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.

Effect of Eyelid Treatments on Bacterial Load and Lipase Activity in Relation to Contact Lens Discomfort.

OBJECTIVES: To evaluate the effect of microblepharon exfoliation on the number of eyelid bacteria and their lipase activity and the relationship of these to contact lens discomfort. METHODS: Thirty experienced contact lens wearers had their eyelid margin physiology, tear properties, and comfort scores assessed. The number, type, and frequency of lower eyelid margin bacteria, and their lipase activity, were measured. Eyelids were treated with a foam cleanser or microblepharon exfoliation. Clinical and microbiological tests were repeated at each visit. Changes and correlations were examined. RESULTS: Symptomatic lens wearers had a higher ratio for the number and frequency of gram-positive rods and cocci. Microblepharon exfoliation reduced the number and ratio of gram-positive rods to cocci from baseline for symptomatic wearers that lasted 7 to 10 days after treatment (P<0.05). Numbers of bacteria, the ratio of rods to cocci, and lipase activity correlated with lash contamination (r≥0.385; P≤0.046) and anterior blepharitis (r≥0.359; P≤0.048). Bacterial lipase correlated with meibomian gland secretions (r=0.422; P=0.038) and the tear evaporation rate (r=0.479; P=0.022). Microblepharon exfoliation produced a significant reduction in CLDEQ-8 scores and converted 10 symptomatic into asymptomatic lens wearers. CONCLUSIONS: There was dysbiosis in the lid microbiome of symptomatic lens wearers. Microblepharon exfoliation reduced the number, frequency of isolation, and ratio of gram-positive rods and cocci. Bacterial numbers and their lipase production correlated with changes to clinical signs and symptoms. Symptomatic lens wearers could be converted to asymptomatic lens wearers after microblepharon exfoliation.