Lubricating drops for contact lens discomfort in adults.

BACKGROUND: Contact lens discomfort is a symptom-based clinical diagnosis that affects 13% to 75% of contact lens wearers. The Tear Film and Ocular Surface Society defines contact lens discomfort as "a condition characterized by episodic or persistent adverse ocular sensations related to lens wear either with or without visual disturbance, resulting from reduced compatibility between the lens and ocular environment, which can lead to decreased wearing time and discontinuation from lens wear." Signs of the condition include conjunctival hyperemia, corneal and conjunctival staining, altered blinking patterns, lid wiper epitheliopathy, and meibomian gland dysfunction. Eye care specialists often treat contact lens discomfort with lubricating drops, including saline, although there is no clear evidence showing this treatment is effective and safe. OBJECTIVES: To evaluate the efficacy and safety of lubricating drops for ocular discomfort associated with contact lens wear in adults. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register), MEDLINE, Embase.com, two other databases, and two trials registries to May 2024, without date or language restrictions. SELECTION CRITERIA: We included parallel-group randomized controlled trials (RCTs) that evaluated lubricating drops, including saline, versus no treatment, or that evaluated lubricating drops versus saline, in adult contact lens wearers. We included studies regardless of publication status, language, or year of publication. DATA COLLECTION AND ANALYSIS: We applied standard Cochrane methodology. The critical outcome was contact lens discomfort. Important outcomes were corneal fluorescein staining and conjunctival redness. Adverse outcomes were incident microbial keratitis, inflammatory corneal infiltrates, and participant discontinuation. We assessed risk of bias for outcomes reported in the summary of findings table using the Cochrane risk of bias tool RoB 2, and we rated the certainty of the evidence using GRADE. MAIN RESULTS: We included seven RCTs conducted in the USA, Canada, Italy, and France. They randomized a total of 463 participants to lubricating drops, saline, or no treatment. Four trials evaluated lubricating drops and saline versus no treatment, but one of them provided no usable outcome data. Three trials evaluated lubricating drops versus saline. Study characteristics All trial participants were adults, and the mean age ranged from 25.7 years to 36.7 years. The proportion of women varied from 15% to 82%. The trials lasted between one and four weeks. Of the five trials that reported contact lens discomfort, we judged three at high risk of bias, and considered the other two had some risk of bias concerns. Lubricating drops (including saline) versus no treatment Lubricating drops compared with no treatment may reduce contact lens discomfort, measured on a 37-point scale (lower is better), but the evidence is very uncertain (mean difference [MD] -5.9 points, 95% confidence interval [CI] -3.74 to -8.05; 2 RCTs; 119 participants). One trial found no difference between lubricating drops and no treatment in "end-of-day" comfort. The trial that compared saline with no treatment provided no results for the control group. Two studies measured corneal fluorescein staining on a scale of 0 to 20 (lower is better). We found low-certainty evidence of little to no difference between lubricating drops and no treatment in changes in the extent (MD -0.15 points, 95% CI -0.86 to 0.56; 2 RCTs; 119 participants), depth (MD -0.01 points, 95% CI -0.44 to 0.42; 2 RCTs; 119 participants), or type (MD 0.04 points, 95% CI -0.38 to 0.46; 2 RCTs; 119 participants) of corneal fluorescein staining scores. Regarding conjunctival redness, measured on a scale of 0 to 4 (lower is better), there was low-certainty evidence of little to no difference between lubricating drops and no treatment in nasal region scores (MD 0.10, 95% CI -0.29 to 0.49; 1 RCT; 73 participants) and temporal region scores (MD 0.00, 95% CI -0.39 to 0.39; 1 RCT; 73 participants). No studies reported microbial keratitis or inflammatory corneal infiltrates, and no trials reported vision-threatening adverse events up to four weeks of treatment. All trials reported the proportion of participants who discontinued participation. In two trials, no participants left any treatment group. Our meta-analysis of another two studies suggests little difference in the number of people who dropped out of the lubricating treatment group versus the no treatment group (risk ratio [RR] 1.42, 95% CI 0.19 to 10.94; 138 participants; low-certainty evidence). Lubricating drops versus saline Lubricating drops may have little to no effect compared with saline on contact lens discomfort measured on a visual analog scale of 0 to 100 (lower is better), but the evidence is very uncertain (MD 9.5 points, 95% CI -4.65 to 23.65; 1 RCT; 39 participants). No studies reported corneal fluorescein staining or conjunctival redness. No studies reported microbial keratitis or inflammatory corneal infiltrates, and no trials reported vision-threatening adverse events up to four weeks of treatment. Our meta-analysis of three studies suggests little difference in the number of people who dropped out of the lubricating treatment group versus the saline group (RR 1.56, 95% CI 0.47 to 5.12; 269 participants; low-certainty evidence). AUTHORS' CONCLUSIONS: Very low-certainty evidence suggests that lubricating drops may improve contact lens discomfort compared with no treatment, but may have little or no effect on contact lens discomfort compared with saline. Low-certainty evidence also suggests that lubricating drops may have no unwanted effects that would lead to discontinuation over one to four weeks. Current evidence suggests that prescribing lubricating drops (including saline) to people with contact lens discomfort is a viable option. However, most studies did not assess patient-reported contact lens (dis)comfort using a validated instrument. Therefore, further well-designed trials are needed to generate high-certainty evidence on patient-reported outcomes as well as on longer-term safety outcomes.

Comparison of manual versus automated thermal lid therapy with expression for meibomian gland dysfunction in patients with dry eye disease.

To compare two types of lipid expression procedures to treat dry eye disease. Standardized treatment and evaluation methods were used in patients treated with either manual thermoelectric lipid expression (MiBoFlo) or automated lipid expression (Lipiflow) of the Meibomian glands. This was a contemporaneous, non-randomized study of both treatment methods. Treatment was per the manufacturers' recommendation. The primary outcome included two types of dry eye questionnaires as well as objective analysis of ocular surface including tear break up time, Schirmer testing, Osmolarity, and fluorescein staining. Baseline characteristics analyzed included floppy lid, conjunctivochalasis and lagophthalmos. Statistical analysis was performed correcting for baseline factors such as age and co existing pathology using multivariable analysis. Both treatments improved the results of the OSDI and SPEED dry eye questionnaire results. Both treatments resulted in improvement of many objective findings including SPK, lissamine green staining and tear break up time with the MiBoFlo showing more improvement than Lipiflow. OSDI was more sensitive to improvement of symptoms than the SPEED questionnaire. Manual expression with MiBoFlo device resulted in statistically more improvement in questionnaire scores than did automated expression with Lipiflow. Negative prognostic factors for symptomatic improvement included blepharitis, autoimmune disease and ocular allergies. Thermal lid therapy along with mechanical expression of lipids from the meibomian glands successfully treats dry eye symptoms and signs. Manual therapy with MiBoFlo resulted in more subjective and objective improvement scores than automated therapy with the Lipiflow device.

Complications and compliance in professionally-managed and self-managed contact lenses compared with non-contact lens wearers.

PURPOSE: To test the impact of professional management of soft contact lens wear on symptoms and ocular complications. METHODS: Subjective symptoms and ocular complications of soft CL users who did not seek professional follow-up care (self-managed, SM), were compared to users who were prescribed CLs and their care professionally managed in optometry practices (PM), and to a control group of non-CL wearers. Habitual visual acuity, subjective dry-eye symptoms, and corneal abnormalities were assessed in all participants. CL wearers filled-out a usage habits questionnaire, and their CL fit was assessed. Outcomes were compared using Kruskal-Wallis and Chi Squared tests. RESULTS: The SM, PM, and non-CL wearers cohorts included 127 (mean age:24.3±5.1, median:23, range:16-45 years,104 female), 132 (mean age:25.5±6.2, median:23, range:18-43 years,103 female), and 56 (mean age:22.3±3.5, median:21, range:18-39 years,36 female) participants, respectively. Meibomian gland dysfunction grade (p = 0.004, p<0.0001), limbal redness (both p = 0.04), corneal neovascularization (both p = 0.003), and papillary conjunctivitis (p<0.0001,p = 0.005) were significantly worse in SM CL wearers compared with both the non-CL wearers and PM CL wearers, respectively. Conjunctival staining was significantly worse in the SM cohort compared with the PM cohort (p = 0.01). 38.6% of the SM compared with 22.8% of the PM CL wearers, had an inappropriate refractive correction (p = 0.006). SM CL wearers wore CLs significantly more years (mean and median 1 year,p = 0.008), for more daily hours (mean and median of 2 hours,p<0.00001), and tended to nap or sleep with their CLs compared with the PM CL wearers (47 vs. 29,p = 0.02). The cohorts did not differ in their subjective symptoms. CONCLUSIONS: Complications are significantly more prevalent in SM CL wearers compared with PM CL wearers, and SM CL wearers tend to wear CLs with incorrect powers, and are less compliant with napping or sleeping with the CLs compared with PM CL wearers. These findings emphasize the importance of fitting, patient education and follow-ups in CL wearers.

Evaluating the role of Demodex infestation and meibomian gland dysfunction in recurrent corneal erosion syndrome.

This investigation aims to observe the effects of demodex infection and meibomian gland function in recurrent corneal erosion syndrome (RCES), as well as the efficacy of intense pulsed light (IPL) in treating RCES. The study enrolled thirty patients diagnosed with RCES (30 eyes) alongside a control group of thirty-one individuals (31 eyes). Both cohorts underwent a series of diagnostic evaluations, including eyelash sampling, Demodex mite enumeration, infrared imaging of the meibomian glands, and blepharolipin scoring. The RCES subjects were further categorized into two subgroups upon stabilization for comparative analysis of treatment outcomes: the RCES-A subgroup received IPL therapy (16 patients), and the RCES-B subgroup was administered medication treatment (14 patients). Post-treatment, all participants were re-evaluated using the initial diagnostic procedures to monitor for recurrence. Preliminary findings indicated significant differences between the RCES and control groups in terms of meibomian gland scores (4 [3.0, 4.0] vs. 2 [1.0, 3.0]), blepharolipin scores (15.5 [11.0, 16.8] vs. 8.0 [5.5, 10.0]), and lid margin scores (3.0 [2.8, 3.0] vs. 2.0 [1.0, 3.0]), with P < 0.01 for all comparisons. Additionally, the Demodex count was significantly higher in the RCES group (8.0 [4.0,9.0]) compared to the control (0 [0, 2]) (Z = - 4.13, P = 0.00), with a Demodex positivity rate of 83.3% in the RCES group versus 38.7% in the control group (χ2 = 7.60, P < 0.01). Post-treatment, the RCES-A subgroup exhibited significant improvements in meibomian gland loss scores, blepharolipin scores, lid margin abnormality scores, and a reduction in Demodex counts (P < 0.01), with a post-treatment Demodex positivity rate of 56.3% (P = 0.11). During the follow-up, the RCES-A subgroup experienced a lower relapse rate compared to the RCES-B subgroup (1 vs. 6 patients). The findings suggest a correlation between meibomian gland dysfunction and Demodex infestation with the incidence of RCES. The application of IPL therapy in combination with meibomian gland massage demonstrates significant potential in enhancing meibomian gland functionality, reducing Demodex counts, and effectively mitigating the recurrence of RCES. Clinical trial registration: https://www.chictr.org.cn/ ChiCTR2000039494 (30/10/2020).

Mechanism of Thunder-Fire Moxibustion in the Treatment of Meibomian Gland Dysfunction Induced by High-Fat Diet.

Objective: An investigation into whether Thunder-Fire Moxibustion improves Meibomian Gland Dysfunction by activating peroxisome proliferator-activated receptor gamma (PPARγ)-related signaling pathway. Methods: C57BL/6 mice were randomly divided into a Control Group (CG), model group (MG), Experimental Group (EG), Treatment Group (TG), and GW9662 (GW), with 10 mice in each group. The obstruction of the meibomian gland opening, tear film rupture time, and corneal fluorescein sodium staining were observed. The morphology of the meibomian gland was observed by HE staining. Observations of oil red staining were made on the meibomian gland to determine its oil content. The expression levels of PPARγ, NF-κB p65, Phospho-NF-κB p65 (p-NF-κB), and IL-6 in the meibomian gland were detected by Western blot. The expression of PPARγ, NF-κB p65, p-NF-κB p65, and IL-6 in the meibomian gland was examined by immunofluorescence staining. Results: The results showed that compared to the Control Group, the Model Group mice exhibited an increased Meibomian Gland Orifices Score (MGOS) (P < .01), an increased MG corneal staining (P < .01), a shorter tear film break-up time (P < .01), eyelid atrophy, disordered arrangement of meibomian gland cells, the presence of a large number of immature adipocytes, varying degrees of cellular inflammation and infiltration, a significant reduction in meibomian gland tissue lipids, decreased expressions of MGPPARγ and NF-κB (P < .01), and elevated expressions of phosphorylated NF-κB and IL-6 (P < .01). However, Western medicine, antagonists, and thunder-fire moxibustion were all able to reverse these phenomena observed in the Model Group mice (P < .01), with thunder-fire moxibustion exhibiting the most significant effect (P < .01). Conclusion: The thunder-fire moxibustion can induce the differentiation of meibomian gland cells, thereby improving the inflammation response.

Efficacy and safety of the disposable eyelid warming masks in the treatment of dry eye disease due to Meibomian gland dysfunction.

BACKGROUND: Warm compresses are the routine treatment for Meibomian gland dysfunction (MGD) in daily life, but in order to achieve satisfactory efficacy, the treatment needs to be sustained over a long time, which can have an impact on the patient compliance. A more convenient warm compresses will help improve the patient compliance. Therefore, the purpose of the study is to investigate the efficacy and safety of the disposable eyelid warming masks for treatment of dry eye disease (DED) due to MGD. METHODS: This was a randomized, controlled, non-masked, two-center clinical trial. One hundred and forty-four patients were treated by the masks or the hot towel twice daily for 12 weeks. Patients were evaluated at baseline, 4-week and 12-week visits for subjective symptoms, objective signs and safety assessments, including ocular symptom scores, ocular surface disease index (OSDI), tear break-up time (BUT), corneal fluorescein staining (CFS), Schirmer I test (SIT), meibum quality, meibum expressibility, and adverse events (AEs). RESULTS: A totle of 134 patients were followed in the study. The mean age of the masks group (14 males and 52 females) and the hot towel group (20 males and 48 females) was 43.7 ± 13.5 years and 39.5 ± 13.9 years, respectively. At 4-week visit, there were significant statistical differences in ocular symptom scores, OSDI and CFS between two groups (P < 0.05). Except for SIT, the treatment group showed a greater improvement in subjective symptoms and objective signs than the control group at 12-week visit. (P < 0.05). In addition, 40 AEs occurred in 27 patients (37.5%) in the treatment group, and 34 AEs occurred in 21 patients (29.17%) in the control group. No serious AEs were reported. CONCLUSIONS: The masks had a good efficacy and safety in the treatment of DED due to MGD, and might offer an attractive treatment option for some patients. TRIAL REGISTRATION: The study was registered at Chinese Clinical Trial Registry (ChiCTR1900025443) on August 26, 2019.

Effects of combined intense pulsed light and cyclosporine 0.05% eyedrops in ocular surface matrix metalloproteinase-9 levels in patients with moderate-to-severe MGD.

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.

Intense pulsed light treatment for the management of meibomian gland dysfunction.

PURPOSE OF REVIEW: Meibomian gland dysfunction (MGD) is one of the most common disorders encountered by ophthalmologists, and its management can prove challenging for both clinicians and patients. Intense pulsed light (IPL), which has been historically used in the field of dermatology, has emerged as a tool to help improve meibomian gland function. The goal of this review is to assess the clinical efficacy, utility, and safety of IPL for the treatment of MGD. RECENT FINDINGS: In recent randomized controlled trials, IPL has been shown to improve meibomian gland function, and subsequently tear film quality and dry eye symptoms. The mechanism of action still remains unclear. Recent literature suggests that IPL may also be used in conjunction with other therapies, such as meibomian gland expression, low-level light therapy, and thermal pulsation. Careful attention should be placed on each patient's Fitzpatrick skin type, as well as protecting the ocular structures to reduce the risk of adverse effects. Cost, accessibility, as well as a limited duration of efficacy may be drawbacks. SUMMARY: There is significant evidence supporting that IPL may be used as a potential well tolerated and effective treatment for MGD, though there are certain caveats regarding its long-term efficacy, accessibility, and cost.

Safety and Efficacy of Dry Eye Intelligent Therapeutic Device in the Treatment of Meibomian Gland Dysfunction in Rabbits.

PURPOSE: To assess the safety and efficacy of the dry eye intelligent therapeutic device in rabbits with meibomian gland dysfunction. METHODS: The meibomian gland dysfunction-afflicted rabbits were subjected to treatment using the dry eye intelligent therapeutic device. Various parameters, including eyelid margin, meibomian gland opening, redness, meibomian gland area, keratoconjunctival fluorescence staining, and intraocular pressure, were examined and analyzed using an ocular surface comprehensive examination instrument, slit lamp, and tonometer at corresponding times points. Hematoxylin and eosin staining was performed to examine the mucosal epithelium and meibomian gland. RESULTS: In this study, eyelid margin congestion and meibomian gland opening obstruction were significantly improved after 3 weeks and 4 weeks of treatment, respectively (p < .01, p < .05). The treatment group showed a significant increase in tear meniscus height after 2 weeks, 3 weeks and 4 weeks of treatment (p < .001, p < .01, p < .05). No significant changes were noted in meibomian gland area, redness, intraocular pressure, and keratoconjunctival fluorescence staining of rabbits before and after treatment. Hematoxylin and eosin staining revealed a complete structure of mucosal epithelium and meibomian gland in the treatment group and that the expansion of the blocked meibomian gland duct was reduced. CONCLUSION: The utilization of the dry eye intelligent therapeutic device in treating meibomian gland dysfunction-afflicted rabbits exhibits potential promising safety, efficacy, and overall benefits, thereby offering a novel alternative for managing meibomian gland dysfunction patients in clinical settings.

Intense pulsed light therapy for ocular surface diseases.

Intense pulsed light (IPL) is a non-laser, high-intensity light source that has been shown to play a valuable role in dermatology and has been adopted in ophthalmology for treating meibomian gland dysfunction (MGD). In this review, we discuss the mechanism of action of IPL, including its benefits in ophthalmology. IPL therapy has been shown to improve tear film stability, meibomian gland (MG) function, and subjective symptoms of ocular dryness in MGD patients. Moreover, emerging evidence suggests that IPL therapy is beneficial for other ocular surface diseases, such as blepharitis and chalazia. Hence, it can be inferred that IPL has potential as a therapeutic modality in future applications. Large clinical and experimental trials are needed to exploit the full potential of IPL as a treatment for recurrent chalazia, Sjögren's syndrome, and other causes of dry eye disease (DED). This paper reviews the published literature related to the application of IPL for treating ocular surface diseases.

Models for Meibomian gland dysfunction: In vivo and in vitro.

Meibomian gland dysfunction (MGD) is a chronic abnormality of the Meibomian glands (MGs) that is recognized as the leading cause of evaporative dry eye worldwide. Despite its prevalence, however, the pathophysiology of MGD remains elusive, and effective disease management continues to be a challenge. In the past 50 years, different models have been developed to illustrate the pathophysiological nature of MGD and the underlying disease mechanisms. An understanding of these models is crucial if researchers are to select an appropriate model to address specific questions related to MGD and to develop new treatments. Here, we summarize the various models of MGD, discuss their applications and limitations, and provide perspectives for future studies in the field.

First-in-human Clinical Trial of a Novel Eyelid warming Device in Meibomian Gland Dysfunction.

BACKGROUND: Meibomian gland dysfunction (MGD) causes significant patient morbidity as well as economic burden. OBJECTIVES: To evaluate a novel eyelid warming and a neuro-stimulating device that delivers heat via low-level infrared radiation to the eyelids of patients with MGD. METHODS: In this prospective interventional study, patients with MGD were recruited at a single medical center. The main outcome measures included changes in tear break-up time (TBUT), Schirmer's test, and Ocular Surface Disease Index (OSDI), overall satisfaction, and corneal signs of dry eye. Patients were instructed to use the device twice daily for 5 minutes on each eye for a total of 14 days. Follow-up assessments were performed after the 2-week treatment. RESULTS: A total of 10 patients were included; mean age was 67 ± 16 years; six males (60%). Changes in pre- vs. post-treatment TBUT (5.0-6.11), OSDI (28.1-23.9), and Schirmer score (8.67-7.11) were not statistically significant. Over a course of 243 treatments, 131 (54%) demonstrated improvement in symptoms, 40% found no change, and 6% experienced worsening of symptoms. General satisfaction was observed overall in 80% of the patients. No adverse events were observed. CONCLUSIONS: In this first study of a novel eyelid warming device, overall subjective satisfaction was reported in 80% of patients. Potential advantages of this user-friendly device include its ability to improve MGD and tear film stability, as well as symptomatic relief, while allowing the user to continue with normal daily functioning while undergoing treatment.

Eyelid margin disease (blepharitis and meibomian gland dysfunction): clinical review of evidence-based and emerging treatments.

Blepharitis is a common ophthalmic condition with multiple etiologies and no definitive, universal treatment. The treatment modalities for managing lid margin diseases vary depending on the disease's cause, location, and severity. For anterior blepharitis, management options include eyelid hygiene with warm compresses, eyelid scrubs, baby shampoo, and over-the-counter eyelid cleansers. Topical antibiotics and antibiotic-steroid combination drops/ointments for the eye and eyelid may accompany these. For posterior blepharitis/meibomian gland dysfunction (MGD), at-home warm compress or in-office administration of heat therapy/thermal pulsation treatment that aims to clear obstruction in the meibomian glands and restore meibum secretions to maintain a healthy tear film is recommended. In addition to the above treatment strategies, various other compounds to manage lid margin diseases are in the late stages of development. This review summarizes the available treatment modalities or those in the pipeline for treating blepharitis and MGD.

LipiFlow for the treatment of dry eye disease.

BACKGROUND: Meibomian gland dysfunction (MGD) is the most common underlying cause of dry eye disease (DED). MGD leads to pathological alteration of the composition or quantity of meibum, or both, which subsequently results in tear evaporation and the typical signs and symptoms associated with DED. The LipiFlow Thermal Pulsation System (LipiFlow) is a medical device used to treat MGD in office; however, it is unclear if LipiFlow can outperform other DED treatments. OBJECTIVES: To evaluate the effectiveness of LipiFlow for treating DED signs and symptoms and the safety of LipiFlow compared with sham or other available treatments for MGD in adults. SEARCH METHODS: The Cochrane Eyes and Vision Information Specialist searched the electronic databases for randomized controlled trials. There were no restrictions on language or date of publication. We searched the Cochrane Central Register of Controlled Trials (CENTRAL, including the Cochrane Eyes and Vision Trials Register; 2022, Issue 6), MEDLINE Ovid, Embase.com, PubMed, LILACS (Latin American and Caribbean Health Science Information database), ClinicalTrials.gov, and World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) electronic databases. We also examined the reference lists of identified trials, review articles, and guidelines for information about relevant trials that may not have been identified by our search strategy. We contacted investigators regarding ongoing trials. The last database search was performed on 24 October 2022. SELECTION CRITERIA: We included studies conducted in adults (over 18 years of age) with DED or MGD as defined by the primary trial investigators. We imposed no restrictions on race, ethnicity, or sex. We considered trials involving contact lens wearers if they were equally represented between groups. DATA COLLECTION AND ANALYSIS: We applied standard Cochrane methodology. MAIN RESULTS: We included 13 trials that randomized a total of 1155 participants (28 to 236 participants randomized per study). Six trials were conducted in the USA, three in China, two in Thailand, one in France, and one in Italy. Eight trials were of single-center design, while four trials were of multicenter design; one trial did not report the number of participating centers. Study characteristics The study population of the included trials was 66% female (range 48% to 80%), with an age range of 19 to 86 years. LipiFlow, used as a stand-alone intervention, was compared with basic warm compresses in five studies, thermostatic device in five studies, oral intervention in one trial, and topical dry eye medications in one trial. LipiFlow was also evaluated together with eyelid hygiene product versus eyelid hygiene products alone in one trial. Findings Five trials compared LipiFlow with a basic warm compress applied for varying durations and frequencies during the trial period; only one of these trials combined a warm compress with eyelid massage. Analyzing symptom scores by different questionnaires (Ocular Surface Disease Index [OSDI] and Standard Patient Evaluation of Eye Dryness [SPEED]) yielded conflicting evidence of a difference in symptoms between LipiFlow and basic warm compresses after four weeks. There was no evidence of a difference in meibomian gland expression, meibum quality, or tear breakup time when comparing LipiFlow with basic warm compresses. Another five trials compared LipiFlow with thermostatic devices. Analysis of symptom scores at four weeks showed that thermostatic devices had reduced OSDI scores by a mean difference (MD) of 4.59 (95% confidence interval [CI] 1.23 to 7.95; I2 = 0, P = 0.007; 553 participants; very low certainty evidence) as compared with LipiFlow. When we compared LipiFlow plus eyelid hygiene with eyelid hygiene alone, there was no evidence of difference in signs or symptoms at any time point evaluated. Only one trial compared LipiFlow with a topical DED medication (lifitegrast 5%). The single-trial estimate suggested that 5% lifitegrast may increase meibomian gland expression scores compared with LipiFlow at day 42 (MD -1.21, 95% CI -2.37 to -0.05; 50 participants; low certainty evidence) by using a meibomian gland expression scale of 0 to 8. One trial compared LipiFlow with an oral intervention (doxycycline), finding that LipiFlow may result in significantly better SPEED scores than doxycycline at three months (MD -4.00, 95% CI -7.33 to -0.67; 24 participants; very low certainty evidence). No other significant differences in signs or symptoms were found between LipiFlow and doxycycline at three months. We did not find any other statistically significant differences in symptoms or signs for any other analysis performed in this review at the one- to four-week time point. Adverse events No trial reported any intervention-related, vision-threatening adverse events. AUTHORS' CONCLUSIONS: LipiFlow performs similarly to other commonly used DED treatments with regard to DED signs and symptoms. The best available evidence was deemed to have a high level of bias, leading to low or very low certainty evidence. Additional research with adequate masking, a standardized testing methodology, and a sample representative of the MGD population is therefore needed before any firm conclusions can be drawn regarding comparative benefits and harms.

Quantum Molecular Resonance Effects on Patients With Dry Eye Disease: A Randomized Controlled Trial.

PURPOSE: The aim of the study was to evaluate the efficacy and safety of quantum molecular resonance in the treatment of dry eye disease. METHODS: This study was a double-blind randomized control trial in 1 academic medical center, for 2 years. Participants received treatment or a placebo with the Rexon-Eye device, once per week for 4 weeks. The primary outcome was the change in dry eye symptoms assessed by the Ocular Surface Disease Index (OSDI). Secondary outcomes were clinical findings associated with the dry eye such as meibomian gland dysfunction (MGD) score, tear break-up time (TBUT), corneal fluorescein staining, Schirmer test, and best-corrected visual acuity (BCVA). RESULTS: Forty patients were recruited, 20 in each arm. The mean age was 63.5 ± 15.1 years and 27 (67.5%) were female. The mean OSDI score significantly improved in the intervention group from 19.15 ± 10.3 to 10.5 ± 7.0 ( P < 0.001), whereas the control group showed no significant change (14.4 ± 8.4 to 15.5 ± 8.6, P = 0.830). MGD scores significantly improved in the intervention group (1.57 ± 1.2 to 0.8 ± 0.9, P = 0.006), whereas showing no significant change in the control group (1.60 ± 0.9 to 1.99 ± 1.0, P = 0.244). The corneal staining score also showed significant improvement in the intervention group ( P = 0.045) and a nonsignificant decline in the placebo group ( P = 0.50). No significant difference was seen in TBUT, visual acuity, and Schirmer scores between groups. No harm resulting from treatment was reported during the duration of the trial. CONCLUSIONS: High-frequency electrotherapy may have a positive effect on symptoms and signs of dry eye. This emerging technology may become part of the arsenal of therapeutic modalities for this condition.

Factors affecting long-term changes of meibomian gland in MGD patients.

PURPOSE: To explore the long-term course of patients with meibomian gland dysfunction (MGD), and to analyse potential factors affecting the recovery of meibomian gland (MG) dropout. METHODS: Seventy-nine MGD patients (79 eyes) aged 36.03±15.78 years old who underwent more than one year of follow-up were enrolled in this retrospective study. Corneal fluorescein staining (CFS), tear meniscus height (TMH), noninvasive breakup time (NIBUT), and noncontact meibography at baseline and last visit were collected and analysed. Then an automatic MG analyzer was used to measure the morphological and functional parameters of MGs, including their area ratio (AR), tortuosity index (TI), and signal index (SI). The patients whose AR increased by more than 5% were defined as MG improvement, and AR decreased by more than 5% was MG worsening. RESULTS: A total of 79 patients (79 eyes) were assessed with at least 1-year of follow-up. More than 1/3 of MGD patients (27 eyes, 34.2%) underwent MG improvement, and 30.4% of MGs became worsened. Age (P=0.002), gender (P<0.001), IPL treatment (P=0.013), the change of CFS (P=0.0015), and the recovery of SI (P=0.035) showed significant differences among different recovery groups. Age(P<0.001), female sex (P=0.003), ΔCFS (P<0.001), AR at baseline (P<0.001) were negative correlation with AR recovery, and the change of SI (P=0.003) and IPL treatment (P=0.003) had a positive correlation with it. Among them, age (P=0.038), the change of CFS (P=0.004), and AR at baseline (P=0.007) were confirmed as negatively correlated factors predicting the long-term change of the MG. CONCLUSION: Although the MGD treatment has continued for more than 1 year, only 34.2% of MGD patients were observed to undergo MG improvement. Younger patients and patients with better CFS recovery seem to have more opportunities to improve their MGs.

Evaluation of the Impact of Meibomian Gland Dysfunction Using a Novel Patient-Reported Outcome Instrument.

Purpose: This study was intended to characterize the impact of meibomian gland dysfunction (MGD) on patients' quality of life. Methods: In this prospective, multicenter, noninterventional clinical study (NCT01979887), eligible individuals (age ≥40 years; absence of uncontrolled ocular/systemic disease) were categorized, based on composite grading of ocular symptoms, Schirmer score, and meibum quality, into (1) non-MGD, (2) mild/moderate MGD, or (3) severe MGD cohorts. The MGD Impact Questionnaire (MGD IQ), a 10-item patient-reported outcome measure, was self-administered at clinic visit on day 1, and readministered on day 22 to assess intervisit agreement regarding MGD IQ responses. Results: In total, 75 subjects were assigned to the study cohorts (25 per cohort). Across cohorts, MGD IQ item scores rose incrementally with increasing MGD severity. The severe MGD cohort experienced greater difficulty with reading and performance of leisure activities, greater time on eye care, and greater bother with eye care and eye appearance than the mild/moderate MGD cohort (all P < 0.05). Compared with the non-MGD cohort, the mild/moderate MGD cohort had greater difficulty working on computer, whereas the severe MGD cohort had greater difficulty reading, driving, and performing leisure activities, more frequent difficulty with outdoor activities, more time on eye care, and greater bother with eye care (all P < 0.05). Intervisit agreement between MGD IQ responses was fair to moderate (weighted kappa statistic 0.33‒0.58). Conclusions: Vision-related activities are negatively impacted by increasing severity of MGD. The MGD IQ instrument can help characterize disease severity and amplify the patient's voice in patient-centric clinical research. ClinicalTrials.gov NCT01979887.

Efficacy of meibomian gland expression combined with Home-Based therapy in the management of dry eye Disease: A systematic review and Meta-Analysis.

PURPOSE: To compare the effectiveness of meibomian gland expression (MGX) combined with home-based therapy versus home-based therapy alone for the treatment of dry eye disease (DED) caused by meibomian gland dysfunction (MGD). METHODS: A systematic review of randomized controlled studies (RCTs), reporting the effects of MGX combined with home-based therapy in 2 databases, PubMed and Web of Science, was performed according to the PRISMA statement. The search period was until August 20, 2023. According to the heterogeneity, a random or fixed effects model was performed in the meta-analysis. The standardized mean difference (SMD) was calculated to analyze dry eye symptoms (DES) score, tear film break-up time (TBUT), total corneal fluorescein staining (tCFS) and meibomian glands expressibility (MGE). All analyses were performed by RevMan Web, version 5.7. The Cochrane risk of bias tool was used to analyze the quality of the studies selected. RESULTS: Two RCTs with a total of 99 patients were included. The studies reported that MGX combined with home-based therapy improves DES score, TBUT, tCFS and MGE compared to the home-based therapy. However, the meta-analysis indicated that MGX combined with home-based therapy only seems to be beneficial in reducing DES score (SMD -0.49; 95 % CI: -0.89 to -0.08; P = 0.02; I2 = 0 %). In addition, although TBUT, tCFS and MGE reported a slight trend in favor of MGX combined with home-based therapy, it was non-significant. CONCLUSIONS: While MGX combined with home-based therapy seem to show some evidence of alleviating dry eye symptoms, there is insufficient evidence to conclude the effects of this treatment definitively particularly in improving dry eye signs caused by MGD, such as TBUT, tCFS and MGE. Therefore, further RCTs are needed to elucidate these results.

[Acaricidal therapy in chronic demodex blepharitis and meibomian gland dysfunctions]. / Akaritsidnoe lechebnoe vozdeistvie pri khronicheskom demodekoznom blefarite i disfunktsii meibomievykh zhelez.

PURPOSE: The study comparatively evaluates the effectiveness of various approaches to acaricidal treatment in patients with chronic demodex blepharitis and meibomian gland dysfunctions. MATERIAL AND METHODS: The study included 40 patients with chronic blepharitis (CB) of demodicosis etiology in conditions of meibomian gland dysfunction (MGD) and dry eye (DE). The 1st group of patients (20 people) received acaricidal treatment as part of therapeutic eyelid hygiene (TEH; 2 times a day) involving the use of «Blefarogel ochishchenie¼, «Blefarolosion¼, «Blefarogel forte¼ (contains sulfur and metronidazole). Acaricidal treatment in the patients of the 2nd group involved applications of a product containing metronidazole (2 times a day) without TEH. Control points: 1) at inclusion in the study; 2) after a course of therapy (45 days). Evaluation included: patient acarograms, symptoms and signs of CB (points); OSDI; tear film break-up time (TBUT, sec), severity of meibomian gland dysfunction (S-MGD, points). Statistical analysis: calculation of M±SD, Mann-Whitney, and Wilcoxon tests. RESULTS: Acaricidal treatment was effective in both groups (reduction in demodex population, which was more pronounced in the 1st group). Symptoms and signs of CB were significantly less pronounced in the patients of the 1st group after therapy. The patients of the 1st group showed a significant decrease in S-MGD, OSDI and an increase in TBUT, the 2nd group - a significant decrease in OSDI and an increase in TBUT at the second control point. The positive OSDI and TBUT trends were significantly more pronounced in the 1st group. CONCLUSION: Acaricidal treatment as part of TEH showed a significantly more pronounced reduction in demodex population, relief of CB symptoms and sign, OSDI decrease and TBUT increase, compared to the 2nd group. Apparently, this was associated with combined acaricidal effect and significant S-MGD decrease in the patients of the 1st group.