Quantitative Assessment of Lid Margin Vascularity Using Swept-Source Optical Coherence Tomography Angiography.

Purpose: To evaluate the ability of swept-source optical coherence tomography angiography (SS-OCTA) to assess lid margin vascularity. Methods: This prospective, cross-sectional trial enrolled 125 participants, including 15 control subjects and 110 meibomian gland dysfunction (MGD) patients. Lid margin blood flow density (LMBFD) was obtained using SS-OCTA. LMBFD was assessed for repeatability in 54 of 125 participants and for reproducibility in 23 of 125 participants. The efficacy of LMBFD was validated in the 125 participants, who were divided into mild (n = 46), moderate (n = 42), and severe groups (n = 37) according to the lid margin vascularity severity shown in the slit-lamp photographs. Correlations between LMBFD and MG-related parameters, such as ocular surface disease index (OSDI), fluorescein tear break-up time (FTBUT), cornea fluorescein staining (CFS), lid margin score (LMS), and meibomian gland expressibility (ME), were analyzed in all 125 participants. Results: Repeatability and reproducibility coefficients were satisfactorily high in the scan mode with a scan area of 6 mm × 6 mm (intraclass correlation coefficient [ICC] repeatability = 0.905; ICC reproducibility = 0.986) and a scan area of 9 mm × 9 mm (ICC repeatability = 0.888; ICC reproducibility = 0.988). The LMBFD gradually increased in the mild, moderate, and severe groups (P < 0.001). LMBFD was significant correlated with OSDI (r = 0.290, P = 0.001), FTBUT (r = -0.195, P = 0.030), CFS (r = 0.352, P < 0.001), ME (r = 0.191, P = 0.033), and LMS (r = 0.370, P < 0.001). Conclusions: LMBFD may be a noninvasive, repeatable, reproducible, and efficient index for the quantitative evaluation of eyelid margin vascularity in the future. Translational Relevance: We demonstrated that SS-OCTA has the potential to evaluate the eyelid margin vascularity in MGD patients and guide future treatment strategies in clinics.

Lid Margin Microbiome in Stevens-Johnson Syndrome Patients With Lid Margin Keratinization and Severe Dry Eye Disease.

Purpose: The current study evaluated the lid margin microbiome of keratinized lid margins of patients with chronic Stevens-Johnson syndrome (SJS) and compared it with healthy controls and historically reported lid margin microbiome of patients with meibomian gland dysfunction (MGD). Methods: Eyelid margin swabs of 20 asymptomatic adults (mean age = 29 ± 12 years) and 10 patients with chronic SJS (mean age = 31.2 ± 14 years) with lid margin keratinization were sequenced using next generation of 16S rDNA V3 to V4 variable region. Within SJS, the keratinized lid margin microbiome was compared with adjacent eyelid skin. Results: All patients had obstructive MGD, and mean Schirmer I value was 2.8 ± 1.9 mm. The phyla were similar in two groups, whereas at the genera level, an increase in the relative abundance of Corynebacterium, Haemophilus, Azotobacter, and Afipia and a decrease of Acinetobacter was noted in SJS compared to healthy lid margins. SJS-associated microbiota displayed lesser diversity and more heterogeneity than healthy controls. The Principal Components Analysis (PCA) plot revealed wide separation in the SJS and the control groups. Correlational network analysis revealed Corynebacterium and Sphingomonas forming a major hub of negative interactions with other bacterial genera in the SJS group. Significant differences exist in the prevalent genera between keratinized lid margins and historically reported meibum microbiome of patients with MGD. In addition, the eyelid skin of patients with SJS had predominant Staphylococcus, whereas Corynebacterium and Pseudomonas were more in the keratinized lid margins compared to the eyelid skin microbiome. Conclusions: Lid margin microbiome is significantly altered in the keratinized lid margins of patients with SJS compared to the eyelid skin of patients with SJS, normal lid margins, and patients with MGD.

Temporal variations in meibomian gland structure-A pilot study.

PURPOSE: To investigate whether there is a measurable change in meibomian gland morphological characteristics over the course of a day (12 h) and over a month. METHODS: The study enrolled 15 participants who attended a total of 11 study visits spanning a 5-week period. To assess diurnal changes in meibomian glands, seven visits were conducted on a single day, each 2 h apart. For monthly assessment, participants attended an additional visit at the same time of the day every week for three consecutive weeks. Meibography using the LipiView® II system was performed at each visit, and meibomian gland morphological parameters were calculated using custom semi-automated software. Specifically, six central glands were analysed for gland length ratio, gland width, gland area, gland intensity and gland tortuosity. RESULTS: The average meibomian gland morphological metrics did not exhibit significant changes during the course of a day or over a month. Nonetheless, certain individual gland metrics demonstrated notable variation over time, both diurnally and monthly. Specifically, meibomian gland length ratio, area, width and tortuosity exhibited significant changes both diurnally and monthly when assessed on a gland-by-gland basis. CONCLUSIONS: Meibomian glands demonstrated measurable structural change over short periods of time (hours and days). These results have implications for innovation in gland imaging and for developing precision monitoring of gland structure to assess meibomian gland health more accurately.

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.

Analysis of Factors Associated with Anterior Location of Marx's Line.

PURPOSE: The study aimed to investigate the factors associated with anterior location of Marx's line in ocular surface and living habits, especially in tear film. MATERIALS AND METHODS: This cross-sectional study enlisted 483 participants with meibomian gland dysfunction, who were divided into two groups: 160 participants with mild anterior location of Marx's line and 323 participants with moderate-to-severe anterior location. Participants completed a survey of demographic characteristics (sex, age, length of visual terminal use, sleep duration, skin property), and the Ocular Surface Disease Index and Standard Patient Evaluation of Eye Dryness questionnaires. They also underwent slit-lamp examinations of the lids, and measurements of non-invasive tear break up time, tear meniscus height, fluorescein tear break up time, lipid layer thickness, partial blink rate, lid wiper epitheliopathy, and meibomian gland dropout. RESULTS: The tear meniscus height (mild:0.21(0.18-0.25), moderate-to-severe:0.19(0.16-0.23), p = 0.004), fluorescein tear break up time(mild:3(2-4),moderate to severe:2(1-3), p = 0.000), max LLT(mild:87(62-100), moderate-to-severe:99(69-100), p = 0.04), average LLT(mild:64.5(47.5-96.75), moderate-to-severe:74(53-100), p = 0.012), min LLT(mild:52(38-75), moderate-to-severe:59(41-85), p = 0.029) differed significantly between mild and moderate-to-severe anterior location of Marx's line, and associated to the anterior location of Marx's line(r=-0.134, p = 0.03; r=-0.194, p = 0.000; r = 0.093, p = 0.041; r = 0.119, p = 0.009; r = 0.105, p = 0.022) However, no statistical significance was observed in the OSDI, SPEED, partial blink rate, non-invasive tear breakup time, lipid layer thickness, meibomian gland dropout and lid wiper epitheliopathy(p > 0.05). Meanwhile, in the demographic characteristics, statistically significant correlations were associated with skin property(r = 0.154, p = 0.001) and sleep duration(r=-0.124, p = 0.006), but not with age, sex, and the length of visual terminal use (p > 0.05). CONCLUSIONS: Lower TMH and shorter TBUT positively correlated with anterior location of the Marx's line, and were risk factors. Meanwhile, participants with oily skin and shorter sleep duration were more likely to exhibit anterior location of Marx's line.

Ocular complications in adults with psoriasis: a cross-sectional study in a referral center in Brazil.

PURPOSE: There is limited literature on the ocular manifestations in patients with psoriasis. Therefore, this study aimed to identify the prevalence of and factors associated with ocular manifestations in adults with psoriasis. METHODS: This cross-sectional study included Brazilian adults with psoriasis. The dermatological evaluation included diagnosis, clinical form, Psoriasis Area and Severity Index (PASI) measurement, and location of the lesions. Patients underwent a full ophthalmological examination, including the Schirmer I test, Rose Bengala staining, and tear breakup time tests. The results were analyzed using chi-square and Pearson's linear correlation tests. RESULTS: Of the 130 patients assessed, 118 (90.8%) exhibited ocular abnormalities, with meibomian gland dysfunction (MGD) being the most prevalent (59.2%), followed by dry eye disease (DED) (56.2%). A significant correlation was observed between MGD and PASI (p = 0.05), and between MGD and certain treatment modalities. DED was significantly associated with PASI (p < 0.05). Concurrent use of acitretin was identified as an independent predictor of MGD (odds ratio [OR] = 3.5, p < 0.05), whereas PASI was a protective factor against DED (OR = 0.39, p < 0.01). CONCLUSION: Given the high prevalence of eye disease among individuals with psoriasis, routine ophthalmological assessments are recommended to prevent possible ocular complications.

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.

Meibum Lipidomic Analysis in Evaporative Dry Eye Subjects.

Meibomian Glands (MG) are sebaceous glands responsible for the production of meibum, the main component of the Tear Film Lipid Layer (TFLL). The TFLL facilitates the spread of the tear film over the ocular surface, provides stability and reduces tear evaporation. Alterations in meibum composition lead to different ocular alterations like Meibomian Gland Dysfunction (MGD) and subsequent Evaporative Dry Eye (EDE). The aim of the present study was to investigate the composition and abundance of meibum lipids and their relationship with eyelid margin abnormalities, lipid layer patterns and MG status. The study utilizes a lipidomic approach to identify and quantify lipids in meibum samples using an Elute UHPLC system. This system considered all four dimensions (mass/charge, retention time, ion mobility and intensity) to provide the accurate identification of lipid species. Samples were categorized as healthy or low/no signs of alteration (group 1) or severe signs of alteration or EDE/MGD (group 2). The current investigation found differences in Variable Importance in Projection lipid abundance between both groups for the MGD signs studied. Changes in meibum composition occur and are related to higher scores in eyelid margin hyperaemia, eyelid margin irregularity, MG orifice plugging, MG loss and lipid layer pattern.

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.

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.

Red filter meibography by smartphones in patients with meibomian gland dysfunction: a validity and reliability study.

OBJECTIVE: The objective of this study is to determine the validity and reliability of the red filter meibography by smartphone compared with infrared in assessing meibomian gland drop-out. METHODS AND ANALYSIS: An analytical cross-sectional study was done with a total of 35 subjects (68 eyes) with suspected MGD based on symptoms and lid morphological abnormalities. Meibomian glands were photographed using two smartphones (Samsung S9 and iPhone XR) on a slit-lamp with added red filter. Images were assessed subjectively using meiboscore by the two raters and drop-out percentages were assessed by ImageJ. RESULTS: There was no agreement in meiboscore and a minimal level of agreement in drop-out percentages between red filter meibography and infrared. Inter-rater reliability showed no agreement between two raters. Intra-rater reliability demonstrated weak agreement in rater 1 and no agreement in rater 2. CONCLUSION: Validity of the red filter meibography technique by smartphones is not yet satisfactory in evaluating drop-out. Further improvement on qualities of images must be done and research on subjective assessment was deemed necessary due to poor results of intrarater and inter-rater reliability.

Thermosensitive TRP Channels Are Functionally Expressed and Influence the Lipogenesis in Human Meibomian Gland Cells.

While the involvement of thermosensitive transient receptor potential channels (TRPs) in dry eye disease (DED) has been known for years, their expression in the meibomian gland (MG) has never been investigated. This study aims to show their expression and involvement in the lipogenesis of the MG, providing a possible new drug target in the treatment of DED. Our RT-PCR, Western blot and immunofluorescence analysis showed the expression of TRPV1, TRPV3, TRPV4 and TRPM8 in the MG at the gene and the protein level. RT-PCR also showed gene expression of TRPV2 but not TRPA1. Calcium imaging and planar patch-clamping performed on an immortalized human meibomian gland epithelial cell line (hMGECs) demonstrated increasing whole-cell currents after the application of capsaicin (TRPV1) or icilin (TRPM8). Decreasing whole-cell currents could be registered after the application of AMG9810 (TRPV1) or AMTB (TRPM8). Oil red O staining on hMGECs showed an increase in lipid expression after TRPV1 activation and a decrease after TRPM8 activation. We conclude that thermo-TRPs are expressed at the gene and the protein level in MGs. Moreover, TRPV1 and TRPM8's functional expression and their contribution to their lipid expression could be demonstrated. Therefore, TRPs are potential drug targets and their clinical relevance in the therapy of meibomian gland dysfunction requires further investigation.

Cellular senescence promotes meibomian gland dysfunction in a chronic graft-versus-host disease mouse model.

PURPOSE: Aging is a well-established risk factor for meibomian gland dysfunction (MGD). We previously reported an accelerated cellular senescence phenomenon in the lacrimal glands of a murine model of chronic graft-versus-host disease (cGVHD). Herein, we aimed to elucidate the relationship between cellular senescence and MGD in cGVHD mice, utilizing the senolytic agent ABT-263. METHODS: A cGVHD mouse model was established through allogeneic bone marrow transplantation (BMT) from B10.D2 to BALB/c mice. Subsequently, cGVHD mice were treated with either ABT-263 or vehicle. The eyelids of recipients were analyzed at 4-week intervals post-BMT in both groups. RESULTS: Meibomian gland (MG) area was significantly smaller in cGVHD mice than in syngeneic control mice. ABT-263-treated mice retained a significantly larger MG area than their vehicle-treated counterparts. Pathological and immunohistochemical examinations revealed significant reductions in eyelid tissue inflammation and pathological fibrosis in the ABT-263 group compared to that in the vehicle-treated group. Additionally, expression of DNA damage markers, senescent cell markers, and senescence-associated secretory phenotype (SASP) factors was elevated in the eyelids of cGVHD mice compared with that in syngeneic mice. The expression of these cellular senescence-associated molecules was considerably suppressed in ABT-263-treated eyelids compared to that in vehicle-treated ones. CONCLUSIONS: Cellular senescence, along with expression of SASP factors, exhibited increased activity in the eyelids, particularly in the MGs of cGVHD mice. ABT-263 mitigated the severity of MGD. These findings highlight the potential of targeting cellular senescence as an effective approach for MGD treatment in cGVHD.

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.

Evaluation of Meibomian gland dysfunction using meibography in patients with xeroderma pigmentosum.

PURPOSE: To assess Meibomian gland dysfunction using meibography in patients with xeroderma pigmentosum and correlate with ocular surface changes. METHODS: This cross-sectional study evaluated patients with xeroderma pigmentosum. All patients underwent a comprehensive and standardized interview. The best-corrected visual acuity of each eye was determined. Detailed ophthalmic examination was conducted, including biomicroscopy examination of the ocular surface, Schirmer test type I, and meibography, and fundus examination was also performed when possible. Meibomian gland dysfunction was assessed by non-contact meibography using Oculus Keratograph® 5M (OCULUS Inc., Arlington, WA, USA). Saliva samples were collected using the Oragene DNA Self-collection kit (DNA Genotek Inc., Ottawa, Canada), and DNA was extracted as recommended by the manufacturer. Factors associated with abnormal meiboscores were assessed using generalized estimating equation models. RESULTS: A total of 42 participants were enrolled, and 27 patients underwent meibography. The meiboscore was abnormal in the upper eyelid in 8 (29.6%) patients and in the lower eyelid in 17 (62.9%). The likelihood of having abnormal meiboscores in the lower eyelid was 16.3 times greater than that in the upper eyelid. In the final multivariate model, age (p=0.001), mutation profile (p=0.006), and presence of ocular surface malignant tumor (OSMT) (p=0.014) remained significant for abnormal meiboscores. For a 1-year increase in age, the likelihood of abnormal meiboscores increased by 12%. Eyes with OSMT were 58.8 times more likely to have abnormal meiboscores than eyes without ocular surface malignant tumor. CONCLUSION: In the final model, age, xeroderma pigmentosum profile, previous cancer, and clinical alterations on the eyelid correlated with a meiboscore of ≥2. Meibomian gland dysfunction was common in patients with xeroderma pigmentosum, mainly in the lower eyelid. The severity of Meibomian gland dysfunction increases with age and is associated with severe eyelid changes.

Is there a relationship between the severity of disease in major depressive disorder patients and dry eye disease?

PURPOSE: To investigate dry eye disease (DED) in newly diagnosed patients with depressive disorder (MDD). METHOD: This observational study included 48 MDD patients in Group 1 and 20 healthy controls in Group 2. Psychiatric and ophthalmic examinations, Beck Depression Inventory (BDI), Ocular Surface Disease Index (OSDI), Schirmer's test, tear breakup time (TBUT), Meibomian gland dysfunction (MGD), and ocular staining were conducted. The results were statistically compared. RESULTS: The participants, comprising 32 men and 36 women, had a mean age of 31.08 ± 11.7 years (18-64 years). Group 1 had a mean BDI score of 30.87 ± 8.56, while Group 2 had a score of 1.3 ± 1.3 (p < 0.001). In Group 1, 28 patients were diagnosed with DED, whereas in Group 2, six subjects were diagnosed with DED. The mean Schirmer's results in Group 1 and Group 2 were (mm/5 min) 10.87 ± 2.44 and 12.70 ± 2.3, respectively, and were significantly lower in Group 1 (p < 0.001). The mean OSDI scores in Group 1 (34.95 ± 15.8) were significantly higher compared to Group 2 (3.2 ± 3.1) (p < 0.001). There was no significant difference in mean TBUT between Group 1 (9.41 ± 2.6 s) and Group 2 (9.8 ± 0.61 s) (p > 0.05). Significant correlations were found between BDI scores and Schirmer's results as well as OSDI scores (p < 0.05, p = 0.02, respectively). No statistically significant correlations were found between BDI scores and TBUT or MGD (p > 0.05). CONCLUSION: DED was found to be more prevalent in the MDD group. The severity of MDD and DED, as indicated by BDI, OSDI, and Schirmer's results, was found to be correlated. It was observed that patients with higher depression scores had more severe dry eye. As a result, we recommend performing ophthalmic examinations in newly diagnosed MDD patients.

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.

New advances in medical management of dry eye: optimizing treatment strategies for enhanced relief.

PURPOSE: Dry eye disease (DED) is a prevalent ocular surface disease that is conventionally characterized by tear film hyperosmolarity and instability. This review presents a summarized classification of DED, followed by a comprehensive discussion of the most recent topical and systemic medications and clinical recommendations for selecting the most appropriate option for each patient. METHODS: An extensive literature search was conducted on electronic databases, such as PubMed, Scopus, and Web of Science, using keywords including "dry eye syndrome," "ocular surface disease," "medical management," "artificial tears," "topical immunomodulators," and "meibomian gland dysfunction." RESULTS: The underlying reasons for DED can range from insufficient aqueous tear production to increased tear evaporation. Recent literature has provided a more in-depth understanding of the pathophysiology of DED by examining the tear film's lipid, aqueous, and mucin layers. However, despite these advancements, medical management of patients with symptomatic DED has not fully reflected this modernized knowledge of its pathophysiology. CONCLUSION: To develop a rationalized strategy for treating DED, it is crucial to have updated knowledge of therapeutic options, their mechanisms of actions, and indications based on the DED type and underlying causes.

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.