Examining treatment strategies for xanthelasma palpebrarum: a comprehensive literature review of contemporary modalities.

Xanthelasma palpebrarum (XP) is the predominant form of cutaneous xanthoma, as it accounts for greater than 95% of cases. It is characterized by the presence of foam cell clusters containing a large amount of low-density lipoprotein (LDL), which are located in the connective tissue of skin, tendons, and fascia. XP lesions commonly present as distinctive yellow-orange macules, papules, or nodules, and are primarily on the upper eyelids as well as the inner canthus. Women are affected twice as often as men, with lesions typically emerging between the ages of 35 and 55. The pathophysiology of XP involves abnormal lipid metabolism and is often associated with hyperlipidemic states like Type II and IV hyperlipidemia, hypothyroidism, weight gain, and fatty diet. Despite the availability of various treatment methods, current XP management lacks standardization, particularly due to limited comparative research. To address this gap, we conducted an extensive literature review of 45 studies published between 2012 to 2023, which provides an updated overview of current XP treatment modalities. This comprehensive analysis will inform researchers and clinicians on the evolving landscape of XP management.

A Magnetic Actuator Device for Fully Automated Blinking in Total Bidirectional Eyelid Paralysis: First Proof of Concept in a Human Participant.

Purpose: Currently, no solution exists to restore natural eyelid kinematics for patients with complete eyelid paralysis due to loss of function of both the levator palpebrae superioris and orbicularis oculi. These rare cases are prone to complications of chronic exposure keratopathy which may lead to corneal blindness. We hypothesized that magnetic force could be used to fully automate eyelid movement in these cases through the use of eyelid-attached magnets and a spectacle-mounted magnet driven by a programmable motor (motorized magnetic levator prosthesis [MMLP]). Methods: To test this hypothesis and establish proof of concept, we performed a finite element analysis (FEA) for a prototype MMLP to check the eyelid-opening force generated by the device and verified the results with experimental measurements in a volunteer with total bidirectional eyelid paralysis. The subject was then fitted with a prototype to check the performance of the device and its success. Results: With MMLP, eye opening was restored to near normal, and blinking was fully automated in close synchrony with the motor-driven polarity reversal, with full closure on the blink. The device was well tolerated, and the participant was pleased with the comfort and performance. Conclusions: FEA simulation results conformed to the experimentally observed trend, further supporting the proof of concept and design parameters. This is the first viable approach in human patients with proof of concept for complete reanimation of a bidirectionally paretic eyelid. Further study is warranted to refine the prototype and determine the feasibility and safety of prolonged use. Translational Relevance: This is first proof of concept for our device for total bidirectional eyelid paralysis.

Assessing the proficiency of artificial intelligence programs in the diagnosis and treatment of cornea, conjunctiva, and eyelid diseases and exploring the advantages of each other benefits.

PURPOSE: It was aimed to determine the knowledge level of ChatGPT, Bing, and Bard artificial intelligence programs related to corneal, conjunctival, and eyelid diseases and treatment modalities, to examine their reliability and superiority to each other. METHODS: Forty-one questions related to corneal, conjunctival, and eyelid diseases and treatment modalities were asked to the ChatGPT, Bing, and Bard chatbots. The answers to the questions were compared with the answer keys and grouped as correct or incorrect. Accuracy rates were compared. RESULTS: ChatGPT gave the correct answer to 51.2 % of the questions asked, Bing gave the correct answer to 53.7 %, and Bard gave the correct answer to 68.3 %. There was no significant difference in the rate of correct or incorrect answers to the questions asked for the 3 artificial intelligence chatbots (p = 0.208, Pearson's chi-square test). CONCLUSION: Although information about the cornea, conjunctiva, and eyelid diseases and treatment modalities can be accessed quickly and accurately using up-to-date artificial intelligence programs, the answers may not always be accurate and up-to-date. Care should be taken when evaluating this information.

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.

[Chinese expert consensus on meibomian gland dysfunction: diagnosis and management (2023)].

Meibomian gland dysfunction (MGD) is a common ocular surface disease. In recent years, the meibomian gland-related examination and treatment technologies have evolved rapidly. In order to further optimize the diagnostic process of MGD in China and improve the treatment efficiency of MGD, the Chinese Branch of the Asian Dry Eye Society has organized relevant experts to discuss the clinical characteristics of MGD in China and the progress of research at home and abroad. Based on the expert consensus formed in 2017, the updated consensus opinions have been developed for clinical physicians to refer to in the diagnosis and management of MGD.

[Chinese expert consensus on meibomian gland dysfunction: definition and classification (2023)].

Meibomian gland dysfunction (MGD) is a common clinical ocular surface disease. In recent years, great progress has been made in basic and clinical research on MGD, and new diagnostic and therapeutic methods have been continuously applied to clinical practice. To improve the understanding of MGD among Chinese ophthalmologists and standardize the diagnosis and treatment of MGD, the Chinese Branch of the Asia Dry Eye Society and relevant academic groups organized experts to discuss the definition and classification of MGD based on recent research progress and clinical experience at home and abroad, forming consensus opinions for the reference of clinicians.

A Review of Applications and Intracellular Mechanisms of Intense Pulsed Light in Eyelid Inflammatory Diseases.

Objective: To evaluate relevant clinical outcomes and conclude possible mechanisms of intense pulsed light (IPL) in eyelid inflammation. Background: IPL devices were primarily applied in cutaneous vascular malformations and have been used in ocular diseases for about 20 years, mostly including meibomian gland dysfunction (MGD), blepharitis, and ocular rosacea. Recent findings: Seventy-two original clinical researches were included, 57 for MGD, 4 for blepharitis or blepharitis-related keratoconjunctivitis, and 11 for rosacea. Dry eye symptoms, (tear) break-up time (BUT), and meibomian structure and/or functions were improved in most patients, but production of reactive oxygen species is an important link in the photobiomodulation mediated by IPL, which can influence numerous signal pathways to achieve anti-inflammatory, anti-infective, and prodifferentiation effects. Conclusions: The evidence suggests that IPL is an effective therapeutic tool for most patients with MGD, but more clinical evidence is needed for other indications.

Efficacy of vector thermal pulsation treatment in reducing postcataract surgery dry eye disease in patients affected by meibomian gland dysfunction.

PURPOSE: To evaluate the effect of a single LipiFlow vector thermal pulsation treatment performed before cataract surgery in reducing signs and symptoms of postoperative dry eye disease (DED) in patients with mild-moderate meibomian gland dysfunction (MGD). SETTING: Eye Clinic, Careggi Hospital, University of Florence, Florence, Italy. DESIGN: Prospective unmasked randomized controlled clinical trial. METHODS: This study included patients affected by age-related cataract and mild-moderate MGD, who were randomized into 2 groups: (1) a single LipiFlow treatment performed at 5 preoperative weeks and (2) warm compresses and eyelid massages twice a day for 1 preoperative month (control group). Noninvasive break-up time (NI-BUT), Schirmer test, Standard Patient Evaluation of Eye Dryness (SPEED) questionnaire, and MG functionality parameters were evaluated at visit 0 (5 preoperative weeks), visit 1 (1 preoperative week), and visit 2 (1 postoperative month). Confocal microscopy of the MG of lower eyelids was performed at visit 0 and visit 2. RESULTS: A total of 46 patients (46 eyes) were enrolled. In the LipiFlow group (n = 23), NI-BUT, SPEED questionnaire, and MG functionality parameters significantly improved at visit 1 ( P < .05) and visit 2 ( P < .05) compared with baseline and remained stable postoperatively. In the control group (n = 23), they did not significantly improve after treatment, while worsened postoperatively. Moreover, the changes in all parameters from baseline were significantly different between the 2 groups. Confocal microscopy imaging highlighted lower postoperative MG alterations in the LipiFlow group. CONCLUSIONS: A single preoperative LipiFlow treatment was effective in preventing postcataract surgery DED in patients with mild-moderate MGD. Postoperatively, treated patients displayed a better ocular surface status compared with warm compresses.

Hot towels: The bedrock of Meibomian gland dysfunction treatment - A review.

BACKGROUND: Meibomian gland dysfunction (MGD) reduces quality-of-life and hinders work productivity of millions of patients, with high direct and indirect societal costs. Thickened meibum obstructs the glands and disrupts ocular surface health. Heating the eyelids to soften and express meibum from the glands can be beneficial. The most accessible method for eyelid warming uses heated, wet towels. However, the efficacy of this treatment is reliant on the methodology, and evidence-based best-practice recommendations are needed. PURPOSE: To evaluate the literature on hot towels in MGD treatment and recommend a best-practice protocol for future research and patient treatment. METHODS: Studies were identified through PubMed on the May 28, 2021, with the search terms: (warm* OR heat* OR thermal* OR towel OR wet towel) AND (meibomian OR MGD OR eyelid OR "dry eye" OR DED). All relevant original articles with English full-text were included. RESULTS: The search yielded 903 results, of which 22 met the inclusion criteria. Across studies, hot towels were found to be effective at reducing ocular symptoms. However, without reheating, the temperature quickly fell below the therapeutic range, which was deemed to be between 40 °C and 47 °C. Towels heated to around 45 °C and reheated every-two minutes were most effective at increasing eyelid temperature, comparable or better than several commercially available eyelid warming devices. No adverse effects were reported in the studies. CONCLUSION: Hot towel treatment effectively warms the eyelids and reduces ocular symptoms, but must be standardized, and towels reheated to achieve maximum benefit. Future research should assess patient satisfaction with different hot towel treatment methods that reheat or replace the towel at least every-two minutes, to establish which methods yield the greatest compliance. Guidelines or clinical recommendations that do not mention the need for regular reheating during hot towel compress treatment should be updated to include this.

Floppy eyelid syndrome and obstructive sleep apnea: a unique phenotype?

INTRODUCTION: Floppy eyelid syndrome (FES) is an underdiagnosed condition stereotypically found in obese, middle-aged men, characterized by a lax eyelid tarsus which readily everts without excess mechanical manipulation. Obstructive sleep apnoea (OSA) is the most frequently reported comorbidity in patients suffering from FES. The aim of this study was to determine whether or not individuals with FES present with distinct anthropometric characteristics in comparison to patients without FES suspected of having OSA. METHODS: A retrospective case-control study in which FES patients and controls all referred for investigation of suspected OSA, matched for sex, ethnicity, residential location, age (± 2 years), date of sleep study (± 1 month), and type of sleep study were compared for anthropometric, comorbidity, and sleep data differences. RESULTS: OSA prevalence and severity, assessed by apnoea-hypopnea index (AHI), revealed no significant differences between patients with FES (n = 39) and those without (n = 75), (85% vs 88%, p = 0.91 and 31.9 ± 28.7 vs 28.5 ± 16.6, p = 0.81 respectively), despite patients with FES being more obese (p = 0.02). Patients with FES had significantly lower Epworth sleepiness scale (ESS) scores after treatment with CPAP (5.3 ± 4.1 vs 9.4 ± 5.0, p = 0.028). Patients with FES exhibited increased prevalence of hernias (15% vs 4%, p = 0.032), dermatological (41% vs 17%, p = 0.006) and rheumatological (15% vs 3%, p = 0.012) comorbidities. CONCLUSION: FES patients appear to exhibit a distinct phenotype with increased prevalence of comorbidities related to matrix metalloproteinase dysfunction and significant improvement of daytime hypersomnolence with continuous positive airway pressure (CPAP) treatment.

Efficacy and Safety evaluation of a single thermal pulsation system treatment (Lipiflow®) on meibomian gland dysfunction: a randomized controlled clinical trial.

PURPOSE: Evaluate the efficacy and safety of LipiFlow® thermal pulsation treatment system compared with lid massage combined warm compress in Chinese patients with meibomian gland dysfunction (MGD). METHODS: Patients (n = 100 eyes, 50 subjects) diagnosed with MGD were recruited for this prospective, randomized, 3-month clinical trial. In Lipiflow group, patients (n = 50 eyes) received a single LipiFlow® thermal pulsation system treatment. In warm compress group, patients (n = 50 eyes) underwent warm compress daily for two weeks after an initial manual lid massage. Patients' symptoms were evaluated using Standard Patient Evaluation for Eye Dryness (SPEED) questionnaire. Safety parameters included best-corrected visual acuity (BCVA), intraocular pressure (IOP) and objective parameters including meibomian glands yielding lipid secretion (MGYLS) number, meibomian glands secretion (MGS) score, lipid layer thickness (LLT), tear-film breakup time (TBUT), corneal fluorescein staining (CFS) were measured and presented from baseline and to 3 months post-treatment. RESULTS: Baseline parameters in both groups were comparable (p > 0.05). SPEED score and TBUT improved in two groups from baseline to 3 months. MGYLS number, MGS score, LLT improved in LipiFlow group and these improvements were maintained with no significant regression at 3 months. CFS showed significant improvement in warm compress group at 1 month compared with LipiFlow group. Moreover, the correlation analysis indicated LLT was positively correlated with TBUT, MGS score, and MGYLS number. CONCLUSION: A single 12-min LipiFlow treatment is an effective therapy for MGD patients and can achieve improvements in symptoms alleviation and meibomian gland lipid secretion function lasting for at least 3 months.

Effect of a single vectored thermal pulsation treatment of Meibomian gland dysfunction patients under controlled environmental conditions.

To assess the prophylactic effect of LipiFlow treatment in Meibomian gland dysfunction (MGD) patients exposed to an adverse environmental humidity. MGD patients were exposed to normal (23 °C; 50% relative humidity; 30 min) and adverse (23 °C; 10% relative humidity; 2 h) controlled environments consecutively during baseline and follow-up visits (3, 6, and 12 months) after a single LipiFlow treatment. Ocular Surface Disease Index (OSDI), lipid layer thickness (LLT), fluorescein tear break-up time (TBUT), corneal and conjunctival staining, change in dry eye symptoms questionnaire (CDES-Q), and Meibomian gland yielding liquid secretion (MGYLS), were assessed. Linear mixed-effects and cumulative logit mixed models were fitted to assess the effect of the LipiFlow treatment over time and within the controlled environments. Seventeen females and 4 males (59.6 ± 9.4 years) completed the study. LLT and TBUT did not vary significantly (p > 0.05) after LipiFlow treatment. OSDI, corneal and conjunctival staining, and MGYLS scores were improved (p ≤ 0.01) 12 months after treatment. After the adverse exposure, corneal staining increased at all visits (p = 0.01), and there was no significant improvement in CDES-Q scores after LipiFlow treatment (p ≥ 0.07). One LipiFlow treatment improved objective and subjective outcomes in MGD disease for at least one year. Further studies are needed to support that LipiFlow might also help as an adjuvant to avoid acute flares against an adverse environmental humidity.

Effect of intense pulsed light using acne filter on eyelid margin telangiectasia in moderate-to-severe meibomian gland dysfunction.

Evaluate the improvement in clinical signs and symptoms in patients with moderate-to-severe meibomian gland dysfunction (MGD) treated with intense pulsed light (IPL) using an acne filter. A retrospective chart review of 70 eyes of 35 patients with moderate-to-severe MGD treated with IPL using the acne filter was performed. IPL treatment was administered using the acne filter four times at 2- to 3-week intervals to upper and lower eyelids. We evaluated tear break-up time (TBUT), matrix metalloproteinase (MMP)-9, Sjögren's International Clinical Collaborative Alliance (SICCA) staining score, and Oxford staining grade. We performed Schirmer's test I without topical anesthesia, slit-lamp microscopic examination of lid margin and meibomian gland, and patient's symptom score assessment and evaluated the incidence of adverse effects in the ocular and periocular areas at baseline and 30 days after the final treatment. Significant improvements (P < 0.001) were observed in TBUT, SICCA staining score, Oxford staining grade, quality of meibum, consistency of meibum, lid margin telangiectasia, MGD grade, and patient's symptom scores after acne filter IPL treatment. Furthermore, the positivity (100 to 71.43%, P = 0.002) and level (2.43 ± 0.98 to 1.14 ± 0.78, P < 0.001) of MMP-9 significantly decreased after treatment. However, there was no significant improvement in Schirmer's test I (P = 0.224). No systemic or regional adverse effects were observed in any patient. IPL treatment using the acne filter is an effective and safe therapeutic modality for treating moderate-to-severe MGD, especially for lid margin telangiectasia and MMP-9.

Change in rat meibomian gland structure with external pressure on the eyelid.

PURPOSE: This study investigated structural changes in rat meibomian glands following repeated and sustained application of external pressure on the eyelids using a magnet and then subsequent removal of the external pressure. METHODS: Twenty-eight Sprague-Dawley rats were used. The upper eyelid was externally compressed using a pair of magnets. One magnet was placed inside the upper eyelid, another was placed outside the eyelid, and varying periods of pressure were investigated. Untreated eyes were used as controls. Meibography was performed, and the transverse eyelid tissue sections were stained with hematoxylin and eosin and anti-cytokeratin 5 antibody at one hour, two and four weeks after removing the magnets. RESULTS: Meibography showed increased meibomian gland loss (30.0 ± 5.0%), and tissue sections showed decreased area of secretory acini (0.04 ± 0.08 mm2) at one hour after applying external pressure using magnets versus in the control eyes (5.0 ± 5.0% and 0.08 ± 0.08 mm2, respectively). On the other hand, there was no meibomian gland loss or reduction of the area of secretory acini at two and four weeks after removing the magnets in comparison with the control eyes. CONCLUSIONS: Repeated and sustained application of external pressure on the eyelid could induce meibomian gland loss; however, this meibomian gland loss can be restored when the external pressure is removed. Therefore, the repeated application of external pressure on the eyelid is a safe treatment method for obstructive MGD.

Chambered warm moist air eyelid warming devices - a review.

BACKGROUND: Eyelid warming is an important treatment for meibomian gland dysfunction (MGD). Specialized chambered devices, using warm moist air have been developed. PURPOSE: To critically evaluate the literature on the safety and efficacy of chambered warm moist air devices in MGD treatment and pinpoint areas of future research. METHODS: PubMed and Embase were searched on 06 June 2021. The search term was '(warm OR heat OR steam OR goggle OR spectacle OR moist air) AND (meibomian OR MGD OR blepharitis OR eyelid OR dry eye OR DED)'. All relevant articles with available English full text were included. RESULTS: Eighteen articles assessing the application of chambered warm moist air eyelid warming devices were identified. In single-application studies, steam-based eyelid warming increased the eyelid temperature and improved symptoms, lipid layer thickness, and tear film breakup time (TBUT). In treatment studies, the steam-based devices improved TBUT and symptom scores. However, in the only randomized controlled trial (RCT) comparing chambered steam-based heat to hot towel treatment, there was no difference between groups for the primary outcome measure; the proportion of subjects noting symptom improvement after 4 weeks. CONCLUSION: Currently available chambered warm moist air eyelid warming devices are safe and effective at raising eyelid temperature to therapeutic levels and improving signs and symptoms of dry eye. However, it is not clear if they provide a greater benefit than other eyelid warming therapies. Further well-conducted RCTs comparing moist and dry heat devices should be conducted on patients across the range of DED severities and subtype spectrum.

[Thermal pulsation system (LipiFlow®) for treatment of meibomian gland dysfunction (MGD) from the perspective of an ophthalmologist in private practice]. / Thermo-Pulsations-System (LipiFLow®) zur Behandlung der Meibom-Drüsen-Dysfunktion (MDD) aus der Sicht eines niedergelassenen Augenfacharztes.

PURPOSE: Thermal pulsation (LipiFlow®, Johnson&Johnson, Santa Ana, CA, USA) has been advocated for meibomian gland dysfunction (MGD) treatment and was found to be useful in many studies. The aim of this study was to show the efficacy of the method and to compare it to a daily eyelid margin massage in a non-university institution. METHODS: A non-blinded, single-center interventional study comparing thermal pulsation with eyelid margin massage for the treatment of MDD. In this study 30 patients were recruited during daily office hours. Symptoms (OSDI) and ocular surface (NIK-BUT, tear ferning test, tear meniscus height, LIPCO folds, meibography, meibomian gland evaluator) were assessed before treatment. A total of 15 patients (9 women) underwent thermal pulsation (single session), while 15 patients (8 women) performed eyelid margin massage (once daily) as instructed for 3 months. RESULTS: Before the two treatment methods, there were no differences in the above parameters, gender and age were also normally distributed. After treatment, both subjective and objective criteria improved in the two groups but significantly more in the thermal pulsation arm. In particular, the limited compliance of 30% in the eyelid margin massage arm should be noted. Safety parameters, such as visual acuity and intraocular pressure (IOP) remained normal in all patients. CONCLUSION: A single session of thermal pulsation showed significantly better results in the efficacy and safety profile after 3 months compared to eyelid margin massage once daily; however, the high costs for the patients due to the single use mode of the activators must be taken in account.

A Single-center Retrospective Trial of a Blink-assisted Eyelid Device in Treating the Signs and Symptoms of Dry Eye.

SIGNIFICANCE: The clinical features of meibomian gland disease include altered tear film stability, damage to the ocular surface, symptoms of ocular surface irritation, and visual fluctuations. Finding an adequate treatment to alleviate a patient's signs and symptoms is vital to caring for those with dry eye disease resulting from meibomian gland disease. PURPOSE: The purpose of this analysis was to determine whether the controlled heating of meibomian glands with the SmartLid devices (TearCare) combined with evacuation of the liquefied meibum using a handheld clearance assistant would improve a patient's dry eye symptoms (as measured by the Standardized Patient Evaluation of Eye Dryness [SPEED] questionnaire) and signs (as measured by meibomian gland expression [MGE] scores). METHODS: This study involved a retrospective analysis of data gathered in a single-center ophthalmology/optometry practice. The symptom frequency and severity were assessed using the SPEED questionnaire, and the signs were assessed via MGE scores before and after (8 to 12 weeks) treatment. A further analysis evaluating efficacy in subgroups based on age, race, and sex was performed. A statistical analysis was performed with t tests for group comparisons. RESULTS: A SPEED questionnaire was answered by 92 patients with dry eye disease. In addition, each patient's meibomian gland function was recorded as MGE scores for each eye (176 eyes). These procedures were completed before and approximately 8 weeks after a single bilateral TearCare treatment. The median total SPEED score was reduced from 16 to 9, and the total MGE scores improved from 5.0 to 9.0 in the right eye and 4.0 to 9.0 in the left eye after a single TearCare treatment. CONCLUSIONS: A single TearCare treatment was effective in reducing both the signs and symptoms of dry eye in all subjects.