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

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

Luz pulsada intensa combinada con expresión de las glándulas de Meibomio para el tratamiento del chalación / Intense pulsed light combined with meibomian gland expression for chalazion management

Objetivo Investigar la eficacia y la seguridad del protocolo de luz pulsada intensa (IPL) combinando el protocolo de tratamiento con IPL para la disfunción de las glándulas de Meibomio/enfermedad de ojo seco con IPL aplicada directamente en los párpados, asociada a la expresión de las glándulas de Meibomio (GM) para el tratamiento del chalación. Material y métodos Estudio retrospectivo de serie de casos. Los pacientes que presentaron chalación, recibieron un tratamiento combinado de terapia con IPL que consistió en usar el protocolo habitual de IPL para disfunción de las glándulas de Meibomio/enfermedad de ojo seco empleando una fluencia de acuerdo al tipo de piel según Fitzpatrick, seguido de una segunda fase (en la misma sesión) de aplicación IPL directamente sobre los párpados de ambos ojos empleando una fluencia de 10J/cm2. A continuación, todos los pacientes recibieron expresión de las GM, higiene de los párpados, antibiótico tópico y medicación ocular antiinflamatoria tópica. Los efectos adversos relacionados con este protocolo se evaluaron en cada sesión de IPL. Resultados Se incluyeron 26 chalaciones de diecinueve pacientes (24 ojos) con una edad media de 49,89±20,43 años. Fueron necesarias 2,07±0,97 sesiones de IPL de media para la resolución del chalación. El tratamiento combinado de protocolo IPL y expresión de GM mostró un 96,15% de eficacia y no se observaron efectos adversos. Conclusiones El tratamiento combinado de IPL para disfunción de las glándulas de Meibomio/enfermedad de ojo seco con IPL aplicado directamente sobre los párpados y expresión de GM podría ser eficaz y seguro para el tratamiento de los chalaciones (AU)

Objective To investigate the efficacy and safety of an intense pulsed light (IPL) combined IPL treatment protocol for meibomian gland dysfunction (MGD)/dry eye disease (DED) with IPL applied directly to the eyelids, associated with meibomian gland (MG) expression for the treatment of chalazion. Material and Methods Retrospective case series study. Patients presenting with chalazion received a combined IPL therapy treatment consisting of using the usual IPL protocol for DGM/EOS using a fluence according to skin type according to Fitzpatrick, followed by a second phase (in the same session) of IPL application directly on the eyelids of both eyes using a fluence of 10 J/cm2. All patients then received GM expression, eyelid hygiene, topical antibiotic and topical ocular anti-inflammatory medication. Adverse effects related to this protocol were assessed at each IPL session. Results Twenty-six chalazions from nineteen patients (24 eyes) with a mean age of 49.89 ± 20.43 years were included. An average of 2.07 ± 0.97 IPL sessions were required for chalazion resolution. The combined treatment of IPL protocol and GM expression showed 96.15% efficacy and no adverse effects were observed. Conclusions Combined IPL treatment for DGM/EOS with IPL applied directly on the eyelids and GM expression could be effective and safe for the treatment of chalazions (AU)

Pathophysiology of Meibomian Glands - An Overview.

Purpose: The meibomian glands are located in the tarsal plate of the upper and lower eyelid and are responsible for the production of a lipid-rich secretion, the meibum, which forms the outer component of the tear film. Meibomian gland dysfunction results in excessive evaporation of the tear film and is the leading cause of dry eye disease (DED). Despite the high prevalence of DED, the etiology of meibomian gland dysfunction is only basically understood. In addition, the molecular mechanisms of meibomian gland maturation and physiological function are currently the focus of research.Methods: A systematic literature search was performed using the main scientific databases, including all relevant published articles up to September 2020.Results: This article provides an overview of the current state of knowledge about meibomian gland stem cells, cell surface marker expression and PPARγ signaling, as well as the pathological causes of meibomian gland dysfunction.Conclusion: Androgen deficiency, hyperkeratinization, PPARγ signaling and inflammatory reactions including neutrophil extracellular traps (NETs) seem to be key factors within the pathological processes of the meibomian gland.

Meibomian glands dropout in patients with inactive thyroid related orbitopathy.

PURPOSE: To evaluate the structure and function of meibomian glands in patients with thyroid related orbitopathy (TRO) compared with age- and sex-matched controls without TRO. METHODS: This cross-sectional study included 106 eyes of 53 patients with TRO and 106 eyes of 53 age- and sex-matched controls without TRO. Patients with TRO were assessed for thyroid hormone status, activity and severity of TRO. All participants completed OSDI questionnaires. Their meibomian glands' structure and function were assessed, including the area of meibomian gland dropout, lipid layer thickness (LLT), meibum expressibility and quality scores, tear break-up time (TBUT), corneal and conjunctival staining scores. A generalized estimating equation (GEE) was used to compare between the two groups. The correlations between the area of meibomian gland dropout with symptoms and signs of TRO were evaluated using GEE and Spearman correlation. RESULTS: All patients with TRO had inactive status. The mean area of meibomian gland dropout was higher in the TRO group (34.5±11.2%) compared with that of controls (30.1±10.7%, P = 0.03). Both mean meibum quality (TRO, 1.6±0.7; Controls, 2.0 ±0.5) and expressibility (TRO, 1.5 ±0.7; Controls, 1.7 ±0.6) scores were slightly better in the TRO group compared with those of controls (P = 0.01). There was no significant difference in OSDI, corneal and conjunctival staining, TBUT and LLT. The area of meibomian gland dropout in patients with TRO was correlated with euthyroid status (P<0.05) and lagophthalmos (P = 0.03). CONCLUSIONS: Patients with inactive TRO showed significantly higher meibomian gland dropout compared with that of age- and sex-matched controls without TRO.

Ocular Pathophysiology of Sjögren's Syndrome.

The purpose of this review is to delve into the clinical and research understanding of the pathophysiology and presentation of Sjögren's-related keratoconjunctivitis sicca in order address the diagnostic and management challenge that it represents, as well as to provide a basis for appreciating the pharmacotherapies designed to treat the ophthalmic symptoms of Sjögren's disease.

Effects of Vectored Thermal Pulsation on Objective Tear Film Measures.

PURPOSE: To assess the effect of vectored thermal pulsation treatment for meibomian gland dysfunction on objective measures of lipid layer thickness (LLT) and tear osmolarity. METHODS: One hundred patients with meibomian gland dysfunction diagnosis were recruited to participate. At their initial visit, baseline study parameters were recorded, and vectored thermal pulsation treatment was administered. At the 2- to 3-month follow-up visit, the study parameters were reevaluated. Subjective symptoms were evaluated using the Ocular Surface Disease Index questionnaire. LLT was measured using an ocular surface interferometer. Tear osmolarity was calculated using impedance measurement of tear fluid collected from the eyelid margin. RESULTS: Ninety-six patients (192 eyes) completed the follow-up. Mean improvement in Ocular Surface Disease Index was 5.6 points (95% confidence interval [CI], -9.0 to -2.1, P = 0.002). There was no significant change in tear osmolarity (mean change -1.6 mOsm/L, 95% CI, -4.7 to +1.3 mOsm/L, P = 0.3). There was no significant change in LLT (mean change -4.3 nm, 95% CI, -9.1 to +0.5 nm, P = 0.08). CONCLUSIONS: The hypothesis that vectored thermal pulsation treatment would decrease tear osmolarity and increase LLT was not substantiated. Although we detected significant improvement in subjective symptoms, the improvement was smaller than the improvements reported in previous studies. Our results suggest that the current understanding of the effects of vectored thermal pulsation treatment is incomplete.

Comparative study on the effect of hyperthermic massage and mechanical squeezing in the patients with mild and severe meibomian gland dysfunction: An interventional case series.

BACKGROUND: Meibomian glands exist beneath the palpebral conjunctiva; thus, it is invisible to the naked eye without infrared imaging. This study used meibography to group patients with meibomian gland dysfunction (MGD) and assessed the effects of hyperthermic massage and mechanical squeezing in both groups. MATERIALS AND METHODS: Patients with MGD were divided into two groups, according to the degree of meibomian gland loss: group 1, in which the sum of eyelid scores ranged from 0 to 4 (mild to moderate gland loss) and group 2, in which the sum of eyelid scores ranged from 5 to 6 (severe gland loss). Hyperthermic massage and mechanical squeezing were given to both groups once a week for 4 weeks, and only non-preservative artificial tears were allowed. Ocular surface disease index (OSDI), Schirmer's test, meibography score, tear break-up time (TBUT), ocular surface staining, expressible meibomian gland, and quality before and after treatment were compared. RESULTS: Of the 49 patients who completed the 4 weeks of treatment and the evaluation at week 5, 29 were assigned to group 1 and 20 were assigned to group 2. Meibography scores, OSDI, TBUT, and expressibility of meibum had significant differences before and after treatments in both groups. However, there was no significant difference between the changes in clinical signs between group 1 and 2 after treatment. Without grouping, all patients showed significant decreases in meibography score, OSDI, cornea staining score, and increases in TBUT and expressibility of meibum after treatment. CONCLUSIONS: Considering the results of the current study, hyperthermic massage and mechanical squeezing may be effective in patients with meibomian gland loss, regardless of the degree of severity.

An Emerging Method to Assess Tear Film Spread and Dynamics as Possible Tear Film Homeostasis Markers.

Purpose: This study aims to assess the performance of an analysis method to measure in vivo the movement speed of tear film particles post-blink as a measure of tear film spreading.Materials and methods: Ocular surface parameters and the recording of tear film particles' spreading post-blink were assessed in eighty-one healthy volunteers (43.7 ± 27.0 years) using Keratograph 5 M. The developed software automatically decomposed the video into frames to manually track particles' position for 1.75 seconds after a blink. The following tear film-dynamic metrics were automatically calculated: mean, median, maximum, and minimum particles' speed at different times after blinking and time for particle speed to decrease to <1.20 mm/second. Repeatability of each tear film-dynamic metric and its correlations with ocular surface signs and symptoms were analyzed. Binomial logistic regression was performed to assess the predictability of new metrics to ocular parameters.Results: Repeatability tended to be lower just after blinking (variability of 12.24%), whereas the metrics from 0.5 s onwards had acceptable repeatability (variability below 10%). Tear film-dynamic metrics correlated positively with Non-Invasive Break-Up Time (NIKBUT) while negatively with meibomian gland drop-out. Binomial logistic regression analysis revealed that tear film-dynamic metrics were able to predict NIKBUT. Nevertheless, no statistically significant association was found with gland drop-out. This means that higher particle speed is related to larger NIKBUT. The metric "time for particle speed to decrease to <1.20 mm/second" can be considered the best metric to assess the quality of the tear film, since it was more strongly correlated with NIKBUT (r = 0.42, p = .004), it was more strongly associated in the binomial logistic regression analysis with NIKBUT and showed good repeatability (variability = 5.49%).Conclusions: Tear film-dynamic metrics are emerging homeostasis parameters for assessing indirectly the tear film quality in natural conditions with acceptable repeatability.

Meibomian Gland Contrast Sensitivity and Specificity in the Diagnosis of Lipid-deficient Dry Eye: A Pilot Study.

SIGNIFICANCE: Lipid deficiency due to meibomian gland (MG) dysfunction is believed to account for the vast majority of patients with dry eye compared with aqueous deficiency. Clinicians commonly evaluate MG length to determine a disease, but our research with isotretinoin users suggests that MG contrast is also an important characteristic to consider. PURPOSE: This study aimed to determine the sensitivity and specificity of MG contrast for the diagnosis of lipid-deficient dry eye (LDDE). METHODS: This case-control study used demographic data, Standard Patient Evaluation of Eye Dryness (SPEED) scores, average tear lipid layer thickness (TLLT), fluorescein tear breakup time (FTBUT), upper eyelid meibography images, and meibum quality and quantity scores for individuals with LDDE (SPEED score ≥10 and TLLT ≤35 interferometric color units) and normal individuals (SPEED ≤2 and TLLT ≥80 interferometric color units). RESULTS: Thirty-one eyes of 22 controls (mean ± SD age, 22.7 ± 5.5 years) and 13 eyes of 12 cases (mean ± SD age, 43.9 ± 17.2 years) were included. Normalized MG contrast was significantly correlated with FTBUT (r = 0.35, P = .02), percent MG atrophy (r = -0.50, P < .001), and SPEED scores (r = -0.49, P < .001). The receiver operating characteristic curve for LDDE diagnosis classifiers MG contrast, MG atrophy, and meibum quantity score had areas under the curve of 0.83, 0.64, and 0.73, respectively. Meibomian gland contrast cutoff at 28.3 intensity units yielded optimal correct classification of subjects (84.1%; sensitivity, 0.69; specificity, 0.90). Cases had shorter FTBUT (P < .001), worse meibum quality (P = .02) and quantity (P = .02) scores, and lower MG contrast (P < .001) compared with controls. Subjects with low MG contrast (≤28.3) had 14.9 higher odds of having LDDE (95% confidence interval, 2.84 to 78.4) compared with subjects with high MG contrast (>28.3). CONCLUSIONS: Meibomian gland contrast correlates well with clinical parameters and symptoms, shows good sensitivity and excellent specificity for diagnosing LDDE, and can be a useful diagnostic parameter for monitoring MG changes due to age, disease, or intervention.

Changes of tear lipid mediators after eyelid warming or thermopulsation treatment for meibomian gland dysfunction.

Meibomian gland dysfunction (MGD) represents a major cause of dry eye and ocular discomfort. Lipid mediators, often termed oxylipins, can be produced enzymatically or non-enzymatically, and may modulate inflammatory processes in MGD. Here, we aimed to assess the longitudinal changes of lipid mediators after various eyelid treatments (eyelid warming and thermopulsation) over 12 weeks. Secondly, we aimed to assess the chirality of mono-hydroxyl lipid mediators from tears of MGD and healthy participants. Tears lipid mediators were extracted from Schirmer's strips and levels were quantified by liquid chromatography mass spectrometry (LC-MS) techniques. We quantified 33 lipid mediators in the tear, 18 of which (including 11-HETE, 20-OH-LTB4, and 15-oxoETE) were reduced significantly after treatment. Changes in concentrations of 10-HDoHE (r = 0.54) and 15-oxoETE (r = 0.54) were correlated to the number of meibomian gland plugs at baseline, so increased severity of MGD was associated with treatment-induced change in lipid mediators. The chiral analysis demonstrated that 5(S)-HETE, 12(S)-HETE, 15(S)-HETE, 14(S)-HDoHE, 17(S)-HDoHE and 11(R)-HETE were produced with significant enantiomeric excess (ee %) in controls compared to patients, due to enantiomer selective enzymatic action, whereas most lipid mediators were racemates in patients, due to dominance of oxidative effects which have no enantiomeric preference. Treatment of MGD restored the concentrations of 15(S)-HETE, 14(S)-HDoHE and 17(S)-HDoHE with significant ee values, suggesting reduction in oxidative action. Overall, MGD therapy reduced pro-inflammatory molecules generated by lipoxygenase and oxidative stress.

Efficacy of baby shampoo and commercial eyelid cleanser in patients with meibomian gland dysfunction: A randomized controlled trial.

BACKGROUND: To compare the efficacy between Johnson's baby shampoo top-to-toe (No More Tears formula) and OCuSOFT Lid Scrub Original Foaming Eyelid Cleanser (OSO) in patients with grade 2 meibomian gland dysfunction (MGD). METHODS: Sixty participants with grade 2 MGD were enrolled and analyzed based on intention to treat basis in a prospective, randomized, single-blind trial for eye scrub using either diluted baby shampoo or OSO. The data collection included the Ocular Surface Disease Index (OSDI) questionnaire, compliance, and complications. The eye examinations were according to the Tear Film and Ocular Surface Society at baseline and at post-treatment weeks 4 and 12. RESULTS: The mean (±SD) age of the 60 patients who presented with grade 2 MGD was 48.0 ±â€Š13.8 years and 75.0% were females. The OSDI scores of these participants between pre-treatment and post-treatment weeks 4 and 12 improved significantly in both groups (all P < .001). The mean (±SD) differences of the improvement of OSDI score from baseline were not statistically significantly different between the baby shampoo and OSO groups at post-treatment weeks 4 and 12 (P = .57 and P = .54, respectively). The compliance and complications were also not statistically significant between the 2 groups. CONCLUSIONS: Eyelid scrub using either baby shampoo or OSO and warm compresses could significantly reduce eye irritability and uncomfortable symptoms in grade 2 MGD patients. In this study, the efficacy, compliance, and complications between the 2 groups were not statistically significantly different.

Functional and Morphological Evaluation of Meibomian Glands in the Assessment of Meibomian Gland Dysfunction Subtype and Severity.

PURPOSE: To classify subtypes of meibomian gland dysfunction (MGD) and evaluate the dependency of dry eye signs, symptoms, and parameters on MGD subtype. DESIGN: Cross-sectional study. STUDY POPULATION: the right eyes of 447 patients with MGD of various subtypes and 20 healthy volunteers. METHODS: Patients were divided into 4 subtypes of MGD based on meibum expression, meibum quality, and MG loss on meibography images (meibograde of 0-6). Subtypes were patients with high meibum delivery (hypersecretory and nonobvious MGD) and those with low meibum delivery (hyposecretory and obstructive MGD). Additional clinical tests included tear film break-up time (TFBUT), ocular staining, osmolarity, Schirmer I, blink interval timing and the Ocular Surface Disease Index (OSDI) questionnaire. RESULTS: A total of 78 eyes had hypersecretory MGD; 49 eyes had nonobvious MGD; 66 eyes had hyposecretory MGD; and 254 eyes had obstructive MGD. Increased tear film osmolarity and lower TFBUT were found in the low-delivery groups; hyposecretory (P = 0.006, P = 0.016) and obstructive MGD (P = 0.008, P = 0.006) relative to high-delivery MGD (hypersecretory and nonobvious groups, respectively). Worse ocular symptoms and ocular staining were also found in low-delivery MGD groups than the high delivery MGD groups (P < 0.01 and P < 0.006, respectively). CONCLUSIONS: Patients with low-delivery MGD had worse dry eye parameters and ocular symptoms than those with high meibum delivery, indicating the pivotal role of meibum secretion in ocular surface health that should be targeted in MGD therapy. Furthermore, nonobvious MGD cannot be diagnosed using conventional dry eye tests and requires morphologic assessment of meibography images to confirm MG loss.

Reliable, Noncontact Imaging Tool for the Evaluation of Meibomian Gland Function: Sirius Meibography.

OBJECTIVES: To investigate the correlation between the clinical grading of the severity of meibomian gland dysfunction (MGD) and meibomian gland area (MGA) loss detected using Sirius meibography in the upper and lower eyelids and to correlate these parameters with dry eye signs and symptoms. METHODS: One hundred thirty eyes of 130 volunteer patients were enrolled. Meibomian gland dysfunction was defined as the presence of signs consistent with meibomian gland terminal duct obstruction and categorized between grades 1 and 4. Upper and lower MGA loss percentages were evaluated using Sirius meibography by two blinded examiners. Patients were categorized into two groups (positive and negative for MGD) based on their Ocular Surface Disease Index (OSDI) scores (≥15 and <14, respectively) and MGD grades (≥1 and 0, respectively). RESULTS: The MGA loss percentage and ocular surface test results of the MGD group were greater than in the non-MGD group in both eyelids (P=0.001). Meibomian gland dysfunction grade and MGA loss for the lower eyelid was greater than that of the upper eyelids (P=0.002 and P<0.001, respectively). The OSDI score, tear film break-up time, and lissamine green staining were all significantly correlated with MGD grade and MGA loss in both eyelids (P<0.001). For the average measures of the MGA loss percentage in each scan, the intraclass correlation value was found as 0.994 (95% confidence interval [CI]: 0.992-0.995) for reader 1 and 0.988 (95% CI: 0.982-0.992) for reader 2. CONCLUSIONS: Our findings suggest that Sirius meibography, a noncontact imaging device, is a reliable tool for evaluating meibomian gland structure in patients with MGD and non-MGD of various ages and regardless of sex.

A Review on Evidence-Based Treatments for Meibomian Gland Dysfunction.

OBJECTIVES: To evaluate recent studies on available therapies for meibomian gland dysfunction (MGD). METHODS: A literature search on recent publications, within the last five years, concerning treatment options for MGD was performed. RESULTS: A total of 35 articles were reviewed after curation by the authors for relevance. In general, all modalities of treatments were shown to have clinical efficacy in alleviating dry eye signs and symptoms, although the extent of improvement and persistency of outcomes varied between the different treatments. Evidence from published studies demonstrate that thermal pulsation produces the longest lasting effect per treatment, but it also incurs the highest per-treatment cost. Reusable methods for warm compress with lipid/semi-fluorinated alkane-containing eye drops are recommended as first-line treatment for mild-to-moderate dry eye patients, because this option is most technically feasible and cost-effective in clinical practice. Intense pulsed light (IPL) therapy and thermal pulsation may be suitable as second line for patients unresponsive to warm compress therapy; however, their respective limitations need to be considered. For refractory MGD with features of periductal fibrosis or severe blepharitis, supplementary treatment with meibomian gland probing or oral antibiotics may be used. CONCLUSIONS: All eight forms of treatments, including self-applied eyelid warming, thermal pulsation, IPL, MG probing, antibiotics, lipid-containing eye drops, and perfluorohexyloctane, were effective against MGD, although with varying extent of clinical improvements. A better understanding on the mechanisms of actions may guide physicians to make better treatment decisions targeting the root causes.

Correlation between type 2 diabetes, dry eye and Meibomian glands dysfunction / Correlación entre diabetes tipo 2, ojo seco y disfunción de las glándulas de Meibomio

PURPOSE: To assess the Meibomian glands, ocular surface and tear function in patients with type 2 diabetes, and study the correlation between these conditions. METHODS: Prospective study of 76 males, 37 with type 2 diabetes with an average of duration between 7 ± 5 years, and 36 males from control group. After completing an ocular surface disease index (OSDI) questionnaire, the non-invasive tear film break-up time (NIBUT) and the tear lipid layer pattern was performed using interferometry system and tear meniscus height/TMH. Ocular surface was studied with lissamine green staining and morphology of the glands with evaluation of Marx's line (lid margin abnormalities); meibomian secretion was expressed and was also assessed the quality. The results were analyzed using the statistical Kruskal-Wallis and Mann-Whitney, and correlations by Spearman Rho. RESULTS: The mean age was 59 ± 8 years; 71% of participants presented MGD (76% diabetics and 67% controls). OSDI were significantly higher (p = 0.01) in the diabetic group. A positive correlation was found between glycemia and symptoms (p = 0.0005) and strong correlation between Hb1Ac and OSDI in MGD. NIBUT was lower in the control group (2.47 ± 1.2s) than for the diabetic group (2.9 ± 1.2s), with a significant inverse correlation (52.22%) with MG inflammation. CONCLUSIONS: MGD in type 2 diabetic patients is more severe compared with nondiabetic patients. Longer duration of diabetes is associated with major symptoms and changes in MG. Diabetic group showed major changes in lids and tear function, accounting for evaporative dry eye and presenting a high degree of correlation with MG inflammation and obstruction

OBJETIVO: Evaluar las glándulas de Meibomio, la superficie ocular y la función de la lágrima en pacientes con diabetes tipo 2, y estudiar la correlación entre estas situaciones. MÉTODOS: Estudio prospectivo de 76 varones, 37 de ellos con diabetes tipo 2, con una media de duración de entre 7 ± 5 años, y 36 mujeres como grupo control. Tras completar el cuestionario del índice de enfermedad de la superficie ocular (OSDI), se obtuvieron el tiempo de ruptura lagrimal no invasivo (NIBUT) y el patrón de la capa lipídica de la lágrima utilizando interferometría y altura del menisco lagrimal/AML. Se estudió la superficie ocular con tinción verde de lisamina y la morfología de las glándulas con evaluación de la línea de Marx (anomalías del margen del párpado); se expresó la secreción de las glándulas de Meibomio, así como su calidad. Los resultados se analizaron utilizando la pruebas estadísticas Kruskal-Wallis y Mann-Witney, y las correlaciones con Rho de Spearman. RESULTADOS: La edad media fue de 59 ± 8 años; el 71% de los participantes presentaron DGM (76% diabéticos y 67% controles). OSDI fue significativamente superior (p = 0,01) en el grupo diabético. Se encontró una correlación positiva entre glucemia y síntomas (p = 0,0005), y una fuerte correlación entre Hb1Ac y OSDI en DGM. NIBUT fue inferior en el grupo control (2,47 ± 1,2 s) que en el grupo diabético (2,9 ± 1,2 s), con una correlación inversa significativa (52,22%) con la irregularidad del borde palbebral y queratinización del OM. CONCLUSIONES: DGM en los pacientes con diabetes tipo 2 es más grave, en comparación con los pacientes no diabéticos. La mayor duración de la diabetes se asocia a síntomas mayores y cambios en la GM. El grupo diabético reflejó cambios mayores en los párpados y la función de la lágrima, lo cual supone ojo seco evaporativo, y un alto grado de correlación con irregularidad del margen palpebral y obstrucción de la GM

Diagnostic Test Efficacy of Meibomian Gland Morphology and Function.

Meibomian gland dysfunction (MGD) is the leading cause of dry eye and proposed treatments are based on disease severity. Our purpose was to establish reliable morphologic measurements of meibomian glands for evaluating MGD severity. This retrospective, cross-sectional study included 100 MGD patients and 20 controls. The patients were classified into dry eye severity level (DESL) 1-4 based on symptoms and clinical parameters including tear-film breakup time, ocular staining and Schirmer I. The gland loss, length, thickness, density and distortion were analyzed. We compared the morphology between patients and controls; examined their correlations to meibum expressibility, quality, and DESL. Relative to controls, the gland thickness, density and distortion were elevated in patients (p < 0.001 for all tests). The area under the receiver operating characteristic curve was 0.98 (95% confidence interval [CI], 0.96-1.0) for gland loss, and 0.96 (CI 0.91-1.0) for gland distortion, with a cutoff value of six distorted glands yielding a sensitivity of 93% and specificity of 97% for MGD diagnosis. The gland distortion was negatively correlated to the meibum expressibility (r = -0.53; p < 0.001) and DESL (r = -0.22, p = 0.018). In conclusion, evaluation of meibomian gland loss and distortion are valuable complementary clinical parameters to assess MGD status.

Effects of Preservative-free 3% Diquafosol in Patients with Pre-existing Dry Eye Disease after Cataract Surgery: A Randomized Clinical Trial.

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

Effects of chronic smoking on the meibomian glands.

PURPOSE: To evaluate the effects of chronic smoking on tear function tests and meibomian glands. METHODS: This prospective study included 40 volunteers with a long-term (> 5 years) cigarette smoking history (study group) and 43 non-smoking healthy individuals (control group). The symptoms of all the participants were scored using the Ocular Surface Disease Index (OSDI) questionnaire, and a detailed ophthalmological examination was performed including the tear breakup time (TBUT) and Schirmer test (with anaesthesia). The upper and lower lid meibomian glands were evaluated with meibography using the Sirius anterior segment analysis system (Sirius, CSO, Florence, Italy). RESULTS: The groups showed homogenous distribution in respect of age and gender (p > 0.05). The patients in the study group were determined with 22.59 ± 17.25 packet/year cigarette usage. The mean OSDI score was 36.67 ± 21.47 in the study group and 31.65 ± 15.60 in the control group (p = 0.64). The TBUT and Schirmer test values were determined as 9.65 ± 6.14 s and 8.90 ± 4.95 mm, respectively, in the study group and 11.23 ± 5.94 s and 13.08 ± 8.61 mm in the control group (p > 0.05). In the upper lid meibography, loss of 24.68 ± 16.54% was determined in the study group and 17.87 ± 7.06% in the control group (p = 0.01). No statistically significant difference was determined between the groups in respect of the lower lid meibomian gland loss: study group 14.70 ± 8.49% versus control group 12.48 ± 6.44% (p = 0.20). CONCLUSIONS: Smoking results in meibomian gland damage which may be a risk factor for dry eye. In cases of ocular surface disorders related to chronic smoking, meibomian gland damage should be taken into consideration.

Evaluation of the Safety and Efficacy of Intense Pulsed Light Treatment with Meibomian Gland Expression of the Upper Eyelids for Dry Eye Disease.

Objective: To investigate the safety of and change from baseline of tear breakup time and visual analog pain scales in dry eye disease subjects with upper lid Meibomian gland dysfunction after intense pulsed light (IPL) treatment assessing global ocular pain severity, ocular pain frequency, and ocular pain in the previous 24 h. This is a prospective single-site study. Methods: All patients received active treatment consisting of four treatments spaced no fewer than 2 weeks apart and no longer than 4 weeks apart. The IPL therapy was performed with a Lumenis M22 (Lumenis Ltd., Yokneam, Israel) xenon-based micropulsed IPL utilizing a 590 nm filter with a 6 mm clear SapphireCool cylindrical lightguide for the upper lids with a fluence of 10 J/cm2 across the upper eyelids, including the tragus for two passes. Patients then received expression of their meibomian glands using two cotton-tipped applicators. Tear breakup data were collected as well as global ocular pain, ocular pain episodes in the past 24 h and frequency of ocular pain episodes. Results: All of the assessments for the treated eyes improved over the course of treatment. Statistically significant physician increases in measured tear breakup times were measured for each eye independently. Statistically significant decreases in global eye dryness scale, eye dryness in the preceding 24 h, and frequency of ocular pain episodes between treatments were observed. There were no serious or nonserious adverse events in the trial. Conclusions: This pilot study suggests that a new specialized 6 mm cylindrical handpiece for the M22 Lumenis IPL machine is safe and effective in increasing physician-measured tear breakup time as well as several scales of the symptoms of ocular dryness, including global symptoms, frequency of symptoms, and ocular dryness occurring within the previous 24 h before the study visit.

Characteristics of meibomian gland dysfunction in patients with Stevens-Johnson syndrome.

To evaluate the characteristics of meibomian gland dysfunction (MGD) in patients with Stevens-Johnson Syndrome (SJS) and investigate the risk factors for severe MGD.Sixteen patients with a history of SJS were evaluated for MGD. To assess the SJS severity acute ocular involvement score (AOS), acute systemic involvement score (ASS), and chronic ocular manifestation score (COMS) were measured. Meibomian gland parameters were evaluated using meibomian gland dropout score (meiboscore - using a Keratograph 5 M), meibum expression score (MES), meibum quality score (MQS), and lid margin abnormality score (LMAS). Correlations between severity of meibomian gland parameters and degree of ocular and systemic involvement of SJS were analyzed. Risk factors for development of severe MGD were identified.The patients' mean age was 32.0 ±â€Š14.3 years. Four patients were men and 12 were women. MGD had developed in 14 patients (87.5%). The meibomian gland parameters were significantly correlated with ocular and systemic degree of SJS as evaluated using AOS (P < .01), ASS (P < .01), and COMS (P < .01). Patients with severe MGD had a higher AOS (P < .01) and COMS (P = .02) values than those without severe MGD. On multivariate analysis, AOS higher than 2 was a significant risk factor for developing severe MGD (P = .03).MGD was a common ocular manifestation with SJS patients. Severity of meibomian gland parameters was correlated with AOS, ASS, and COMS, and the presence of acute ocular complications was a risk factor for severe MGD in patients with SJS.