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Purpose To investigate the effects of preoperative Lipiflow (Johnson & Johnson, Jacksonville, FL, USA) treatment before cataract surgery on meibomian gland dysfunction (MGD) and dry eye induced by surgery. Design Prospective, randomized controlled study. Methods This study comprised 124 eyes of 124 patients with planned surgery for senile cataract. Participants were randomly allocated into control and Lipiflow groups based on administration of Lipiflow treatment 3 weeks before cataract surgery. For meibomian gland (MG) evaluation, MG atrophy, degree of gland expressibility, and quality of gland secretions were examined at the baseline visit and 1 and 3 months postoperatively. Ocular surface parameters of tear film break-up time, Oxford corneal staining score, and tear film lipid layer thickness were measured at each visit. Ocular Surface Disease Index and Dry Eye Questionnaire were also assessed. Results The control group exhibited a significant decrease in MG expressibility, worsened meibum quality, decreased lipid layer thickness, and worsened corneal staining after cataract surgery. Also, dry eye symptom showed significant worsening. Conversely, the Lipiflow group showed significantly improved MG patency and meibum quality, increased tear film break-up time, and reduced corneal staining, and presented improved subjective outcomes reported on both Ocular Surface Disease Index and Dry Eye Questionnaire. The improvement of each parameter in the Lipiflow group showed a linear correlation with baseline MGD grade. In addition, patients without baseline MGD showed less worsening or improvement of MGD and dry eye induced by surgery, with preoperative Lipiflow treatment. Conclusions Preoperative Lipiflow treatment conducted before cataract surgery may be a safe and effective intervention for relieving MGD and dry eye induced by surgery. It might be recommended not only for the patients with preoperative MGD but also for those without baseline MGD, to prevent the development of MGD and dry eye induced by ocular surgeries.

Purpose: The purpose of this study is to establish consensus among experts on outcomes and methods to be used in clinical trials to assess adverse effects of anti-glaucomatous eye drops. Design: Modified Delphi method. Methods: Clinical experts from Europe, North America, South America, the Middle East, and Asia were invited to participate in two sequential web-based surveys administered from June 27 to August 29, 2021. A total of 91 clinical experts were invited to participate. Of these, 71 (78%) experts from 23 different countries accepted the invitation and answered the first questionnaire. The importance of items was ranked using a 10-point scale (1 as not important, 10 as very important). Results: A total of 84 items were rated in round one by 71 participants. Of these, 68 (81%) reached consensus. In round two, 19 items, including three additional items, were rated by 53 (75%) participants. Consensus was reached in 98% of investigated items. Eight outcomes were agreed as important to assess when conducting future trials: ocular surface, dryness, epithelial damage, local adverse effects related to eye drops as reported by patients, periocular surroundings and eyelids, quality of life questionnaires, hyperemia, visual acuity, tear film, and anterior chamber inflammation. Conclusion: We propose a consensus-based series of outcomes and assessment methods to be used in clinical trials assessing adverse effects of anti-glaucomatous eye drops. This will hopefully improve the comparability of results from future trials and thus facilitate meta-analyses and progress in this field.

The purpose of this study was to compare the efficacy of Intense Pulsed Light (IPL) therapy for meibomian gland dysfunction (MGD) using the new AQUA CEL (AC, Jeisys) device and the traditional M22 (Lumenis) device. A total of 59 eyes of 59 patients with MGD (12 men and 47 women, mean age 49 ± 12 years) were enrolled. They randomly received four sessions of IPL therapy every three weeks either with AC (30 eyes) or M22 (29 eyes). Standard Patient Evaluation of Eye Dryness (SPEED) questionnaire score, noninvasive breakup time (NIBUT), lid margin abnormalities, corneal and conjunctival fluorescein staining, fluorescein breakup time (FBUT), Schirmer’s test, meiboscore and meibum grade were evaluated before treatment and one month after treatment. Before IPL, no significant differences were seen in age, gender, or measured parameters between the AC and M22 groups (p > 0.05, respectively). SPEED score, NIBUT, lid margin abnormalities, fluorescein staining, FBUT, and meibum grade improved significantly in both groups after IPL compared to before IPL (p < 0.001, respectively). There were no significant differences in measured parameters between the two groups after IPL (p > 0.05, respectively). IPL therapy with AC and M22 devices has been shown to be equally effective for the treatment of MGD.

The meibomian glands are lipid-secreting glands located in the tarsal plates, whose secretory products cover the tear film, thereby reducing evaporation as well as ensuring lubrication of the ocular surface. The meibomian glands can be visualized at different levels of magnification by infrared meibography, laser confocal microscopy, and optical coherence tomography. These imaging modalities have been subject to much research and progress in clinical practice and have shaped our current understanding of meibomian glands in health and disease. In this review, we explore the evolution of meibography over the past decades, the major contributions of various meibographic modalities, and discuss their clinical significance.

This review examines currently available non‐pharmaceutical treatment modalities for meibomian gland dysfunction. A detailed search of the PubMed and MEDLINE databases was performed to identify original articles in English that have evaluated such nonpharmaceutical therapies in patients with this condition. Conventional therapies such as application of a warming compress, the practice of lid hygiene, and manual expression of meibomian glands as well as more technologically advanced approaches such as intraductal probing, thermal pulsation, and intense pulsed light therapy are included in the review. These non‐pharmaceutical treatment options may each have a role to play in the management of meibomian gland dysfunction, but more studies are necessary to compare treatments directly under identical experimental conditions in order to determine their relative efficacy. Additional large‐scale, randomised, controlled trials are also required to provide more information such as the specific indications best suited to each treatment modality, the efficacy of such approaches in combination with pharmaceutical‐based therapy, and the mechanisms of action of some of the more technologically advanced systems.

Purpose To review the published literature related to application of intense pulsed light (IPL) for treating meibomian gland dysfunction (MGD). Methods The literature search included the PubMed database and used the keywords “Intense Pulsed Light and Meibomian Gland Dysfunction”. Results IPL is a new instrumental treatment modality for MGD. This treatment modality was originally developed for use in dermatology and was later adopted in ophthalmology for treating MGD. IPL therapy for MGD can improve tear film stability, meibomian gland functionality, as well as subjective feeling of ocular dryness. However, in the reviewed literature, there was great variability in patient selection, evaluation criteria, and treatment protocols and durations. Conclusion Numerous studies report that IPL is effective for treating MGD and a safe procedure. There is great potential for further improvements to the procedure, as large comparative studies employing different treatment modalities are lacking.

Purpose To examine the safety and efficacy of azithromycin eyedrops in Japanese individuals with meibomian gland dysfunction (MGD)-associated posterior blepharitis. Methods Individuals with MGD-associated posterior blepharitis who visited the Itoh Clinic, Saitama, Japan, were randomly assigned to receive azithromycin (1%) eyedrops (AZM group, 16 eyes of 16 patients) or preservative-free artificial tears (control group, 20 eyes of 20 patients) for 2 weeks. All subjects also applied a warming eyelid compress twice per day. Subjective symptoms (Standardized Patient Evaluation of Eye Dryness [SPEED] score), lipid layer thickness (LLT) and interferometric pattern of the tear film, plugging and vascularity of the lid margin, noninvasive break-up time of the tear film (NIBUT) and fluorescein-based break-up time of the tear film (TBUT), corneal-conjunctival fluorescein staining score, tear meniscus height, meibum grade, meiboscore, tear osmolarity, and Schirmer test value were determined before and after treatment. Side effects of treatment were also recorded. Results In the AZM group, SPEED score, LLT, interferometric pattern, plugging and vascularity of the lid margin, NIBUT, TBUT, meibum grade, and tear osmolarity were significantly improved after treatment compared with baseline. The SPEED score, interferometric pattern, plugging, vascularity, meibum grade, and tear osmolarity were also significantly improved after treatment in the AZM group compared with the control group. Common side effects in the AZM group were transient eye irritation and blurred vision. Conclusion Azithromycin eyedrops improved eyelid inflammation, the quality and quantity of the lipid layer of the tear film, and tear film stability. Such eyedrops thus seem to be a safe and effective treatment for MGD-associated posterior blepharitis.

The primary role of meibomian glands (MGs) is to actively synthesize and secret lipids and proteins spread onto the tear film, and the glandular lipids promote tear stability, prevent evaporation, and reduce friction. Meibomian gland dysfunction (MGD) is the leading cause of dry eye disease and one of the most common ophthalmic problems worldwide. MGs are densely innervated and regulated by hormones and growth factors. However, since the polar and nonpolar lipids are produced through processes in MGs that are not completely understood, a relevant question has been raised: Would the altered systemic lipids metabolism affect the physiology and structure of MGs? This review introduces the recent update regarding the relationships between serum lipid and MGD in clinical and basic research while providing answers to this question. A causal relationship remains to be established; however, serum lipid level or dyslipidemia may be related to MGD directly or indirectly, or both. Further studies are warranted to establish the role of serum lipid level and meibocyte differentiation/maturation and lipid synthesis.

Stress might activate sympathetic nerve activity, causing dry eye (DE). We investigated biological parameters reflecting autonomic nerve activity in DEs with decreased tear stability. This prospective, cross-sectional, comparative study enrolled 34 eyes of 34 participants (mean age: 52.5 ± 13.4 years; range: 20–81 years) without keratoconjunctival damage. The 19 eyes in the DE group showed DE symptoms and tear break-up time (BUT) ≤ 5 seconds (short BUT DE); the 15 eyes in the non-DE group showed no DE symptoms. Autonomic nerve activity was measured for 10 minutes—starting and ending 5 minutes before and after instilling ophthalmic solution—and evaluated using the low-frequency component (LF) to the high-frequency component (HF) ratio of heart rate variability (autonomic balance). The pre-instillation LF/HF ratio was not significantly different (P = 0.86). The pre-instillation standard deviation of the LF/HF ratio (LF/HF-SD) was higher in the DE group than in the non-DE group (P = 0.05). DE symptoms intensity was significantly related to LF/HF-SD (P = 0.005). The LF/HF-SD significantly decreased post-instillation in the DE group (P = 0.03). The large fluctuations observed in the autonomic balance were related to DE symptom intensity in short BUT DE and may improve understanding of the DE-symptom mechanism.

Symptom overlap between meibomian gland dysfunction (MGD) and dry eye (DE) makes it difficult to distinguish between these two conditions on the basis of symptoms alone. We searched for characteristic symptoms that might help to distinguish MGD from DE on the basis of a population-based study. Subjects comprised 311 residents of Takushima island (18 to 96 years), including 117 individuals with MGD and 114 with DE. Responses to a symptom-related questionnaire (19 items) were subjected to factor analysis, and univariate regression analysis was performed to identify ocular surface parameters associated with characteristic symptoms of MGD. Factor analysis revealed aggregation of symptoms according to three factors: Factor 1 related to Symptom Score, Factor 2 to DE, and Factor 3 to MGD. Symptoms associated with DE included 11 items, whereas the only item related to MGD was tearing sensation. Pearson’s correlation analysis revealed that tearing sensation was associated with tear meniscus height (TMH), noninvasive tear-film breakup time, fluorescein staining score, meiboscore, meibum grade, and Schirmer value. Subjects with MGD experienced significantly more tearing and had a larger TMH than did those without MGD (p = 0.0334). Tearing sensation may thus be a characteristic symptom of MGD. Physicians should suspect MGD who complain of tearing sensation.

Glaucoma is a leading cause of irreversible blindness. The use of topical eye drops to reduce intraocular pressure remains the mainstay treatment. These eye drops frequently contain preservatives designed to ensure sterility of the compound. A growing number of clinical and experimental studies report the detrimental effects of not only these preservatives but also the active pharmaceutical compounds on the ocular surface, with resultant tear film instability and dry eye disease. Herein, we critically appraise the published literature exploring the effects of preservatives and pharmaceutical compounds on the ocular surface. publishedVersion

1&alpha, 25-dihydroxy-22-oxacalcitriol (maxacalcitol) is a non-calcemic vitamin D3 analog clinically approved to treat psoriasis, and its role has been increasingly recognized in suppressing keratinocyte proliferation, mediating inflammation, and regulating the immune response. A large number of studies have suggested that vitamin D plays an important role in maintaining ocular surface health. However, its topical effects on the Meibomian gland (MG) has been insufficiently investigated. Here, we introduce an experimental MG orifice injury model, where the partial glandular loss occurred after electrical cauterization on a limited number of MG orifices, and investigate the efficacy and safety of maxacalcitol ointment in treating this MG orifice injury model. We confirm the alleviation of MG atrophy and ductal dilation by maxacalcitol ointment application. The recovery of injured MG visualizing as the residual MG area is significantly better in the maxacalcitol group (p = 0.020) compared with the Vaseline&reg, group, especially during the first two weeks. The cornea and other ocular tissues were not affected by maxacalcitol ointment application during our two-month observation period. Altogether, this work indicates that maxacalcitol has therapeutic potential in the amelioration of initial injury of MG orifices caused by electrocautery.

Purpose To evaluate the prevalence and risk factors of and the relationship between meibomian gland dysfunction (MGD) and dry eye (DE) in Japan. Design A population-based cross-sectional study. Methods Participants filled in questionnaires regarding ocular symptoms, systemic diseases, and lifestyle factors. Meibomian gland-related parameters and tear film-related parameters were evaluated. Risk factors for MGD and DE were analyzed by using univariate and multivariate logistic regression. Age-specific prevalence of MGD and DE was estimated by using a general additive model with degree-3 natural splines. The structural relation between MGD and DE was assessed by factor analysis using the principal components method and promax rotation. Results A total of 356 residents of Takushima Island (133 males, 223 females) at the mean ± SD age of 55.5 ± 22.4 years (range, 6-96 years) were enrolled. The prevalence of MGD and DE was 32.9% and 33.4%, respectively, with a coexistence rate of 12.9%. The prevalence of MGD was associated with male sex (odds ratio [OR], 2.42), age (OR per decade increment,1.53), and oral intake of lipid-lowering agents (OR, 3.22). The prevalence of DE was associated with female sex (OR, 3.36), contact lens wear (OR, 2.84), conjunctivochalasis (OR, 2.57), and lid margin abnormalities (OR, 3.16). The age-specific prevalence of MGD and DE differed, and factor analysis for 16 parameters showed that MGD and DE had independent hidden sources (interfactor correlation, −0.017). Conclusions MGD and DE are common in this population. Although their ocular symptoms are similar, the pathogenesis of MGD differs from that of DE.

Objective To investigate meibomian gland (MG) morphology by noncontact infrared meibography in Shih Tzu dogs with or without keratoconjunctivitis sicca (KCS). Procedures Fourteen eyes of 12 Shih Tzu dogs (mean age of 10.7 years, range of 7‐13 years) presented to Yakumo Animal Hospital or Triangle Animal Eye Clinic from 2011 to 2017 with clinical signs and a Schirmer tear test (STT) result consistent with KCS ( 15 mm/min served as healthy controls. Both groups of dogs underwent routine slitlamp biomicroscopy followed by noncontact infrared meibography of the upper eyelid with both desktop‐type and mobile‐type systems. Results Meibography revealed morphological abnormalities of MGs in 13 eyes of 11 dogs with KCS. The abnormalities included gland shortening in 64% and gland dropout in 64% of the 14 eyes in the KCS group. Morphological changes were also observed in MGs of 16 eyes of 10 dogs in the control group. These changes included shortening in 46% and dropout in 17.8% of the 28 eyes in the control group. Dropout was significantly more common in eyes with KCS than in control eyes (P

The unstable balance in secretions of lipids and aqueous fluid to tear film is a significant cause of dry eye disease (DED). Arita et al. demonstrated a simple but very effective method that classifies dry eye types to the aqueous deficient dry eye (ADDE) and the evaporative dry eye (EDE) by focusing on the dry eye type-unique appearances of interference fringe colors and patterns of tear films. We thought this simple classification is very helpful for diagnoses and treatments. However, diagnostic bias by unskilled observers remains an issue to be solved. The artificial intelligence (AI)-based support for diagnosis is one of the hottest topics in the field of ophthalmology research. We expected that the AI-based model would reduce bias in DED-type diagnoses. Many studies have been reported targeting retinal diseases like age-related macular degeneration and/or diabetic retinopathy. Most of the works established AI-based predicting models using images taken by fundus cameras and/or optical coherence tomography (OCT) devices to capture disease-related structural disorders. In contrast, the interference fringes dynamically change the colors and patterns spatiotemporally. To the best of our knowledge, there is no AI-based model studied for distinguishing ADDE and EDE using interference fringe images. However, an AI-based study classifying the condition of the tear lipid layer by analyzing the textures of interference fringes compared to the device-unique grades has been reported. This suggested the possibility of using the unstructured characteristics, such as colors and/or complexities of interference fringes, as the numerical image features when building AI-based prediction models. In this study, we first examined several types of image characteristics extracted from the colors and patterns of fringes to obtain effective image features for the DED-type classification. We then evaluated whether the AI-based models would have sufficient abilities for this type of prediction by comparing their diagnoses with those made by an ophthalmologist skilled in this classification (the founder of this type classification).

Purpose: To analyze the correlation between systemic lipid profile levels and each meibomian gland dysfunction (MGD) subtype in Korea.Methods: The ophthalmic data of 95 eyes and the serum lipid profiles of 95 patients were reviewed. These factors were compared with those of the general population using data from the Korean National Health and Nutrition Examination Survey (KNHANES), which evaluated 2,924 subjects. Of these, 475 propensity score-matched normal controls were selected for comparison with the 95 MGD patients based on a 1:5 ratio. In addition, we analyzed the correlations between serum lipid profile levels and MGD subtypes in MGD patients.Results: The mean high-density lipoprotein (HDL) value of the MGD patients was significantly higher than that of the general population (P < 0.0001). However, the mean total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL) levels of the MGD patients were not significantly different from those of the general population (TC: P = 0.3950, TG: P = 0.6331, LDL: P = 0.2079). In addition, no serum lipid levels statistically differed among the MGD subtypes (TC: P = 0.7650, HDL: P = 0.2480, LDL: P = 0.3430, TG: P = 0.7030).Conclusion: A statistically significant, but marginal, increase in HDL concentration was observed in the MGD group, although there was no difference in any serum lipid level among the MGD subtypes.

To evaluate the efficacy and safety of intense pulsed light (IPL) combined with meibomian gland expression (MGX) for the treatment of refractory multiple and recurrent chalazia without surgery or curettage. This was a retrospective controlled study. Patients with multiple and recurrent chalazia, who had performed the conventional treatment at least 2 months without any surgery or curettage, were enrolled in this study. Twenty-nine consecutive multiple recurrent chalazia (12 patients) were assigned to receive either the combination of IPL and MGX or MGX alone as a control. Each eye underwent one to four treatment sessions with 2-week intervals. Parameters were evaluated before and 1 month after the final treatment session. Clinical assessments included symptom, size of each chalazion, lid margin abnormalities, corneal and conjunctival fluorescein staining, meibum grade, the number of Demodex mites, the Schirmer value and meiboscore. All parameters except meiboscore and the Schirmer value were significantly improved with IPL-MGX therapy, whereas only meibum grade was significantly improved with MGX alone. There were no adverse events which occurred in either group. IPL-MGX was safe and effective for multiple and recurrent chalazia without surgery or curettage by reducing the size of chalazion and improving lid margin abnormalities and meibum grade.

Meibomian gland dysfunction (MGD) is a major cause of dry eye, affecting millions worldwide. Intraductal meibomian gland probing (MGP) aims to open obstructed meibo-mian glands using a small probe to promote meibum secretion. MGP has received increasing interest since 2010, and we critically evaluated the literature on the efficacy and safety of MGP. Despite positive results of MGP on dry eye symptoms in early single-group studies, MGP was not shown to consistently outperform controls in later controlled trials. Furthermore, MGP alone did not show improvement beyond placebo in the only placebo-controlled RCT conducted. Overall, the procedure appears safe. Self-limited intra-operative bleeding was frequent, but no major complications were reported. In conclusion, MGP has not yet been shown to be an effective treatment for MGD. Larger placebo-controlled trials need to be conducted to establish the potential effect of this novel treatment modality. (c) 2020 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Aqueous-deficient dry eye (ADDE) and meibomian gland dysfunction (MGD) can be refractory to therapy. Intense pulsed light (IPL) was recently introduced as an effective treatment for MGD. We here evaluated the efficacy of IPL combined with MG expression (MGX) compared with MGX alone (n = 23 and 20, respectively) for patients with refractory ADDE with mild MGD at three sites. Symptom score, visual acuity (VA), noninvasive breakup time (NIBUT) and lipid layer thickness (LLT) of the tear film, lid margin abnormalities, fluorescein BUT (FBUT), fluorescein staining, tear meniscus height (TMH), meibum grade, meiboscore, and Schirmer&rsquo, s test value were assessed at baseline and 1 and 3 months after treatment. LLT, plugging, vascularity, FBUT and NIBUT were improved only in the IPL-MGX group at three months compared with baseline. All parameters with the exception of VA, meiboscore, TMH, Schirmer&rsquo, s test value were also improved in the IPL-MGX group compared with the control group at three months, as was VA in patients with central corneal epitheliopathy. Although IPL-MGX does not affect aqueous layer, the induced improvement in quality and quantity of the lipid layer may increase tear film stability and ameliorate symptoms not only for evaporative dry eye but for ADDE.

PURPOSE Meibomian glands are subject to regulation by sex hormones. We have now investigated the possible relation between benign prostate hyperplasia (BPH) and meibomian gland dysfunction (MGD). METHODS Men diagnosed with BPH and receiving treatment with tamsulosin and age-matched male control subjects who attended Itoh Clinic, Saitama, Japan, were enrolled. An ocular symptom score, lid margin abnormality score, and superficial punctate keratopathy score as well as the meiboscore (0-6), meibum grade, breakup time of the tear film, and Schirmer test values were evaluated. Male pattern baldness was also graded according to the Hamilton-Norwood scale. RESULTS Forty-four eyes of 44 men with BPH (mean age ± SD, 76.1 ± 2.2 years) and 46 eyes of 46 control subjects (mean age ± SD, 75.3 ± 6.2 years) were enrolled. The meiboscore in the BPH group (4.5 ± 1.4) was significantly higher than that in the control group (1.8 ± 1.5, P < 0.0001). Breakup time of the tear film was significantly shorter (3.6 ± 1.7 vs. 5.6 ± 2.5 seconds, P < 0.0001), and Schirmer test value was significantly smaller (9.8 ± 4.8 vs. 13.3 ± 8.0 mm, P = 0.048) in the BPH group than that in the control group. Other ocular parameters did not differ significantly between the 2 groups. The proportion of men with androgenic alopecia was also higher in the BPH group than that in the control group. CONCLUSIONS BPH was associated with meibomian gland loss and instability of the tear film as well as with the presence of androgenic alopecia.

Purpose: To evaluate the efficacy of intense pulsed light (IPL) therapy combined with meibomian gland expression (MGX) for refractory meibomian gland dysfunction (MGD) in a prospective study conducted at 3 sites in Japan. Methods: Patients with refractory obstructive MGD were enrolled and underwent 4 to 8 IPL-MGX treatment sessions at 3-week intervals. Clinical assessment included the Standard Patient Evaluation of Eye Dryness questionnaire; noninvasive breakup time of the tear film and interferometric fringe pattern as determined by tear interferometry; lid margin abnormalities, fluorescein breakup time of the tear film, corneal and conjunctival fluorescein staining (CFS), and meibum grade as evaluated with a slit-lamp microscope; meibomian gland morphology (meiboscore); and tear production as measured by the Schirmer test without anesthesia. Results: Sixty-two eyes of 31 patients (17 women, 14 men; mean age ± SD, 47.6 ± 16.8 years) were enrolled. The Standard Patient Evaluation of Eye Dryness score (P < 0.001), noninvasive breakup time (P < 0.001), and interferometric fringe pattern (P < 0.001) were significantly improved after therapy, with 74% of eyes showing a change in the interferometric fringe pattern from 1 characteristic of lipid deficiency to the normal condition. Meibum grade, lid margin abnormality scores, fluorescein breakup time, and CFS were also significantly improved (P < 0.001, P < 0.001, P < 0.001, and P = 0.002, respectively) after treatment, whereas the meiboscore and Schirmer test value remained unchanged. Conclusions: IPL-MGX ameliorated symptoms and improved the condition of the tear film in patients with refractory MGD and is therefore a promising treatment option for this disorder.

Meibomian glands secrete lipids (meibum) that form the surface lipid layer of the tear film and thereby prevent excessive evaporation of tear fluid. Meibomian gland dysfunction is a major cause of evaporative dry eye, which is more prevalent than aqueous-deficient dry eye. Noninvasive meibography with infrared light and an infrared charge-coupled device camera can detect morphological changes of meibomian glands in both upper and lower eyelids, whereas tear interferometry allows qualitative and quantitative evaluations of the lipid layer of the tear film. Such assessment of meibomian gland morphology provides clinical information that contributes to the diagnosis of evaporative dry eye, whereas that of the lipid layer of the tear film allows the monitoring of meibomian gland function. In addition, the balance between the lipid and aqueous layers of the tear film revealed by tear interferometry has provided both support for the operation of a compensatory system that maintains tear film homeostasis as well as insight into the pathophysiology of dry eye.

Purpose To evaluate the effect of 3% diquafosol ophthalmic solution on tear film lipid layer thickness (LLT) in normal human eyes by tear interferometry. Methods Forty-seven healthy men (mean age of 42.4 years) randomly received one drop of artificial tears in one eye and one drop of 3% diquafosol ophthalmic solution in the other. LLT of each eye was quantified by tear interferometry before and 15, 30, and 60 min after instillation. Ocular symptoms were assessed before and 30 min after instillation. Baseline LLT, tear film breakup time (TBUT), meibomian gland area (meiboscore) of the upper and lower eyelids, and Schirmer test value were evaluated on a different day before treatment. Results LLT before and 15, 30, and 60 min after diquafosol instillation was 62.3 ± 31.1, 77.0 ± 39.5, 79.3 ± 40.5, and 77.7 ± 43.6 nm, respectively, with the diquafosol-induced increase in LLT being significant at each time point. Artificial tears did not result in a significant increase in LLT. TBUT (ρ = 0.32, P = 0.026), meiboscore of the lower eyelid (ρ = −0.33, P = 0.022), and the maximum difference in LLT between before and after diquafosol instillation (ΔLLT max ) (ρ = 0.35, P = 0.016) were significantly correlated with baseline LLT in the diquafosol group. Age was not significantly related to baseline LLT or ΔLLT max . Symptoms did not differ significantly between the two groups. Conclusions Topical instillation of 3% diquafosol ophthalmic solution increased LLT for up to 60 min in normal human eyes regardless of age.

PurposeTo examine effects of alkali injury of the ocular surface on meibomian gland pathology in mice.MethodsThree μL of 1N NaOH were applied under general anesthesia to the right eye of 10-week-old BALB/c (n=54) mice to produce a total ocular surface alkali burn. The meibomian gland morphology was examined at days 1, 2, 5, 10, and 20 by stereomicroscopy and non-contact infrared meibography. Mice were then sacrificed and eyelids processed for histology with hematoxylin-eosin and immunohistochemistry for ELOVL4, PPARγ, myeloperoxidase (a neutrophil marker) and F4/80 macrophage antigen, as well as TUNEL staining. Another set of specimens was processed for cryosectioning and Oil red O staining.ResultsAlkali injury to the ocular surface produced cellular apoptosis, infiltration of neutrophils and macrophages, degeneration of the meibomian gland, and ductal dilation. Inflammation in and destruction of acunal stricture seemed more prominent in the lower eyelid, while duct dilation was more frequently observed in the upper eyelid during healing. Surviving acinar cells were labeled for ELOVL4 and PPARγ. Oil red O staining showed that the substance in the dilated duct contained predominantly neutral lipid.ConclusionsAlkali injury to the ocular surface results in damage and destruction of the eyelid meibomian glands. The pattern of the tissue damage differs between glands of the upper and lower eyelids.

Meibomian glands secrete meibum, which gives rise to the lipid layer of the tear film and thereby prevents excessive evaporation of tear fluid. Meibomian gland dysfunction (MGD) is a major causative condition of evaporative dry eye, which is more common than the aqueous-deficient type of dry eye. Noninvasive meibography relies on infrared light and an infrared-sensitive camera to reveal the morphology of meibomian glands in both the upper and lower eyelids, whereas tear interferometry allows both qualitative and quantitative evaluation of the lipid layer of the tear film. These two techniques not only provide valuable clinical information related to dry eye but also allow clinical evaluation of MGD. Tear interferometry also has the potential to distinguish the condition of the tear film between normal individuals and dry eye patients. Furthermore, combined evaluation of the noninvasive breakup time of the tear film and the interferometric fringe pattern as determined by tear interferometry allows classification of the subtype of dry eye disease.

The role of the Tear Film and Ocular Surface Society (TFOS) Dry Eye Workshop (DEWS) II Diagnostic Methodology Subcommittee was 1) to identify tests used to diagnose and monitor dry eye disease (DED), 2) to identify those most appropriate to fulfil the definition of DED and its sub-classifications, 3) to propose the most appropriate order and technique to conduct these tests in a clinical setting, and 4) to provide a differential diagnosis for DED and distinguish conditions where DED is a comorbidity. Prior to diagnosis, it is important to exclude conditions that can mimic DED with the aid of triaging questions. Symptom screening with the DEQ-5 or OSDI confirms that a patient might have DED and triggers the conduct of diagnostic tests of (ideally non-invasive) breakup time, osmolarity and ocular surface staining with fluorescein and lissamine green (observing the cornea, conjunctiva and eyelid margin). Meibomian gland dysfunction, lipid thickness/dynamics and tear volume assessment and their severity allow sub-classification of DED (as predominantly evaporative or aqueous deficient) which informs the management of DED. Videos of these diagnostic and sub-classification techniques are available on the TFOS website. It is envisaged that the identification of the key tests to diagnose and monitor DED and its sub-classifications will inform future epidemiological studies and management clinical trials, improving comparability, and enabling identification of the sub-classification of DED in which different management strategies are most efficacious.

Purpose: We measured tear film parameters, including the morphology and function of meibomian glands, in junior high school students at 15 years of age. Methods: A total of 111 eyes of 111 students (56 males and 55 females) were enrolled in the study. The ocular symptom score (0–14), after-school study time, lipid layer thickness (LLT) of the tear film, partial blink rate, lid margin abnormalities (0–4), tear film breakup time, corneal and conjunctival epithelial damage (fluorescein staining score, 0–9), meiboscore as determined by noncontact meibography (0–6), Schirmer test value, and meibum grade (0–3) were determined. The relationships between parameters were evaluated with the Spearman correlation coefficient (ρ). Results: The meiboscore was 2.8 ± 1.2, and the meibum grade was 1.8 ± 1.2. The meiboscore significantly correlated with the meibum grade (ρ = 0.272, P = 0.004), Schirmer test value (ρ = −0.220, P = 0.021), and LLT (ρ = −0.264, P = 0.005). The breakup time significantly correlated with LLT (ρ = 0.261, P = 0.006), meibum grade (ρ = −0.338, P < 0.001), and fluorescein staining score (ρ = −0.214, P = 0.025). The partial blink rate significantly correlated with the Schirmer test value (ρ = −0.240, P = 0.011). The meiboscore (P < 0.001) and meibum grade (P = 0.032) were significantly greater in males than in females. Conclusions: The morphology and function of meibomian glands are altered even at 15 years of age, with the changes being more prominent in males than in females.

Objective To compare the superficial punctate fluorescein staining in dogs with and without aqueous tear deficiency. Procedures An eye from each client‐owned dogs presented to Triangle Animal Eye Clinic between January and December 2018 underwent tear and ocular surface tests, which included the Schirmer tear test (STT), phenol red thread test (PRT), and strip meniscometry tube tear test (SMT). Punctate fluorescein staining of the cornea (PFS‐C) and the upper palpebral conjunctiva (PFS‐UPC) were also performed. Fifty‐seven dogs with STT results of

Purpose To develop and assess a method for quantitation of lower tear meniscus height (TMH) with the Kowa DR-1α tear interferometer. Methods Sixty-nine eyes of 49 men and 20 women (36 healthy volunteers, 33 patients with aqueous-deficient dry eye [ADDE]; mean age ± SD, 50.0 ± 14.0 years) were enrolled. TMH of each subject was measured by two observers both with DR-1α and newly developed software and with anterior-segment swept-source optical coherence tomography (SS-OCT). Intraoperator repeatability and interoperator and intersession reproducibility of measurements were assessed based on the within-subject SD (Sw), coefficient of variation (CV), and intraclass correlation coefficient (ICC). Agreement between the two devices was assessed by regression and Bland-Altman analysis. Results The CV for system repeatability of DR-1α was

Meibomian glands are located in the eyelids and secrete meibum, which gives rise to the lipid layer of the tear film. Changes to these glands can lead to the development of meibomian gland dysfunction (MGD), which is associated with various ocular symptoms such as fatigue, dryness, burning sensation, and heavy sensation. The diagnosis of MGD thus relies on evaluation of ocular symptoms, meibum condition, and lid margin abnormalities. The recent development of noninvasive meibography and tear interferometry has provided important insight into meibomian gland structure and function, respectively. Wearers of contact lenses complain of ocular symptoms that are thought to be attributable to a variety of causes, such as a diminished aqueous or mucin layer of the tear film, changes in tear protein concentration, and altered meibomian gland structure or function. Many studies have examined the relation between contact lens wear and meibomian gland changes. Such studies have found that lens wear is associated with adverse changes in meibomian gland morphology and in the condition of the lid margin and meibum, suggesting that contact lenses negatively affect meibomian glands. Meibomian gland dysfunction-like changes in meibomian glands induced by contact lens wear may thus be responsible for at least some of the ocular symptoms in lens wearers.

Intervention studies have shown that n-3 polyunsaturated fatty acid (PUFA) supplementation is effective for the treatment of meibomian gland dysfunction (MGD). Ointment containing an analog of vitamin D has also been found to improve symptoms and signs of MGD. We have now evaluated the relation of MGD prevalence to dietary intake of fatty acids (FAs) and vitamin D among a Japanese population. Subjects comprised 300 adults aged 20 to 92 years residing on Takushima Island. MGD was diagnosed on the basis of subjective symptoms, lid margin abnormalities, and meibomian gland obstruction. Dietary FA and vitamin D intake was estimated with a brief-type self-administered diet history questionnaire. MGD prevalence was 35.3%. Multivariate adjusted odds ratios (95% confidence intervals) between extreme quintiles of intake for MGD prevalence were 0.40 (0.16&ndash, 0.97) for total fat, 0.40 (0.17&ndash, 0.97) for saturated FAs, 0.40 (0.17&ndash, 0.97) for oleic acid, 0.52 (0.23&ndash, 1.18) for n-3 PUFAs, 0.63 (0.27&ndash, 1.49) for n-6 PUFAs, 1.32 (0.59&ndash, 2.95) for the n-6/n-3 PUFA ratio, and 0.38 (0.17&ndash, 0.87) for vitamin D. Total fat, saturated FA, oleic acid, and vitamin D intake may thus be negatively associated with MGD prevalence in the Japanese.

Although the pathophysiology of meibomian gland dysfunction (MGD) remains incompletely understood, many treatment options have recently become available. According to an international workshop report, treatment selection for MGD should be based on a comprehensive stage classification dependent on ocular symptoms, lid margin abnormalities, meibum grade, and ocular surface staining. However, it is often difficult to evaluate all parameters required for such classification in routine clinical practice. We have now retrospectively evaluated therapeutic efficacy in MGD patients who received five types of treatment in the clinic setting: (1) meibocare (application of a warm compress and practice of lid hygiene), (2) meibum expression plus meibocare, (3) azithromycin eyedrops plus meibocare, (4) thermal pulsation therapy plus meibocare, or (5) intense pulsed light (IPL) therapy plus meibocare. Patients in each treatment group were classified into three subsets according to the meiboscore determined by noncontact meibography at baseline. Eyes in the IPL group showed improvement even if the meiboscore was high (5 or 6), whereas meibocare tended to be effective only if the meiboscore was low (1 or 2). The meiboscore may thus serve to guide selection of the most appropriate treatment in MGD patients. Prospective studies are warranted to confirm these outcomes.

Meibography allows observation of meibomian glands in an objective and repeatable manner. Original meibography systems were invasive and not readily adopted by ophthalmology clinics. The development of noncontact infrared meibography allowed the rapid and noninvasive observation of meibomian glands, and such systems have now been widely adopted for standard examinations in dry eye clinics. Noncontact meibography has also spurred research into meibomian glands and has been applied to evaluation of their structure and status in various ocular surface diseases. Although the images obtained by meibography are objective and repeatable, the interpretation of these images is subjective, with the relationship between image features and actual gland structure and composition remaining unclear. Additional clinical and basic research with regard to the interpretation of meibography images is thus necessary. Future improvements to meibography will likely provide new insights into the pathophysiology of meibomian gland diseases as well as enhance its contribution to the diagnosis and evaluation of treatments for such diseases.

To evaluate the efficacy and safety of intense pulsed light (IPL) combined with meibomian gland expression (MGX) for treatment of refractory meibomian gland dysfunction (MGD).Ninety eyes of 45 patients were randomly assigned to receive either the combination of IPL and MGX or MGX alone (control). Each eye underwent eight treatment sessions at 3-week intervals. Parameters were evaluated before and during treatment as well as at 3-11 weeks after the last treatment session. Measured parameters included the Standard Patient Evaluation of Eye Dryness (SPEED) questionnaire score, noninvasive breakup time (NIBUT), fluorescein breakup time (BUT), lipid layer grade, lipid layer thickness (LLT), lid margin abnormalities, corneal and conjunctival fluorescein staining (CFS) score, meibum grade, and meiboscore.A significant improvement in lipid layer grade was apparent in the IPL-MGX group from 6 to 32 weeks after treatment onset (adjusted P 0.001) but was not observed in the control group. The IPL-MGX group also showed significant improvements in LLT, NIBUT, BUT, lid margin abnormalities, and meibum grade compared with the control group at 24 and 32 weeks (adjusted P 0.001) as well as significant improvements in the SPEED score at 32 weeks (adjusted P = 0.044) and in CFS score at 24 (adjusted P = 0.015) and 32 (adjusted P = 0.006) weeks.The combination of IPL and MGX improved homeostasis of the tear film and ameliorated ocular symptoms in patients with refractory MGD and is thus a promising modality for treatment of this condition.

Purpose The aim of this prospective, noncomparative, observational case series was to evaluate changes to meibomian gland morphology in patients undergoing S-1 chemotherapy with the use of noninvasive meibography and analytical software. Methods Patients aged ≥20 years and undergoing S-1 chemotherapy were included. Ophthalmologic examinations were performed before S-1 administration (Pre) and at 1, 3, and 6 months afterward (1M, 3M, and 6M, respectively). Meibography images were analyzed using analytical software. The ratio of the total meibomian gland area relative to the whole measurement area (meibomian gland area ratio [MGAR]) and the rate of change to the MGAR (MGAR at Pre, 1M, 3M, or 6M)/(MGAR at Pre) × 100 were calculated. Results In total, 28 eyelids of seven men (mean age, 68.9 ± 6.3 years) were studied. The mean MGAR of the upper and lower eyelids significantly decreased at 3M (P = 0.0246 and P = 0.00892, respectively) and 6M (P < 0.0001 and P < 0.0001, respectively). There was a significant negative correlation between the cumulative dose of S-1 and the rate of change to the MGAR of the upper (P < 0.0001, r = -0.77) and lower (P < 0.0001, r = -0.785) eyelids. However, there was no other significant difference. Conclusions The meibomian gland area decreased after S-1 administration with significant correlations between the rate of change to the MGAR and the mean cumulative dose of S-1. Translational Relevance Systemic S-1 administration decreased the MGAR in a dose-dependent manner; thus, clinicians should pay more attention to morphologic changes to the meibomian glands during early treatment with S-1.

Purpose To evaluate the effects of commercially available eyelid warming devices on ocular temperatures, tear film function, and meibomian glands in normal subjects and patients with meibomian gland dysfunction (MGD). Methods Ten healthy volunteers were enrolled to evaluate the effects of a single warming and of repeated warming for 2 weeks. Ten MGD patients were enrolled for evaluation of repeated warming over 1 month. Two non-wet (Azuki no Chikara, Eye Hot R) and three wet (hot towel, Hot Eye Mask, Memoto Este) devices were compared in a masked manner. Visual analog scale (VAS) score for ocular symptoms, tear film breakup time (TFBUT), meibum grade, temperatures (eyelid skin, tarsal conjunctiva, central cornea), Schirmer test value, and meibomian gland area were measured before and after warming application. Results The single application of the five warming devices improved the VAS score, TFBUT, and ocular temperatures. In the repeated warming application, Azuki no Chikara as a representative non-wet warming device induced a stable and significant improvement in TFBUT and increased the tarsal conjunctival temperature and meibomian gland area in both normal subjects and MGD patients. It also improved meibum grade in MGD patients. Conclusion Our results suggest that repeated eyelid warming with a non-wet device improves tear film function in normal individuals and may have beneficial effects on both tear film and meibomian gland function in MGD patients.

Purpose To compare tear film parameters as well as meibomian gland morphologic features and function among patients with meibomian gland dysfunction (MGD), those with non–Sjogren syndrome aqueous-deficient dry eye (non-SS ADDE), those with non-SS ADDE and MGD, and normal subjects. Design Multicenter, cross-sectional, observational case series. Participants Forty-one eyes of 41 patients (all women; mean age ± standard deviation, 62.1±9.9 years) with non-SS ADDE, 70 eyes of 70 patients (all women; 66.0±8.7 years) with MGD, 17 eyes of 17 patients (all women; 72.4±7.8 years) with non-SS ADDE and MGD, and 70 eyes of 70 normal control subjects (all women; 65.0±7.1 years). Methods Ocular symptoms were scored from 0 to 14 and lid margin abnormalities from 0 to 4 according to their respective number. Meibomian gland changes were scored from 0 to 6 (meiboscore) on the basis of noncontact meibography findings, and meibum was graded from 0 to 3 depending on its volume and quality. Conjunctival and corneal epithelial damage were scored from 0 to 9 (fluorescein score). Tear film break-up time (TBUT) was measured as an index of tear film stability, and tear fluid production was evaluated with Schirmer's test. Main Outcome Measures Ocular symptom score, lid margin abnormality score, meiboscore, meibum grade, fluorescein score, TBUT, and Schirmer's test value. Results The ocular symptom score did not differ significantly between the MGD and non-SS ADDE groups ( P = 0.762). The lid margin abnormality score, meiboscore, and meibum grade were significantly higher in the MGD group than in the non-SS ADDE group ( P = 0.0012, P P P P = 0.0061, and P P = 8.3×10 −6 ). Conclusions An increase in tear fluid production likely compensates for loss of meibomian glands in individuals with MGD.

Meibomian glands secrete the oily layer of the tear film, which prevents excessive evaporation of tear fluid. Dysfunction of meibomian glands is not only one of the causes of evaporative dry eye but also one of the main causes of entire dry eye. To understand the pathophysiology of meibomian gland dysfunction, it is important to evaluate both the morphology and function of the meibomian gland. We previously reported that meibography enabled visualization of the morphology of the meibomian gland. Meanwhile, tear interferometry was introduced as an evaluation method for the function of the meibomian gland. We combined observations of the oily layer and the aqueous layer of the tear film and found that a tear film compensatory system may work toward maintenance of tear film homeostasis. In this review, we describe both morphological evaluation systems for the meibomian gland, including noninvasive meibography, and functional evaluation systems, including tear interferometry. We further describe the morphological changes of the meibomian glands in various ocular surface diseases. Finally, we demonstrate the concept of a tear film compensatory system and propose a method for tear film component-oriented diagnosis.

Shima Fukuoka,1–3 Reiko Arita,2–4 Rika Shirakawa,2,3 Naoyuki Morishige2,5 1Department of Ophthalmology, Omiya Hamada Eye Clinic, 2Lid and Meibomian Gland Working Group (LIME), Saitama-shi, Saitama, 3Department of Ophthalmology, University of Tokyo School of Medicine, Bunkyo-ku, Tokyo, 4Department of Ophthalmology, Itoh Clinic, Saitama-shi, Saitama, 5Department of Ophthalmology, Oshima Eye Hospital, Fukuoka-shi, Fukuoka, Japan Purpose: To examine the changes in meibomian gland morphology and ocular higher-order aberrations (HOAs) in eyes with chalazion and its excision. Methods: Seven male patients with previous history of chalazion excision and seven control male subjects were enrolled. Changes in meibomian gland morphology (meiboscores, gland dropout, and shortening) were evaluated by using meibography equipped in a wavefront analyzer KR-1W and in a slit-lamp device BG-4M. Ocular HOAs were measured sequentially with KR-1W. The tear film breakup time (BUT) was measured. Results: Both KR-1W and BG-4M visualized meibomian gland as clear similar images. The tear film BUT (mean ± SD, 5.6±3.0 vs 9.4±2.3 seconds, P=0.025), the total meiboscore (median [interquartile range], 2 (2-3) vs 0 (0-1), P=0.007) as well as the meibomian gland dropout rate (86% vs 14%, P=0.008) and shortening rate (100% vs 29%, P=0.031) differed significantly between the patient and control groups. The first total ocular HOAs (0.142±0.063 vs 0.130±0.015, P=0.80) were similar in both groups, whereas the stability index of the total HOAs over time (0.0041±0.0048 vs -0.0012±0.0020, P=0.030) differed significantly between the patient and control groups. Conclusions: Chalazion and its excision were associated with dropout and shortening rate of meibomian glands. The morphological changes of meibomian glands in chalazion may be associated to instability of the tear film, which was suggested by the tear film BUT and the stability of ocular HOAs. Keywords: meibomian gland, meibography, wavefront analyzer, higher-order aberrations, chalazion excision