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    The application of in vivo laser confocal microscopy to the diagnosis and evaluation of meibomian gland dysfunction. Matsumoto Yukihiro,Sato Enrique Adan,Ibrahim Osama M A,Dogru Murat,Tsubota Kazuo Molecular vision PURPOSE:To evaluate the morphological changes of the meibomian glands (MG) in patients with meibomian gland dysfunction (MGD) compared to normal subjects by in vivo confocal microscopy and to investigate the relation of these changes to the clinical ocular surface findings and tear functions. METHODS:Twenty MGD patients and 15 normal subjects were recruited into this prospective study. Patients and controls underwent slit lamp examinations, tear film break-up time (BUT) measurements, fluorescein and Rose-Bengal stainings, Schirmer test I without anesthesia, tear evaporation rate assessment (TEROS), tear film lipid layer interferometry (DR-1), transillumination of the lids (meibography), MG expressibility test, and in vivo laser confocal microscopy of the lids (HRTII-RCM). RESULTS:The BUT, DR-1 tear film lipid layer interferometry grades, fluorescein and Rose-Bengal staining scores, MG drop out grade in meibography, and MG expressibility grades were significantly worse in MGD patients compared to normal controls (p<0.05). The severity of both MG dropout and MG expressibility related significantly with the BUT, DR-1 grades, and TEROS (p<0.05). The mean density of acinar units of MGs as measured by HRTII-RCM was significantly lower in MGD patients (47.6+/-26.6/mm(2)) than in control subjects (101.3+/-33.8/mm(2); p<0.05). The mean acinar unit diameter as determined by HRTII-RCM was significantly larger in MGD patients (98.2+/-53.3 mum) than in controls (41.6+/-11.9 mum; p<0.05). Both the density and diameter of MG acinar units related significantly with the severity of MG dropout and MG expression grades (p<0.05). CONCLUSIONS:In vivo confocal microscopy can effectively demonstrate the morphological changes of the MG in patients with MGD. Glandular acinar density and acinar unit diameter seemed to be promising new parameters of in vivo confocal microscopy, which is significantly related to the clinical ocular surface and tear function findings of MGD.
    Confocal Microscopy Evaluation of Meibomian Gland Dysfunction in Dry Eye Patients with Different Symptoms. Zhao Hui,Chen Jing-Yao,Wang Yu-Qian,Lin Zhi-Rong,Wang Shen Chinese medical journal BACKGROUND:Dry eye patients suffer from all kinds of symptoms. Sometimes, the clinical signs evaluation does not disclose any obvious difference in routine examination; in vivo confocal microscopy (IVCM) is a powerful tool for ocular surface disease. This study aimed to clarify meibomian gland (MG) alterations in dry eye patients with different symptoms and to compare the findings using IVCM. METHODS:A total of sixty patients were recruited, all subjected to Ocular Surface Disease Index (OSDI) and Salisbury Eye Evaluation Questionnaire (SEEQ), and questionnaires for the assessment of dry eye symptoms before clinical sign examinations were given to the patients. Finally, IVCM was applied to observe MG's structure. Statistical analysis was performed using the t-test, Mann-Whitney U-test and Spearman correlation analysis. The differences were statistically significant when P< 0.05. RESULTS:In the severe symptom group, OSDI and SEEQ scores were significantly higher (P< 0.05) compared with the mild symptoms group. All other clinical sign examinations had no statistical difference in the two groups (P> 0.05). However, all the IVCM-observed data showed that patients with severe symptoms had more significant fibrosis in MG (acinar unit area 691.87 ± 182.01 μm2 for the severe, 992.17 ± 170.84 μm2 for the mild; P< 0.05) and severer decrease in the size of MG acinar units than those observed in patients with mild symptoms (MG acinar unit density [MGAUD] 70.08 ± 18.78 glands/mm2, MG acinar unit longest diameter [MGALD] 51.50 ± 15.51 μm, MG acinar unit shortest diameter [MGASD] 20.30 ± 11.85 μm for the severe, MGAUD 89.53 ± 39.88 glands/mm2, MGALD 81.57 ± 21.14 μm, MGASD 42.37 ± 14.55 μm for the mild;P< 0.05). Dry eye symptoms were negatively correlated with MG confocal microscopic parameters and positively correlated with conjunctival inflammatory cells and Langerhans cells (P< 0.05). CONCLUSIONS:IVCM application provides a strong support to differentiate dry eye patients with different symptoms: meibomian gland dysfunction (MGD) plays a pivotal role in dry eye aggravation, and using IVCM to observe MG fibrosis, changes in size and density of MG as well as status of inflammation cells can help not only correctly diagnose the type and severity of dry eye, but also possibly prognosticate in routine eye examination in the occurrence of MGD. 10.4103/0366-6999.192782
    [A new classification for meibomian gland diseases with in vivo confocal microscopy]. Randon M,Liang H,Abbas R,Michée S,Denoyer A,Baudouin C,Labbé A Journal francais d'ophtalmologie INTRODUCTION:Meibomian gland dysfunction (MGD) is a frequent disorder often associated with dry eye disease. Slit-lamp examination with digital expression of the tarsal Meibomian glands allows examination of the contents of the distal Meibomian gland and the meatus. However, the Meibomian epithelium, interglandular space and proximal secretions cannot be clinically assessed. In vivo confocal microscopy (IVCM) is a rapid and non-invasive imaging technique that provides high-resolution images of the ocular surface and eyelids. The primary objective of the present study was to establish a classification of MGD with IVCM. Secondary objectives were to evaluate this scoring system by analyzing the correlation with OSDI, infrared (IR) meibography and Demodex infestation. MATERIAL AND METHODS:Forty-six dry eye patients (Ocular Surface Disease Index [OSDI] >13) associated with MGD were enrolled. Ten healthy subjects without dry eye disease or blepharitis were also included as controls. An OSDI questionnaire, clinical examination, IVCM and infrared meibography of the lower lid were performed in all subjects by the same examiner. RESULTS:A new MGD score was established based on IVCM findings: the first stage was Meibomian obstruction with a clear epithelium, the second stage was an inflammatory state with Meibomian gland obstruction, epithelial and interglandular inflammation, and the last stage was glandular fibrosis. This score was significantly correlated with the meiboscore obtained with infrared meibography (correlation coefficient 0.47, CI95% [0.22-0.66]). CONCLUSION:IVCM of the Meibomian gland complex complements the clinical examination by determining the stage of dysfunction and may help clinicians evaluate and treat MGD. 10.1016/j.jfo.2015.07.015
    In vivo confocal microscopy of meibomian glands in Sjögren's syndrome. Villani Edoardo,Beretta Silvia,De Capitani Michela,Galimberti Daniela,Viola Francesco,Ratiglia Roberto Investigative ophthalmology & visual science PURPOSE:To evaluate morphologic changes in meibomian glands (MGs) and the status of periglandular inflammation in patients with primary and secondary Sjögren's Syndrome (SS) using in vivo confocal laser microscopy (LSCM). METHODS:Twenty patients with primary SS (SSI), 25 with secondary SS (SSII), 20 with MG dysfunction (MGD), and 25 age- and gender-matched control subjects were enrolled consecutively. Each participant completed an Ocular Surface Disease Index questionnaire and underwent a full eye examination, including tear film break-up time (BUT), fluorescein and lissamine green staining, Schirmer test, and an LSCM examination of the MGs, the last to determine acinar unit density and diameter, glandular orifice diameters, meibum secretion reflectivity, inhomogeneous appearance of glandular interstice, and acinar wall. RESULTS:All parameters indicated statistically significant differences among groups (P < 0.001, Kruskal-Wallis test). LSCM demonstrated no differences between SSI and SSII (Mann-Whitney U test). Compared with control subjects, SS subjects' MGs showed more periglandular inflammation and higher secretion reflectivity (P < 0.001, Mann-Whitney U test). Compared with MGD patients, SS patients' MGs had higher acinar density, smaller diameters, greater density of periglandular inflammatory cells, and lower secretion reflectivity (P < 0.001, Mann-Whitney U test). In SS patients, the two measured confocal signs of inflammation were significantly interrelated and correlated with corneal fluorescein staining (P ≤ 0.01, Spearman correlation coefficient). Acinar density and diameters were strongly correlated among themselves (P < 0.001) and with BUT (P < 0.05). CONCLUSIONS:LSCM is capable of effectively revealing morphologic and inflammatory changes in MGs and showed discernible patterns of MG abnormalities in SS and MGD not easily distinguishable by the usual clinical exams. 10.1167/iovs.10-5995
    Deep Neural Network-Based Method for Detecting Obstructive Meibomian Gland Dysfunction With in Vivo Laser Confocal Microscopy. Maruoka Sachiko,Tabuchi Hitoshi,Nagasato Daisuke,Masumoto Hiroki,Chikama Taiichiro,Kawai Akiko,Oishi Naoko,Maruyama Toshi,Kato Yoshitake,Hayashi Takahiko,Katakami Chikako Cornea PURPOSE:To evaluate the ability of deep learning (DL) models to detect obstructive meibomian gland dysfunction (MGD) using in vivo laser confocal microscopy images. METHODS:For this study, we included 137 images from 137 individuals with obstructive MGD (mean age, 49.9 ± 17.7 years; 44 men and 93 women) and 84 images from 84 individuals with normal meibomian glands (mean age, 53.3 ± 19.6 years; 29 men and 55 women). We constructed and trained 9 different network structures and used single and ensemble DL models and calculated the area under the curve, sensitivity, and specificity to compare the diagnostic abilities of the DL. RESULTS:For the single DL model (the highest model; DenseNet-201), the area under the curve, sensitivity, and specificity for diagnosing obstructive MGD were 0.966%, 94.2%, and 82.1%, respectively, and for the ensemble DL model (the highest ensemble model; VGG16, DenseNet-169, DenseNet-201, and InceptionV3), 0.981%, 92.1%, and 98.8%, respectively. CONCLUSIONS:Our network combining DL and in vivo laser confocal microscopy learned to differentiate between images of healthy meibomian glands and images of obstructive MGD with a high level of accuracy that may allow for automatic obstructive MGD diagnoses in patients in the future. 10.1097/ICO.0000000000002279
    Application of In Vivo Confocal Microscopy in Dry Eye Disease. Matsumoto Yukihiro,Ibrahim Osama M A Investigative ophthalmology & visual science Confocal microscopy is a new, emerging, noninvasive technology that can aid in the in vivo assessment of structural changes in several ocular surface diseases at the cellular level. In the dry eye field, in vivo confocal microscopy has been applied to the examination of the cornea, bulbar and palpebral conjunctiva, Meibomian gland, and lacrimal gland. The device can assess the morphology, including superficial/wing/basal epithelial cell density, stromal keratocyte density, endothelial cell density, nerve fiber density, the number of beadings, nerve tortuosity, nerve reflectivity, and inflammatory cell density in the cornea. Furthermore, the device can not only assess epithelial cell density and area, goblet cell, microcyst, and inflammatory cell density but also the cellular architecture, including nucleocytoplasmic ratio in conjunctiva. The device also can disclose acinar unit density, acinar unit longest diameter, acinar unit shortest diameter, and inflammatory cell density in the Meibomian gland and lacrimal gland by other potential applications. Relevant research in Europe and the United States focused on the morphologic changes in the cornea in the dry eye field, while Japanese research focused on the conjunctival, Meibomian gland, and lacrimal gland alterations. The application of in vivo confocal microscopy in dry eye disease will be a powerful method to evaluate the morphologic change of the ocular surface around the world in the future. 10.1167/iovs.17-23602