Morphological Analysis of Meibomian Glands | NCT04052841

NCT04052841

Protocol Section

Identification Module

Results Section

No data available

No data is available for this block.

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Status Module

Description Module

Detailed Description

Meibomian glands are essential for maintaining ocular surface health and integrity secrete various lipid components to forms a lipid layer to prevent excessive tear evaporation. Functional disorders of the meibomian glands, referred to today as meibomian gland dysfunction (MGD), are increasingly recognized as a high incidence disease commonly characterized by terminal duct obstruction and/or abnormal glandular secretion, often results in ocular surface epithelium damage, chronic blepharitis and dry eye disease that significantly reduces quality of life. A wide variation of the prevalence of MGD were reported from 0.39% to 69.3%, which is likely due to lack of diagnostic methods. To identify which clinical features are likely to be predictive of progressive disease in MGD may indicate the early diagnosis and proper treatment strategies.

Histologic section through the normal meibomian glands and the obstructed human meibomian gland revealed that obstruction of orifice in MGD could lead to dilation of the central duct, damage of the secretory meibocytes and finally result in atrophy of dilated meibomian glands and glands drop-out. It was thus be accepted that detailed changes of meibomian glands morphology are key signs to diagnose and evaluate the severity of MGD. The detailed changes including dilation, distortion, shortening and loss of visualisation of glands which can be directly observed and visual assessment by the developed of non-contact meibomian gland infrared imaging technology. Quantitative evaluations of meibomian glands were obtain by developing imaging processing techniques. The most common use is the image editing software Image J (National Institute of Health; http://imagej.nih.gov/ij) which can identify the gland region on the image manually by the users and may lead to inter-observer variability. Koh et al., first applied original algorithms to automatically analysed gland loss in meibography images with a manually pre-processing. Reiko et al., then develop an objective and automatic system to measure the meibomian gland area. However, the existing methods of meibomian gland analysis have been limited to clinical use where large number of images needs to be analyzed efficiently due to the inter-observer variability or time-consuming process.

Meanwhile, the existing quantitative morphological parameters obtain by those imaging processing techniques, including percentage of MG drop-out and gland atrophy area, were suggested to not only be advanced stages or terminal changes in MGD, but also occurs as an age-related atrophic process. The early findings of MGD induced by the primary pathologic obstruction including degenerative gland dilation, irregularly shapes of gland and change of meibum quality are still difficult to be evaluated automatically and quantitively from the image. Moreover, the meibomian gland drop-out is still an approximate assessment without specific pattern. Whether the atrophy or loss occur in upper or lower eyelids, central, distal or proximal, total loss of gland or partial loss of gland has the greatest effect on the pathology progress of MGD will be important to identify. Thus, a comprehensive analysis technique to automatically detect multi-information of meibomian gland morphology will benefit the future early diagnosis and management of MGD.

Recently, an automated quantitative meibomian gland analyzer based on all kinds of infrared meibomian gland images was develop to obtain more detail in meibomian gland, including width, length, area, signal intensity correlated to the quality of meibum, deformation index and ratio of area of each visible specific gland. The purpose of this study is present as separate sections the following points: (1) to compared the detailed characteristics of meibomian glands in normal subjects and MGD patients by the automated quantitative analyzer; (2) to identify the inter-examiner and intra-examiner repeatability of the new technique; (3) to explore the correlation among morphological and functional parameters of meibomian gland and risk factors，clinical symptoms and signs; (4) to explore the sensitivity and specificity of meibomian gland morphological and functional parameters in MGD diagnosis. (5) using morphological and functional parameters as new assessment of MGD severity and efficacy indicators for treatment.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
MGD-thermal pulsation group	Experimental	A 12 minutes LIPIFLOW treatment was performed.	Procedure: Thermal pulsation
MGD-IPL group	Experimental	IPL was performed every 3 weeks，3 times in total (0, 3w, 6w).	Procedure: Intense pulsed light therapy
MGD-manual warm compresses	Experimental	Manual warm compresses were performed every 2 weeks，5 times in total (0, 2w, 4w, 6w, 8w).	Procedure: Manual warm compresses
Normal health subject group	No Intervention	Normal health subject without intervention.

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Thermal pulsation	Procedure	Participants underwent a single LipiFlow® thermal pulsation system (TearScience Inc., Morrisville, NC,USA) treatment on the first visit: after lid hygiene with wet cotton swabs(OCuSOFT, Inc., Texas, USA) and instillation of anesthetic eye drops (Alcaine, proparacaine hydrochloride 0.4 ml/2mg) in both eyes, sterile eye cups were placed on to the conjunctival sac as instructed by the manufacturer, after 12 minutes of upper and lower palpebral conjunctival surfaces heat while simultaneously graded pulsatile pressure applying, eye cups were removed slightly.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Mophology of meibomian glands	Infrared photography of inversed upper meibomian glands were measured by Meibography pattern of Keratograph 5M (Oculus, Wetzlar, Germany). The infrared images of Meibography were analysed using the new developed software for identifying the mophology features of meibomian glands in millimeter.	30 days after commencement of treatment
Functional feature of meibomian glands	Infrared photography of inversed upper and lower meibomian glands were measured by Meibography pattern of Keratograph 5M (Oculus, Wetzlar, Germany). The infrared images of Meibography were analysed using the new developed software for identifying the mean signal intensity of meibomian glands in millimeter.	30 days after commencement of treatment

Secondary Outcomes

Measure	Description	Time Frame
Non-invasive tear-film break-up time	Non-invasived tear-film break-up time is measured by tear film pattern of Keratograph 5M (Oculus, Wetzlar, Germany) with a scale of seconds. Higher values represent a better outcome	Baseline
Non-invasive tear-film break-up time

Eligibility Module

Eligibility Criteria

General Inclusion Criteria:

Age from 18 to 70 years.
Patients and healthy volunteers who are willing and capable to participate in this clinical study with signed Informed Consent Form.

Inclusion Criteria of patients:

Clinical diagnosis of MGD: The diagnosis of MGD was based on an altered quality of expressed secretions and/or decreased or absent expression.
Patients without ≥2/3 Meibomian glands atrophy.
Fitzpatrick skin type 1-4.

Inclusion Criteria of healthy volunteers:

Negative history or condition of ocular or systemic illness based on evaluation by a research physician.

General Exclusion Criteria:

Patients and healthy volunteers with ocular allergies, trauma, contact lens wear, continuous medications usage such as tretinoin, isotretinoin, antidepressant medications, photosensitive drugs, glucocorticoids and immunomodulators, or have used them within one month.
Patients and healthy volunteers who have a history of ocular surface surgery.
Patients and healthy volunteers who have active ocular surface infection or have suffered from ocular surface infection within one month.
Patients and healthy volunteers who have endophthalmitis or a medical history of endophthalmitis.
Patients and healthy volunteers who have a medical history of viral keratitis infection.
Women who are pregnant, planning to become pregnant during the course of the study or breast-feeding (women of child-bearing age will be asked by the physician).
Meibography images were blurred or with obvious tarsus folds, incomplete exposure and large hyperreflective area.
Patients and healthy volunteers who are not suitable for the trial as determined by investigators.

Exclusion Criteria of patients:

Patients have abnormalities of ocular surface function or eyelid function, or presence of precancerous lesions, cancer or pigmentation in the eyelid area.
Patients who have plans to receive ocular surgeries (e.g., cataract, myopic refractive surgery) within 6 months.
Patients who have been treated with lacrimal punctum embolization within one month.
Patients with disease that could lead to ADDE, such as Sjogren syndrome and a lacrimal gland abnormality.

Name	Role	Phone	Extension	Email
Yuqing Deng, MD	Contact	18120557291		15927646647@163.com

Name	Affiliation	Role
Jin Yuan, PHD	Zhongshan Ophthalmic Center, Sun Yat-sen University	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Zhongshan Ophthalmic Center, Sun Yat-Sen University	Recruiting	Guangzhou	Guangdong	510080	China

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
23813417	Result	Arita R, Suehiro J, Haraguchi T, Shirakawa R, Tokoro H, Amano S. Objective image analysis of the meibomian gland area. Br J Ophthalmol. 2014 Jun;98(6):746-55. doi: 10.1136/bjophthalmol-2012-303014. Epub 2013 Jun 27.
21450914	Result	Nelson JD, Shimazaki J, Benitez-del-Castillo JM, Craig JP, McCulley JP, Den S, Foulks GN. The international workshop on meibomian gland dysfunction: report of the definition and classification subcommittee. Invest Ophthalmol Vis Sci. 2011 Mar 30;52(4):1930-7. doi: 10.1167/iovs.10-6997b. Print 2011 Mar. No abstract available.

ID	Term
D005141	Eyelid Diseases
D005128	Eye Diseases

ID	Term
D010789	Phototherapy
D013812	Therapeutics