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Morphological Analysis of Meibomian Glands

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ClinicalTrials.gov Identifier: NCT04052841
Recruitment Status : Recruiting
First Posted : August 12, 2019
Last Update Posted : April 7, 2022
Sponsor:
Information provided by (Responsible Party):
Jin Yuan, Zhongshan Ophthalmic Center, Sun Yat-sen University

Brief Summary:
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 morphology of meibomian glands in normal subjects, Meibomian gland dysfunction (MGD) patients and aqueous deficiency dry eye (ADDE) 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 parameters of meibomian gland and risk factors,clinical symptoms and signs; (4) to explore the sensitivity and specificity of meibomian gland morphological parameters in MGD diagnosis. (5) using morphological parameters as new assessment of MGD severity and efficacy indicators for treatment.

Condition or disease Intervention/treatment Phase
Meibomian Gland Dysfunction Procedure: Thermal pulsation Procedure: Intense pulsed light therapy Procedure: Manual meibomian gland expression Not Applicable

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 morphology of meibomian glands in normal subjects, MGD patients and ADDE 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 parameters of meibomian gland and risk factors,clinical symptoms and signs; (4) to explore the sensitivity and specificity of meibomian gland morphological parameters in MGD diagnosis. (5) using morphological parameters as new assessment of MGD severity and efficacy indicators for treatment.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 180 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: The recruitment of subjects must meet the diagnosis criteria of obstructive MGD the international workshop on meibomian gland dysfunction.
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Automated Morphological Analysis of Meibomian Glands
Actual Study Start Date : October 12, 2020
Estimated Primary Completion Date : July 1, 2023
Estimated Study Completion Date : December 1, 2023

Arm Intervention/treatment
Experimental: MGD-thermal pulsation group
Undergo a 15-minute Lipiflow treatment lid hygiene, then receive topical eye drops for 3 months.
Procedure: Thermal pulsation
Lipiflow (TearScience®, Inc. Morrisville, USA): the lipiflow thermal pulsation system consists of a console and a single-use sterile device, known as the Activator, and has a drug-free mechanism of action. Eye care professionals use the Lipiflow System to treat MGD patients in-office with confidence and efficiency.

Experimental: MGD-IPL group
Undergo 3 times intense pulsed light therapies for each 3 weeks, then receive topical eye drops for 3 months.
Procedure: Intense pulsed light therapy
Intense pulsed light (IPL) devices employ high intensity pulses of polychromatic lights with a broad range of wavelength (515-1200 nm). IPL treatment has been utilized for years in the field of dermatology, and then its use was applied to ophthalmology for the treatment of MGD.

Experimental: MGD-manual meibomian gland expression
Warm compresses and lid hygiene per day, lid massage up to four times per day for 15 minutes for 3 months. Then receive topical eye drops for 3 months.
Procedure: Manual meibomian gland expression
Using an eyelid massaging devices -Eyepeace (Eye Comfort Ltd, Belfast, UK)) for lid massage. The Eyepeace was placed on closed eyelids and gently squeeze and release between 5-10 times daily.

No Intervention: Normal health subject group
Normal health subject without intervention.



Primary Outcome Measures :
  1. Mophology of meibomian glands [ Time Frame: 30 days after commencement of treatment ]
    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.

  2. Functional feature of meibomian glands [ Time Frame: 30 days after commencement of treatment ]
    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.


Secondary Outcome Measures :
  1. Non-invasive tear-film break-up time [ Time Frame: 30 days after commencement of treatment ]
    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

  2. Non-invasive tear-film break-up time [ Time Frame: 60 days after commencement of treatment ]
    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

  3. Non-invasive tear-film break-up time [ Time Frame: 90 days after commencement of treatment ]
    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

  4. Non-invasive tear meniscus height [ Time Frame: Baseline ]
    Non-invasived tear meniscus height is measured by tear film pattern of Keratograph 5M (Oculus, Wetzlar, Germany) in millimeter. The value higher than 0.20 mm was provided as a normal condition of tear secretion.

  5. Non-invasive tear meniscus height [ Time Frame: 30 days after commencement of treatment ]
    Non-invasived tear meniscus height is measured by tear film pattern of Keratograph 5M (Oculus, Wetzlar, Germany) in millimeter. The value higher than 0.20 mm was provided as a normal condition of tear secretion.

  6. Non-invasive tear meniscus height [ Time Frame: 90 days after commencement of treatment ]
    Non-invasived tear meniscus height is measured by tear film pattern of Keratograph 5M (Oculus, Wetzlar, Germany) in millimeter. The value higher than 0.20 mm was provided as a normal condition of tear secretion.

  7. Tear film lipid layer thicknesses [ Time Frame: Baseline ]
    Tear film lipid layer thicknesses were averaged in nanometer(0-100nm) during 20 seconds by LipiView II (Tear Science, Morrisville, NC).

  8. Tear film lipid layer thicknesses [ Time Frame: 60 days after commencement of treatment ]
    Tear film lipid layer thicknesses were averaged in nanometer(0-100nm) during 20 seconds by LipiView II (Tear Science, Morrisville, NC).

  9. Tear film lipid layer thicknesses [ Time Frame: 90 days after commencement of treatment ]
    Tear film lipid layer thicknesses were averaged in nanometer(0-100nm) during 20 seconds by LipiView II (Tear Science, Morrisville, NC).

  10. Tear film lipid layer thicknesses [ Time Frame: 180 days after commencement of treatment ]
    Tear film lipid layer thicknesses were averaged in nanometer(0-100nm) during 20 seconds by LipiView II (Tear Science, Morrisville, NC).

  11. The pattern of eye blinks [ Time Frame: Baseline ]
    The pattern of eye blinks including numbers of incompleted and completed blinks during 20 seconds were measured by LipiView II (Tear Science, Morrisville, NC).

  12. The pattern of eye blinks [ Time Frame: 30 days after commencement of treatment ]
    Tear film lipid layer thicknesses and numbers of incomplete blinks during 20 seconds were measured by LipiView II (Tear Science, Morrisville, NC).

  13. The pattern of eye blinks [ Time Frame: 60 days after commencement of treatment ]
    Tear film lipid layer thicknesses and numbers of incomplete blinks during 20 seconds were measured by LipiView II (Tear Science, Morrisville, NC).

  14. The pattern of eye blinks [ Time Frame: 90 days after commencement of treatment ]
    Tear film lipid layer thicknesses and numbers of incomplete blinks during 20 seconds were measured by LipiView II (Tear Science, Morrisville, NC).

  15. The pattern of eye blinks [ Time Frame: 180 days after commencement of treatment ]
    Tear film lipid layer thicknesses and numbers of incomplete blinks during 20 seconds were measured by LipiView II (Tear Science, Morrisville, NC).

  16. Lid margin signs [ Time Frame: baseline ]
    Three lid margin abnormalities (irregular lid margin, plugging of meibomian gland orifices, and anterior or posterior replacement of the mucocutaneous junction) were scored from 0 through 4 according to the number of these abnormalities that were present in each eye. Higher scores represent a worse outcome.

  17. Lid margin signs [ Time Frame: 30 days after commencement of treatment ]
    Three lid margin abnormalities (irregular lid margin, plugging of meibomian gland orifices, and anterior or posterior replacement of the mucocutaneous junction) were scored from 0 through 4 according to the number of these abnormalities that were present in each eye. Higher scores represent a worse outcome.

  18. Lid margin signs [ Time Frame: 60 days after commencement of treatment ]
    Three lid margin abnormalities (irregular lid margin, plugging of meibomian gland orifices, and anterior or posterior replacement of the mucocutaneous junction) were scored from 0 through 4 according to the number of these abnormalities that were present in each eye. Higher scores represent a worse outcome.

  19. Lid margin signs [ Time Frame: 90 days after commencement of treatment ]
    Three lid margin abnormalities (irregular lid margin, plugging of meibomian gland orifices, and anterior or posterior replacement of the mucocutaneous junction) were scored from 0 through 4 according to the number of these abnormalities that were present in each eye. Higher scores represent a worse outcome.

  20. Lid margin signs [ Time Frame: 180 days after commencement of treatment ]
    Three lid margin abnormalities (irregular lid margin, plugging of meibomian gland orifices, and anterior or posterior replacement of the mucocutaneous junction) were scored from 0 through 4 according to the number of these abnormalities that were present in each eye. Higher scores represent a worse outcome.

  21. Meibum expressibility [ Time Frame: baseline ]

    Meibum expressibility were measured by firm digital pressure of Meibomian gland diagnostic Expressibility (Tear Sience, Morrisville, NC):

    For each of these glands, the secretion was graded as follows: 0:no secretion; 1: inspissated/ toothpaste consistency; 2: cloudy liquid secretion and 3: clear liquid secretion19. The scores were then summed in 15 glands to a single meibomian gland yield secretion score (MGYSS) with a range from 0 to 45. Higher values represent a better outcome.


  22. Meibum expressibility [ Time Frame: 30 days after commencement of treatment ]

    Meibum expressibility were measured by firm digital pressure of Meibomian gland diagnostic Expressibility (Tear Sience, Morrisville, NC):

    For each of these glands, the secretion was graded as follows: 0:no secretion; 1: inspissated/ toothpaste consistency; 2: cloudy liquid secretion and 3: clear liquid secretion19. The scores were then summed in 15 glands to a single meibomian gland yield secretion score (MGYSS) with a range from 0 to 45. Higher values represent a better outcome.


  23. Meibum expressibility [ Time Frame: 60 days after commencement of treatment ]

    Meibum expressibility were measured by firm digital pressure of Meibomian gland diagnostic Expressibility (Tear Sience, Morrisville, NC):

    For each of these glands, the secretion was graded as follows: 0:no secretion; 1: inspissated/ toothpaste consistency; 2: cloudy liquid secretion and 3: clear liquid secretion19. The scores were then summed in 15 glands to a single meibomian gland yield secretion score (MGYSS) with a range from 0 to 45. Higher values represent a better outcome.


  24. Meibum expressibility [ Time Frame: 90 days after commencement of treatment ]

    Meibum expressibility were measured by firm digital pressure of Meibomian gland diagnostic Expressibility (Tear Sience, Morrisville, NC):

    For each of these glands, the secretion was graded as follows: 0:no secretion; 1: inspissated/ toothpaste consistency; 2: cloudy liquid secretion and 3: clear liquid secretion19. The scores were then summed in 15 glands to a single meibomian gland yield secretion score (MGYSS) with a range from 0 to 45. Higher values represent a better outcome.


  25. Meibum expressibility [ Time Frame: 180 days after commencement of treatment ]

    Meibum expressibility were measured by firm digital pressure of Meibomian gland diagnostic Expressibility (Tear Sience, Morrisville, NC):

    For each of these glands, the secretion was graded as follows: 0:no secretion; 1: inspissated/ toothpaste consistency; 2: cloudy liquid secretion and 3: clear liquid secretion19. The scores were then summed in 15 glands to a single meibomian gland yield secretion score (MGYSS) with a range from 0 to 45. Higher values represent a better outcome.


  26. Corneal Fluorescein Staining [ Time Frame: baseline ]
    Fluorescein was administered into the conjunctival sac under a cobalt blue light from the slit lamp. Corneal epithelial cell disruption was measured via corneal staining (National Eye Institute (NEI) scale (0-3 scale for each area of 5 areas, total score 15). Higher values represent a worse outcome.

  27. Corneal Fluorescein Staining [ Time Frame: 30 days after commencement of treatment ]
    Fluorescein was administered into the conjunctival sac under a cobalt blue light from the slit lamp. Corneal epithelial cell disruption was measured via corneal staining (National Eye Institute (NEI) scale (0-3 scale for each area of 5 areas, total score 15). Higher values represent a worse outcome.

  28. Corneal Fluorescein Staining [ Time Frame: 60 days after commencement of treatment ]
    Fluorescein was administered into the conjunctival sac under a cobalt blue light from the slit lamp. Corneal epithelial cell disruption was measured via corneal staining (National Eye Institute (NEI) scale (0-3 scale for each area of 5 areas, total score 15). Higher values represent a worse outcome.

  29. Corneal Fluorescein Staining [ Time Frame: 90 days after commencement of treatment ]
    Fluorescein was administered into the conjunctival sac under a cobalt blue light from the slit lamp. Corneal epithelial cell disruption was measured via corneal staining (National Eye Institute (NEI) scale (0-3 scale for each area of 5 areas, total score 15). Higher values represent a worse outcome.

  30. Corneal Fluorescein Staining [ Time Frame: 180 days after commencement of treatment ]
    Fluorescein was administered into the conjunctival sac under a cobalt blue light from the slit lamp. Corneal epithelial cell disruption was measured via corneal staining (National Eye Institute (NEI) scale (0-3 scale for each area of 5 areas, total score 15). Higher values represent a worse outcome.

  31. Schirmer I test [ Time Frame: baseline ]
    The tear production was measured with Schirmer strips without anaesthesia 15 minutes after corneal staining.

  32. Schirmer I test [ Time Frame: 30 days after commencement of treatment ]
    The tear production was measured with Schirmer strips without anaesthesia 15 minutes after corneal staining.

  33. Schirmer I test [ Time Frame: 60 days after commencement of treatment ]
    The tear production was measured with Schirmer strips without anaesthesia 15 minutes after corneal staining.

  34. Schirmer I test [ Time Frame: 90 days after commencement of treatment ]
    The tear production was measured with Schirmer strips without anaesthesia 15 minutes after corneal staining.

  35. Schirmer I test [ Time Frame: 180 days after commencement of treatment ]
    The tear production was measured with Schirmer strips without anaesthesia 15 minutes after corneal staining.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Clinical diagnosis of Obstructive MGD: The diagnosis of obstructive MGD was based on an altered quality of expressed secretions and/or decreased or absent expression, with presence of ocular symptoms, lid margin signs.
  • Age over 18 years.
  • Voluntary participation, willing to cooperate with treatment and follow-up

Exclusion Criteria:

  • Ocular allergies, contact lens wear, continuous medications usage such as tretinoin or isotretinoin, which could be potential confounder of meibomian gland atrophy.
  • History of eye surgery and systemic or ocular disease that might interfere with tear film production or function
  • Individuals who are pregnant, nursing, or could become pregnant.
  • Infrared image that were not sufficiently clear for automatic analysis were excluded.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04052841


Contacts
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Contact: Yuqing Deng, MD 18120557291 15927646647@163.com

Locations
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China, Guangdong
Zhongshan Ophthalmic Center, Sun Yat-Sen University Recruiting
Guangzhou, Guangdong, China, 510080
Contact: Saiqun Li, M.D., Ph.D.    86-013642710612    123213197@qq.com   
Principal Investigator: Jin Yuan, M.D., Ph.D.         
China
Deng Yuqing Recruiting
Guangzhou, China, 510060
Contact: Yuqing Deng, MD    18120557291    15927646647@163.com   
Principal Investigator: Jin Yuan, PHD         
Sponsors and Collaborators
Zhongshan Ophthalmic Center, Sun Yat-sen University
Investigators
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Principal Investigator: Jin Yuan, PHD Zhongshan Ophthalmic Center, Sun Yat-sen University
Publications of Results:

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Responsible Party: Jin Yuan, Principal Investigator, Zhongshan Ophthalmic Center, Sun Yat-sen University
ClinicalTrials.gov Identifier: NCT04052841    
Other Study ID Numbers: 20190722
First Posted: August 12, 2019    Key Record Dates
Last Update Posted: April 7, 2022
Last Verified: March 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: Study protocol

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
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Meibomian Gland Dysfunction
Eyelid Diseases
Eye Diseases