Morphological Analysis of Meibomian Glands

Sponsor
Zhongshan Ophthalmic Center, Sun Yat-sen University (Other)
Overall Status
Recruiting
CT.gov ID
NCT04052841
Collaborator
(none)
180
2
4
37.6
90
2.4

Study Details

Study Description

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
  • Procedure: Thermal pulsation
  • Procedure: Intense pulsed light therapy
  • Procedure: Manual meibomian gland expression
N/A

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.

Study Design

Study Type:
Interventional
Anticipated 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.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 :
Oct 12, 2020
Anticipated Primary Completion Date :
Jul 1, 2023
Anticipated Study Completion Date :
Dec 1, 2023

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

  1. Mophology of meibomian glands [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [baseline]

    The tear production was measured with Schirmer strips without anaesthesia 15 minutes after corneal staining.

  32. Schirmer I test [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 [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 [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 [180 days after commencement of treatment]

    The tear production was measured with Schirmer strips without anaesthesia 15 minutes after corneal staining.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 70 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
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.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Zhongshan Ophthalmic Center, Sun Yat-Sen University Guangzhou Guangdong China 510080
2 Deng Yuqing Guangzhou China 510060

Sponsors and Collaborators

  • Zhongshan Ophthalmic Center, Sun Yat-sen University

Investigators

  • Principal Investigator: Jin Yuan, PHD, Zhongshan Ophthalmic Center, Sun Yat-sen University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Jin Yuan, Principal Investigator, Zhongshan Ophthalmic Center, Sun Yat-sen University
ClinicalTrials.gov Identifier:
NCT04052841
Other Study ID Numbers:
  • 20190722
First Posted:
Aug 12, 2019
Last Update Posted:
Apr 7, 2022
Last Verified:
Mar 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Undecided
Plan to Share IPD:
Undecided
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:

Study Results

No Results Posted as of Apr 7, 2022