Back to results

Efficiency and Changes of Cytokines Expression in Tear After Intense Pulsed Light Treating Dry Eye Disease

Primary Purpose

Dry Eye Syndromes

Status

Completed

Phase

Not Applicable

Locations

China

Study Type

Interventional

Intervention

OPT IPL

Sham OPT IPL

MGX

About this trial

This is an interventional treatment trial for Dry Eye Syndromes focused on measuring Optimal pulsed technology intense pulsed light, meibomian gland dysfunction, demodicosis, Dry Eye Disease

Eligibility Criteria

18 Years - 100 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Subject is able to read, understand and sign an Informed Consent (IC) form
18-100 years of age
Subject is able and willing to comply with the treatment/follow-up (FU) schedule and requirements
In the study eye, tear break up time ≤ 7 seconds
In the study eye, Meibomian Gland Score (MGS) ≤ 12
In the study eye, at least 5 non-atrophied meibomian glands in the lower eyelid
Symptoms self-assessed using the Ocular Surface Disease Index (OSDI) questionnaire ≥ 23

Exclusion Criteria:

Fitzpatrick skin type V or VI
Contact lens wear within the month prior to screening
Unwilling to discontinue use of contact lenses for the duration of the study
Ocular surgery or eyelid surgery, within 6 months prior to screening
Neuro-paralysis in the planned treatment area, within 6 months prior to screening
Other uncontrolled eye disorders affecting the ocular surface, for example active allergies
Current use of punctal plugs
Pre-cancerous lesions, skin cancer or pigmented lesions in the planned treatment area
Uncontrolled infections or uncontrolled immunosuppressive diseases
Subjects with ocular infections, within 6 months prior to screening
Prior history of cold sores or rashes in the perioral area or in the planned treatment area that could be stimulated by light at a wavelength of 560 nm to 1200 nm, including: Herpes simplex 1 & 2, Systemic Lupus erythematosus, and porphyria
Within 3 months prior to screening, use of photosensitive medication and/or herbs that may cause sensitivity to 560-1200 nm light exposure, including: Isotretinoin, Tetracycline, Doxycycline, and St. John's Wort
Over exposure to sun, within 4 weeks prior to screening
Use of prescription eye drops for dry eye, within 7 days prior to screening, excluding artificial tears and glaucoma drops
Radiation therapy to the head or neck, within 12 months prior to screening
Planned radiation therapy, within 8 weeks after the last treatment session
Treatment with chemotherapeutic agent, within 8 weeks prior to screening
Planned chemotherapy, within 8 weeks after the last treatment session
New topical treatments within the area to be treated, or oral therapies, within 3 months prior to screening- except over-the-counter acetaminophen-based analgesics for pain management, new oral omega 3 fatty acid supplements and topical artificial tears
Change in dosage of any systemic medication, within 3 months prior to screening
Anticipated relocation or extensive travel outside of the local study area preventing compliance with follow-up over the study period
Legally blind in either eye
History of migraines, seizures or epilepsy
Facial IPL treatment, within 12 months prior to screening
Any thermal treatment of the eyelids, including Lipiflow, within 6 months prior to screening
Expression of the meibomian glands, within 6 months prior to screening
In either eye, moderate to severe (Grade 3-4) inflammation of the conjunctiva, including: allergic, vernal or giant papillary conjunctivitis
In either eye, severe (Grade 4) inflammation of the eyelid, including: blepharochalasis, staphylococcal blepharitis or seborrheic blepharitis
Ocular surface abnormality that may compromise corneal integrity in either eye (e.g., prior chemical burn, recurrent corneal erosion, corneal epithelial defect, Grade 3 corneal fluorescein staining, or map dot fingerprint dystrophy)
Eyelid abnormalities that affect lid function in either eye, including: entropion, ectropion, tumor, edema, blepharospasm, lagophthalmos, severe trichiasis, and severe ptosis
Any systemic condition that may cause dry eye disease, including: Stevens-Johnson syndrome, vitamin A deficiency, rheumatoid arthritis, Wegener's granulomatosis, sarcoidosis, leukemia, Riley-Day syndrome, systemic lupus erythematosus, and Sjögren's syndrome
Unwilling or unable to abstain from the use of medications known to cause dryness (e.g., isotretinoin, antihistamines) throughout the study duration. Subjects must discontinue these medications for at least 1 month prior to the baseline visit.
Any condition revealed whereby the investigator deems the subject inappropriate for this study

Sites / Locations

The First affiliated hospital of harbin medical university

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Sham Comparator

Arm Label

OPT IPL followed by MGX

Sham OPT IPL followed by MGX

Arm Description

Subjects in the experimental arm will receive OPT IPL followed by MGX: OPT IPL pulses will be administered on the skin of the malar region (both cheeks, from tragus to tragus including the nose) and below the lower eyelids. Following OPT IPL therapy, subjects will undergo MGX of both eyelids in both eyes. Interventions: Device: IPL Procedure: MGX

Subjects in the sham comparator arm will receive Sham OPT IPL followed by MGX: Sham OPT IPL pulses will be administered on the skin of the malar region (both cheeks, from tragus to tragus including the nose) and below the lower eyelids. Following Sham OPT IPL therapy, subjects will undergo MGX of both eyelids in both eyes. Interventions: Device: Sham IPL Procedure: MGX

Outcomes

Primary Outcome Measures

change of baseline demodex counts

Six lashes with cylindrical dandruff (CD) were epilated from each eye (3 in upper eyelid and 3 in lower eyelid) under slit lamp and mounted on glass slides and were examined under optical microscopy to confirm the presence of D folliculorum. Demodex counts greater than or equal to 1 were Demodex-positive.

change of baseline tear cytokines levels

Change of IL-1α, IL-1β, IL-6, IL-7, IL-12p40, IL-13, IL-17A, IL-8, MMP-3, MMP-9 in the study eye, from baseline to follow-up, in both eyes

Secondary Outcome Measures

Change from baseline of Ocular Surface Disease Index score

The ocular surface disease index score was assessed as a subjective parameter to evaluate the ocular symptoms of dry eye on a score of zero to 100, and subject with a score of greater than 12 was considered abnormal.

change from baseline of schirmer I test

Schirmer I test (without anesthesia) was used to assess tear production by inserting in each eye a sterile dry strip (Jingming, Tianjin, China) into the lateral canthus of the lower eyelid away from the cornea over 5 minutes. The length of the strip that was wetted by absorbed tears was then measured in millimeter to evaluate tear secretion function. Values of less than 7.0 mm are considered a diagnosis of aqueous tear deficiency.

change from baseline of the Lid margin abnormalities score

The slit-lamp biomicroscopy was used to score the lid margin abnormalities: the following four parameters were scored as 0 (absent) or 1 (present) of lid margin abnormalities: lid margin irregularity, plugging of the meibomian orifices, lid margin vascular engorgement, and anterior or posterior replacement of mucocutaneous junction. The sum was recorded as 0-4.

change from baseline of meibum grade score

Meibum grade was assessed in each of eight glands of the central third of the lower lid on a scale of zero to three for each gland: zero (clear), one (cloudy), two (cloudy with debris, granular) and three (thick, like toothpaste). Total score range, 0 to 24

change from baseline of corneal fluorescein staining score

The corneal fluorescein staining score was assessed by instilling fluorescein into the lower conjunctival sac with a fluorescein strip (Jingming, Tianjin, China) moistened with preservative-free saline solution. The grading system recommended by NEI divides the cornea into 5 zones (central, superior, temporal, nasal and inferior). For each zone, the corneal fluorescein staining score was graded on a scale from 0 to 3. Therefore, the maximum score was 15

change of baseline of lashes in vivo confocal microscopy laser

In vivo confocal microscopy laser (IVCM, HRTII Cornea Module; Heidelberg Engineering GmbH, Dossenheim, Germany) was used to examine almost 10-20 eyelashes in both eyes. Demodex folliculorum identified in the infundibulum of the eyelashes and the space adjacent to the eyelash shafts as hypo-reflective elongated bodies with a hyperreflective head. Demodex counts greater than or equal to 1were considered positive.

change from baseline of fluorescein tear break up time

The fluorescein tear beak up time was evaluated immediately after the assessment of staining. The patient was required to blink several times to ensure adequate coating of the dye on the cornea. Using a cobalt blue filter and slit-lamp biomicroscopy, the interval between the last complete blink and appearance of the first dry spot in the stained tear film was recorded as the fluorescein tear beak up time. The test was repeated 3 times and the average fluorescein tear beak up time was calculated in second. Values of less than 10 seconds are considered abnormal.

Full Information

NCT ID

NCT04165785

First Posted

November 10, 2019

Last Updated

November 13, 2019

Sponsor

First Affiliated Hospital of Harbin Medical University

1. Study Identification

Unique Protocol Identification Number

NCT04165785

Brief Title

Efficiency and Changes of Cytokines Expression in Tear After Intense Pulsed Light Treating Dry Eye Disease

Official Title

Efficiency and Changes of Cytokines Expression in Tear After Intense Pulsed Light Treating Evaporated Dry Eye With Demodicosis

Study Type

Interventional

2. Study Status

Record Verification Date

October 2019

Overall Recruitment Status

Completed

Study Start Date

August 20, 2018 (Actual)

Primary Completion Date

June 28, 2019 (Actual)

Study Completion Date

July 28, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

First Affiliated Hospital of Harbin Medical University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Yes

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

5. Study Description

Brief Summary

The aim of the current study is to investigate changes of tear cytokines levels as well as the efficacy and the reduction of demodex infestation after OPT IPL treatment in patients with meibomian gland dysfunction-Associated demodicosis. The effect of OPT IPL will be examined in a study designed as a randomised controlled trial. In the study arm, subjects will undergo 4 treatment sessions, consisting of OPT IPL pulses immediately followed by meibomian gland expression (MGX). In the control arm, subjects will undergo the same treatments, except that the OPT IPL pulses will be disabled. For each subject, the duration of the study will be 2 months , as explained in the detailed description.

Detailed Description

All subjects will receive 4 treatments at 2 weeks intervals. In each treatment session, a subject allocated to the study group will be treated with Optimal pulsed technology intense pulsed light (OPT IPL) administered in the malar region, from tragus to tragus including the nose, 2-3 mm below the lower eyelids. Immediately following the OPT IPL administration, the subject will undergo meibomian gland expression (MGX) in both eyelids of both eyes. Subjects in the control arm will receive exactly the same treatment, except that the OPT IPL administration will be sham. A single follow-up will occur at 2 months after the baseline (or 2 weeks after the 4th treatment session). At the follow-up, the changes in the outcome measures will be evaluated, and compared between the two arms. For each subject, the duration of the study will be 2 months: 1st treatment at baseline; 2nd treatment at 2 weeks after baseline; 3rd treatment at 4 weeks after baseline; 4th treatment at 6 weeks after baseline; and a single follow-up at 8 weeks after baseline). Statistically significant differences between the two arms will support the study hypothesis that IPL treatment is potentially reduce demodex counts and decrease levels of cytokines , and relief to both signs and symptoms of dry eye disease.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Dry Eye Syndromes

Keywords

Optimal pulsed technology intense pulsed light, meibomian gland dysfunction, demodicosis, Dry Eye Disease

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Model Description

Subjects will be randomized 1:1 to a study arm and a control arm. Subjects in the study arm will be treated with OPT IPL and meibomian gland expression. Subjects in the control arm will be treated with sham OPT IPL and meibomian gland expression.

Masking

Participant

Masking Description

Subjects in the study arm will receive a series of OPT IPL pulses using the M22 IPL handpiece. In subjects of the control arm, the device will be disabled. The subject will feel the lightguide on the skin, will hear clicking sounds, but no light will be actually produced by the M22 device. Since during treatment both eyes of the subject will be fully occluded, no subject will be able to see if the treatment is actual or sham. There is no way to completely mask the subjects, since the IPL generally causes slight redness of the skin, and in some patients is may also cause some discomfort

Allocation

Randomized

Enrollment

64 (Actual)

8. Arms, Groups, and Interventions

Arm Title

OPT IPL followed by MGX

Arm Type

Experimental

Arm Description

Arm Title

Sham OPT IPL followed by MGX

Arm Type

Sham Comparator

Arm Description

Intervention Type

Device

Intervention Name(s)

OPT IPL

Intervention Description

Intense pulsed light (IPL) is a non-invasive and non-laser light treatment that is FDA-approved for various conditions in dermatology. Subjects will receive a total of 4 IPL treatments over the course of the study, at intervals of 2 weeks. Each treatment will include applications of 24 IPL pulses in the malar region and close to the lower eyelids, followed by meibomian gland expression.

Intervention Type

Device

Intervention Name(s)

Sham OPT IPL

Intervention Description

Sham Optimal pulsed technology intense pulsed light IPL will be implemented with an IPL device in which all light is blocked by a filter. Subjects will receive a total of 4 sham treatments over the course of the study, at intervals of 2 weeks. Each treatment will include applications of 24 sham pulses in the malar region and close to the lower eyelids, followed by meibomian gland expression.

Intervention Type

Procedure

Intervention Name(s)

MGX

Intervention Description

Meibomian gland expression (MGX) will be implemented by squeezing the meibomian glands with the aid of stainless steel jaeger lid plate positioned in the inferior fornix space between the tarsal and bulbar conjunctiva, and a cotton swab in another side.

Primary Outcome Measure Information:

Title

change of baseline demodex counts

Description

Time Frame

2 months

Title

change of baseline tear cytokines levels

Description

Change of IL-1α, IL-1β, IL-6, IL-7, IL-12p40, IL-13, IL-17A, IL-8, MMP-3, MMP-9 in the study eye, from baseline to follow-up, in both eyes

Time Frame

2 months

Secondary Outcome Measure Information:

Title

Change from baseline of Ocular Surface Disease Index score

Description

Time Frame

2 months

Title

change from baseline of schirmer I test

Description

Time Frame

2 months

Title

change from baseline of the Lid margin abnormalities score

Description

Time Frame

2 months

Title

change from baseline of meibum grade score

Description

Time Frame

2 months

Title

change from baseline of corneal fluorescein staining score

Description

Time Frame

2 months

Title

change of baseline of lashes in vivo confocal microscopy laser

Description

Time Frame

2 months

Title

change from baseline of fluorescein tear break up time

Description

Time Frame

2 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

100 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Subject is able to read, understand and sign an Informed Consent (IC) form 18-100 years of age Subject is able and willing to comply with the treatment/follow-up (FU) schedule and requirements In the study eye, tear break up time ≤ 7 seconds In the study eye, Meibomian Gland Score (MGS) ≤ 12 In the study eye, at least 5 non-atrophied meibomian glands in the lower eyelid Symptoms self-assessed using the Ocular Surface Disease Index (OSDI) questionnaire ≥ 23 Exclusion Criteria: Fitzpatrick skin type V or VI Contact lens wear within the month prior to screening Unwilling to discontinue use of contact lenses for the duration of the study Ocular surgery or eyelid surgery, within 6 months prior to screening Neuro-paralysis in the planned treatment area, within 6 months prior to screening Other uncontrolled eye disorders affecting the ocular surface, for example active allergies Current use of punctal plugs Pre-cancerous lesions, skin cancer or pigmented lesions in the planned treatment area Uncontrolled infections or uncontrolled immunosuppressive diseases Subjects with ocular infections, within 6 months prior to screening Prior history of cold sores or rashes in the perioral area or in the planned treatment area that could be stimulated by light at a wavelength of 560 nm to 1200 nm, including: Herpes simplex 1 & 2, Systemic Lupus erythematosus, and porphyria Within 3 months prior to screening, use of photosensitive medication and/or herbs that may cause sensitivity to 560-1200 nm light exposure, including: Isotretinoin, Tetracycline, Doxycycline, and St. John's Wort Over exposure to sun, within 4 weeks prior to screening Use of prescription eye drops for dry eye, within 7 days prior to screening, excluding artificial tears and glaucoma drops Radiation therapy to the head or neck, within 12 months prior to screening Planned radiation therapy, within 8 weeks after the last treatment session Treatment with chemotherapeutic agent, within 8 weeks prior to screening Planned chemotherapy, within 8 weeks after the last treatment session New topical treatments within the area to be treated, or oral therapies, within 3 months prior to screening- except over-the-counter acetaminophen-based analgesics for pain management, new oral omega 3 fatty acid supplements and topical artificial tears Change in dosage of any systemic medication, within 3 months prior to screening Anticipated relocation or extensive travel outside of the local study area preventing compliance with follow-up over the study period Legally blind in either eye History of migraines, seizures or epilepsy Facial IPL treatment, within 12 months prior to screening Any thermal treatment of the eyelids, including Lipiflow, within 6 months prior to screening Expression of the meibomian glands, within 6 months prior to screening In either eye, moderate to severe (Grade 3-4) inflammation of the conjunctiva, including: allergic, vernal or giant papillary conjunctivitis In either eye, severe (Grade 4) inflammation of the eyelid, including: blepharochalasis, staphylococcal blepharitis or seborrheic blepharitis Ocular surface abnormality that may compromise corneal integrity in either eye (e.g., prior chemical burn, recurrent corneal erosion, corneal epithelial defect, Grade 3 corneal fluorescein staining, or map dot fingerprint dystrophy) Eyelid abnormalities that affect lid function in either eye, including: entropion, ectropion, tumor, edema, blepharospasm, lagophthalmos, severe trichiasis, and severe ptosis Any systemic condition that may cause dry eye disease, including: Stevens-Johnson syndrome, vitamin A deficiency, rheumatoid arthritis, Wegener's granulomatosis, sarcoidosis, leukemia, Riley-Day syndrome, systemic lupus erythematosus, and Sjögren's syndrome Unwilling or unable to abstain from the use of medications known to cause dryness (e.g., isotretinoin, antihistamines) throughout the study duration. Subjects must discontinue these medications for at least 1 month prior to the baseline visit. Any condition revealed whereby the investigator deems the subject inappropriate for this study

Facility Information:

Facility Name

The First affiliated hospital of harbin medical university

City

Harbin

State/Province

Heilongjiang

ZIP/Postal Code

150000

Country

China

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Efficiency and Changes of Cytokines Expression in Tear After Intense Pulsed Light Treating Dry Eye Disease

We'll reach out to this number within 24 hrs