Screening and Identification of Biomarkers for High Myopia by a Rapid Method

To screen and identify sensitive biomarkers for high myopia via a robust, convenient, and cost-effective approach according to the association between high myopia and concentration of biomarkers in tear fluid, saliva and blood among adults and children.

Study Overview

• Status: Active, not recruiting
• Conditions: High Myopia
• Intervention / Treatment: Diagnostic test: blood sample

Detailed Description

Myopia has emerged as a serious public health issue, with the prevalence increasing rapidly worldwide, especially in East Asia. Increasingly early onset of myopia leads to high myopia with sight-threatening complications (e.g., secondary cataracts, glaucoma, and retinal detachment) that cannot be treated by optical means.

A key goal of myopia research over the past decades has been to identify those sensitive biomarkers. Accurate monitoring of myopic-specific biomarkers is desirable for achieving early diagnosis, progression assessment, and prognostic management.

However, measurement of levels of MMPs in human have been restricted to aqueous humors, which is invasive and the findings are difficult to be replicated in other studies. In order to achieve the goal of convenient high myopic detection, the use of a panel of biomarkers using a multiplex approach may indeed be rapid and highly reproducible with potentially higher sensitivity and specificity than single biomarkers, such as MMP 2 for the early detection of high myopia.

In this study we have used a newly developed immunoassay technology, and identified a panel of novel biomarkers for early detection of high myopia by non-invasively evaluating several biomarkers that are measurable in the saliva and tear fluid of adults.

• Study Type: Observational
• Enrollment (Anticipated): 120

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100073
      • Beijing Tongren Hospital, Capital Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 35 years (Child, Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

There are two levels of research, namely children and adults. Each level is divided into three groups of 20 subjects each. So about 120 subjects are anticipated in total. Taken into account the proportion of exclusion, 150 subjects are invited to recruitment.

Description

Children Inclusion Criteria

1. Children aged 6-17
2. Removing flexible lenses for at least 1 week, flexible astigmatism and hard lenses for at least 3 weeks, orthokeratology lenses for at least 3 months;
3. Best corrected visual acuity of either eye were all ≥ 1.0;
4. The range of myopia in either eye was -15 D ≤ SE ≤ +1.0 D;
5. Astigmatism of either eye less than -5.0 D;
6. Anisometropia ≤ -1.5 D;
7. There was no active ocular inflammatory diseases; no obvious corneal cloud or macula, anormal corneal topography, and no tendency of keratoconus.
8. Intraocular pressure of either eye is of 10 to 21 mmHg;
9. On the basis of full understanding, children and their guardians sign the informed consent;

Adults Inclusion Criteria

1. adults aged 18-35
2. Removing flexible lenses for at least 1 week, flexible astigmatism and hard lenses for at least 3 weeks, orthokeratology lenses for at least 3 months;
3. Best corrected visual acuity of either eye were all ≥ 1.0;
4. The range of myopia in either eye was -15 D ≤ SE ≤ +1.0 D;
5. Astigmatism of either eye less than -5.0 D;
6. Anisometropia ≤ -1.5 D;
7. There was no active ocular inflammatory diseases; no obvious corneal cloud or macula, anormal corneal topography, and no tendency of keratoconus.
8. Intraocular pressure of either eye is of 10 to 21 mmHg;
9. On the basis of full understanding, adults sign the informed consent;

Exclusion Criteria:

1. Amblyopia: best corrected visual acuity (BCVA) of either eye less than 1.0 for adults and children over 6 years old;
2. Active ocular inflammatory diseases, such as uveitis and other inflammatory diseases;
3. Secondary myopia, genetic disease or connective tissue- related myopia;
4. Moderate or severe ptosis;
5. Congenital cataract, glaucoma;
6. Other fundus diseases other than myopic related fundus lesions;
7. Intraocular or refractive surgery history;
8. The refractive medium is turbid, and it is impossible to take a clear fundus image; (9)Unable to cooperate with fundus image shooting and other examination;

(10)Do not receive cycloplegia or have contraindications; (11)Poor overall condition, unable to follow up for a long time; (12)The subject refuses to participate in the research; (13)Other cases in which the researcher judges that it is not suitable for participation in the study.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Emmetropic subjects; Spherical equivalent (Diopter, D) to be between -0.5 and +0.5 D	Diagnostic test: blood sample; Blood collection Circulating serum concentrations of melatonin and dopamine were determined from fasting blood samples. Participants were required to fast from 10 pm the previous evening. A 5 mL serum blood sample was collected from the antecubital vein between 8.30 am and 10 am. Tear collection Tear samples were collected using Schirmer's strip without anesthesia between 8:30-10:00am. Tears were extracted in 200 μl of 1 X Phosphate Buffered Saline with 0.1% Tween-20 (PBST). Saliva collection Saliva samples were collected via the "passive drool" method with subjects in a seated position. Subjects were asked to rinse their mouth with water 10 minutes prior to saliva collection and to refrain from using lip makeup during the sampling period.; Other Names: saliva, tear fluid
Low and moderate myopic subjects; Spherical equivalent (Diopter, D) to be less than -0.5 but over -6.0D	Diagnostic test: blood sample; Blood collection Circulating serum concentrations of melatonin and dopamine were determined from fasting blood samples. Participants were required to fast from 10 pm the previous evening. A 5 mL serum blood sample was collected from the antecubital vein between 8.30 am and 10 am. Tear collection Tear samples were collected using Schirmer's strip without anesthesia between 8:30-10:00am. Tears were extracted in 200 μl of 1 X Phosphate Buffered Saline with 0.1% Tween-20 (PBST). Saliva collection Saliva samples were collected via the "passive drool" method with subjects in a seated position. Subjects were asked to rinse their mouth with water 10 minutes prior to saliva collection and to refrain from using lip makeup during the sampling period.; Other Names: saliva, tear fluid
High myopic subjects; Spherical equivalent (Diopter, D) to be over or equal to -6.0D	Diagnostic test: blood sample; Blood collection Circulating serum concentrations of melatonin and dopamine were determined from fasting blood samples. Participants were required to fast from 10 pm the previous evening. A 5 mL serum blood sample was collected from the antecubital vein between 8.30 am and 10 am. Tear collection Tear samples were collected using Schirmer's strip without anesthesia between 8:30-10:00am. Tears were extracted in 200 μl of 1 X Phosphate Buffered Saline with 0.1% Tween-20 (PBST). Saliva collection Saliva samples were collected via the "passive drool" method with subjects in a seated position. Subjects were asked to rinse their mouth with water 10 minutes prior to saliva collection and to refrain from using lip makeup during the sampling period.; Other Names: saliva, tear fluid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentration of TNF-α in tear fluid, saliva and blood sample among emmetropic, low and moderate myopic, and high myopic groups	TNF-α: Tumor necrosis factor is an adipokine and a cytokine.	June 30, 2023

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentration of IL-1 in tear fluid, saliva and blood sample among emmetropic, low and moderate myopic, and high myopic groups	IL-1: Interleukin 1	June 30, 2023

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentration of IL-10 in tear fluid, saliva and blood sample among emmetropic, low and moderate myopic, and high myopic groups	IL-10: Interleukin 10, an anti-inflammatory cytokine	June 30, 2023
Concentration of IL-6 in tear fluid, saliva and blood sample among emmetropic, low and moderate myopic, and high myopic groups	IL-6: Interleukin 6, a pro-inflammatory cytokine	June 30, 2023
Concentration of TIMP in tear fluid, saliva and blood sample among emmetropic, low and moderate myopic, and high myopic groups	TIMP: Tissue inhibitor of metalloproteinases, a family of proteins that act as enzyme inhibitors	June 30, 2023
Concentration of MMP2 in tear fluid, saliva and blood sample among emmetropic, low and moderate myopic, and high myopic groups	MMP2: Proteins of the matrix metalloproteinase (MMP) family are involved in the breakdown of extracellular matrix in normal physiological processes	June 30, 2023
Concentration of EGF in tear fluid, saliva and blood sample among emmetropic, low and moderate myopic, and high myopic groups	EGF:Epidermal growth factor (EGF) is a protein that stimulates cell growth.	June 30, 2023

Collaborators and Investigators

• Sponsor: Beijing Tongren Hospital
• Collaborators: Tsinghua University
• Investigators: Principal Investigator: Shi-Ming Li, Beijing Tongren Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 20, 2023
• Primary Completion (Anticipated): May 31, 2023
• Study Completion (Anticipated): July 31, 2023

Study Registration Dates

• First Submitted: March 26, 2023
• First Submitted That Met QC Criteria: March 26, 2023
• First Posted (Actual): April 7, 2023

Study Record Updates

• Last Update Posted (Actual): April 7, 2023
• Last Update Submitted That Met QC Criteria: March 26, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: biomarkers
• Additional Relevant MeSH Terms: Eye Diseases; Refractive Errors; Myopia
• Other Study ID Numbers: 010133

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No