Clinical Characteristics of Patients Developing Chronic Dry Eye After Refractive Surgery

Study Overview
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Brief Summary
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In recent years, many scholars have studied the ocular surface damage of patients with dry eye disease（DED）after FS-LASIK, but there has been a lack of comprehensive observation and research on the relationship and difference between dry eye （DE）patients with and without LASIK. Therefore, the purpose of this study was to investigate the characteristics of ocular surface and cytokines after FS-LASIK, and further explain the pathogenesis of chronic dry eyes after FS-LASIK. In addition, we will also compare clinical characteristics and tear neuropeptide concentrations in patients with dry eye disease (DED) with and without chronic ocular pain following FS-LASIK, and to investigate correlations between ocular pain, clinical characteristics, and tear neuropeptide levels.

Detailed Description
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A single visit cross-sectional study was performed. Approximately 40 chronic dry eye participants who had FS-LASIK more than 12month prior were recruited. Approximately 40 dry eye participants without refractive surgery history and 40 healthy participants without dry eye were also recruited as control groups. In addition, the patients with post-FS-LASIK DED were categorized into two groups based on the presence or absence of chronic ocular pain: (1) post-FS-LASIK DED patients with chronic ocular pain and (2) post-FS-LASIK DED patients without chronic ocular pain.

Official Title
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Clinical Characteristics of Patients Developing Chronic Dry Eye After Refractive Surgery

Conditions
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Dry Eye

Intervention / Treatment
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* Procedure: FS-LASIK


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18years to 40 years Male or female DED patients based on Chinese Dry Eye Diagnosis Standard (2020) with or without FS-LASIK Provision of written informed consent. Exclusion Criteria: active ocular infection, ocular inflammation, active ocular allergy, severe blepharitis or obvious inflammation of the eyelid margin, which in the judgment of the investigator may interfere with the interpretation of the study results. Pregnant and lactating women, or those planning a pregnancy over the course of the study Uncontrolled systemic disease Suffer from diseases that may affect corneal nerves, such as keratoconus, trigeminal neuralgia, allergic conjunctivitis, etc.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| DED after FS-LASIK<br>patients with dry eye disease (DED) after refractive surgery (RS） | Procedure: FS-LASIK<br>* Laser-assisted in situ keratomileusis, commonly referred to laser eye surgery or laser vision correction, is a type of refractive surgery for the correction of myopia, hypermetropia, and astigmatism.<br>* Other names: Femtosecond laser-assisted in situ keratomileusis;|
| DED without FS-LASIK<br>patients with dry eye who did not have refractive surgery | |
| normal control<br>subjects with no ocular symptoms and no previous ocular surgeries | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ocular surface disease index (OSDI) | OSDI is one of the most frequently used questionnaires for evaluation of dry eye . This includes 12 questions which measure the frequency of symptoms over the recent week, and the scores range from 0 to 100. | baseline | 
| numerical rating scale (NRS) | The NRS was used to evaluate ocular pain and consists of a numbered line from 0 to 10 scores that measures pain intensity: 0-1: no pain; 2-4: mild pain; 5-7: moderate pain; and 8-10: severe pain. | baseline | 
| NPSI-Eye (range 0-100 score) | Neuropathic Pain Symptom Inventory modified for the Eye (NPSI-Eye) (range 0-100 over a 24-hour recall period) | baseline | 
| Tear break-up time (TBUT)(s) | BUT is the time from normal blinking to the first appearance of a break in the tear film. | baseline | 
| Corneal fluorescein staining (CFS) | The degree of fluorescein staining of the cornea was evaluated using the National Eye Institute (NEI) scale of five corneal regions (central, superior, temporal, nasal, and inferior). The scores range from 0 to 15. | baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the concentration of Interleukin-1β（IL-1β) (pg/ml) | basal tears will be collected from the inferior meniscus of each subject to test this inflammatory cytokine. IL-1β levels will be quantified by Luminex immunoassay. | baseline | 
| the concentration of Interleukin-6 (IL-6) (pg/ml) | basal tears will be collected from the inferior meniscus of each subject to test this inflammatory cytokine. IL-6 levels will be quantified by Luminex immunoassay. | baseline | 
| the concentration of Interleukin-10 (IL-10) (pg/ml) | basal tears will be collected from the inferior meniscus of each subject to test this inflammatory cytokine. IL-10 levels will be quantified by Luminex immunoassay. | baseline | 
| the concentration of Interleukin-23 (IL-23) (pg/ml) | basal tears will be collected from the inferior meniscus of each subject to test this inflammatory cytokine. IL-23 levels will be quantified by Luminex immunoassay. | baseline | 
| the concentration of Interleukin-17A (IL-17A) (pg/ml) | basal tears will be collected from the inferior meniscus of each subject to test this inflammatory cytokine. IL-17A levels will be quantified by Luminex immunoassay. | baseline | 
| the concentration of tumor necrosis factor-α (TNF-α)(pg/ml) | basal tears will be collected from the inferior meniscus of each subject to test this inflammatory cytokine. TNF-α levels will be quantified by Luminex immunoassay. | baseline | 
| the concentration of interferon-γ (IFN-γ)(pg/ml) | basal tears will be collected from the inferior meniscus of each subject to test this inflammatory cytokine. IFN-γ levels will be quantified by Luminex immunoassay | baseline | 
| the concentration of granulocyte-macrophage colony-stimulating factor (GM-CSF)(pg/ml) | basal tears will be collected from the inferior meniscus of each subject to test this inflammatory cytokine. GM-CSF levels will be quantified by Luminex immunoassay. | baseline | 
| the concentration of substance P (SP)(pg/ml) | basal tears will be collected from the inferior meniscus of each subject to test this neuropeptide. SP levels will be quantified by Luminex immunoassay. | baseline | 
| the concentration of alpha-melanocyte-stimulating hormone (α-MSH) (pg/ml) | basal tears will be collected from the inferior meniscus of each subject to test this neuropeptide. α-MSH levels will be quantified by Luminex immunoassay. | baseline | 
| the concentration of β-endorphin (pg/ml) | basal tears will be collected from the inferior meniscus of each subject to test this neuropeptide. β-endorphin levels will be quantified by Luminex immunoassay. | baseline | 
| the concentration of neurotensin(pg/ml) | basal tears will be collected from the inferior meniscus of each subject to test this neuropeptide. neurotensin levels will be quantified by Luminex immunoassay. | baseline | 
| the concentration of oxytocin(pg/ml) | basal tears will be collected from the inferior meniscus of each subject to test this neuropeptide. oxytocin levels will be quantified by Luminex immunoassay. | baseline | 
| Schirmer Ⅰ test (SⅠt) (mm/5 minutes) | The Schirmer I test is performed using sterile strips without anesthesia. The strips are placed in the lateral part of the inferior fornix of the eye for 5min and the extent of tear flow down was measured in millimeters. | baseline | 
| tear meniscus height (TMH)(mm) | The amounts of basal tears between the upper and lower eyelid margin. | baseline | 
| Lissamine green staining | To grade the temporal zone, the subject looks nasally; to grade the nasal zone the subject looks temporally. The upper and lower conjunctiva can also be graded. | baseline | 
| meibomian gland dropout rate | grade 0: no gland atrophy; grade 1: ≤1/3 gland atrophy; grade 2: 1/3 to 2/3 gland atrophy；grade 3: >2/3 gland atrophy. | baseline | 
| corneal sensitivity (range, 60-0 mm) | Corneal sensitivity will be measured in the right eye only using the Cochet-Bonnet aesthesiometer and the ascending method of limits to determine the threshold of stimulus detection. | baseline | 
| sub-basal corneal nerve density (mm/mm2) | Sub-basal corneal nerve plexus image will be acquired using a laser scanning confocal microscope. | baseline | 
| Hamilton anxiety scale | to evaluate the psychological status of patients. A total score of less than 7 indicates normal. | baseline | 
| Hamilton Depression scale | to evaluate the psychological status of patients. A total score of less than 7 indicates normal. | baseline |