Analysis of the Results of Intense Pulsed Light Treatment Previously to Laser Refractive Surgery

Study Overview
=================
Brief Summary
-----------------
Dry eye is often reported as the most common complication after a laser refractive surgery. Any refractive procedure can lead an impact on the corneal surface and the tear film. The main cause of this dry eye is the corneal denervation caused by the destruction of the anterior stromal nerves during the ablative procedure. This loss of corneal sensitivity leads to a decrease in the blink reflex, a decrease in the secretion rate of the meibomian glands and finally an evaporated dry eye. There is also a chronic inflammation at the corneal surface that produces an increase of inflammatory cytokines and a dysfunction of the meibomian glands. Yu et al have described incidences of dry eye closed to 60% after the first month of LASIK. Hovanesian et al have observed dry eye symptoms in 50% of patients 6 months after surgery. Donnenfeld et al describe 15% of moderate dry eye in the following 3 months and 5% of severe dry eye in the first 6 months. A small number of patients will present with chronic dry eye symptoms for more than 1 year. Bower et al analyzed its incidence in 0.8% Alterations in the tear film also decrease the quality of the retinal image and produce greater number of high-order due to the irregular. Pulsed light therapy (IPL) applied preoperatively in patients who undergo a laser refractive surgery may prevent the post-surgical dry eye and improve the refractive results. The aim of our study is to evaluate the usefulness of the applied therapy for the prevention of dry eye in patients that undergo a corneal refractive procedure.

Detailed Description
-----------------
Design Clinical experimental controlled trial, double-blind in which participants will be randomized into 2 groups: a study group (IPL + laser refractive surgery) and a control group (laser refractive surgery without IPL). The study will be conducted in accordance with Law 14/2007 of 3 July, on Biomedical Research, the Declaration of Helsinki (October 2013 version), standards of Good Clinical Practice and legislation in this area. All participants included in the study should read the Information Sheet and sign the informed and voluntary consent. Participants Participants from Vissum Clinic that present the inclusion criteria and none of the exclusion criteria. The investigators will start the study with a preliminary project and depending on the results obtained, the investigators will apply these values to calculate the final sample size using the T-student-Fischer test for unilateral hypotheses and for a type 1 or α error of 5%. and a type 2 or β error of 20%. Parameters evaluated Primary measures: age, sex, skin phototype, visual acuity with and without correction, refraction, cycloplegic refraction, OSDI and VAS questionnaire, use of artificial tears, oxford scale, lacrimal meniscus height, tear break-up time, conjunctival hyperemia, meibography and slit lamp examination. Secondary measures: corneal topography and tomography (MS-39, CSO, Italy), corneal aberrometry (MS-39, CSO, Italy), ocular aberrometry (Osiris, CSO, Italy), analysis of contrast sensitivity (CSV-1000, Vector vision), photographic capture of the epithelial defect in PRK, pre-surgical and postsurgical photographic capture of the eyelid changes in PRK. The measurement of the different objective variables will be carried out in the clinic. The measurement of the subjective variables will be carried out by two ophthalmologists, both masked. Surgery and follow-up Participants who are candidates for a LASIK or SMILE procedure will receive, after randomization, IPL treatment in both eyes (experimental group) or sham IPL (control group). In the case of participant candidate for a PRK procedure, an intra-subject control group will be used, where one eye will receive the IPL treatment (right eyes) and the left contralateral eye the sham IPL treatment (control). Refractive surgeries will be performed exclusively two ophthalmologists following the same surgical protocol. IPL therapy (M22, Lumenis LTD, Israel) will be performed following the same protocol (standardized facial and periocular application with automatically adjusted energy according to Fitzpatrick skin classification). Three IPL sessions will be applied (simulated in the case of the control group): 7 days before the intervention, 7 days after the intervention, and 30 days after the intervention. The total postsurgical follow-up will be 6 months. Statistical analyses All demographic and clinical data will be collected in a database and analyzed with the SPSS statistical package for Windows version 22.0. A p <0.05% will be considered significant.

Official Title
-----------------
Analysis of the Efficacy and Safety of Intense Pulsed Light Treatment for the Ocular Surface in Patients Who Will Undergo Laser Refractive Surgery

Conditions
-----------------
Meibomian Gland Dysfunction, Blepharitis

Intervention / Treatment
-----------------
* Device: Study group
* Other: Control group


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients over 18 years of age who are undergoing a corneal laser refractive surgery after a medical indication by the Vissum ophthalmologist Exclusion Criteria: Pregnancy Piercings Fitzpatrick skin classification V and VI Autoimmune diseases Epilepsy Previous history of herpes or ocular pathology Pathological or suspicious corneal topography Treatment in the previous month with corticosteroids, antihistamines or topical vasoconstrictors.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Clinical experimental controlled trial, double-blind in which participants will be randomized into 2 groups: a study group and a control group
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study group<br>IPL + laser refractive surgery | Device: Study group<br>* The IPL therapy consists in a polychromatic pulses of light not coherent and not collimated. The therapy leads to a series of processes such as the destruction of superficial blood vessels and thus the reduction of local inflammation, the liquefy of the meibum and an antimicrobial, anti-inflammatory and antioxidant effects. The therapy is performed over the cheeks, nose and upper eyelids.<br>* Other names: Intense pulsed light therapy (Lumenis M22);|
| Placebo Comparator: Control group<br>Laser refractive surgery without IPL | Other: Control group<br>* Same procedure but without energy<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| OSDI questionnaire | It measures the severity of ocular surface symptoms and includes 12 items organized into 3 subscales; eye discomfort, functionality and environmental factors. After completing the questionnaire, a final score is obtained that when it is higher than 13 indicates ocular surface pathology. | 0 day | 
| Change from Baseline OSDI questionnaire | It measures the severity of ocular surface symptoms and includes 12 items organized into 3 subscales; eye discomfort, functionality and environmental factors. After completing the questionnaire, a final score is obtained that when it is higher than 13 indicates ocular surface pathology. | 7 day | 
| Change from Baseline OSDI questionnaire | It measures the severity of ocular surface symptoms and includes 12 items organized into 3 subscales; eye discomfort, functionality and environmental factors. After completing the questionnaire, a final score is obtained that when it is higher than 13 indicates ocular surface pathology. | 30 day | 
| Change from Baseline OSDI questionnaire | It measures the severity of ocular surface symptoms and includes 12 items organized into 3 subscales; eye discomfort, functionality and environmental factors. After completing the questionnaire, a final score is obtained that when it is higher than 13 indicates ocular surface pathology. | 90 day | 
| Change from Baseline OSDI questionnaire | It measures the severity of ocular surface symptoms and includes 12 items organized into 3 subscales; eye discomfort, functionality and environmental factors. After completing the questionnaire, a final score is obtained that when it is higher than 13 indicates ocular surface pathology. | 180 day | 
| Lacrimal meniscus height | Measured in millimeters by Ocular Keratograph 5M, a value greater than 0.20 mm is considered normal | 0 day | 
| Change from Baseline Lacrimal meniscus height | Measured in millimeters, a value greater than 0.20 mm is considered normal | 7 day | 
| Change from Baseline Lacrimal meniscus height | Measured in millimeters, a value greater than 0.20 mm is considered normal | 30 day | 
| Change from Baseline Lacrimal meniscus height | Measured in millimeters, a value greater than 0.20 mm is considered normal | 90 day | 
| Change from Baseline Lacrimal meniscus height | Measured in millimeters, a value greater than 0.20 mm is considered normal | 180 day | 
| Tear Break-up-time | Time elapsed from the last blink to the appearance of the first tear discontinuity measured by Ocular Keratograph 5M. A title longer than 5 seconds is considered normal. | 0 day | 
| Change from Baseline Tear Break-up-time | time elapsed from the last blink to the appearance of the first tear discontinuity measured by Ocular Keratograph 5M. A title longer than 5 seconds is considered normal. | 7 day | 
| Change from Baseline Tear Break-up-time | time elapsed from the last blink to the appearance of the first tear discontinuity measured by Ocular Keratograph 5M. A title longer than 5 seconds is considered normal. | 30 day | 
| Change from Baseline Tear Break-up-time | time elapsed from the last blink to the appearance of the first tear discontinuity measured by Ocular Keratograph 5M. A title longer than 5 seconds is considered normal. | 90 day | 
| Change from Baseline Tear Break-up-time | time elapsed from the last blink to the appearance of the first tear discontinuity measured by Ocular Keratograph 5M. A title longer than 5 seconds is considered normal. | 180 day | 
| Conjunctival and ciliary hyperemia. | Grade of red eye measured by Ocular Keratograph 5M. Jenvis ranking from 0 to 4 (normal, mild, moderate, severe) | 0 day | 
| Change from Baseline Conjunctival and ciliary hyperemia. | Grade of red eye measured by Ocular Keratograph 5M. Jenvis ranking from 0 to 4 (normal, mild, moderate, severe) | 7 day | 
| Change from Baseline Conjunctival and ciliary hyperemia. | Grade of red eye measured by Ocular Keratograph 5M. Jenvis ranking from 0 to 4 (normal, mild, moderate, severe) | 30 day | 
| Change from Baseline Conjunctival and ciliary hyperemia. | Grade of red eye measured by Ocular Keratograph 5M. Jenvis ranking from 0 to 4 (normal, mild, moderate, severe) | 90 day | 
| Change from Baseline Conjunctival and ciliary hyperemia. | Grade of red eye measured by Ocular Keratograph 5M. Jenvis ranking from 0 to 4 (normal, mild, moderate, severe) | 180 day | 
| Upper and lower meibography | Measured by Oculus Keratograph 5M. Observes and evaluates morphological changes of the meibomian glands Meiboscore classification Grade 0: no loss of meibomian glands. Grade 1: loss of less than 1/3 of the total surface of the meibomian glands. Grade 2: loss of 1/3 to 2/3 of the total area. Grade 3: loss of more than 2/3 of the surface. | 0 day | 
| Change from Baseline Upper and lower meibography | Measured by Oculus Keratograph 5M. Observes and evaluates morphological changes of the meibomian glands Meiboscore classification Grade 0: no loss of meibomian glands. Grade 1: loss of less than 1/3 of the total surface of the meibomian glands. Grade 2: loss of 1/3 to 2/3 of the total area. Grade 3: loss of more than 2/3 of the surface. | 7 day | 
| Change from Baseline Upper and lower meibography | Measured by Oculus Keratograph 5M. Observes and evaluates morphological changes of the meibomian glands Meiboscore classification Grade 0: no loss of meibomian glands. Grade 1: loss of less than 1/3 of the total surface of the meibomian glands. Grade 2: loss of 1/3 to 2/3 of the total area. Grade 3: loss of more than 2/3 of the surface. | 30 day | 
| Change from Baseline Upper and lower meibography | Measured by Oculus Keratograph 5M. Observes and evaluates morphological changes of the meibomian glands Meiboscore classification Grade 0: no loss of meibomian glands. Grade 1: loss of less than 1/3 of the total surface of the meibomian glands. Grade 2: loss of 1/3 to 2/3 of the total area. Grade 3: loss of more than 2/3 of the surface. | 90 day | 
| Change from Baseline Upper and lower meibography | Measured by Oculus Keratograph 5M. Observes and evaluates morphological changes of the meibomian glands Meiboscore classification Grade 0: no loss of meibomian glands. Grade 1: loss of less than 1/3 of the total surface of the meibomian glands. Grade 2: loss of 1/3 to 2/3 of the total area. Grade 3: loss of more than 2/3 of the surface. | 180 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual acuity | Visual acuity with and without correction, measured on a decimal scale, determined by the Snellen panel, placing the examined person at a distance of 6 meters, will be collected by an optician. | 0 day | 
| Change from Baseline Visual acuity | Visual acuity with and without correction, measured on a decimal scale, determined by the Snellen panel, placing the examined person at a distance of 6 meters, will be collected by an optician. | 180 day | 
| Corneal topography | Performs an analysis of the cornea, which allows evaluating the shape and quantifying the power of the different curvatures | 0 day | 
| Change from Baseline Corneal topography | Performs an analysis of the cornea, which allows evaluating the shape and quantifying the power of the different curvatures | 180 day | 
| Corneal aberrometry | Technique that analyzes complex systems of light waves to quantify the set of optical aberrations that exist within the ocular structure. | 0 day | 
| Change from Baseline Corneal aberrometry | Technique that analyzes complex systems of light waves to quantify the set of optical aberrations that exist within the ocular structure. | 180 day | 
| Analysis of contrast sensitivity | Contrast Sensitivity is a test that assesses a person's ability to identify an object and separate it from the background Contrast sensitivity is evaluated with charts that can be used as projected or wall acuity charts. | 0 day | 
| Change from Baseline Analysis of contrast sensitivity | Contrast Sensitivity is a test that assesses a person's ability to identify an object and separate it from the background Contrast sensitivity is evaluated with charts that can be used as projected or wall acuity charts. | 180 day | 
| VAS questionnaire | investigates the intensity of the ocular surface symptoms from 0 to 100 (normal- severe) | 0 day | 
| Change from Baseline VAS questionnaire | investigates the intensity of the ocular surface symptoms from 0 to 100 (normal- severe) | 180 day | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Intense pulsed light, LASIK / SMILE