Autologous Platelet-rich Plasma in the Treatment of Persistent Epithelial Defects

Study Overview
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Brief Summary
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Persistent epithelial defects (PED) are corneal ulcers that do not heal within the first two weeks of treatment with artificial tears or ocular lubricant ointment. It is believed that this condition is the result of the loss of certain substances normally present in the tears that aid in the healing process of the cornea. When the eye is healthy, these ulcers typically heal rapidly. However, when there is an underlying disease such as diabetes, this healing process is altered and it takes longer for the ulcer to heal. Autologous platelet-rich plasma (PRP) is a substance that is obtained from the patient's own blood and it is believed this substance may replace those missing factors in the tears of patients with PED. The purpose of this investigation is to find out whether PRP combined with a bandage contact lens is better than preservative free lubricant combined with bandage contact lens or than eye patch with ocular lubricant ointment for the treatment of PED. Participants will be randomly assigned to one of the three groups and will get the treatment until the ulcer heals completely. We will count the days it takes for the PED to heal and based on that we will determine wich treatment is more effective (the treatment that takes the least days to heal will be considered the most effective). Since this disease is difficult to treat and doesn't have a gold standard treatment, usually the available treatments are not as good as we would like, therefore, the ulcer might progress even to perforation regardless of the treatment. In these cases, we will provide appropriate treatment for progressive corneal thinning and corneal perforation.

Detailed Description
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Persistent epithelial defects (PED) are corneal lesions that do not heal within the first two weeks of conventional treatment (i.e. preservative-free lubricant, bandage contact lens (BCL), ocular lubricant ointment, eye patching). These defects are the result of the loss of certain lacrimal factors that maintain the integrity and homeostasis of the corneal epithelium and ocular surface. Normally, PED heal rapidly in the healthy eye. However, underlying ocular surface pathology can slow down the healing process and contribute to the persistence of the epithelial defect. Hematopoietic derivatives such as autologous platelet-rich plasma (PRP) may replace these missing components and eventually lead to complete healing in a faster and more comfortable way for the patient. The objective of this study is to determine if PRP combined with BCL is more effective than preservative-free lubricant combined with BCL or than eye patch with ocular lubricant ointment for the treatment of PED. Participants will be randomly assigned to one of the three groups and treatment will be administered until achieving complete defect closure. The effectiveness of each treatment will be measured in terms of days taken to achieve complete closure. Since PED is a complex disease that is difficult to treat, the available treatments are not very effective, therefore, PED might progress even to perforation regardless of the treatment. In this last scenario, we will provide appropriate treatment for progressive corneal thinning and corneal perforation

Official Title
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Autologous Platelet-rich Plasma in the Treatment of Persistent Corneal Epithelial Defects

Conditions
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Persistent Epithelial Defect

Intervention / Treatment
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* Combination Product: PRP plus BCL
* Combination Product: BCL plus PFL
* Combination Product: Eye patch plus ocular lubricant ointment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with persistent epithelial defect and at least one of the following diagnoses: Recurrent corneal epithelial defect. Neurotrophic corneal ulcer. Neurotrophic keratopathy secondary to any disease (i.e. diabetes mellitus, infection with herpes simplex virus or herpes zoster virus, microbial keratitis sequelae, multiple sclerosis, Parkinson's disease, VII cranial nerve palsy, chemical or thermic burn sequelae, trauma, surgery, iatrogenic, chronic dry eye, rheumatic disease). Exclusion Criteria: Patients diagnosed with: Peripheral ulcerative keratitis, or Mooren's ulcer. Active infectious keratitis and/or ulcers.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Subjects will be randomly assigned to three groups. Demographic characteristics and underlying etiologies will be identified. Subjects will undergo a general ophthalmologic evaluation (baseline) and PED size will be measured. Treatments will be administered until complete defect healing is achieved and visits will be scheduled weekly or as needed for continued ophthalmologic evaluation. After complete closure, subjects will be followed for three months with visits every 2 to 4 weeks to evaluate progress and identify recurrences.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PRP plus BCL<br>Bandage contact lens (BCL) plus 1 autologous platelet-rich plasma (PRP) eye drop every 1 to 3 hours. | Combination Product: PRP plus BCL<br>* Bandage contact lens (BCL) plus 1 autologous platelet-rich plasma (PRP) eye drop every 1 to 3 hours.<br>|
| Active Comparator: BCL plus PFL<br>Bandage contact lens (BCL) plus 1 preservative-free lubricant (PFL) eye drop every 1 to 3 hours. | Combination Product: BCL plus PFL<br>* Bandage contact lens (BCL) plus 1 preservative-free lubricant (PFL) eye drop every 1 to 3 hours.<br>|
| Active Comparator: Eye patch plus ocular lubricant ointment<br>Eye patch plus ocular lubricant ointment every 24 hours. | Combination Product: Eye patch plus ocular lubricant ointment<br>* Eye patch plus ocular lubricant ointment every 24 hours.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Persistent epithelial defect healing time. | Persistent epithelial defect healing time measured in days. | From the first day of treatment until the date of complete defect closure, assessed up to 3 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in corneal sensitivity | Corneal sensitivity will be assessed with corneal esthesiometer Cochet-Bonnet. | Change from baseline corneal sensitivity at the date of defect closure, up to 3 months. | 
| Uncorrected visual acuity | Uncorrected visual acuity will be assessed using Snellen cards. Measurements will be converted to LogMar values for statistical analysis. | Every week (or sooner, if needed) from date of randomization until the date of complete defect closure, up to 3 months. | 
| Best corrected visual acuity | Best corrected visual acuity will be assessed using Snellen cards. Measurements will be converted to LogMar values for statistical analysis. | Every week (or sooner, if needed) from date of randomization until the date of complete defect closure, up to 3 months. | 
| Ocular pain | Ocular pain will be assessed using the Wong-Baker Faces Pain Rating Scale. The scale ranges from 0 (no pain) to 10 (maximum pain), and includes 6 faces (visual representation), numbers, and written descriptions that represent the level of pain. The first face represents a pain score of 0 and it reads no hurt; the second face represents a pain score of 2 and it reads hurts little bit; the third face represents a pain score of 4 and it reads hurts little more; the fourth face represents a pain score of 6 and it reads hurts even more; the fifth face represents a pain score of 8 and it reads hurts whole lot; the last face represents a pain score of 10 and it reads hurst worst. Lower values represent a better outcome. | Every week (or sooner, if needed) from date of randomization until the date of complete defect closure, up to 3 months. | 
| Ocular surface symptoms | Ocular surface symptoms as assessed by the Symptom Assessment in Dry Eye (SANDE) questionnaire. The SANDE questionnaire consists of two questions presented in visual analog scale. The first question assesses the frequency of dry eye syndrome and the scale ranges from rarely to all the time on a 100 mm line. The second question assesses the severity of dry eye syndrome and the scale ranges from very mild to very severe on a 100 mm line. Patients are asked to place a mark on the line to represent the extent of their symptoms, then the location of the marks on each line are measured from left to right in mm. The SANDE score is calculated by multiplying the frequency value times the severity value and obtaining the square root. Lower scores represent a better outcome. | Every week (or sooner, if needed) from date of randomization until the date of complete defect closure, up to 3 months. | 
| Ocular surface symptoms | Ocular surface symptoms as assessed by the Ocular Surface Disease Index (OSDI). The OSDI questionnaire consists of 12 questions that assess dry eye symptoms and their effects on vision related function. The questionnaire is divided in 3 subscales: ocular symptoms, vision-related function, and environmental triggers. Patients are asked to rate their responses on a 0 to 4 scale where 0 represents none of the time, 1 some of the time, 2 half of the time, 3 most of the time, and 4 all of the time. The total score is calculated using the following formula: ([sum of scores for all questions answered x 100] / [total number of questions answered x 4]). Lower scores represent a better outcome. | At date of randomization and at date of defect closure, up to 3 months. | 
| Quality of life questionnaire | Quality of life as assessed by the National Eye Institute Visual Function Questionnaire (NEI VFQ-25). The NEI VFQ-25 questionnaire consists of 25 questions that assess the effect of visual impairment on the patient's quality of life. The 25-item questionnaire gives a score on a scale of 0 to 100, where 0 is the worst score and 100 is the best score. Higher scores represent a better outcome. | At date of randomization and at date of defect closure, up to 3 months. | 
| Frequency of adverse events, recurrences and/or treatment failure | Frequency of adverse events, recurrences and/or treatment failure will be evaluated during the ophthalmic evaluation. | These will be evaluated from the beginning of the treatment until three months after defect closure. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Platelet-Rich Plasma, Persistent Epithelial Defect