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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Persistent Epithelial Defect
• Intervention / Treatment: Combination product: PRP plus BCL; Combination product: BCL plus PFL; Combination product: Eye patch plus ocular lubricant ointment

Detailed Description

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

• Study Type: Interventional
• Enrollment (Anticipated): 54
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Karim Mohamed-Noriega, M.D.; Phone Number: +52 8183469259; Email: karim.mohamednrg@uanl.edu.mx

Study Locations

• Mexico
  • Nuevo Leon
    • Monterrey, Nuevo Leon, Mexico, 64460
      • Recruiting
      • Departamento de Oftalmologia, Hospital Universitario "Dr. Jose Eleuterio Gonzalez"
      • Contact: Karim Mohamed-Noriega, M.D.; Phone Number: +52 81 83469259; Email: karim.mohamednrg@uanl.edu.mx

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: Universidad Autonoma de Nuevo Leon
• Collaborators: Hospital Universitario Dr. Jose E. Gonzalez
• Investigators: Principal Investigator: Karim Mohamed-Noriega, M.D., Departamento de Oftalmologia, Hospital Universitario Dr. Jose Eleuterio Gonzalez

Publications and helpful links

General Publications

• Tsubota K, Goto E, Shimmura S, Shimazaki J. Treatment of persistent corneal epithelial defect by autologous serum application. Ophthalmology. 1999 Oct;106(10):1984-9. doi: 10.1016/S0161-6420(99)90412-8.
• Chen J, Chen P, Backman LJ, Zhou Q, Danielson P. Ciliary Neurotrophic Factor Promotes the Migration of Corneal Epithelial Stem/progenitor Cells by Up-regulation of MMPs through the Phosphorylation of Akt. Sci Rep. 2016 May 13;6:25870. doi: 10.1038/srep25870.
• Ljubimov AV, Saghizadeh M. Progress in corneal wound healing. Prog Retin Eye Res. 2015 Nov;49:17-45. doi: 10.1016/j.preteyeres.2015.07.002. Epub 2015 Jul 18.
• Nugent RB, Lee GA. Ophthalmic use of blood-derived products. Surv Ophthalmol. 2015 Sep-Oct;60(5):406-34. doi: 10.1016/j.survophthal.2015.03.003. Epub 2015 Apr 15.
• Alio JL, Rodriguez AE, WrobelDudzinska D. Eye platelet-rich plasma in the treatment of ocular surface disorders. Curr Opin Ophthalmol. 2015 Jul;26(4):325-32. doi: 10.1097/ICU.0000000000000169.
• Alio JL, Abad M, Artola A, Rodriguez-Prats JL, Pastor S, Ruiz-Colecha J. Use of autologous platelet-rich plasma in the treatment of dormant corneal ulcers. Ophthalmology. 2007 Jul;114(7):1286-1293.e1. doi: 10.1016/j.ophtha.2006.10.044. Epub 2007 Feb 26.
• Kim KM, Shin YT, Kim HK. Effect of autologous platelet-rich plasma on persistent corneal epithelial defect after infectious keratitis. Jpn J Ophthalmol. 2012 Nov;56(6):544-50. doi: 10.1007/s10384-012-0175-y. Epub 2012 Sep 13.

Study record dates

Study Major Dates

• Study Start (Actual): August 30, 2018
• Primary Completion (Anticipated): August 1, 2024
• Study Completion (Anticipated): August 1, 2024

Study Registration Dates

• First Submitted: August 16, 2018
• First Submitted That Met QC Criteria: August 28, 2018
• First Posted (Actual): August 31, 2018

Study Record Updates

• Last Update Posted (Actual): May 11, 2023
• Last Update Submitted That Met QC Criteria: May 10, 2023
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Platelet-Rich Plasma; Persistent Epithelial Defect
• Other Study ID Numbers: OF18-00003

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