Clinical trial NCT03653650: Autologous Platelet-rich Plasma in the Treatment of Persistent Epithelial Defects
Official title: Autologous Platelet-rich Plasma in the Treatment of Persistent Corneal Epithelial Defects
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Persistent Epithelial Defect
Keywords: Platelet-Rich Plasma
Persistent Epithelial Defect
Lead sponsor: Universidad Autonoma de Nuevo Leon
Sponsor class: OTHER
Collaborators: name: Hospital Universitario Dr. Jose E. Gonzalez
First posted: 2018-08-31
Enrollment: 54
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

Brief summary: 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: 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

Eligibility criteria: 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.

Primary outcomes:
measure: Persistent epithelial defect healing time.
timeFrame: From the first day of treatment until the date of complete defect closure, assessed up to 3 months.
Secondary outcomes:
measure: Change in corneal sensitivity
timeFrame: Change from baseline corneal sensitivity at the date of defect closure, up to 3 months.
measure: Uncorrected visual acuity
timeFrame: Every week (or sooner, if needed) from date of randomization until the date of complete defect closure, up to 3 months.
measure: Best corrected visual acuity
timeFrame: Every week (or sooner, if needed) from date of randomization until the date of complete defect closure, up to 3 months.
measure: Ocular pain
timeFrame: Every week (or sooner, if needed) from date of randomization until the date of complete defect closure, up to 3 months.
measure: Ocular surface symptoms
timeFrame: Every week (or sooner, if needed) from date of randomization until the date of complete defect closure, up to 3 months.
measure: Ocular surface symptoms
timeFrame: At date of randomization and at date of defect closure, up to 3 months.
measure: Quality of life questionnaire
timeFrame: At date of randomization and at date of defect closure, up to 3 months.
measure: Frequency of adverse events, recurrences and/or treatment failure
timeFrame: These will be evaluated from the beginning of the treatment until three months after defect closure.
Other outcomes:
Locations:
city: Monterrey
country: Mexico
facility: Departamento de Oftalmologia, Hospital Universitario "Dr. Jose Eleuterio Gonzalez"
state: Nuevo Leon
Study officials:
affiliation: Departamento de Oftalmologia, Hospital Universitario Dr. Jose Eleuterio Gonzalez
name: Karim Mohamed-Noriega, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.