Transplantation of Cultivated Corneal Epithelial Sheet in Patients With Ocular Surface Disease

Study Overview
=================
Brief Summary
-----------------
The aim of the study is to assess if transplantation of cultivated corneal epithelial stem cells could restore vision in patients with severe ocular surface disorder with a favourable safety profile that warrants further comparative study.

Detailed Description
-----------------
Objectives: Efficacy: To determine the efficacy of cultivated corneal epithelial stem cells as a treatment for patients with severe ocular surface disorder. The corneal limbal epithelial stem cell transplant (CLET) successful outcome will be measured by improvement of vision, maintenance of corneal re-epithelisation with absence of recurrence of surface disease and subjective improvement of symptoms.

Official Title
-----------------
Transplantation of Cultivated Corneal Epithelial Sheet in Patients With Ocular Surface Disease

Conditions
-----------------
Eye Injury

Intervention / Treatment
-----------------
* Biological: conservative
* Procedure: Medical Therapy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or non-pregnant females between 18 and 75 years of age. Written informed consent obtained from patient or parents/guardian. Patients with unilateral limbal stem deficiency 2-12 months presenting with any of the following Conjunctivalisation Absence of limbal palisades of Vogts Chronic inflammation Persistent or recurrent corneal epithelial defect Patients who had 2-12 months of conservative treatment. * Diagnostic criteria for limbal stem cell deficiency are as follows: Symptoms of decreased vision, redness, watering, photophobia and recurrent attacks of pain Triad of signs: conjunctivalisation, neovascularisation and chronic inflammation Stippled appearance of cunjunctivalised cornea with loss of palisades of Vogt Recurrent and persistent epithelial defects Superficial vascularisation, scarring, thick fibrovascular pannus, ulceration, melting and perforation Exclusion Criteria: Patients with any of the following are not eligible for enrollment into the study: Pregnant or nursing woman or women of childbearing potential except if post-menopausal, surgically sterile or using accepted method(s) of birth control or having negative pregnancy test. Participation in any drug trial in which the patient received an investigational drug within 30 days or 5 half-lives (whichever is longer) preceding the screening phase of this study. Those persons directly involved in the conduct of the study. Any history of severe infection such as hepatitis, renal, gastrointestinal, endocrine or neurological disease. Evidence of corneal stromal scarring, cataract, macular oedema or scarring, retinal detachment and conjunctival keratinisation Positive for HIV, Hepatitis B, C and VDRL History of Pulmonary tuberculosis, hepatitis B, History of alcohol or substance abuse History of malignancy within previous 5 years History of organ transplant Any serious medical conditions or disability, which in the opinion of the investigator, would interfere with treatment or assessment or preclude completion of this study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

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

Accepts Healthy Volunteers
-----------------
No

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

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: corneal stem cell transplant<br> | Biological: conservative<br>* Undergo autologous transplantation of limbal epithelial cells cultured on amniotic membrane<br>|
| No Intervention: conservative medical therapy<br> | Biological: conservative<br>* Undergo autologous transplantation of limbal epithelial cells cultured on amniotic membrane<br>Procedure: Medical Therapy<br>* Under usual care treatment<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement of vision at one week | The primary efficacy variable will be improved visual acuity Vision will be assessed using ETDRS logMAR visual acuity measurements. An improvement of > 1 line | One week | 
| Improvement of vision at one month | The primary efficacy variable will be improved visual acuity Vision will be assessed using ETDRS logMAR visual acuity measurements. An improvement of > 1 line | One month | 
| Improvement of vision at three month | The primary efficacy variable will be improved visual acuity Vision will be assessed using ETDRS logMAR visual acuity measurements. An improvement of > 1 line | Three month | 
| Improvement of vision at six month | The primary efficacy variable will be improved visual acuity Vision will be assessed using ETDRS logMAR visual acuity measurements. An improvement of > 1 line | Six month | 
| Improvement of vision at nine month | The primary efficacy variable will be improved visual acuity Vision will be assessed using ETDRS logMAR visual acuity measurements. An improvement of > 1 line | Nine month | 
| Improvement of vision at twelve month | The primary efficacy variable will be improved visual acuity Vision will be assessed using ETDRS logMAR visual acuity measurements. An improvement of > 1 line | Twelve month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events reporting, vital signs, and physical examinations. | To evaluate the safety and tolerability of transplantation of limbal epithelial cells cultured on amniotic membrane for a follow-up period of one year in patients. Safety will be evaluated using adverse events reporting, vital signs, and physical examinations. |  | 
| Maintenance of corneal re-epithelisation with absence of recurrence of surface disease |  |  | 
| Subjective improvement of symptoms |  |  |