Limbus-derived Stem Cells for Prevention of Postoperative Corneal Haze

Study Overview
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Brief Summary
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This is a investigator-initiated pilot clinical trial to ascertain the safety and efficacy of application of ex-vivo cultivated limbal stem cells in human eyes for treating Corneal Haze after Photo-Therapeutic/Refractive Keratectomy (PTK/ PRK) and Collagen Cross Linking (CXL). Instead of using adjunctive medical therapy like application of MMC (Mitomycin), a technique of cell delivery with fibrin sealant can be used. These cells are harvested from therapeutically accepted and serologically tested cadaveric corneas. The isolated limbal epithelial and mesenchymal or stromal cell suspension will then be cultured in CGMP laboratories and be tested for sterlity. These cells have also been shown to be effective in treating haze in laser refractive surgery in an animal model. Our initial experience of using these cells in a previous clinical trial showed that they were effective in preventing corneal haze in patients with burns and ulcers.

Detailed Description
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In this pilot clinical trial, patients undergoing Photo Therapeutic/Refractive Keratectomy (PTK/ PRK) and Collagen Cross Linking (CXL), will be given human Limbus-derived Corneal Stem cells to assess the safety of these cells. Cells will be cultivated in a cGMP laboratory using standardized culture technique; from the limbal rims of cadaveric corneoscleral donor tissues that are therapeutically accepted and serologically tested. Briefly the limbal tissue will be cut up into small pieces and digested overnight using an enzyme (Collagenase L). The cells obtained from the digest will be cultured on a petri-dish using 2% serum and growth factors. A mixture of limbal epithelial cells and limbal stromal cells obtained from these cultures will be used in surgical procedures in a ratio of 2:1, after all the sterility checks. Mixed suspension of the limbal epithelial and the stromal cells at a concentration of 50000 cells/uL diluted in the thrombin component of fibrin sealant (TISEEL, Baxter) will be applied. The primary outcome measure is safety of this treatment and the secondary outcome measure is their efficacy that will be assessed at 1 month time points by (1) Clinical photography using a standard method where multiple blinded observers will grade the clinically apparent change in haze and (2) Objective quantification of the amount of light scattering using densitometry analysis function in Oculus Pentacam (OCULUS Optikgeräte GmbH).

Official Title
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Pilot Clinical Trial to Assess the Safety of Limbus-derived Corneal Stem Cells in Prevention of Corneal Haze After Photo Therapeutic/Refractive Keratectomy (PTK/ PRK) and Collagen Cross Linking (CXL)

Conditions
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Corneal Scars and Opacities

Intervention / Treatment
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* Biological: Stem cells
* Other: Vehicle


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients between20 to 40 years of age Meeting standard selection criteria for bilateral PTK/PRK or CXL No systemic diseases Eligible to give informed consent No other ocular co-existing pathologies Exclusion Criteria: Undergoing surgery in only one eye Grossly asymmetric pathology Refusal to give informed consent Not agreeable or uncooperative for corneal imaging Unlikely to come for follow-up for 1 month International and out-station patients

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 40 Years

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
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: Standard Surgery with Vehicle<br>After the standard surgical procedure (PRK/PTK or CXL), patients will receive 50uL Fibrin Sealant (sham) without cells. | Other: Vehicle<br>* 50uL of commercially available fibrin sealant (Baxter, TISEEL)<br>|
| Experimental: Standard Surgery with Stem Cells<br>After the standard surgical procedure (PRK/PTK or CXL), patients will receive 50uL of a mixture of limbus derived corneal epithelial cells and limbus derived corneal stromal cells in a ratio of 2:1, at a concentration of 50000 cells/uL diluted in the thrombin component of Fibrin Sealant (TISEEL, Baxter). | Biological: Stem cells<br>* Mixture of limbus derived corneal epithelial cells and limbus derived corneal stromal cells in a ratio of 2:1, at a concentration of 50000 cells/uL diluted in fibrin sealant<br>Other: Vehicle<br>* 50uL of commercially available fibrin sealant (Baxter, TISEEL)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maintenance of pre-operative best-spectacle corrected visual acuity |  | 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy in reducing corneal light scatter using Scheimpflug imaging | Efficacy in reducing corneal light scatter using Scheimpflug imaging at 1 month by: Objective quantification of the amount of light scattering using densitometry analysis function in Oculus Pentacam (OCULUS Optikgeräte GmbH). • All routine clinical and imaging protocols performed for patients undergoing PTK/PRK and CXL will be diligently followed. | 1 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phototherapeutic Keratectomy (PTK), photorefractive Keratectomy (PRK), Collagen Cross-linking (CXL), Stem Cell Therapy