Limbus-derived Stem Cells for Prevention of Postoperative Corneal Haze

L.V. Prasad Eye Institute

Status and phase: Unknown; Phase 1

Conditions: Corneal Scars and Opacities

Treatments: Other: Vehicle; Biological: Stem cells

Study type: Interventional

Funder types: Other

Identifiers

NCT03295292

LEC 07-17-068

Details and patient eligibility

About

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.

Full description

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).

Enrollment: 15 estimated patients

Sex: All

Ages: 20 to 40 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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15 participants in 2 patient groups

Standard Surgery with Vehicle

Sham Comparator group

Description:

After the standard surgical procedure (PRK/PTK or CXL), patients will receive 50uL Fibrin Sealant (sham) without cells.

Treatment:

Other: Vehicle

Standard Surgery with Stem Cells

Experimental group

Description:

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).

Treatment:

Other: Vehicle

Biological: Stem cells