Autologous ex Vivo Conjunctival Epithelial Cell Expansion for Ocular Surface Transplantation

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Brief Title

Autologous ex Vivo Conjunctival Epithelial Cell Expansion for Ocular Surface Transplantation

Official Title

Autologous ex Vivo Conjunctival Epithelial Cell Expansion for Ocular Surface

Brief Summary

      To evaluate the use of cultivated conjunctival epithelial equivalents for the treatment of
      ocular diseases
    

Detailed Description

      Ex-vivo autologous conjunctiva expansion on human amniotic membrane (HAM), followed by
      clinical transplantation surgery

      Preparation of HAM. Human amniotic membrane (HAM) prepared for human use will be obtained
      from the Singapore Eye Bank. HAM will be rapidly thawed in a 37oC water bath, and washed with
      phosphate buffered saline. The amniotic epithelium will be removed using a combination of
      Dispase digestion and mechanical scraping. Complete removal of the amniotic epithelial cells
      will be confirmed by microscopy. The HAM is then placed on a culture plate, with the
      basement-membrane side up, and incubated with DMEM at 37oC in an atmosphere of 5% CO2 and 95%
      air overnight before use.

      Ex-vivo expansion of conjunctival cells on HAM. A forniceal conjunctival biopsy will be
      performed in patients undergoing pterygium surgery. The tissue will be cultured on the HAM
      either as a cell suspension or as explants, with the methods described above. The media is
      changed every 2 days and the culture is maintained for 2-3 weeks. The cells will form a
      confluent sheet and begin to stratify and differentiate. The tissue will then be raised to an
      air-liquid interface to promote differentiation.

      Histological analysis. The conjunctival epithelial cell sheets on the amniotic membrane will
      be examined by light microscopy. Samples of the tissue will be fixed and processed with the
      use of standard histological procedures and stained with H&E and PAS reagents. Electron
      microscopic examination will be carried for the tissue. The sections will also be subjected
      to immunohistochemical analysis for cytokeratin markers.

      Clinical Transplantation of cultivated conjunctival epithelial cells on HAM

      Preparation of cultivated conjunctival cells on amniotic membrane Patients with various
      ocular surface disorders will be selected for the initial series of transplantations. All
      patients will undergo full counselling for informed consent for the procedures. A forniceal
      conjunctival biopsy will be performed on the contralateral healthy eye. PI will perform the
      transplantations of autologous conjunctival sheet grown on human amniotic membrane in these
      patients. The diseased area will be excised using the standard surgical technique. The defect
      will be covered with the sheet of cultured conjunctival cells on the HAM with the epithelial
      side up. The graft is secured to the adjacent conjunctiva with interrupted 8/0 vicryl
      sutures. A planotherapeutic bandage contact lens is placed to protect the tissue from lid
      trauma. Topical steroid and antibiotic eyedrops will be administered daily to reduce the
      ocular inflammation. Survival of conjunctiva on the amniotic membrane will be closely
      monitored and patients will be followed-up at 3 monthly intervals up to one year. During
      these visits, these patients will have anterior segment photographs taken and fluorescein
      staining to monitor the progress of healing.

      Transplantations may also be carried out on selected patients with ocular surface disease,
      for example, ocular cicatricial pemphigoid, Stevens Johnson syndrome and alkali injury. For
      these severe conditions, this procedure may prove to be an important adjunct to other
      procedures, such as limbal stem cell transplantation. If the initial study is successful, a
      randomised clinical trial comparing this procedure with conventional conjunctival
      autografting and conventional amniotic membrane transplantation will be planned. Therefore if
      found to be successful, transplantation of cultured conjunctival cells on HAM may eventually
      be used as a primary procedure or as an adjunctive procedure for these visually debilitating
      conditions.
    

Study Phase

Phase 3

Study Type

Interventional


Primary Outcome

Epithelialisation

Secondary Outcome

 Degree of scarring

Condition

Pterygium

Intervention

Cultivated conjunctival transplantation


Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Procedure

Estimated Enrollment

80

Start Date

October 2001

Completion Date

December 2003


Eligibility Criteria

        Inclusion Criteria:

          1. Patients with ocular surface disorders, e.g. primary pterygium, scheduled for elective
             surgical excision

          2. Indications for surgery will be the presence of ocular surface symptoms in the
             affected eye, loss of visual acuity from visual axis obscuration or irregular
             astigmatism, or cosmesis.

          3. Only one eye of a patient will be eligible for study entry.

          4. Patients who are adult males and females who are aged 21 or older, and are considered
             mentally sound

          5. Patients who are willing to undergo long-term follow-up, as outlined in this protocol

          6. Patients who have signed an informed consent form that has been approved by the SNEC
             Ethics Committee.

        Exclusion Criteria:

          1. Patients less than 21 years of age

          2. Patients who are incapable, either by law or of mental state, of giving consent in
             their own right

          3. Patients who are either unable or unwilling to keep scheduled appointments and adhere
             to the other aspects of the protocol

          4. Patients who are pregnant or breastfeeding

          5. Patients with a history of drug allergy

          6. Patients who have received an investigational drug within 28 days preceding surgery

          7. Patients with intraocular pressure over 21 mmHg or history of ocular hypertension or
             glaucoma

          8. Patients who are documented to be steroid responders
      

Gender

All

Ages

21 Years - 90 Years

Accepts Healthy Volunteers

Accepts Healthy Volunteers

Contacts

Leonard P Ang, FRCS, , 

Location Countries

Singapore

Location Countries

Singapore

Administrative Informations


NCT ID

NCT00346450

Organization ID

R198/24/2000



Study Sponsor

Singapore National Eye Centre

Collaborators

 International Stem Cell Forum

Study Sponsor

Leonard P Ang, FRCS, Principal Investigator, SNEC, NUS


Verification Date

January 2010