SBIR-STTR Award

Glaucoma drainage devices (GDDs) have widely been used in the treatment of high risk refractory glaucoma. To avoid tube exposure, which may lead to serious eye infection, the implanted GDD tube has to be covered by a patch graft made of donor sclera or pericardium. However, such a patch graft still carries a high rate of progressive thinning and erosion, a complication that we speculate is resulted from the lack of cellular infiltration from the surrounding host conjunctival stroma, thus leading to poor integration of these patch grafts to the host tissue. We further speculate that a thicker version of cryopreserved amniotic membrane (AM) could offer better tensile strength, suitable for tectonic support, and biologically active to promote cellular infiltration by the surrounding host conjunctival stroma, thus ameliorating the patch graft thinning/erosion. This hypothesis is supported by our preliminary studies showing that a thicker AM, termed AmnioGraft(R)-G (AG-G), has successfully been developed, that AG- G can be used to cover the GDD tube during the primary implantation, and that anterior segment optical coherence tomography (OCT) can be used to monitor host cell interaction with the transplanted AG-G. In this Phase I application, we will demonstrate the short-term (6 months) efficacy of AG-G for covering the tube in primary GDD surgery (Aim 1), and confirm the host cell integration into AG-G, but not pericardium, using OCT after transplantation over the GDD tube (Aim 2). Accomplishment of the above two Aims will allow us to collect adequate short-term stability/efficacy data to better design a prospective controlled study in the Phase II application to assess long term clinical efficacy of using AG-G to secure GDD tube and its overall superiority over sclera or pericardium in preventing tube exposure, providing a better esthetic appearance, being less likely to cause corneal dellen due to less conjunctival elevation, and allowing laser suture lysis needed to treat postoperative hypertensive phase. The new knowledge of how AM may modulate wound healing in the subconjuntival space will allow us in Phase II investigate whether it can also be considered as a graft to augment the success of trabeculectomy with mitomycin C in high risk refractory glaucoma.

Public Health Relevance:
Our study will demonstrate that a thicker AM, termed AmnioGraft(R)-G (AG-G), could be used to cover the glaucoma drainage device (GDD) tube during the primary implantation in cases with complicated glaucoma, and confirm its overall superiority over existing patches in offering better tensile strength suitable for tectonic support and preventing tube exposure to improve the surgical outcome and prevent complications in high risk glaucoma patients.

Public Health Relevance Statement:
PROJECT NARRATIVE Our study will demonstrate that a thicker AM, termed AmnioGraft(R)-G (AG-G), could be used to cover the glaucoma drainage device (GDD) tube during the primary implantation in cases with complicated glaucoma, and confirm its overall superiority over existing patches in offering better tensile strength suitable for tectonic support and preventing tube exposure to improve the surgical outcome and prevent complications in high risk glaucoma patients.

Project Terms:
Anterior; Anterior Chamber; Anterior Chamber of the Eye; Anterior chamber of eye structure; Appearance; Aqueous Humor; Aqueous Humor Shunts; Aqueous Shunts; Baerveldt Implants; Body Tissues; Cell Communication; Cell Interaction; Cell-to-Cell Interaction; Cells; Cellular Infiltration; Complication; Controlled Study; Cornea; Cytolysis; Data; Devices; Doppler OCT; Drainage; Drainage procedure; Electromagnetic, Laser; Esthetics; Exposure to; Eye; Eye Infections; Eyeball; Flaps; Glaucoma; Glaucoma Drainage Implants; Glaucoma Filtration Implants; Human; Human, General; Incidence; Infection; Infiltration; Intraocular Fluid; Island Flaps; Knowledge; Lasers; Lead; Left; Literature; Lysis; Man (Taxonomy); Man, Modern; Measures; Membrane; Mitomycin Antibiotic; Mitomycins; Monitor; OCT Tomography; Ocular Infections; Operation; Operative Procedures; Operative Surgical Procedures; Optical Coherence Tomography; Outcome; Patients; Pb element; Pericardial sac structure; Pericardium; Phase; Post-Operative; Postoperative; Postoperative Period; Preventive; Process; Publishing; Radiation, Laser; Recurrence; Recurrent; Refractory; Risk; Sclera; Secure; Surgical; Surgical Flaps; Surgical Interventions; Surgical Procedure; Surgical sutures; Sutures; Tensile Strength; Thick; Thickness; Tissues; Tomography, Optical Coherence; Trabeculectomy; Trabeculoplasty; Transplantation; Tube; White of Eye; Wound Healing; Wound Repair; anterior chamber; clinical efficacy; conjunctiva; corneal; design; designing; glaucomatous; heavy metal Pb; heavy metal lead; high risk; implantation; improved; melting; membrane structure; prevent; preventing; prospective; public health relevance; success; surgery; tissue repair; transplant

Glaucoma drainage devices (GDDs) have widely been used in the treatment of high-risk refractory glaucoma. To avoid tube exposure, which may lead to serious eye infection, the implanted GDD tube must be covered by a patch graft traditionally made of either donor sclera or pericardium. However, these patch grafts still carry a high rate of progressive thinning and erosion, a complication that we speculate results from the lack of cellular infiltration from the surrounding host conjunctival stroma and poor integration of these patch grafts to the host tissue. We further speculate that a thicker version of cryopreserved amniotic membrane (AM), manufactured by Bio-Tissue, Inc., a 100%-owned subsidiary of TissueTech, Inc., could offer better tensile strength, be suitable for tectonic support, and have biological activities to promote cellular infiltration by the surrounding host conjunctival stroma, thus reducing progressive allogeneic patch graft thinning/erosion. Through SBIR Phase I grant support (R43 EY19785), we have evaluated the thicker AM as an alternative patch graft for covering the GDD tube during the primary implantation. We further monitored the host cell interaction using anterior segment optical coherence tomography (OCT). We have successfully accomplished the proposed aims of the above studies which demonstrated the short-term stability/efficacy of AM in covering the tube in primary GDD surgery (Phase I- Aim 1), and confirmed the feasibility of using OCT to distinguish host cell infiltration into the AM after transplantation over the GDD tube (Phase I- Aim 2). In this Phase II application, we propose to conduct a prospective, controlled study to compare the long-term safety and efficacy of the thicker AM (AmnioGuard", Bio-Tissue, Inc, Miami, FL) to the pericardium (Tutoplast(R), IOP Inc, Costa Mesa, CA) in securing the GDD tube and reducing tube exposure and graft thinning in patients with high risk glaucoma. We will also study the risk factors that may contribute to GDD tube exposure. Accomplishment of this Phase II study will position AM as an effective alternative to the existing patch grafts to reduce tube exposure and enhance the success of GDD implantation while providing a better aesthetic appearance and allowing visualization of the tube in patients with high risk glaucoma. This will also allow the Company to expand its market space from ocular surface to glaucoma diseases. We speculate that such a graft might also have other clinical applications outside of covering GDD tubes.

Public Health Relevance:
Our proposed prospective, randomized and comparative study described in this Phase II application aims to demonstrate the clinical safety and efficacy of transplanting a thicker version of amniotic membrane (AM) as an alternative tectonic substrate to cover glaucoma drainage device (GDD) tubes. Through SBIR Phase I grant support (EY019785), we found that this thicker AM offers superior tectonic support and biological activity to promote integration by the host conjunctival stromal cells, thus reducing patch graft thinning/erosion. The completion of the study described herein will allow eye surgeons to adopt this new AM graft to improve surgical outcomes and prevent complications in GDD surgery for high risk glaucoma patients. This will also allow the Company to expand its market space and provide services to glaucoma indications.