Amniotic Membrane Patch Graft to Cover Glaucoma Drainage Tube

描述（由申请人提供）：青光眼引流装置（GDD）已广泛用于治疗高危难治性青光眼。为了避免导管暴露，这可能导致严重的眼部感染，植入的GDD导管必须由供体巩膜或心包制成的补片移植物覆盖。然而，这种补片移植物仍然具有高的进行性变薄和侵蚀率，我们推测这是由于缺乏周围宿主结膜基质的细胞浸润导致的并发症，从而导致这些补片移植物与宿主组织的整合不良。我们进一步推测，较厚的冻存羊膜（AM）可以提供更好的抗张强度，适合构造支持，并具有生物活性，以促进周围宿主结膜基质的细胞浸润，从而改善补片移植物变薄/侵蚀。我们的初步研究支持了这一假设，表明已成功开发了称为AmnioGraft（R）-G（AG-G）的较厚AM，AG-G可用于在初次植入期间覆盖GDD管，并且前段光学相干断层扫描（OCT）可用于监测宿主细胞与移植的AG-G的相互作用。在本I期申请中，我们将证明AG-G在初次GDD手术中覆盖导管的短期（6个月）有效性（目标1），并在移植到GDD导管上后使用OCT确认宿主细胞整合到AG-G中，但不整合到心包中（目标2）。上述两个目的的实现将使我们能够收集足够的短期稳定性/有效性数据，以更好地设计II期申请中的前瞻性对照研究，以评估使用AG-G固定GDD管的长期临床有效性及其在防止管暴露方面优于巩膜或心包的总体优效性，提供更好的美学外观，由于结膜抬高较少，不太可能引起角膜脱落，并允许激光缝线松解治疗术后高血压期。关于AM如何调节结膜下间隙伤口愈合的新知识将使我们在II期研究中能够研究是否也可以将其视为一种移植物，以增加高风险难治性青光眼中丝裂霉素C小梁切除术的成功率。公共卫生相关性：我们的研究将证明，在复杂性青光眼患者的初次植入过程中，可以使用称为AmnioGraft（R）-G（AG-G）的较厚AM覆盖青光眼引流装置（GDD）管，并证实其在提供更好的抗张强度以适用于构造支撑和防止管暴露方面优于现有贴片，以改善手术结局并预防高危青光眼患者的并发症。

DESCRIPTION (provided by applicant): 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.