Development of MIDI-Ray Implant for Glaucoma

描述(由申请人提供)：这个小企业创新研究第一阶段项目的目标是开发下一代青光眼引流植入物，称为MIDI-Ray。MIDI-Ray的名字来源于迈阿密-InnFocus-Duction-Implants(MIDI)；Ray来自于它与MANTA-Ray相似的事实。第一代设备名为MIDI-Tube，由InnFocus LLC和巴斯科姆·帕尔默眼科研究所开发。它的独特功能包括：1)使用Hagen-Poiseuille压力流动原理设计的微管，限制流量，从而防止低渗；2)一种名为聚(苯乙烯-嵌段-异丁烯-嵌段-苯乙烯)(SIBS)的新型生物材料，它不会在眼睛中形成临床上显著的瘢痕组织；3)特征1和2的组合，提供了一种非常无创的设备，不会显示侵蚀或迁移，在兔模型中一年内显示100%通畅。这种第一代设备在有限的临床研究中显示出了实用性；然而，在没有使用抗代谢药物丝裂霉素C(MMC)的情况下，它在非常严重的青光眼患者中就没有那么有效。抗代谢药物在青光眼患者中的使用仍然存在争议，因为这些药物的长期效果取决于这些药物的剂量、使用方法、冲洗方法、使用位置和结膜及巩膜的健康状况。MIDI-Ray类似于MIDI-Tube，但在MIDI-Tube的远端结合了一个薄的微型板，以防止结膜下/Tenon瓣愈合闭合。这笔赠款的目的是确定这种新的MIDI-Ray设计在使用和不使用药物的情况下是否可以在兔眼中发挥作用。接受测试的药物将是抗增殖药物紫杉醇，它比MMC温和，不会杀死细胞，相反，它会使细胞无菌。该药物将以受控方式从MIDI-Ray微型板释放，以消除在植入时以非受控方式引入的传统抗代谢物药物的输送差异。引流装置可能是最有效和最后的治疗方法；然而，它们存在许多问题。例如，目前市场上销售的设计是由硅橡胶和聚乙烯或聚丙烯制成的，这种材料会在眼睛内造成广泛的纤维化，从而减少滤过。此外，钢板(及其胶囊)和管子相当大，伴随着复视和低眼压的风险；这通常需要二次干预，如缝合松解。MIDI-Ray由极其柔软的SIBS材料制成，具有可控的过滤速度，可防止侵蚀、疤痕组织形成和低渗。如果它能像预期的那样发挥作用，它将在广泛的患者中发挥作用，而且由于其体积小，植入将相对简单。生物相容的SIBS材料将最大限度地减少眼内的胶囊，紫杉醇从设备中释放将防止滤过泡纤维化。这与波士顿科学公司商业化的紫杉醇涂层冠状动脉支架的概念相同，称为TAXUS。支架(PI是发明者)，通过限制平滑肌增殖来防止冠状动脉再狭窄。预计这种简单的设备将为青光眼和眼前段外科医生提供更好的选择，以一致、可控的方式有效地治疗他们的患者；希望在视力受到影响之前的早期阶段。预计该装置的第一阶段测试将证明其化学和生物可行性。第二阶段将着眼于优化、该设备的长期体内测试、GLP临床前测试、监管提交，并加快生产以实现商业化。与公众健康相关：该项目寻求开发一种易于植入的青光眼引流装置来治疗日益严重的人口老龄化问题，老龄化目前是美国第二大最常见的致盲原因。这种可预防的失明在某种程度上可以通过积极的药物治疗、滤过手术和/或使用房水分流植入物来治疗；然而，目前产品的长期效果并不理想。MIDI-Ray是一种新型的青光眼引流装置，由一种新的生物稳定的聚合物材料组成，这种材料在眼睛中具有极高的生物相容性，与硅橡胶相比，MIDI-Ray的包裹性微乎其微，如果必要的话，与抗增殖药物紫杉醇相结合，并可控制释放，应可防止疾病的发展。

DESCRIPTION (provided by applicant): The goal of this Small Business Innovation Research Phase I project is to develop a next generation glaucoma drainage implant, called the MIDI-Ray . The MIDI-Ray name is derived from the Miami-InnFocus-Drainage- Implant ( MIDI ); the Ray comes from the fact that it resembles a Manta-Ray. The first generation device, called the MIDI-Tube , was developed by InnFocus LLC, and the Bascom Palmer Eye Institute. Its unique features include; 1) a micro tube designed using the Hagen-Poiseuille pressure flow principle that limits flow and thereby prevents hypotony, 2) a novel biomaterial called poly(styrene-block-isobutylene-block-styrene) ( SIBS ) that does not form clinically significant scar tissue in the eye and 3) a combination of features 1 and 2 which provides a very atraumatic device that does not demonstrate erosion or migration and that demonstrates 100% patency at one year in the rabbit model. This first generation device demonstrated practicality in a limited clinical study; however, it was not as effective in very severe glaucoma patients without the use of the anti-metabolite drug Mitomycin-C (MMC). The use of anti-metabolites in glaucoma patients is still controversial as the long-term effects of these drugs vary depending upon dosage, method of application, method of rinsing out, site of application and health of the conjunctiva/Tenons and sclera. The MIDI-Ray is similar to the MIDI- Tube but incorporates a thin microplate at the distal end of the tube to prevent the subconjunctival/Tenon flap from healing closed. The goal of this grant is to determine if this new MIDI-Ray design will function in the rabbit eye with and without the use of a drug. The drug to be tested will be the antiproliferative drug paclitaxel, which is milder than MMC and does not kill cells, rather it renders them sterile. The drug will be released in a controlled manner from the MIDI-Ray microplate to eliminate variances experienced with the delivery of conventional anti-metabolite drugs that are introduced in a non-controlled manner at the time of implantation. Drainage devices may be the most effective and last resort treatment; however, they suffer from many problems. For example, currently marketed designs are made of silicone rubber and polyethylene or polypropylene which creates extensive fibrosis within the eye which can lead to reduced filtration. In addition, the plates (with their capsules) and tubes are rather large with concomitant risk of diplopia and hypotony; which often require secondary interventions such as suturelysis. The MIDI-Ray is made from an extremely soft SIBS material with a controlled filtration rate that should prevent erosion, scar tissue formation and hypotony. If it functions as anticipated, it will be effective in a wide range of patients and will be relatively simple to implant due to its small size. The biocompatible SIBS material will minimize encapsulation in the eye and the release of paclitaxel from the device will prevent the bleb from fibrosing. This is the same concept as the paclitaxel- coated coronary stent commercialized by Boston Scientific Corporation, called the TAXUS. stent (PI is the inventor), which prevents re-stenosis in the coronary arteries by limiting smooth muscle proliferation. It is expected that this simple device will provide a better option to both the glaucoma and anterior segment surgeons to effectively treat their patients in a consistent, controlled manner; hopefully at an earlier stage before visual acuity is affected. It is anticipated that Phase I testing of the device will demonstrate chemical and biological viability. Phase II will be geared toward optimization, long-term in vivo testing of the device, GLP pre-clinical testing, regulatory submissions and stepping up production for commercialization. OUBLIC HEALTH RELEVANCE: This project is sought develop an easy to implant glaucoma drainage device to treat a growing problem with the aging population which is presently the second most common cause of blindness in the U.S. This preventable blindness is treatable to some degree through aggressive drug therapy, filtering surgery and/or use of aqueous shunt implants; however, the long-term outcomes with the current products are less than desirable. The MIDI-Ray is a novel glaucoma drainage device comprised of a new biostable polymeric material that is extremely biocompatible in the eye, and has shown insignificant encapsulation as compared to silicone rubber and when combined if necessary, with an antiproliferative drug, paclitaxel, and is controllably released from it, should prevent the progression of the disease.