Development of MIDI-Ray Implant for Glaucoma

描述（由申请人提供）：该小型企业创新研究I期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的名称来源于Miami-InnFocus-Drainage- Implant（Miami-InnFocus-Drainage-Implant）; Ray的名称来源于它类似于Manta-Ray的事实。第一代设备，称为MIDI管，是由InnFocus LLC和巴斯科姆帕尔默眼科研究所开发的。其独特的功能包括; 1）使用Hagen-Poietille压力流动原理设计的微管，其限制流动并由此防止张力减退，2）一种新型生物材料，称为聚乙烯（苯乙烯-嵌段-异丁烯-嵌段-苯乙烯）（SIBS），其不会在眼睛中形成临床上显著的瘢痕组织，和特征1和2的组合，其提供了一种非常无创的装置，该装置不表现出侵蚀或移位，并且表现出100%的兔模型中1年时的通畅率。这种第一代装置在有限的临床研究中证明了实用性;然而，在不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并不有效。抗代谢药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作用取决于剂量、应用方法、冲洗方法、应用部位以及结膜/眼球筋膜和巩膜的健康状况。MIDI-Ray类似于球结膜管，但在球结膜管的远端加入了一个薄的微型板，以防止结膜下/Tenon瓣愈合闭合。这项资助的目的是确定这种新的MIDI-Ray设计是否会在使用和不使用药物的情况下在兔眼中发挥作用。要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，而是使它们无菌。药物将以受控方式从MIDI-Ray微孔板中释放，以消除植入时以非受控方式引入的常规抗代谢药物输送所经历的差异。 引流装置可能是最有效和最后的治疗手段;然而，它们存在许多问题。例如，目前市售的设计由硅橡胶和聚乙烯或聚丙烯制成，这在眼睛内产生广泛的纤维化，这可能导致过滤减少。此外，板（及其囊）和管相当大，伴有复视和张力减退的风险;这通常需要二次干预，如缝线松解。MIDI-Ray由极软的SIBS材料制成，具有受控的过滤速率，可防止侵蚀，疤痕组织形成和张力减退。如果它的功能符合预期，它将在广泛的患者中有效，并且由于其尺寸小，植入相对简单。生物相容性SIBS材料将使眼睛中的包封最小化，并且紫杉醇从装置中的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（称为TAXUS）的概念相同。支架（PI是发明者），其通过限制平滑肌增殖来防止冠状动脉中的再狭窄。预计这种简单的装置将为青光眼和眼前节外科医生提供一种更好的选择，以一致、可控的方式有效治疗他们的患者;希望在视力受到影响之前的早期阶段。 预计器械的I期试验将证明其化学和生物活性。第二阶段将致力于优化，长期体内测试的设备，GLP临床前测试，监管提交和加紧生产的商业化。 明确的健康相关性：该项目旨在开发一种易于植入的青光眼引流装置，以治疗日益严重的老龄化问题，这是目前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，目前产品的长期结局不太理想。MIDI-Ray是一种新型青光眼引流装置，由一种新的生物稳定聚合物材料组成，该材料在眼睛中具有极强的生物相容性，与硅橡胶相比，其包封作用不明显，如果需要，与抗增殖药物紫杉醇结合使用，并可控制地从中释放，应可防止疾病的进展。

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.