PDF(Pubmed)
Abstract：
Selective scleral crosslinking has been proposed as a novel treatment to increase scleral stiffness to counteract biomechanical changes associated with glaucoma and high myopia. Scleral stiffening has been shown by transpupillary peripapillary scleral photocrosslinking in rats, where the photosensitizer, methylene blue (MB), was injected retrobulbarly and red light initiated crosslinking reactions with collagen. Here, we adapted a computational model previously developed to model this treatment in rat eyes to additionally model MB photocrosslinking in minipigs and humans. Increased tissue length and subsequent diffusion and light penetration limitations were found to be barriers to achieving the same extent of crosslinking as in rats. Per cent inspired O2, injected MB concentration and laser fluence were simultaneously varied to overcome these limitations and used to determine optimal combinations of treatment parameters in rats, minipigs and humans. Increasing these three treatment parameters simultaneously resulted in maximum crosslinking, except in rats, where the highest MB concentrations decreased crosslinking. Additionally, the kinetics and diffusion of photocrosslinking reaction intermediates and unproductive side products were modelled across space and time. The model provides a mechanistic understanding of MB photocrosslinking in scleral tissue and a basis for adapting and screening treatment parameters in larger animal models and, eventually, human eyes.
摘要：
选择性巩膜交联已被提出作为一种新的治疗方法，以增加巩膜硬度，以抵消与青光眼和高度近视相关的生物力学变化。大鼠经瞳孔周围巩膜光交联已显示巩膜硬化，光敏剂，亚甲蓝(MB),球后注射，红光引发与胶原蛋白的交联反应。这里,我们调整了先前开发的计算模型,用于在大鼠眼中对这种治疗进行建模,以另外在小型猪和人类中对MB光交联进行建模.发现组织长度增加以及随后的扩散和光穿透限制是实现与大鼠相同程度的交联的障碍。同时改变激发O2的百分比，注射MB浓度和激光通量以克服这些限制，并用于确定大鼠治疗参数的最佳组合。小型猪和人类同时增加这三个处理参数导致最大交联，除了老鼠，其中最高的MB浓度降低了交联。此外,在空间和时间上模拟了光交联反应中间体和非生产性副产物的动力学和扩散。该模型提供了对巩膜组织中MB光交联的机械理解，并为在较大的动物模型中适应和筛选治疗参数提供了基础，最终,人类的眼睛。
