Wollensak Gregor, Iomdina Elena, Dittert Dag-Daniel, Salamatina Olga, Stoltenburg Gisela
Moscow Helmholtz Research Institute of Eye Diseases, Moscow, Russia.
Acta Ophthalmol Scand. 2005 Aug;83(4):477-82. doi: 10.1111/j.1600-0420.2005.00447.x.
Scleral biomechanical weakness and thinning is known to be one of the main factors in the pathogenesis of progressive myopia. We tried to strengthen rabbit sclera by cross-linking scleral collagen using ultraviolet A (UVA) and the photosensitizer riboflavin.
Circumscribed 10 x10 mm sectors of the posterior--equatorial sclera of six chinchilla rabbit eyes were treated in vivo using a UVA double diode with 4.2 mW/cm(2) UVA at 370 nm and applying 0.1% riboflavin-5-phosphate drops as photosensitizer for 30 min. 1 day postoperatively biomechanical stress--strain measurements of three treated scleral strips were performed using a microcomputer-controlled biomaterial testing device and compared to non-treated contralateral control sclera. In addition, three treated eyes were examined histologically by light microscopy, TUNEL staining and electron microscopy to evaluate side-effects.
Following the cross-linking treatment, the ultimate stress was 11.87+/-1.8 MPa versus 3.63+/-0.40 in the controls (increase of 227.9%, p=0.014), Young's modulus 27.67+/-4.16 MPa versus 4.9+/-.15 MPa in the controls (increase of 464.7%, p=0.021) and ultimate strain 92.2+/-7.43% versus 165.63+/-19.09% in the controls (decrease of 54.52%, p=0.012). Histologically, serious side-effects were found in the entire posterior globe with almost complete loss of the photoreceptors, the outer nuclear layer and the retinal pigment epithelium (RPE).
Our new method of scleral collagen cross-linking proved very effective in increasing the scleral mechanical strength; the new treatment may represent an option for strengthening scleral tissue in progressive myopia. However, serious side-effects were observed in the outer retina. In future studies these side-effects could be avoided by reducing the irradiation dose below the cytotoxic level of the retina. Before its clinical application, the new method should be tested in a myopia animal model.
巩膜生物力学薄弱和变薄是进行性近视发病机制的主要因素之一。我们试图通过使用紫外线A（UVA）和光敏剂核黄素交联巩膜胶原蛋白来增强兔巩膜。
对六只龙猫兔眼的后赤道巩膜进行10×10mm的局部区域体内治疗，使用波长370nm、UVA强度为4.2mW/cm²的UVA双二极管，并滴入0.1%的核黄素-5-磷酸作为光敏剂，持续30分钟。术后1天，使用微机控制的生物材料测试装置对三条处理过的巩膜条进行生物力学应力-应变测量，并与未处理的对侧对照巩膜进行比较。此外，对三只处理过的眼睛进行组织学检查，通过光学显微镜、TUNEL染色和电子显微镜评估副作用。
交联处理后，极限应力为11.87±1.8MPa，而对照组为3.63±0.40MPa（增加227.9%，p=0.014）；杨氏模量为27.67±4.16MPa，对照组为4.9±0.15MPa（增加464.7%，p=0.021）；极限应变92.2±7.43%，对照组为165.63±19.09%（减少54.52%，p=0.012）。组织学检查发现，整个眼球后部出现严重副作用，几乎完全丧失光感受器、外核层和视网膜色素上皮（RPE）。
我们新的巩膜胶原蛋白交联方法在提高巩膜机械强度方面非常有效；这种新治疗方法可能是加强进行性近视患者巩膜组织的一种选择。然而，在外层视网膜观察到严重副作用。在未来的研究中，可以通过将照射剂量降低到视网膜细胞毒性水平以下来避免这些副作用。在临床应用之前，应在近视动物模型中对这种新方法进行测试。
