Brekelmans Jurriaan, Goz Alexandra, Dickman Mor M, Brandis Alexander, Sui Xiaomeng, Wagner H Daniel, Nuijts Rudy M M A, Scherz Avigdor, Marcovich Arie L
University Eye Clinic Maastricht, Maastricht, The Netherlands.
Department of Plant Sciences and Environmental Health, the Weizmann Institute of Science, Rehovot, Israel.
Invest Ophthalmol Vis Sci. 2017 Aug 1;58(10):4089-4095. doi: 10.1167/iovs.17-22108.
To determine the long-term safety and efficacy of WST-D/near-infrared (NIR) corneal stiffening.
One eye of 23 New Zealand White rabbits was de-epithelialized mechanically followed by topical application of 2.5 mg/mL WST11, combined with dextran-500 (WST-D) for 20 minutes. Subsequently, samples were irradiated with a NIR (755 nm) laser at 10 mW/cm2 for 30 minutes. Untreated fellow eyes served as controls. One week (n = 4), 1 month (n = 6), 4 months (n = 9), or 8 months (n = 4) after treatment rabbits were euthanized. Corneal strips were cut in superior-inferior direction for extensiometry testing (1, 4, and 8 months), and histologic sections were prepared for evaluation of keratocyte distribution (1 week and 8 months).
Elastic modulus after treatment was significantly higher than in paired controls (16.0 ± 2.3 MPa versus 9.6 ± 3.6 MPa [P = 0.008], 18.1 ± 4.5 MPa versus 12.6 ± 2.3 MPa [P = 0.003], and 18.6 ± 3.6 MPa versus 14.2 ± 3.6 MPa [P = 0.010], at 1, 4, and 8 months, respectively). A significant decrease in keratocyte count at the anterior stroma was observed directly after treatment (1.5 ± 1.7 vs. 19.0 ± 4.1 [P = 0.002]). At 8 months keratocyte repopulation appeared completed, with similar distribution in treated and untreated corneas (15.9 ± 1.1 vs. 14.5 ± 2.5 [P = 0.562]). Corneal thickness was comparable between treated and untreated corneas at all time points.
WST-D/NIR treatment resulted in significant and persistent long-term increase in corneal stiffness. Initial keratocyte apoptosis in the anterior stroma is followed by repopulation to normal level at 8 months after treatment. The safe nature of NIR light allows treatment of corneas of any thickness without endangering corneal endothelium or deeper ocular structures, potentially benefiting patients deemed unsuitable for riboflavin/UV-A cross-linking.
确定WST-D/近红外(NIR)角膜强化术的长期安全性和有效性。
对23只新西兰白兔的一只眼睛进行机械性去上皮,然后局部应用2.5mg/mL WST11与葡聚糖-500(WST-D)混合液20分钟。随后,用波长755nm的近红外激光以10mW/cm²的功率照射样本30分钟。未处理的对侧眼作为对照。治疗后1周(n = 4)、1个月(n = 6)、4个月(n = 9)或8个月(n = 4)对兔子实施安乐死。沿上下方向切取角膜条进行拉伸测试(1、4和8个月),并制备组织学切片以评估角膜细胞分布(1周和8个月)。
治疗后弹性模量显著高于配对对照(1个月时分别为16.0±2.3MPa对9.6±3.6MPa [P = 0.008],4个月时为18.1±4.5MPa对12.6±2.3MPa [P = 0.003],8个月时为18.6±3.6MPa对14.2±3.6MPa [P = 0.010])。治疗后直接观察到前基质层角膜细胞数量显著减少(1.5±1.7对19.0±4.1 [P = 0.002])。8个月时角膜细胞重新增殖似乎已完成,治疗组和未治疗组角膜中的分布相似(15.9±1.1对14.5±2.5 [P = 0.562])。所有时间点治疗组和未治疗组角膜厚度相当。
WST-D/NIR治疗导致角膜硬度显著且持续的长期增加。治疗后前基质层角膜细胞最初发生凋亡,随后在8个月时重新增殖至正常水平。近红外光的安全性使得可以治疗任何厚度的角膜,而不会危及角膜内皮或更深层的眼内结构,这可能使那些被认为不适合核黄素/紫外线A交联治疗的患者受益。