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Abstract：
OBJECTIVE: The purpose of the study is to evaluate the safety and outcomes of corneal collagen cross-linking (CXL) and different CXL protocols in progressive keratoconus (PK) population at short and long-term.
METHODS: A systematic review and meta-analysis was conducted. A total of eight literature databases were searched (up to February 15, 2022). Randomized controlled trials (RCTs) comparing CXL versus placebo/control or comparing different CXL protocols in the PK population were included. The primary objective was assessment of outcomes of CXL versus placebo and comparison of different CXL protocols in terms of maximum keratometry (Kmax) or Kmax change from baseline (Δ), spherical equivalent, best corrected visual acuity (BCVA), and central corneal thickness (CCT) in both at short term (6 months) and long term (1st, 2nd, and 3rd year or more). The secondary objective was comparative evaluation of safety. For the meta-analysis, the RevMan5.3 software was used.
RESULTS: A total of 48 RCTs were included. Compared to control, CXL was associated with improvement in Δ Kmax at 1 year (4 RCTs, mean difference [MD], -1.78 [-2.71, -0.86], P = 0.0002) and 2 and 3 years (1 RCT); ΔBCVA at 1 year (7 RCTs, -0.10 [-0.14, -0.06], P < 0.00001); and Δ CCT at 1 year (2 RCTs) and 3 years (1 RCT). Compared to conventional CXL (C-CXL), deterioration in Δ Kmax, ΔBCVA and endothelial cell density was seen at long term in the transepithelial CXL (TE-CXL, chemical enhancer). Up to 2 years, there was no difference between TE-CXL using iontophoresis (T-ionto) and C-CXL. At 2 and 4 years, C-CXL performed better compared to accelerated CXL (A-CXL) in terms of improving Kmax. Although CCT was higher in the A-CXL arm at 2 years, there was no difference at 4 years. While exploring heterogeneity among studies, selection of control eye (fellow eye of the same patient vs. eye of different patient) and baseline difference in Kmax were important sources of heterogeneity.
CONCLUSIONS: CXL outperforms placebo/control in terms of enhancing Kmax and CCT, as well as slowing disease progression over time (till 3 years). T-ionto protocol, on the other hand, performed similarly to C-CXL protocol up to 2 years.
METHODS: A systematic review and meta-analysis was conducted. A total of eight literature databases were searched (up to February 15, 2022). Randomized controlled trials (RCTs) comparing CXL versus placebo/control or comparing different CXL protocols in the PK population were included. The primary objective was assessment of outcomes of CXL versus placebo and comparison of different CXL protocols in terms of maximum keratometry (Kmax) or Kmax change from baseline (Δ), spherical equivalent, best corrected visual acuity (BCVA), and central corneal thickness (CCT) in both at short term (6 months) and long term (1st, 2nd, and 3rd year or more). The secondary objective was comparative evaluation of safety. For the meta-analysis, the RevMan5.3 software was used.
RESULTS: A total of 48 RCTs were included. Compared to control, CXL was associated with improvement in Δ Kmax at 1 year (4 RCTs, mean difference [MD], -1.78 [-2.71, -0.86], P = 0.0002) and 2 and 3 years (1 RCT); ΔBCVA at 1 year (7 RCTs, -0.10 [-0.14, -0.06], P < 0.00001); and Δ CCT at 1 year (2 RCTs) and 3 years (1 RCT). Compared to conventional CXL (C-CXL), deterioration in Δ Kmax, ΔBCVA and endothelial cell density was seen at long term in the transepithelial CXL (TE-CXL, chemical enhancer). Up to 2 years, there was no difference between TE-CXL using iontophoresis (T-ionto) and C-CXL. At 2 and 4 years, C-CXL performed better compared to accelerated CXL (A-CXL) in terms of improving Kmax. Although CCT was higher in the A-CXL arm at 2 years, there was no difference at 4 years. While exploring heterogeneity among studies, selection of control eye (fellow eye of the same patient vs. eye of different patient) and baseline difference in Kmax were important sources of heterogeneity.
CONCLUSIONS: CXL outperforms placebo/control in terms of enhancing Kmax and CCT, as well as slowing disease progression over time (till 3 years). T-ionto protocol, on the other hand, performed similarly to C-CXL protocol up to 2 years.
摘要：
目的：本研究的目的是评估短期和长期进行性圆锥角膜（PK）人群角膜胶原交联（CXL）和不同CXL方案的安全性和结果。
方法：进行系统评价和荟萃分析。共检索了8个文献数据库（截至2022年2月15日）。包括比较CXL与安慰剂/对照或比较PK群体中不同CXL方案的随机对照试验(RCT)。主要目标是评估CXL与安慰剂的结果，并根据最大角膜曲率（Kmax）或Kmax相对于基线的变化（Δ）比较不同的CXL方案。球形当量，最佳矫正视力（BCVA），和中央角膜厚度（CCT）在短期（6个月）和长期（第1，2nd,和第三年或更长时间)。次要目标是安全性的比较评价。对于荟萃分析，使用RevMan5.3软件。
结果：共纳入48个随机对照试验。与控制相比，CXL与1年时ΔKmax的改善相关(4项RCT，平均差[MD]，-1.78[-2.71,-0.86],P=0.0002)和2年和3年(1个RCT)；1年时的ΔBCVA(7个RCT，-0.10[-0.14,-0.06],P<0.00001）；1年（2个RCT）和3年（1个RCT）的ΔCCT。与传统CXL(C-CXL)相比，ΔKmax恶化，ΔBCVA和内皮细胞密度长期可见于跨上皮CXL（TE-CXL，化学增强剂)。长达2年,使用离子电渗疗法（T-ionto）的TE-CXL和C-CXL之间没有差异。在2年和4年，与加速CXL(A-CXL)相比,C-CXL在提高Kmax方面表现更好。虽然CCT在A-CXL臂在2年时较高，在4年没有差异。在探索研究之间的异质性的同时，对照眼的选择(同一位患者的同眼与不同患者的眼睛）和Kmax的基线差异是异质性的重要来源。
结论：CXL在增强Kmax和CCT方面优于安慰剂/对照，以及随着时间的推移（直到3年）减缓疾病进展。T-ionto协议，另一方面,类似于C-CXL方案进行长达2年。
方法：进行系统评价和荟萃分析。共检索了8个文献数据库（截至2022年2月15日）。包括比较CXL与安慰剂/对照或比较PK群体中不同CXL方案的随机对照试验(RCT)。主要目标是评估CXL与安慰剂的结果，并根据最大角膜曲率（Kmax）或Kmax相对于基线的变化（Δ）比较不同的CXL方案。球形当量，最佳矫正视力（BCVA），和中央角膜厚度（CCT）在短期（6个月）和长期（第1，2nd,和第三年或更长时间)。次要目标是安全性的比较评价。对于荟萃分析，使用RevMan5.3软件。
结果：共纳入48个随机对照试验。与控制相比，CXL与1年时ΔKmax的改善相关(4项RCT，平均差[MD]，-1.78[-2.71,-0.86],P=0.0002)和2年和3年(1个RCT)；1年时的ΔBCVA(7个RCT，-0.10[-0.14,-0.06],P<0.00001）；1年（2个RCT）和3年（1个RCT）的ΔCCT。与传统CXL(C-CXL)相比，ΔKmax恶化，ΔBCVA和内皮细胞密度长期可见于跨上皮CXL（TE-CXL，化学增强剂)。长达2年,使用离子电渗疗法（T-ionto）的TE-CXL和C-CXL之间没有差异。在2年和4年，与加速CXL(A-CXL)相比,C-CXL在提高Kmax方面表现更好。虽然CCT在A-CXL臂在2年时较高，在4年没有差异。在探索研究之间的异质性的同时，对照眼的选择(同一位患者的同眼与不同患者的眼睛）和Kmax的基线差异是异质性的重要来源。
结论：CXL在增强Kmax和CCT方面优于安慰剂/对照，以及随着时间的推移（直到3年）减缓疾病进展。T-ionto协议，另一方面,类似于C-CXL方案进行长达2年。
