Nanavaty Mayank A, Shortt Alex J
Queen Victoria Hospital NHS Foundation Trust, Holtye Road, East Grinstead, West Sussex, UK, RH19 3DZ.
Cochrane Database Syst Rev. 2011 Jul 6(7):CD008420. doi: 10.1002/14651858.CD008420.pub2.
Fuchs endothelial dystrophy (FED), first described by Ernst Fuchsis in 1910, is a condition in which there is premature degeneration of corneal endothelial cells. When the number of endothelial cells is reduced to a significant degree fluid begins to accumulate within the cornea. As a result the cornea loses its transparency and the individual suffers a reduction in vision. The only successful surgical treatment for this condition is replacement of part or all of the cornea with healthy tissue from a cadaveric donor. The established procedure, penetrating keratoplasty (PKP), has been used for many years and its safety and efficacy are well known. Endothelial keratoplasty (EK) is a relatively new surgical procedure and the safety and efficacy relative to PKP are unknown.
The objective of this review is to collate information on the benefits and complications related to two surgical methods (PKP and EK) of replacing the diseased endothelial layer of the cornea with a healthy layer in people with FED.
We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2011, Issue 2), MEDLINE (January 1950 to February 2011), EMBASE (January 1980 to February 2011), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to February 2011), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com) and ClinicalTrials.gov (www.clinicaltrials.gov). There were no date or language restrictions in the electronic searches for trials. The electronic databases were last searched on 6 February 2011.
We included all randomised controlled trials (RCTs) comparing EK versus PKP for people (of any age and gender) who had been clinically diagnosed with FED. When assessing the primary and secondary outcome measures, only RCTs were included in the analysis. As per our protocol a description of data from non-randomised comparative studies is also reported. As RCTs may not detect differences in frequency of adverse events, when assessing these we included data from cohort studies with more than 50 participants and a follow-up of up to five years.
Two authors independently assessed trial quality and extracted data.
The electronic searches identified one RCT, five non-randomised comparative studies and 34 cohort studies with a sample size of over 50 participants for inclusion. The RCT was conducted in the USA and included 28 eyes of 25 participants with FED. Although this is a very good RCT, there may be potential for bias due to lack of masking of assessors and possible selective reporting not being clearly reported. In this RCT, comparing EK versus PKP, best corrected visual acuity (BCVA) was similar at 24 months (PKP 0.20 ± 0.20 logMAR; EK 0.34 ± 0.35 logMAR; P = 0.23) and higher order aberrations (HOAs) (deviations of the performance of an optical system from the predictions of paraxial optics) were lower with EK. No other data were reported by the trial. Based on data obtained from both non-randomised comparative studies and individual cohort studies the endothelial rejection rate was between 5.3% and 23.2% for PKP and 2% and 4% for EK. However the mean follow-up duration in the EK cohort studies was noticeably shorter. The rate of EK graft dislocation requiring repositioning ranged from 3% to 63%, with the majority of studies having a rate of < 10%.
AUTHORS' CONCLUSIONS: There is no high quality evidence that EK is superior to PKP in the treatment of FED considering the studies that satisfied our primary and secondary outcome measures. One RCT demonstrated that HOAs are lower following EK and some lower quality evidence suggests that endothelial rejection episodes may be less with EK. These findings should be interpreted with caution as they are based on data with risk of biases. Further RCTs of visual and refractive outcomes needs to be performed in this field, comparing EK to PKP, with a larger sample size and at least five years of follow up. To avoid bias due to a surgeon's learning curve, procedures should be performed by experienced surgeons only. Quality of life and vision should also be evaluated. The risk of endothelial rejection will be difficult to address in the context of a RCT because of power considerations but large non-randomised comparative case series and corneal graft registry outcome data will be useful in this regard.
富克斯内皮营养不良（FED）于1910年由恩斯特·富克斯首次描述，是一种角膜内皮细胞过早退化的病症。当内皮细胞数量显著减少时，角膜内开始积液。结果，角膜失去透明度，患者视力下降。针对这种病症唯一成功的外科治疗方法是用尸体供体的健康组织替换部分或全部角膜。已确立的穿透性角膜移植术（PKP）已使用多年，其安全性和有效性众所周知。内皮角膜移植术（EK）是一种相对较新的外科手术，相对于PKP的安全性和有效性尚不清楚。
本综述的目的是整理有关用健康层替换FED患者患病内皮角膜层的两种手术方法（PKP和EK）的益处和并发症的信息。
我们检索了Cochrane中心对照试验注册库（CENTRAL）（包含Cochrane眼科和视力组试验注册库）（《Cochrane图书馆》2011年第2期）、MEDLINE（1950年1月至2011年2月）、EMBASE（1980年1月至2011年2月）、拉丁美洲和加勒比健康科学文献数据库（LILACS）（1982年1月至2011年2月）、对照试验元注册库（mRCT）（www.controlled-trials.com）和ClinicalTrials.gov（www.clinicaltrials.gov）。电子检索试验时没有日期或语言限制。电子数据库最后一次检索时间为2011年2月6日。
我们纳入了所有比较EK与PKP的随机对照试验（RCT），研究对象为临床诊断为FED的任何年龄和性别的人群。在评估主要和次要结局指标时，分析中仅纳入RCT。根据我们的方案，还报告了非随机对照研究的数据描述。由于RCT可能无法检测不良事件发生率的差异，在评估这些事件时，我们纳入了样本量超过50名参与者且随访时间长达五年的队列研究数据。
两位作者独立评估试验质量并提取数据。
电子检索确定了一项RCT、五项非随机对照研究和34项样本量超过50名参与者的队列研究以供纳入。该RCT在美国进行，纳入了25名FED患者的28只眼。尽管这是一项非常好的RCT，但由于评估者未设盲以及可能存在未明确报告的选择性报告，可能存在偏倚。在该RCT中，比较EK与PKP，24个月时最佳矫正视力（BCVA）相似（PKP为0.20±0.20 logMAR；EK为0.34±0.35 logMAR；P = 0.23），且EK的高阶像差（HOAs）（光学系统性能与近轴光学预测的偏差）更低。该试验未报告其他数据。根据从非随机对照研究和个别队列研究获得的数据，PKP的内皮排斥率在5.3%至23.2%之间，EK的内皮排斥率在2%至4%之间。然而，EK队列研究的平均随访时间明显较短。需要重新定位的EK移植片脱位率在3%至63%之间，大多数研究的脱位率<10%。
考虑到满足我们主要和次要结局指标的研究，没有高质量证据表明EK在治疗FED方面优于PKP。一项RCT表明EK术后HOAs更低，一些质量较低的证据表明EK的内皮排斥发作可能更少。这些发现应谨慎解读，因为它们基于存在偏倚风险的数据。需要在该领域进行进一步的RCT，比较EK与PKP的视觉和屈光结局，样本量更大且至少随访五年。为避免因外科医生学习曲线导致的偏倚，手术应仅由经验丰富的外科医生进行。还应评估生活质量和视力。由于样本量考虑，在RCT背景下内皮排斥风险将难以解决，但大型非随机对照病例系列和角膜移植登记结局数据在这方面将很有用。
