角膜上皮干细胞移植治疗严重眼表疾病

Treatment of severe ocular-surface disorders with corneal epithelial stem-cell transplantation.

作者信息

Tsubota K, Satake Y, Kaido M, Shinozaki N, Shimmura S, Bissen-Miyajima H, Shimazaki J

机构信息

Department of Ophthalmology, Tokyo Dental College, Chiba, Japan.

出版信息

N Engl J Med. 1999 Jun 3;340(22):1697-703. doi: 10.1056/NEJM199906033402201.

DOI:10.1056/NEJM199906033402201

PMID:10352161

Abstract

BACKGROUND

Conditions that destroy the limbal area of the peripheral cornea, such as the Stevens-Johnson syndrome, ocular pemphigoid, and chemical and thermal injuries, can deplete stem cells of the corneal epithelium. The result is scarring and opacification of the normally clear cornea. Standard corneal transplantation cannot treat this form of functional blindness.

METHODS

We performed and evaluated 70 transplantations of corneal epithelial stem cells from cadaveric eyes into 43 eyes of 39 patients with severe ocular-surface disorders and limbal dysfunction. Medical treatment had failed in all patients. The patients had a mean preoperative visual acuity of 0.004 (only being able to count the number of fingers presented by the examiner) in the affected eyes, which satisfies the criteria for legal blindness in most countries. In 28 eyes, we also performed standard corneal transplantation. Stem-cell transplantations were performed as many as four times on 1 eye if the initial results were not satisfactory; 19 eyes had multiple transplantations. Patients were followed for at least one year after transplantation.

RESULTS

A mean of 1163 days after stem-cell transplantation, 22 of the 43 eyes (51 percent) had corneal epithelialization; of the 22 eyes, 7 eyes had corneal stromal edema and 15 eyes had clear corneas. Mean visual acuity improved from 0.004 to 0.02 (vision sufficient to distinguish the largest symbol on the visual-acuity chart from a distance of 1 m) (P<0.001). The 15 eyes in which the cornea remained clear had a final mean visual acuity of 0.11 (the ability to distinguish the largest symbol from a distance of 5 m). Complications of the first transplantation included persistent defects in the corneal epithelium in 26 eyes, ocular hypertension in 16 eyes, and rejection of the corneal graft in 13 of 28 eyes. The epithelial defects eventually healed in all but two of the eyes.

CONCLUSIONS

Transplantation of corneal epithelial stem cells can restore useful vision in some patients with severe ocular-surface disorders.

摘要

背景

诸如史蒂文斯 - 约翰逊综合征、眼部类天疱疮以及化学和热烧伤等破坏周边角膜缘区域的病症，会耗尽角膜上皮干细胞。其结果是正常透明的角膜出现瘢痕形成和混浊。标准的角膜移植无法治疗这种功能性失明。

方法

我们对39例患有严重眼表疾病和角膜缘功能障碍的患者的43只眼睛进行了70次来自尸体眼的角膜上皮干细胞移植，并对其进行评估。所有患者的药物治疗均告失败。患者患眼术前平均视力为0.004（仅能数出检查者伸出的手指数量），在大多数国家，这符合法定失明标准。在28只眼中，我们还进行了标准角膜移植。如果初次结果不令人满意，一只眼睛最多可进行4次干细胞移植；19只眼睛接受了多次移植。移植后对患者进行了至少一年的随访。

结果

干细胞移植后平均1163天，43只眼中有22只（51%）实现了角膜上皮化；在这22只眼中，7只眼出现角膜基质水肿，15只眼角膜清亮。平均视力从0.004提高到了0.02（视力足以在1米远处分辨视力表上最大的符号）（P<0.001）。角膜保持清亮的15只眼最终平均视力为0.11（能够在5米远处分辨最大的符号）。首次移植的并发症包括26只眼角膜上皮持续缺损、16只眼眼压升高以及28只眼中13只眼发生角膜移植排斥反应。除两只眼外，上皮缺损最终均愈合。