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异体角膜基质透镜移植治疗角膜穿孔：2例病例报告及文献复习

Allogeneic corneal stromal lamellar keratoplasty in the treatment of corneal perforation: two case reports and literature review

来源期刊： 眼科学报 | 2025年10月 第40卷 第10期： 875-884 发布时间：2025-10-28 收稿时间：2025/10/27 10:29:21 阅读量：29
作者：
张莉言,
张明媚,
陈利群,
易湘龙,
关键词：
角膜基质透镜飞秒激光小切口角膜基质透镜取出术(SMILE)角膜病角膜穿孔
corneal stromal lamella femtosecond laser small incision lenticule extraction (SMILE) corneal disease corneal perforation
DOI：
10.12419/25010201
收稿时间：
2025-01-20 
修订日期：
2025-04-01 
接收日期：
2025-07-25 
角膜基质透镜是带有一定屈光度的角膜组织，为利用激光或板层刀等在角膜基质层内雕刻出一个精确对焦点的光学透镜。随着角膜屈光手术的不断发展，术中产生了大量的角膜基质透镜, 越来越多的学者也将目光聚焦于此。我国角膜供体来源匮乏与手术量需求严重不匹配, 眼库严重缺乏供体角膜，而对角膜组织的需求却越来越大。角膜穿孔作为角膜疾病的终末阶段，严重威胁患者的视力,甚至要面临摘除眼球的风险, 是对患者身体与心理的双重打击。绝大多数的角膜穿孔需要紧急手术处理, 对于一些常规治疗无效或角膜病变更严重的，角膜移植术可能是唯一有效的手段。对原本废弃的透镜重新利用, 将其用于治疗角膜溃疡、修补角膜穿孔以及辅助治疗各类角膜疾病的危重阶段, 均观察到其取得了良好的效果, 这在一定程度上缓解了临床上角膜供体缺乏的现状。本文报道了2例由角膜白斑引起的角膜穿孔患者使用异体角膜基质透镜移植治疗的病例, 术后2名患者病情均得到稳定。同时探讨了角膜基质透镜移植的局限性, 本文并未观察到角膜透镜移植对于感染性、免疫性等其他原因造成的角膜穿孔的疗效, 因此在行角膜移植之前，要正确认识及处理原发病，尽量避免一些并发症和排斥反应的发生。
Corneal stromal lenses are corneal tissues with specific refractive power, created by precisely sculpting an optical lens within the corneal stromal layer using lasers or microkeratomes. With the ongoing development of corneal refractive surgery, a large amount of corneal stromal lenses are generated during procedures, drawing increasing attention from researchers. In China, there exists a severe mismatch between the scarcity of corneal donors and the high demand for surgical procedures. This has led to a critical shortage of donor corneas in eye banks, while the need for corneal tissue keeps rising. Corneal perforation, which is the end-stage of various corneal diseases, poses a significant threat to patients' vision and may even result in enucleation, causing considerable physical and psychological distress. Most cases of corneal perforation require urgent surgical intervention. For patients with severe conditions or those for whom conventional treatments are ineffective, corneal transplantation may be the only viable option. Reusing stromal lenses that were previously discarded to treat corneal ulcers, repair corneal perforations, and assist in managing critical stages of various corneal diseases has shown promising results. This, to some extent, helps alleviate the clinical shortage of donor corneas. This article presents two cases of corneal perforation caused by corneal leukoma, both of which were successfully treated with allogeneic corneal stromal lens transplantation. Both patients achieved stable conditions after the operation. Additionally, this paper discusses the limitations of corneal stromal lens transplantation. The efficacy of corneal lens transplantation for perforations caused by infectious or immunological etiologies was not observed in this study. Therefore, it is essential to accurately diagnose and manage the underlying disease before transplantation and to minimize the occurrence of complications and rejection reactions.

文章亮点

1. 关键发现

 • SMILE 来源的角膜基质透镜移植术在一定程度上弥补了角膜供体来源不足的现状，是一种比较安全有效的替代方法。

2. 已知与发现

 • 目前我国角膜供体来源匮乏与手术量需求严重不匹配。同时，角膜移植的成本较高，且存在排斥或移植失败等并发症，这些都限制了新鲜角膜组织的应用。随着 SMILE 手术在国内的兴起，大量废弃的角膜基质透镜也随之产生，大量学者“废物利用”将角膜基质透镜用于治疗角膜溃疡及穿孔等眼部疾病，取得了较好的效果。

3. 意义与改变

 • 对于角膜移植术是唯一有效治疗手段的危重患者来说 , 在面对漫长等待角膜供体的情况时 ,SMILE 来源的异体角膜基质透镜移植可以是一种比较安全有效的替代方案。

       飞秒激光小切口角膜基质透镜取出术（small incision lenticuleextraction, SMILE）是近年来新兴起的一种治疗屈光不正的手术[1]。随着手术方式的不断完善发展，术中获得的角膜基质透镜组织也得到了广泛的关注。既往学者们已经探索了角膜基质透镜的应用，在矫正老视、散光，修补角膜缺陷类疾病，治疗圆锥角膜、辅助治疗青光眼、复发性翼状胬肉等方面均取得可观效果[2-8]。将角膜基质透镜变废为宝，这在一定程度上缓解了临床上角膜供体缺乏的现状，并为多种眼部疾病的治疗提供了更多可能性。本文报道了2例由角膜白斑引起的角膜穿孔患者使用异体角膜基质透镜移植治疗的病例, 旨在观察角膜基质透镜移植的有效性及安全性。

1 病例报告

1.1  病例1

       患者女，43岁，以“左眼眼痛伴视力下降38年，加重2个月”为主诉于2024年1月22日入院。患者自诉于38年前左眼被木枝划伤后出现渐进性视力下降，偶伴有眼胀、眼痛，无分泌物，否认头痛不适，否认视物变形、变色，近2个月患者自觉视力下降严重，为求进一步诊治就诊于我科门诊，以“左眼角膜穿孔”门诊收住我科。病程中患者神志清晰，二便正常。体质量和体力无明显改变。专科查体：右眼视力0.6，眼压18 mmHg（1 mmHg=0.133 kPa），眼前段未见明显异常，瞳孔大小3 mm×3 mm，光反应灵敏，晶状体密度增高，玻璃体轻度混浊，眼底小瞳下所见网膜在位；左眼视力指数/10 cm，眼压指测Tn，结膜睫状充血，角膜中央偏颞下方可见约5 mm×4 mm大小白斑，余透明，下方前房浅，下方虹膜可见前粘连，瞳孔欠圆，居中，光反应灵敏，晶状体密度增高，玻璃体轻度混浊，眼底视不入。患者一般情况良好，否认高血压、糖尿病等全身疾病史，否认家族遗传病史。本院辅助检查：2023年11月22日，眼前段照相：左眼角膜中央偏颞下方可见约5 mm×4 mm大小白斑，余透明（图1A）；2024年12月20日，眼前段照相：可见角膜穿孔（图1B）；2023年12月20日、2024年1月3日，眼前节光学相干断层扫描（anterior segment optical coherence tomography, AS-OCT）：左眼角膜穿孔处病灶厚度分别为222 μm（图2A）、211 μm（图2B）；2023年11月22日，共聚焦显微镜：左眼上皮层较粗糙，可见多量炎症细胞及活化的树突状细胞，病变区结构不清，浅基质细胞模糊且可见较多炎症细胞，内皮层结构模糊；2023年11月22日，B超：未见明显异常。初步诊断：左眼角膜穿孔、左眼粘连性角膜白斑、右眼角膜云翳、双眼屈光不正。经本院医学伦理委员会审批，患者签署手术知情同意书后，于入院后3天行左眼异体角膜基质透镜移植术，术中见角膜中央偏下方溃疡，溃疡灶中央可见部分虹膜嵌顿于穿孔处，刮除溃疡灶及周边正常组织部分上皮，取经SMILE获取的角膜基质透镜2片覆盖于病灶处，10-0线间断缝合角膜植片8针，术毕角膜闭合良好，眼压指测正常。术后左眼视力为0.02，眼压指测Tn。给予患者抗炎及抗免疫眼液点眼。眼前段照相及AS-OCT示：左眼角膜植片透明，对位良好，缝线在位，层间无积液（图1B、图2C）。随访：术后可见角膜轻度水肿，随后逐渐下降，植片透明度逐渐增加（图1C、D、E及图2D、E、F）。患者眼部情况稳定，术后半年，于我院行左眼角膜拆线（图1F、图2G）。术后1年患者于当地医院复查，视力左眼指数/30 cm，眼压9 mmHg，角膜植片稍混浊，余未见明显异常。

图 1 角膜穿孔患者1异体角膜基质透镜移植治疗手术前后眼前段照相资料
Figure 1 Preoperative and postoperative photographic data of the anterior segment of patient 1 with corneal perforation treated by allocorneal stromal lens transplantation

20251106105644_6452.png
(A)术前(2023年11月22日)，病灶外观图；(B)术前(2023年12月20日)，角膜中央黑点为脱出的虹膜；(C)术后1天，结膜轻度充血，缝线在位；(D)术后2周，植片透明度逐渐增加；(E)术后1个月，7点位缝线松动，予以拆除处理；(F)术后2个月；(G)术后半年，角膜全部缝线拆除。
(A) Pre-operation(2023-11-22), lesion appearance map; (B) Pre-operation(2023-12-20), central black spot of cornea is protruded iris; (C) 1 day after surgery, conjunctival mild congestion, suture in place; (D) 2 weeks after surgery, implant transparency gradually increased; (E) 1 month after surgery, the suture became loose at 7 o 'clock and was removed; (F) 2 months after surgery; (G) Six months after surgery, All corneal sutures were removed.

图 2 角膜穿孔患者1异体角膜基质透镜移植治疗手术前后AS-OCT资料
Figure 2 AS-OCT of patient 2 with corneal perforation before and after allograft corneal stromal lens transplantation

20251106105857_9238.png
(A，B)术前；(C)术后1天，与术前同一方位同一位置扫描及测量显示此时角膜及透镜总厚度为459 μm，角膜水肿，植片对位良好，层间无积液，角膜绷带镜在位；(D)术后2周，左眼角膜及透镜总厚度为434 μm，角膜水肿逐渐下降； (E)术后1个月，左眼角膜及透镜总厚度为330 μm；(F)术后2个月，左眼角膜及透镜总厚度为263 μm；(G)术后半年，左眼角膜及透镜总厚度为255 μm。
(A, B) Preoperative; (C) Postoperative Day 1: Scanning and measurement at the same position as preoperative showed a total thickness of 459 μm for the cornea and lens combined. Corneal edema was present, the graft was well-positioned with no interlamellar fluid, and the corneal bandage contact lens was in place. (D) Postoperative Week 2: Total thickness of the left eye cornea and lens combined was 434 μm, with gradual reduction in corneal edema. (E) Postoperative Month 1: Total thickness of the left eye cornea and lens combined was 330 μm. (F) Postoperative Month 2: Total thickness of the left eye cornea and lens combined was 263 μm. (G) Postoperative Six Months: Total thickness of the left eye cornea and lens combined was 255 μm.

1.2  病例2

       患者男，15岁，以“揉眼后右眼视力下降伴流热泪2周”为主诉于2024年5月29日入院。患者自诉于1年前嬉戏玩耍时不慎被麻绳击打右眼后出现渐进性视力下降，否认眼胀、眼痛，无分泌物，否认头痛不适，否认视物变形、变色，前往当地医院就诊，完善相关检查后诊断为：右眼角膜溃疡，给予局部点药处理，患者自觉症状好转。2周前患者自诉右眼进入异物后揉眼，随后出现视力下降伴流热泪，于当地医院就诊后未给予治疗，建议患者转往上级医院就诊。患者为求进一步诊治就诊于我科门诊，以“右眼角膜穿孔”门诊收住我科。病程中患者神志清晰，二便正常。体重和体力无明显改变。专科查体：右眼视力手动/10 cm，眼压8 mmHg，结膜混合充血，角膜中央可见约4 mm×5 mm不规则灰白色病灶，病灶中央可见一约0.10 mm×0.15 mm泡状隆起，其中隐见棕色异物嵌入层间，上下方前房呈裂隙状，余前房消失，鼻侧及颞侧虹膜可见新生血管长入及少量出血，瞳孔大小3 mm×3 mm，光反应灵敏，余视不入；左眼视力1.0，眼压16 mmHg，眼前段未见明显异常，瞳孔大小3 mm×3 mm，光反应灵敏，晶状体透明，玻璃体轻度混浊，眼底小瞳下视盘界清色可，C/D约0.3，黄斑区反光未见，视网膜未见明显出血及渗出。患者一般情况良好，否认高血压、糖尿病等全身疾病史，否认家族遗传病史。本院辅助检查：2024年5月29日，眼前段照相：右眼角膜中央可见约4 mm×5 mm不规则灰白色病灶，中央隐见棕色异物嵌入（图3A）；2024年5月29日，AS-OCT：右眼角膜穿孔处病灶厚度为276 μm（图4A）。初步诊断：右眼角膜穿孔、右眼角膜溃疡、右眼角膜白斑、右眼角膜异物、右眼虹膜新生血管、双眼屈光不正。于入院后第二天行右眼异体角膜基质透镜移植术。术后右眼视力手动/30cm，眼压指测Tn。植片在位，层间无积液，中央前房深度约1/2 CT（图3B、C、D及图4B、C、D）。给予患者抗免疫排斥及抗炎滴眼液点眼。术后1月余患者出现眼痛畏光流泪等症状，于当地医院就诊诊断为“右眼角膜移植排斥？”，给予患者点眼药（具体不详），症状并未好转，患者为求进一步诊治，就诊于北京爱尔英智眼科医院，完善相关检查（具体不详）后诊断为右眼角膜上皮损伤、右眼角膜移植状态”，将患者收入住院行右眼角膜移植手术治疗，术后给予滴眼液治疗（具体不详），但右眼角膜上皮持续缺损，并可见新生血管长入角膜，故于术后2月余再次入院治疗（先后在局部麻醉下行“右眼羊膜移植术”“右眼眼睑缝合术”“右眼结膜瓣和角膜修补术”），病情好转稳定后出院。后续患者于伊犁州中医院进行复查（图3E、F、G及H），术后8个月，右眼视力0.1，眼压未测出，右眼结膜充血，角膜植片在位，缝线固定无脱落。

图 3 角膜穿孔患者2右眼手术前后眼前段照相资料
Figure 3 Pre- and postoperative anterior segment photographic data of the right eye in patient 2 with corneal perforation

20251106110031_3598.png
(A)第一次手术术前，病灶外观图；(B)第一次手术术后1天，结膜充血，角膜水肿，缝线在位；(C)第一次手术术后4天，角膜水肿减轻；(D)第一次手术术后2周，植片对位良好，透明度增加；(E、F)第二次手术术后3个月眼前段及角膜荧光素钠染色照相，结膜充血，角膜植片在位，缝线固定，角膜可见着染，下方可见新生血管长入；(G、H)第二次手术术后4个月，结膜充血较前减轻，角膜植片在位，缝线固定，下方新生血管长入面积较前减轻。
(A) Preoperative to First Surgery: Lesion appearance image. (B) Postoperative Day 1 of First Surgery: Conjunctival congestion, corneal edema, sutures in place. (C) Postoperative Day 4 of First Surgery: Corneal edema reduced. (D) Postoperative Week 2 of First Surgery: Graft wellpositioned, transparency increased. (E, F) Threemonths postoperative of Second Surgery: Anterior segment and corneal fluorescein staining: Conjunctival congestion, graft in place, sutures fixed, cornea shows staining, with new vessels visible at the bottom. (G, H) Four months postoperative of Second Surgery: Conjunctival congestion reduced compared to before, graft in place, sutures fixed, area of new vessel ingrowth at the bottom reduced compared to before.

图 4 角膜穿孔患者2异体角膜基质透镜移植治疗手术前后AS-OCT资料
Figure 4 AS-OCT of patient 2 with corneal perforation before and after allograft corneal stromal lens transplantation

20251106110129_9478.png
(A)术前；(B)术后1天，与术前同一方位同一位置扫描及测量显示此时右眼角膜及透镜总厚度为679 μm，角膜水肿，植片对位良好，层间无积液；(C)术后4天，右眼角膜及透镜总厚度为661 μm，角膜绷带镜在位；(D)术后2周：右眼角膜及透镜总厚度为618 μm，角膜水肿减轻。
(A) Preoperative; (B) Postoperative Day 1: Scanning and measurement at the same position as preoperative showed a total thickness of 679 μm for the right eye cornea and lens combined. Corneal edema was present, the graft was well-positioned with no interlamellar fluid. (C) Postoperative Day 4: Total thickness of the right eye cornea and lens combined was 661 μm, with the corneal bandage contact lens in place. (D) Postoperative Week 2: Total thickness of the right eye cornea and lens combined was 618 μm, with a reduction in corneal edema.

2  讨论

       角膜穿孔是角膜疾病的终末阶段，严重威胁视力。引起角膜穿孔的病因极其复杂，外伤与感染（细菌性、病毒性、真菌性等）是常见的原因，也可由某些非创伤性原因引起，例如邻近组织的病变波及角膜[9-10]。此外，角膜的毛细血管和淋巴管通道也极易受到全身代谢性疾病或自身免疫性疾病的影响[11]。角膜疾病发生时的病理生理学包括胶原纤维和角膜细胞外基质成分的基质蛋白水解降解，导致持续性角膜上皮缺损，可能继续导致基质降解和变薄[12]。如果不及时治疗，角膜变薄会引起穿孔，最终导致各种并发症，包括眼前节解剖完整性的严重丧失、眼球感染扩散导致眼内炎、葡萄膜炎、继发性青光眼等，发生不可逆的视力丧失，甚至最终需要眼球摘除，给患者造成巨大的心理和生理创伤。角膜疾病的诊断可通过标准化裂隙灯生物显微镜检查、眼前段照相检查、超声生物显微镜检查（ultrasound biomicroscopy, UBM）和AS-OCT等来确认[13-15]。
       绝大多数的角膜穿孔需要紧急手术处理, 治疗方法的选择主要取决于穿孔的情况,对于穿孔较小或者病变较轻的患者，可考虑多层羊膜移植、自体结膜移植等；当上述治疗无效或角膜病变更严重时，角膜移植术则是唯一有效的治疗手段，包括板层角膜移植术（lamellar keratoplasty，LKP）、内皮移植术(corneal endothelial keratoplasty，EK)、穿透性角膜移植术(penetrating keratoplasty, PKP)以及外周新月体LKP和中央PKP的组合等[16-19]。角膜组织是世界上最常见的移植器官。然而，在发展中国家，眼库严重缺乏供体角膜，记录显示，近年来中国的角膜移植从5 000例增加到8 000多例，对角膜组织的需求越来越大，角膜供体来源匮乏与手术量需求严重不匹配[20]。同时，角膜移植的成本较高，且存在排斥或移植失败等并发症，这些都限制了新鲜角膜组织的应用。
       随着SMILE手术在国内的兴起，大量废弃的角膜基质透镜也随之产生，大量学者“废物利用”将角膜基质透镜用于治疗角膜溃疡及穿孔等眼部疾病[21-22]，取得了较好的效果。Pant等[23]对吉林大学第一医院眼科进行的18例角膜移植患者进行了回顾性研究，结果表明角膜基质透镜移植是一种安全有效的方法来治疗角膜疾病。Bhandari等[24]报告了由新鲜透镜修补的7例角膜穿孔患者, 所有术眼在末次随访时植片均透明且对位良好。Wu等[25]对6例角膜穿孔患者进行透镜移植，术后恢复良好。Abd Elaziz等[22]联合透镜与羊膜进行移植，术后1年随访可见术眼角膜痕及血管翳形成, 无排斥反应出现。姚涛等[26]也采用类似方法对角膜创面较大的穿孔进行修补，取得了良好的术后效果。高颖等[27]将透镜用于蚕蚀性角膜溃疡及边缘角膜变性的治疗，术后植片对位良好，无感染及复发。
       目前角膜移植术失败的很大原因是发生了免疫排斥反应。有研究表明，角膜移植术后免疫排斥反应的发生率与角膜植床的血管化程度成正比[28-29]。在化学烧伤、爆炸伤、角膜溃疡期的活动性炎症等角膜移植病例中，总是能观察到更多的术后排斥反应。当角膜新生血管增多，炎症反应引起血-房水屏障破坏，增加了移植抗原与受体免疫系统的沟通机会，从而触发一系列免疫反应[30]。刘娴等[31]对14例行角膜基质透镜联合羊膜移植术的真菌性角膜溃疡患者进行了回顾性研究，结果显示大部分患者疗效较好，但有1例患者发生了角膜基质透镜溶解，后行二次手术进行修复。本报道中病例2情况类似，术后2个月发现角膜新生血管长入，角膜上皮出现缺损，在进行了多次羊膜覆盖及角膜修补后病情得到控制。若未得到及时有效的治疗，眼部很容易受到外界环境微生物的侵袭，严重者如波及角膜深层则并发感染性眼内炎的风险很高，并且有研究表明角膜植床的血管化程度越严重，排斥反应的发生率越高，移植失败率越高[32-33]。回顾总结该患者出现的排斥情况，可能与角膜病灶缺损较大以及术前存在感染等有关。传统角膜移植手术尚有继发青光眼的可能[34]，但目前尚未见到角膜基质透镜移植继发青光眼的报道，且尚未观察到角膜基质透镜移植术与传统的角膜移植手术发生免疫排斥反应概率的差异。
       尽管角膜基质透镜移植在治疗角膜穿孔和圆锥角膜等眼科疾病中取得了令人鼓舞的结果，但仍具有一定的局限性。例如对于远视及散光等方面的矫正，不是简单地将屈光度叠加，而是涉及角膜生物力学、物理学等多方面的变化，还需要更多研究数据来改进这一方面[35]。因此在行角膜移植之前，要正确认识及处理原发病，尽量避免一些并发症和排斥反应的发生。   
       本文尚存在一些不足。据统计，角膜白斑是行角膜移植术最常见的病种，其次为角膜溃疡等感染性角膜病变[36]。但本文2例患者都是围绕陈旧性粘连性角膜白斑引起的病损来进行探讨，并未观察到角膜透镜移植对于感染性、免疫性等其他原因造成的角膜穿孔的疗效。因此不能盲目进行术式的推广，需要今后更大样本量、更长时间以及更多样化机制的相关研究，以此来更加精确地验证角膜基质透镜移植术的有效性及安全性。
       综上所述，对于角膜穿孔患者而言，角膜移植术是恢复视觉功能以及保持眼球解剖结构完整性的最佳方法。SMILE来源的角膜基质透镜移植术在一定程度上弥补了角膜供体来源不足的现状，是一种比较安全有效的替代方法，但其长期的安全性及有效性仍需更多中心更大样本量的研究验证。

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1、国家自然科学基金(81960181)。
This work was supported by National Natural Science Foundation of China (81960181).This work was supported by National Natural Science Foundation of China (81960181). ( )
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