角膜知觉重建的分类与研究进展

doi:10.3969/j.issn.1674-8115.2022.04.016

上海交通大学学报（医学版） ›› 2022, Vol. 42 ›› Issue (4): 528-534.doi: 10.3969/j.issn.1674-8115.2022.04.016

角膜知觉重建的分类与研究进展

吴越¹^,²(), 张嘉莹¹^,², 王炜³(), 李瑾¹^,²()

^1.上海交通大学医学院附属第九人民医院眼科，上海 200011
^2.上海市眼眶病眼肿瘤重点实验室，上海 200011
^3.上海交通大学医学院附属第九人民医院整复外科，上海 200011

收稿日期:2021-10-26 接受日期:2022-04-19 出版日期:2022-04-28 发布日期:2022-04-28
通讯作者: 王炜,李瑾 E-mail:15800762292@163.com;13818054492@163.com;abcd1971206@126.com
作者简介:吴越（1995—），女，博士生；电子信箱：15800762292@163.com。
基金资助:
国家自然科学基金(81870688);上海交通大学医学院附属第九人民医院临床研究助推计划(JYLJ201818)

Classification and research progress of corneal neurotization

WU Yue¹^,²(), ZHANG Jiaying¹^,², WANG Wei³(), LI Jin¹^,²()

^1.Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
^2.Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai 200011, China
^3.Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China

Received:2021-10-26 Accepted:2022-04-19 Online:2022-04-28 Published:2022-04-28
Contact: WANG Wei,LI Jin E-mail:15800762292@163.com;13818054492@163.com;abcd1971206@126.com
Supported by:
National Natural Science Foundation of China(81870688);Clinical Research Program of Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine(JYLJ201818)

摘要/Abstract

摘要：

角膜神经来自三叉神经眼支，主要支配角膜的知觉。三叉神经至眼表的任一节段受损，均有可能导致角膜神经损伤，并可引起角膜知觉减退或缺失。神经营养不良性角膜病变即是因三叉神经损伤继而角膜神经的感觉及营养功能受损所致，主要表现为角膜知觉下降或缺失，并可导致角膜上皮缺损、溃疡或者穿孔。然而，神经营养不良性角膜病变发病早期多仅表现为角膜知觉的轻度下降及泪膜的不稳定，因此在临床上较为隐匿；同时，关于促进角膜神经的修复与再生、恢复角膜知觉的临床处理方法通常也较为单一。目前，药物治疗、非手术干预、手术重建是治疗神经营养不良性角膜病变从而促进角膜神经及知觉恢复的治疗方法。其中，药物治疗的主要目的为抗感染及抗炎，同时维持眼表环境稳定，防止角膜进一步损伤。目前，一些新型生物制剂也正在研发及临床试验中，包括富血小板血浆、自体血清及重组人神经生长因子等。非手术干预的主要目的即减少角膜暴露以保护角膜，通常包含治疗性接触镜及医用胶带、肉毒素注射等多种使眼睑下垂遮盖角膜的治疗方式。关于手术重建，除了常规的各类以修复角膜缺损、减少暴露面积为目的的传统术式之外，还包括角膜神经移植术这一定位于改善角膜知觉及角膜神经支配的新术式，其对于由于三叉神经损伤导致角膜上皮下神经纤维缺失的患者来说，是一种较为理想的手术方式。药物治疗、非手术干预、手术重建在临床应用中并不是割裂的。该文总结了以上3类治疗手段的应用进展，以期为未来临床上根据疾病发展的进程及不同的严重程度选择合适的治疗方式、实现角膜知觉的综合性重建提供参考。

关键词: 角膜营养不良, 三叉神经疾病, 神经移植, 神经再生

Abstract:

The corneal nerve originates from the trigeminal nerve, which mainly innervates the corneal sensation. Therefore, corneal nerve injury and decrease of corneal sensation occur when the trigeminal nerve is damaged. Neurotrophic keratopathy (NK) is a disease related with alterations in corneal nerves, leading to corneal epithelial defects, ulcer and perforation. However, mild NK is mostly manifested as a slight decrease in corneal sensation and instability of the tear film, so it is quite insidious in clinical practice. At the same time, the clinical treatment methods for promoting corneal reinnervation and restoring corneal sensation are usually relatively simple. Currently, medical treatment, non-surgical interventions and surgical interventions are the treatments for NK thus promoting corneal nerve and sensation recovery. In addition to maintaining the stability of the ocular surface, the main purpose of medical treatment is anti-infection and anti-inflammation, and to prevent further damage to the cornea. Novel biological agents are also under clinical trials such as platelet-rich plasma, autologous serum and recombinant human nerve growth factor. Non-surgical intervention which mainly includes therapeutic contact lenses, medical tape and botulinum toxin injections aims to reduce corneal exposure and protect the cornea. With regard to surgical interventions, in addition to the conventional procedures aimed at repairing corneal defects and reducing the exposed area, there is also a new procedure called corneal nerve transplantation, which is aimed at improving corneal sensation and corneal innervation. Corneal nerve transplantation is a new surgical method that is directly targeted at improving corneal sensation and innervation. It is an ideal surgical method for patients with loss of corneal subbasal nerve fibers due to trigeminal nerve injury. In conclusion, medical treatment, non-surgical intervention and surgical neurotization are not separated in clinical practice. This article summarizes the progress of the application of the above three types of treatments in order to provide a reference for the future clinical selection of appropriate treatment modalities and comprehensive reconstruction of corneal sensation according to the course and different severity of disease development.

Key words: corneal dystrophy, trigeminal nerve disease, nerve transplantation, nerve regeneration

中图分类号:

R772.2

吴越, 张嘉莹, 王炜, 李瑾. 角膜知觉重建的分类与研究进展[J]. 上海交通大学学报（医学版）, 2022, 42(4): 528-534.

WU Yue, ZHANG Jiaying, WANG Wei, LI Jin. Classification and research progress of corneal neurotization[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2022, 42(4): 528-534.

图/表 2

图1 现已有报道的各种角膜神经移植术式示意Note：A. The sural nerve was side-to-end coapted to the supratrochlear nerve in unilateral cases. B. The sural nerve was end-to-end coapted to the supratrochlear nerve in unilateral cases. C. The sural nerve was end-to-end coapted to the supraorbital nerve in unilateral cases. D. The sural nerve was end-to-end coapted to the infraorbital nerve in unilateral cases. E. The sural nerve was respectively coapted to bilateral supratrochlear nerves in bilateral cases. F. The sural nerve was coapted to the supratrochlear nerve in bilateral cases. G. Direct nerve transplantation using the supraorbital nerve and supratrochlear nerve on the healthy side. H. Direct nerve transplantation using the supraorbital nerve on the affected side. I. Direct nerve transplantation using the infraorbital nerve on the affected side. The images were requested and licensed online at the British Journal of Ophthalmology website on December 11, 2021.

Fig 1 Corneal neurotization techniques that have been reported and described

图2 微创型角膜知觉重建手术示意图Note：A. Separate and label the supratrochlear nerve and supraorbital nerve on the contralateral side. B. End-to-end anastomosis of sural nerve with supratrochlear nerve and supraorbital nerve. C. Separate nerve graft into four branches. D. Four branches of nerve graft were sutured around the limbus.

Fig 2 Surgical procedures of minimally invasive corneal neurotization

参考文献 54

1	DUA H S, SAID D G, MESSMER E M, et al. Neurotrophic keratopathy[J]. Prog Retin Eye Res, 2018, 66: 107-131.
2	BONINI S, RAMA P, OLZI D, et al. Neurotrophic keratitis[J]. Eye, 2003, 17(8): 989-995.
3	LAUNAY P S, GODEFROY D, KHABOU H, et al. Combined 3DISCO clearing method, retrograde tracer and ultramicroscopy to map corneal neurons in a whole adult mouse trigeminal ganglion[J]. Exp Eye Res, 2015, 139: 136-143.
4	LABETOULLE M, BAUDOUIN C, CALONGE M, et al. Role of corneal nerves in ocular surface homeostasis and disease[J]. Acta Ophthalmol, 2019, 97(2): 137-145.
5	AL-AQABA M A, DHILLON V K, MOHAMMED I, et al. Corneal nerves in health and disease[J]. Prog Retin Eye Res, 2019, 73: 100762.
6	DHILLON V K, ELALFY M S, AL-AQABA M, et al. Corneal hypoesthesia with normal sub-basal nerve density following surgery for trigeminal neuralgia[J]. Acta Ophthalmol, 2016, 94(1): e6-e10.
7	SACCHETTI M, LAMBIASE A. Diagnosis and management of neurotrophic keratitis[J]. Clin Ophthalmol, 2014, 8: 571-579.
8	LOCKWOOD A, HOPE-ROSS M, CHELL P. Neurotrophic keratopathy and diabetes mellitus[J]. Eye (Lond), 2006, 20(7): 837-839.
9	LUM E, MURPHY P J. Effects of ambient humidity on the cochet-bonnet aesthesiometer[J]. Eye (Lond), 2018, 32(10): 1644-1651.
10	ZHANG J Y, ZHAO Z L, SHAO C Y, et al. Degeneration of corneal sensation and innervation in patients with facial paralysis: a cross-sectional study using in vivo confocal microscopy[J]. Curr Eye Res, 2019, 44(11): 1209-1215.
11	KUGADAS A, GADJEVA M. Impact of microbiome on ocular health[J]. Ocul Surf, 2016, 14(3): 342-349.
12	NIWANO Y, IWASAWA A, AYAKI M. Ocular surface cytotoxicity and safety evaluation of tafluprost, a recently developed anti-glaucoma prostaglandin analog[J]. Ophthalmol Eye Dis, 2014, 6: 5-12.
13	GEERLING G, TAUBER J, BAUDOUIN C, et al. The international workshop on meibomian gland dysfunction: report of the subcommittee on management and treatment of meibomian gland dysfunction[J]. Invest Ophthalmol Vis Sci, 2011, 52(4): 2050-2064.
14	HOY S M. Ciclosporin ophthalmic emulsion 0.1%: a review in severe dry eye disease[J]. Drugs, 2017, 77(17): 1909-1916.
15	MIYAZAKI D, FUKUSHIMA A, OHASHI Y, et al. Steroid-sparing effect of 0.1% tacrolimus eye drop for treatment of shield ulcer and corneal epitheliopathy in refractory allergic ocular diseases[J]. Ophthalmology, 2017, 124(3): 287-294.
16	KOH K, JUN I, KIM T I, et al. Long-term results of topical 0.02% tacrolimus ointment for refractory ocular surface inflammation in pediatric patients[J]. BMC Ophthalmol, 2021, 21(1): 247.
17	PELLEGRINI M, SENNI C, BERNABEI F, et al. The role of nutrition and nutritional supplements in ocular surface diseases[J]. Nutrients, 2020, 12(4): 952.
18	GOMES J A P, AZAR D T, BAUDOUIN C, et al. TFOS DEWS Ⅱ iatrogenic report[J]. Ocul Surf, 2017, 15(3): 511-538.
19	SHTEIN R M, SHEN J F, KUO A N, et al. Autologous serum-based eye drops for treatment of ocular surface disease: a report by the American academy of ophthalmology[J]. Ophthalmology, 2020, 127(1): 128-133.
20	MANSOOR H, TAN H C, LIN M T Y, et al. Diabetic corneal neuropathy[J]. J Clin Med, 2020, 9(12): 3956.
21	HAHN J N, KAUSHIK D K, MISHRA M K, et al. Impact of minocycline on extracellular matrix metalloproteinase inducer, a factor implicated in multiple sclerosis immunopathogenesis[J]. J Immunol, 2016, 197(10): 3850-3860.
22	SOLEIMANI M, NADERAN M. Management strategies of ocular chemical burns: current perspectives[J]. Clin Ophthalmol, 2020, 14: 2687-2699.
23	DEEKS E D, LAMB Y N. Cenegermin: a review in neurotrophic keratitis[J]. Drugs, 2020, 80(5): 489-494.
24	CHAN C C, PROKOPICH C L. Lifitegrast ophthalmic solution 5.0% for treatment of dry eye disease: overview of clinical trial program[J]. J Pharm Pharm Sci, 2019, 22(1): 49-56.
25	SOSNE G, RIMMER D, KLEINMAN H K, et al. Thymosin β 4: a potential novel therapy for neurotrophic keratopathy, dry eye, and ocular surface diseases[J]. Vitam Horm, 2016, 102: 277-306.
26	PFLUGFELDER S C, MASSARO-GIORDANO M, PEREZ V L, et al. Topical recombinant human nerve growth factor (cenegermin) for neurotrophic keratopathy: a multicenter randomized vehicle-controlled pivotal trial[J]. Ophthalmology, 2020, 127(1): 14-26.
27	FERRARI M P, MANTELLI F, SACCHETTI M, et al. Safety and pharmacokinetics of escalating doses of human recombinant nerve growth factor eye drops in a double-masked, randomized clinical trial[J]. BioDrugs, 2014, 28(3): 275-283.
28	BONINI S, LAMBIASE A, RAMA P, et al. Phase Ⅰ trial of recombinant human nerve growth factor for neurotrophic keratitis[J]. Ophthalmology, 2018, 125(9): 1468-1471.
29	BONINI S, LAMBIASE A, RAMA P, et al. Phase Ⅱ randomized, double-masked, vehicle-controlled trial of recombinant human nerve growth factor for neurotrophic keratitis[J]. Ophthalmology, 2018, 125(9): 1332-1343.
30	RIESTRA A C, ALONSO-HERREROS J M, MERAYO-LLOVES J. Platelet rich plasma in ocular surface[J]. Arch Soc Esp Oftalmol, 2016, 91(10): 475-490.
31	GIANNACCARE G, VERSURA P, BUZZI M, et al. Blood derived eye drops for the treatment of cornea and ocular surface diseases[J]. Transfus Apher Sci, 2017, 56(4): 595-604.
32	SONI N G, JENG B H. Blood-derived topical therapy for ocular surface diseases[J]. Br J Ophthalmol, 2016, 100(1): 22-27.
33	ALIO J L, RODRIGUEZ A E, ABDELGHANY A A, et al. Autologous platelet-rich plasma eye drops for the treatment of post-LASIK chronic ocular surface syndrome[J]. J Ophthalmol, 2017, 2017: 2457620.
34	WU X D, MA Y J, CHEN X, et al. Efficacy of bandage contact lens for the management of dry eye disease after cataract surgery[J]. Int Ophthalmol, 2021, 41(4): 1403-1413.
35	WABBELS B. Botulinum toxin-new developments in ophthalmology[J]. Klin Monbl Augenheilkd, 2018, 235(6): 721-724.
36	ERVIN A M, LAW A, PUCKER A D. Punctal occlusion for dry eye syndrome[J]. Cochrane Database Syst Rev, 2017, 6(6): CD006775.
37	TONG L, ZHOU L, BEUERMAN R, et al. Effects of punctal occlusion on global tear proteins in patients with dry eye[J]. Ocul Surf, 2017, 15(4): 736-741.
38	KIM B M, OSMANOVIC S S, EDWARD D P. Pyogenic granulomas after silicone punctal plugs: a clinical and histopathologic study[J]. Am J Ophthalmol, 2005, 139(4): 678-684.
39	CHI J J. Management of the eye in facial paralysis[J]. Facial Plast Surg Clin North Am, 2016, 24(1): 21-28.
40	KHOKHAR S, NATUNG T, SONY P, et al. Amniotic membrane transplantation in refractory neurotrophic corneal ulcers: a randomized, controlled clinical trial[J]. Cornea, 2005, 24(6): 654-660.
41	MANTELLI F, NARDELLA C, TIBERI E, et al. Congenital corneal anesthesia and neurotrophic keratitis: diagnosis and management[J]. Biomed Res Int, 2015, 2015: 805876.
42	GUHAN S, PENG S L, JANBATIAN H, et al. Surgical adhesives in ophthalmology: history and current trends[J]. Br J Ophthalmol, 2018, 102(10): 1328-1335.
43	ZEMBA M, STAMATE AC, TATARU C P, et al. Conjunctival flap surgery in the management of ocular surface disease (Review)[J]. Exp Ther Med, 2020, 20(4): 3412-3416.
44	DUA H S, OTRI A M, SAID D G, et al. The 'up-down' sign of acute ocular surface drug toxicity[J]. Br J Ophthalmol, 2012, 96(11): 1439-1440.
45	JONAS J B, RANK R M, BUDDE W M. Tectonic sclerokeratoplasty and tectonic penetrating keratoplasty as treatment for perforated or predescemetal corneal ulcers[J]. Am J Ophthalmol, 2001, 132(1): 14-18.
46	SAMII M. Modern aspects of peripheral and cranial nerve surgery//KRAYENBÜHL H, BRIHAYE J, LOEW F, et al. Advances and technical standards in neurosurgery[M]. Vienna: Spinger, 1975: 33-85.
47	SAMII M. Reconstruction of the trigeminal nerve//SAMII M, JANNETTA P J.The cranial nerves[M]. Berlin: Springer, 1981: 352-358.
48	TERZIS J K, DRYER M M, BODNER B I. Corneal neurotization: a novel solution to neurotrophic keratopathy[J]. Plast Reconstr Surg, 2009, 123(1): 112-120.
49	ELBAZ U, BAINS R, ZUKER R M, et al. Restoration of corneal sensation with regional nerve transfers and nerve grafts: a new approach to a difficult problem[J]. JAMA Ophthalmol, 2014, 132(11): 1289-1295.
50	BAINS RD, ELBAZ U, ZUKER R M, et al. Corneal neurotization from the supratrochlear nerve with sural nerve grafts: a minimally invasive approach[J]. Plast Reconstr Surg, 2015, 135(2): 397e-400e.
51	BIGLIOLI F. Facial reanimations: part Ⅰ: recent paralyses[J]. Br J Oral Maxillofac Surg, 2015, 53(10): 901-906.
52	JACINTO F, ESPANA E, PADILLA M, et al. Ipsilateral supraorbital nerve transfer in a case of recalcitrant neurotrophic keratopathy with an intact ipsilateral frontal nerve: a novel surgical technique[J]. Am J Ophthalmol Case Rep, 2016, 4: 14-17.
53	MALHOTRA R, ELALFY M S, KANNAN R B, et al. Update on corneal neurotisation[J]. Br J Ophthalmol, 2019, 103(1): 26-35.
54	CATAPANO J, FUNG S S M, HALLIDAY W, et al. Treatment of neurotrophic keratopathy with minimally invasive corneal neurotisation: long-term clinical outcomes and evidence of corneal reinnervation[J]. Br J Ophthalmol, 2019, 103(12): 1724-1731.

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角膜知觉重建的分类与研究进展

Classification and research progress of corneal neurotization

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