Muraine M, Descargues G, Franck O, Villeroy F, Toubeau D, Menguy E, Martin J, Brasseur G
Service d'ophtalmologie, Hôpital Charles Nicolle.
J Fr Ophtalmol. 2001 Oct;24(8):798-812.
Amniotic membrane's unique combination of properties including the facilitation of migration of epithelial cells, the reinforcement of basal cellular adhesion and the encouragement of epithelial differentiation [6] together with its ability to modulate stromal scarring and its anti-inflammatory and anti-bacterial activity has led to its use in the treatment of ocular surface pathology as well as an adjunct to stem cell grafts of the corneal limbus [6-4]. We report a prospective study of 30 patients so treated.
We studied 31 eyes of 30 patients subjected to amniotic membrane grafts between September 1999 and May 2000. There were 25 men and 5 women with an average age of 60.1 (range 25-86) years who were followed for a mean of 7.7 (range 4-11) months. 5 groups (A to D) were observed: A: 6 eyes. Small chronic ulcers without limbal involvement. B: 4 eyes. Ulcers of at least 75% corneal area or occupying 75% of the limbus. C: 9 eyes. Corneal burns. D: 8 eyes. Painful bullous corneal dystrophies unresponsive to other treatment. E: 4 eyes. Symblepharons. Amniotic membrane was placed on the corneal lesion, epithelial surface externally [6, 15], trimmed and sutured with interrupted 10/0 nylon, removed at one month. In two patients (11, 12) inflamed conjunctiva was recessed and amnion sutured to the recessed margin. For the bullous dystrophies we removed all the corneal epithelium and either sutured the amnion to peri-limbal conjunctiva (4 eyes) or to the limbus (4 eyes). For the symblepharons the conjunctiva was dissected to reform the fornix which was lined with amniotic membrane, sutured with 8/0 vicryl. Patients were reviewed regularity.
Group A: All healed within 15 days, in most with dissolution of the amnion over 2-3 months although some persisted, covered with corneal epithelium. An eye with a Descemetocoele and one with a microperforation both healed. Vision improved more than two lines in 4 of 6 eyes. Group B: 2 of 4 eyes healed, one despite detachment of the membrane after 15 days. One eye was salvaged by tarsorrhaphy over a fresh keratoplasty after perforation of a neuroparalytic ulcer on failure of three successive amnion grafts. The final cornea vascularised despite an amnion graft for a meta-herpetic ulcer. Group C: 2 of 9 eyes had limbal damage in one quadrant but 7 had vessels in at least three-quarters of the circumference. One (15) also had a limbal autograft. 3 of 9 eyes healed satisfactorily with more than 2/10 improvement in acuity in each case. 2 showed further neovascularisation despite surface healing. One old chemical burn healed satisfactorily but vascularisation remained 5 eyes failed to heal with lysis of the graft, the patient who had a limbal autograft developed a vascular pannus, and in 4 eyes neovascularisation progressed to cover the entire cornea. Group D: 3 eyes settled with loss of symptoms but in 5 the graft detached within 15 days. All eyes where the membrane had been sutured to the conjunctiva beyond the limbus failed whilst 3 of 4 in which it had been sutured anterior to the limbus succeeded, leaving a persistent whitish membrane under the epithelium. Group E: We were able to reconstruct the cul de sac in 3 out of 4 eyes. In one patient with recurrent pterygium good ocular movement was restored, previously limited by scarring. One with associated ocular surface damage from a thermal burn failed by scarring of the cul de sac a month after surgery.
Our best results were in persistent trophic ulcers of the cornea (Groups A and B) with a success rate of 80%, comparable to those of others [49, 37, 38]. The ready availability of amniotic membrane in our facility makes amniotic membrane transplantation the main secondary treatment for such lesions, especially because of the visual improvement we obtained. Because we did not observe any improvement in corneal thickness after this treatment we advise its early use before significant stromal lysis. The technique was not sufficient to control the effect of corneal anaesthesia in two eyes [40] or in chemical burns suggesting that amniotic membrane alone is insufficient to promote corneal healing in the absence of limbal stem cells. Nevertheless, three eyes did benefit. It has been suggested [13] that the anti-apoptotic function of amnion may prevent stem cell loss in such eyes [42], thus it appears logical to offer an amniotic membrane graft first, before stem cell transplantation, which may entrain complications in the donor eye if autografted [43] or because of the rejection risk of an allograft. It may be that an amniotic membrane graft simply becomes a holding procedure allowing time to settle the eye so as to allow secondary procedures to address the underlying cause of further damage. Our treatment of bullous dystrophy only succeeded on confining the graft to within the limbus, 3 out of 4 eyes becoming comfortable. By contrast we found amniotic membrane helpful in reconstructing symblepharons in the absence of local inflammation.
Amniotic membrane grafting is a simple and straightforward surgical technique which should form part of the therapeutic arsenal for the treatment of ocular surface disease. Indications for the technique need further clarification for it is evident that it cannot correct all secondary pathology associated with limbal destruction. It is certainly preferable to conjunctival advancement and has proved useful in the reconstruction of the cul-de-sac.
羊膜具有独特的特性组合,包括促进上皮细胞迁移、增强基底细胞黏附以及促进上皮分化[6],同时具有调节基质瘢痕形成的能力及其抗炎和抗菌活性,这使其可用于治疗眼表疾病以及作为角膜缘干细胞移植的辅助手段[6-4]。我们报告了一项对30例接受该治疗患者的前瞻性研究。
我们研究了1999年9月至2000年5月间接受羊膜移植的30例患者的31只眼。其中男性25例,女性5例,平均年龄60.1岁(范围25 - 86岁),平均随访7.7个月(范围4 - 11个月)。观察了5组(A至D):A组:6只眼。无角膜缘受累的小慢性溃疡。B组:4只眼。至少累及75%角膜面积或占据75%角膜缘的溃疡。C组:9只眼。角膜烧伤。D组:8只眼。对其他治疗无反应的疼痛性大疱性角膜营养不良。E组:4只眼。睑球粘连。将羊膜置于角膜病变处,上皮面在外[6, 15],修剪后用10/0尼龙线间断缝合,1个月后拆除。在2例患者(11、12)中,将发炎的结膜凹陷,羊膜缝合至凹陷边缘。对于大疱性营养不良,我们切除了所有角膜上皮,将羊膜缝合至角膜缘周围结膜(4只眼)或角膜缘(4只眼)。对于睑球粘连,解剖结膜以重建穹窿,内衬羊膜,用8/0可吸收缝线缝合。定期对患者进行复查。
A组:所有患者在15天内愈合,大多数患者羊膜在2 - 3个月内溶解,尽管有些仍持续存在,但角膜上皮覆盖。1例后弹力层膨出和1例微小穿孔的眼均愈合。6只眼中4只眼视力提高超过两行。B组:4只眼中2只眼愈合,1只眼尽管在15天后羊膜脱离仍愈合。1只眼在连续3次羊膜移植失败后神经麻痹性溃疡穿孔,通过睑裂缝合挽救了眼球。尽管进行了羊膜移植治疗复发性疱疹性溃疡,但最终角膜血管化。C组:9只眼中2只眼在一个象限有角膜缘损伤,但7只眼至少四分之三周长有血管。1只眼(15号)还进行了角膜缘自体移植。9只眼中3只眼愈合良好,每例视力提高超过2/10。2只眼尽管表面愈合但有进一步的新生血管形成。1例陈旧性化学烧伤愈合良好,但仍有血管化。5只眼移植溶解未愈合,进行角膜缘自体移植的患者形成血管翳,4只眼新生血管进展至覆盖整个角膜。D组:3只眼症状消失,但5只眼移植在15天内脱离。所有将羊膜缝合至角膜缘外结膜的眼均失败,而4只中将羊膜缝合至角膜缘前的眼有3只成功,上皮下留下持续的白色膜。E组:4只眼中3只眼成功重建了结膜囊。1例复发性翼状胬肉患者恢复了良好的眼球运动,之前因瘢痕而受限。1例因热烧伤伴有眼表损伤的患者术后1个月因结膜囊瘢痕化失败。
我们在持续性角膜营养性溃疡(A组和B组)中取得了最佳结果,成功率为80%,与其他研究[49, 37, 38]相当。我们机构中羊膜易于获取,这使得羊膜移植成为此类病变的主要二线治疗方法,特别是因为我们获得了视力改善。由于我们在该治疗后未观察到角膜厚度有任何改善,我们建议在显著的基质溶解之前尽早使用。该技术不足以控制2只眼[40]或化学烧伤中的角膜麻醉效果,这表明在没有角膜缘干细胞的情况下,仅羊膜不足以促进角膜愈合。然而,有3只眼确实受益。有人提出[13]羊膜的抗凋亡功能可能会防止此类眼中干细胞的丢失[42],因此在干细胞移植之前先进行羊膜移植似乎是合理的,因为自体移植[43]可能会给供眼带来并发症,或者由于同种异体移植的排斥风险。可能羊膜移植仅仅是一种维持性操作,为眼睛恢复稳定留出时间,以便进行二次手术来解决进一步损伤的根本原因。我们对大疱性营养不良的治疗仅在将移植局限于角膜缘内时成功,4只眼中3只眼症状缓解。相比之下,我们发现羊膜在无局部炎症的情况下有助于重建睑球粘连。
羊膜移植是一种简单直接的手术技术,应成为治疗眼表疾病的治疗手段之一。该技术的适应证需要进一步明确,因为显然它不能纠正与角膜缘破坏相关的所有继发性病变。它肯定比结膜推进术更可取,并且已证明在结膜囊重建中有用。