Significant impact of cryopreserved amniotic membrane on acute ocular Stevens-Johnson syndrome and toxic epidermal necrolysis

来源期刊：眼科学报 | 2016年9月第31卷第3期： 121-123 发布时间：收稿时间：2024/12/2 14:08:56 阅读量：281

作者：: Anny M. S. Cheng,

Scheff er C. G. Tseng,

关键词：

DOI：: doi: 10.3978/j.issn.1000-4432.2016.09.02

收稿时间：: 2016-08-18
修订日期：
接收日期：: 2016-08-18

The ocul a r surf a ce is cove red by an epithe l ium encompassing an area including the cornea, the limbus and the conjunctiva bordered by the upper and lower lids. The healthy state of the ocular surface epithelium depends on a stable and protective preocular tear film when the eye is open. A stable preocular tear film is governed by sound ocular surface defense that involves eff ective neuroanatomic integration of compositional and hydrodynamic factors by two neural reflexes ⁽¹⁾. The compositional elements comprise the lacrimal gland, the meibomian gland, and the ocular surface epithelium to provide aqueous, lipid, and mucins in the tear fluid, respectively, whereas the hydrodynamic element includes effective eyelid-blinkingclosure that also regulates tear evaporation, spread, and drainage ^(1,2). Dysfunction of any elements in the aforementioned neuroanatomic integration will result in ocular surface deficits that compromise the visual acuity.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) together with chemical burns represent the worst insult to the ocular surface that may cause corneal blindness. For some patients with SJS/TEN, early blinding complications might be caused by limbal stem cell deff ciency when the epithelial sloughing and stromal ulceration are widespread. Nevertheless, a significant number of patients gradually develop corneal blindness, of which the extent is correlated with a myriad of progressive ocular cicatricial complications ⁽³⁾. These cicatricial complications manifest as lid margin keratinization, scarring, symblepharon, and foreshortening of the fornix. Depending on the anatomical involvement, they can obstruct excretory ductules of the lacrimal gland, obliterate the tear reservoir, interfere with effective replenishment of tears in the meniscus, and cause inadequate blinking/closure, collectively leading to severe dry eye syndrome. Scarring of the tarsus can lead to eyelid misalignment, meibomian gland orifice metaplasia, keratinization of the mucosal surfaces, collectively leading to blink-related trauma that may cause recurrent and persistent corneal epithelial breakdown ^(3,4). To combat this potential corneal blindness at the chronic stage, results are generally not as effective despite surgical attempts are directed to correct these ocular surface deficits so as to restore ocular surface defense ⁽⁵⁾.

It should be noted that all of the aforementioned cicatricial complications are sequelae of prolonged inflammation and ulceration. Hence, a better way of preventing corneal blindness in SJS/TEN patients is to effectively address inflammation and promote epithelial healing in the acute stage. In this regards, it should be noted that conventional treatments including lubrication, removal of pseudomembranes, mechanical lysis of symblepharon, placement of bandage contact lenses, and administration of topical antibiotics or cycloplegic drops have been ineffective. Recent advances that show promising results are short-term systemic administration of a mega dose of steroid ⁽⁶⁾ and amniotic membrane transplantation (AMT). For the latter, the efficacy has been demonstrated in case reports^(3,7-11), consecutive case series with short-^(12,13) and long-term follow-up ^(14,15).

As shown in a recent report in Ophthalmology, one exciting new progress is made by Gregory⁽¹⁶⁾, who reported a new grading system that grades the extent of ocular surface inflammation and ulceration to guide appropriate treatments including AMT at the acute stage of SJS/TEN. This grading system utilizes fluorescein staining to assess the extent and location of epithelial defects involving cornea, conjunctiva and eye lid. It is advised that such assessment needs to be carried out daily from the first day of hospitalization regardless of the extent of the initial skin involvement. Special attention is given to the hidden areas in the fornices by applying lids retraction as well as separate, discrete sections of bulbar/palpebral conjunctiva. According to this report, this grading system helps subdivide a total of 79 SJS/TEN patients (158 eyes) into mild (24 patients), moderate (17 patients), severe (28 patients), and extremely severe cases (10 patients). Importantly, both mild and moderate cases that did not show corneal staining and had minimal conjunctival and lid epithelial defect maintained the visual acuity of 20/20 without chronic ocular sequelae under conventional medical treatments without AMT. However, both severe and extremely severe cases that presented with corneal epithelial defect and varying extents of conjunctiva/eyelid staining required urgent AMT and adjuvant medical treatment to achieve the visual acuity of 20/20 or >20/25 with minimal or mild/ moderate ocular sequelae. Intriguingly, placement of selfretained cryopreserved amniotic membrane facilitated immediate treatment and resulted in promising outcome if there was less extensive bulbar involvement. Gregory⁽¹⁶⁾ recommends urgent AMT because the sooner AMT is performed, the more effectively it can prevent the chronic scarring sequelae. Furthermore, repetitive AMT may be necessary in severe inflamed eyes as the window of preventive treatment begins to close. It remains unclear how late during the acute stage AMT can still be effective.

The devastating cellular demise in acute SJS/TEN occurs via necrosis which is associated with intense inflammation and apoptosis mediated by cytotoxic T lymphocytes [reviewed in ^(17)]. The advent of AMT to achieve the aforementioned successful visual outcome stems from its anti-inflammatory and anti-scarring effects. A water-soluble matrix, HC-HA/PTX3 complex has been purified and identified from cryopreserved AM as the key component responsible for these AM’s efficacies ^(18-20). HC-HA/PTX3 is formed by tight association between pentraxin 3 (PTX3) and HC-HA complex, which consists of high molecular weight hyaluronic acid (HA) covalently linked to heavy chain 1 (HC1) of inter-α-trypsin inhibitor (IαI) through the catalytic action of tumor necrosis factor-stimulated gene-6. Unlike all conventional antiinflammatory agents such as glucocorticosteroids, nonsteroid anti-inflammatory agents, cyclosporine/tarcolimus, or various humanized antibodies that target at a specific action of one particular type of inflammatory/immune cell, HC-HA/PTX3 exerts a broad anti-inflammatory action by targeting inflammatory/immune cells extending from innate to adaptive immune responses, of which the latter is involved in autoimmune dysregulation ⁽²¹⁾. In fact, HCHA/PTX3’s anti-inflammatory action applies to activate but not resting neutrophils ^(18,22), macrophages ⁽²²⁾, and lymphocytes ⁽¹⁸⁾. HC-HA/PTX3 also exerts a direct antiscarring effect on ocular tissue fibroblasts by suppressing TGF-β signaling, thus potentially preventing cicatricial complications ^(18,21). Besides anti-inflammatory and antiscarring actions, HC-HA/PTX3 also uniquely maintains the phenotype of limbal niche cells so as to support the quiescence of limbal epithelial stem cells, an action crucial for regeneration ^(23,24).

These cumulative pieces of evidence strongly support that AMT should be regarded as a standard of care in the management of acute SJS/TEN to turn around the clinical outcome of an otherwise blinding disease. Consequently, we ophthalmologists should take an active role in partaking in the acute care of these patients together with other medical professionals⁽²⁵⁾.

1、Tseng SC, Tsubota K. Important concepts for treating ocular surface and tear disorders. Am J Ophthalmol 1997;124:825-35.

2、Tseng SC. A practical treatment algorithm for managing ocular surface and tear disorders. Cornea 2011;30 Suppl 1:S8-S14.

3、Di Pascuale MA, Espana EM, Liu DT, et al. Correlation of corneal complications with eyelid cicatricial pathologies in patients with Stevens-Johnson syndrome and toxic epidermal necrolysis syndrome. Ophthalmology 2005;112:904-12.

4、Cher I. Blink-related microtrauma: when the ocular surface harms itself. Clin Exp Ophthalmol 2003;31:183-90.

5、Kohanim S, Palioura S, Saeed HN, et al. Acute and Chronic Ophthalmic Involvement in Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis - A Comprehensive Review and Guide to Therapy. II. Ophthalmic Disease. Ocul Surf 2016;14:168-88.

6、Araki Y, Sotozono C, Inatomi T, et al. Successful treatment of Stevens-Johnson syndrome with steroid pulse therapy at disease onset. Am J Ophthalmol 2009;147:1004-11, 1011.e1.

7、John T, Foulks GN, John ME, et al. Amniotic membrane in the surgical management of acute toxic epidermal necrolysis. Ophthalmology 2002;109:351-60.

8、Kobayashi A, Yoshita T, Sugiyama K, et al. Amniotic membrane transplantation in acute phase of toxic epidermal necrolysis with severe corneal involvement. Ophthalmology 2006;113:126-32.

9、Muqit MM, Ellingham RB, Daniel C. Technique of amniotic membrane transplant dressing in the management of acute Stevens-Johnson syndrome. Br J Ophthalmol 2007;91:1536.

10、Tandon A, Cackett P, Mulvihill A, et al. Amniotic membrane grafting for conjunctival and lid surface disease in the acute phase of toxic epidermal necrolysis. J AAPOS 2007;11:612-3.

11、Shay E, Khadem JJ, Tseng SC. Efff cacy and limitation of sutureless amniotic membrane transplantation for acute toxic epidermal necrolysis. Cornea 2010;29:359-61.

12、Hsu M, Jayaram A, Verner R, et al. Indications and outcomes of amniotic membrane transplantation in the management of acute stevens-johnson syndrome and toxic epidermal necrolysis: a case-control study. Cornea 2012;31:1394-402.

13、Sharma N, Thenarasun SA, Kaur M, et al. Adjuvant Role of Amniotic Membrane Transplantation in Acute Ocular Stevens-Johnson Syndrome: A Randomized Control Trial. Ophthalmology 2016;123:484-91.

14、Shammas MC, Lai EC, Sarkar JS, et al. Management of acute Stevens-Johnson syndrome and toxic epidermal necrolysis utilizing amniotic membrane and topical corticosteroids. Am J Ophthalmol 2010;149:203-213.e2.

15、Gregory DG. Treatment of acute Stevens-Johnson syndrome and toxic epidermal necrolysis using amniotic membrane: a review of 10 consecutive cases. Ophthalmology 2011;118:908-14.

16、Gregory DG. New Grading System and Treatment Guidelines for the Acute Ocular Manifestations of Stevens Johnson Syndrome. Ophthalmology 2016;123:1653-8.

17、Kohanim S, Palioura S, Saeed HN, et al. Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis--A Comprehensive Review and Guide to Therapy. I. Systemic Disease. Ocul Surf 2016;14:2-19.

18、He H, Li W, Tseng DY, et al. Biochemical characterization and function of complexes formed by hyaluronan and the heavy chains of inter-alpha-inhibitor (HC*HA) puriff ed from extracts of human amniotic membrane. J Biol Chem 2009;284:20136-46.

19、Zhang S, He H, Day AJ, et al. Constitutive expression of inter-α-inhibitor (IαI) family proteins and tumor necrosis factor-stimulated gene-6 (TSG-6) by human amniotic membrane epithelial and stromal cells supporting formation of the heavy chain-hyaluronan (HC-HA) complex. J Biol Chem 2012;287:12433-44.

20、Zhang S, Zhu YT, Chen SY, et al. Constitutive expression of pentraxin 3 (PTX3) protein by human amniotic membrane cells leads to formation of the heavy chain (HC)-hyaluronan (HA)-PTX3 complex. J Biol Chem 2014;289:13531-42.

21、He H, Tan Y, Duff ort S, et al. In vivo downregulation of innate and adaptive immune responses in corneal allograft rejection by HC-HA/PTX3 complex purified from amniotic membrane. Invest Ophthalmol Vis Sci 2014;55:1647-56.

22、He H, Zhang S, Tighe S, et al. Immobilized heavy chainhyaluronicacid polarizes lipopolysaccharide-activated macrophages toward M2 phenotype. J Biol Chem 2013;288:25792-803.

23、Tseng SC, He H, Zhang S, et al. Niche Regulation of Limbal Epithelial Stem Cells: Relationship between Inflammation and Regeneration. Ocul Surf 2016;14:100-12.

24、Chen SY, Han B, Zhu YT, et al. HC-HA/PTX3 Puriff ed From Amniotic Membrane Promotes BMP Signaling in Limbal Niche Cells to Maintain Quiescence of Limbal Epithelial Progenitor/Stem Cells. Stem Cells 2015;33:3341-55.

25、Fu Y, Gregory DG, Sippel KC, et al. The ophthalmologist's role in the management of acute Stevens-Johnson syndrome and toxic epidermal necrolysis. Ocul Surf 2010;8:193-203.

其他期刊

眼科学报

主管：中华人民共和国教育部
主办：中山大学
承办：中山大学中山眼科中心
主编：林浩添

主管：中华人民共和国教育部
主办：中山大学

浏览
Eye Science

主管：中华人民共和国教育部
主办：中山大学
承办：中山大学中山眼科中心
主编：林浩添

主管：中华人民共和国教育部
主办：中山大学

浏览

一亿年进化出的晶状体有多重要？

发布于: 2022-12-01