A Novel Technique for Amniotic Membrane Transplantation in Patients with Acute Stevens-Johnson Syndrome

doi:10.1016/j.jtos.2015.07.002

The Ocular Surface

Volume 14, Issue 1, January 2016, Pages 31-36

https://doi.org/10.1016/j.jtos.2015.07.002 Get rights and content

Abstract

Cryopreserved amniotic membrane (AM) transplantation is an emerging technique that is becoming the gold standard for the management of acute Stevens-Johnson syndrome (SJS) and its more severe variant, toxic epidermal necrolysis (TEN). We describe a novel surgical technique utilizing a single, large sheet of AM (5 x 10 cm) and a custom-made forniceal ring, which facilitates AM placement. Our technique is easy to use and minimizes suturing and manipulation of ocular tissues, resulting in decreased operative time. This technique may be applied in the management of multiple ocular surface disease processes, including chemical or thermal burns, severe ocular graft versus host disease (GVHD), and other autoimmune diseases.

Introduction

Stevens-Johnson syndrome (SJS) and its more severe variant, toxic epidermal necrolysis (TEN) present with widespread exfoliation of the skin and mucous membranes, which can lead to significant ocular involvement and morbidity. If acute ocular surface inflammation is not recognized and treated, cicatrization ensues, leading to photophobia, intractable dry eye, chronic pain, corneal scarring, and vision loss.¹ In fact, progressive conjunctival scarring and corneal damage are the most disabling long-term complications for SJS and TEN survivors.2, 3 The incidence is approximately 2-6 cases per million per year, but can be significantly higher in children, at up to 35.5 cases per million per year.4, 5, 6

Cryopreserved amniotic membrane transplantation (AMT) is an emerging technique that is becoming the gold standard in the management of acute SJS/TEN.7, 8 Amniotic membrane (AM) arises from the innermost placental membrane and contains a single layer of epithelial cells that are often nonviable in commercially available AM, a thick basement membrane, and a stroma. The basement membrane supports host epithelial cell migration, adhesion, and differentiation, and it inhibits epithelial cell apoptosis. The stroma is rich in cytokines, growth factors, and protease inhibitors,9, 10 providing AM with anti-inflammatory and antiscarring actions. Thus, AM serves as a biological bandage by suppressing inflammation, promoting epithelialization, and thereby preventing sight-threatening sequelae. AM typically dissolves over a period of 1-2 weeks; thus, more than one application may be necessary during the acute phase of the disease.

It is well understood that early intervention with AM during the acute stage of SJS is beneficial,¹⁰ and there are two current methods of applying AM. The first involves PROKERA® (Bio-Tissue, Doral, FL). This product consists of AM stretched across the lumen of a polycarbonate ring, and it is placed on the eye in a way similar to a contact lens. Its advantages include easy bedside insertion without sedation¹¹ and easy replacement if the membrane melts. However, this device only covers the cornea and surrounding bulbar conjunctiva, leaving the rest of the conjunctiva, fornices, and eyelid margins exposed. The second method involves utilizing multiple, pre-cut 3.5 cm or 5 cm square pieces of cryopreserved AM and suturing or gluing these pieces together on the ocular surface and eyelids.8, 12 The advantage of this technique is complete coverage of the mucosal surface of the eye with AM. The disadvantage is that the technique is time-consuming, requires sedation (especially in children), and allows gaps to form between AM sheets in coverage of the ocular surface.

We describe a novel surgical technique utilizing a single, large sheet of AM (5 x 10 cm) and a custom-made forniceal ring for AMT in ocular SJS. This technique combines the ease of application provided by PROKERA® and the complete ocular surface coverage of the multiple AM sheet technique, while minimizing suturing and manipulation of ocular tissues to decrease operative times significantly. Our technique can be applied in the management of multiple ocular surface disease processes, including chemical or thermal burns, severe ocular graft versus host disease (GVHD), and other autoimmune diseases.

Section snippets

Description of the Technique

Because all the patients in our series were children, the procedure was performed under general anesthesia. First, a custom-made symblepharon ring is fashioned from sterile intravenous (IV) tubing (Ultra™ Small Bore Extension Sets, Reference Number MX453HL, Smiths Medical, Dublin, OH). The size of the ring is tailored to each patient to ensure proper apposition of the AM to ocular surfaces. The distance between the superior and inferior orbital rims is measured, and this distance is used to

Outcome Data

A retrospective chart review of consecutive cases of AMT performed in patients with acute SJS at Boston Children's Hospital (BCH) was conducted with institutional review board approval. Cases were identified through billing records between 2011 and 2015. Nine cases were identified, each performed by one of the two attending physicians who manage SJS patients at BCH, assisted by second-year ophthalmology residents and/or pediatric ophthalmology fellows. The first five cases were performed

Discussion

We present a novel technique of AM transplantation utilizing a single 5 x 10 cm piece of AM. We believe this technique has significant advantages over previously reported methods. First, a single, large piece of AM ensures contiguous coverage of the entire affected ocular surface, including eyelid skin and margins, palpebral, forniceal, and bulbar conjunctiva, and the cornea, which is essential in preventing cicatrization of opposing ocular surfaces. Patients receiving AMT with this novel

Conclusion

This novel surgical technique utilizing a single, large sheet of AM (5 x 10 cm) and a custom-made forniceal ring facilitates AM placement. The technique can be applied not only in the acute and chronic phases of SJS/TEN, but also in the treatment of other ocular surface disease processes requiring AMT.

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Cited by (52)

Ocular Manifestations and Outcomes in Children With Stevens–Johnson Syndrome and Toxic Epidermal Necrolysis: A Comparison With Adult Patients
2023, American Journal of Ophthalmology
To compare the clinical features and visual outcomes in children and adults with Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN).
Retrospective comparative case series.
This retrospective study included 280 eyes of 140 patients (35 children and 105 adults) with SJS/TEN treated between 2010 and 2020. The primary outcome measures were the final best-corrected visual acuity (BCVA) and severity of dry eye. The secondary outcome measure was the medical and surgical therapies used.
Among 64 eyes of children recruited in the study, acute ocular involvement was found in 58 eyes (90.6%). The chronic score in pediatric patients was significantly higher than that in adult patients (P = .004). The use of antibiotics/nonsteroidal anti-inflammatory drugs (NSAIDs) and Mycoplasma infection were the more common etiologies in children. In all, 75% of eyes in children maintained a visual acuity of 20/40 or better at a mean follow-up time of 4.3 years. The severity of dryness was comparable between the child and adult groups. The proportion of eyes undergoing amniotic membrane and oral mucosa transplantation was significantly higher in children than in adults in the chronic stage, reflecting that children exhibit much more severe complications.
Although pediatric SJS/TEN patients have more severe ocular complications than adults, most children maintain long-term good vision. Early intervention and aggressive treatment help to preserve vision.
A cocktail of small molecules maintains the stemness and differentiation potential of conjunctival epithelial cells
2023, Ocular Surface
The conjunctival epithelial cells cultured with bovine serum or feeder cells were not suitable for clinical application. Therefore, we developed a novel serum-free and feeder cell-free culture system containing only a cocktail of three chemicals (3C) to expand the conjunctival epithelial cells.
The cell proliferative ability was evaluated by counting, crystal violet staining and Ki67 immunostaining. Co-staining of K7 and MUC5AC was performed to identify goblet cells. PAS staining was used to assess the ability of cells to synthesis and secrete glycoproteins. In vivo, eye drops containing 3C was administered to verify the role of 3C in the mouse conjunctival injury model. PAS, HE and immunofluorescence staining were performed to show conjunctival epithelial repair.
Compared with other small molecule groups and the serum group, the cells in 3C group showed superior morphology and proliferative ability. Meanwhile, 3C maintained the well-proliferative capacity of cells even after fifth passage. The 3C group also exhibited more K7 and MUC5AC double positive cells, and the PAS staining positive areas were present in both the cytoplasm and extracellular matrix. The cell sheets treated with 3C in air-lifted culture were obviously stratified. In vivo, more goblet cells in the conjunctival epithelium were observed in the 3C group.
Overall, our culture system can expand the conjunctival epithelial cells and retain their potential to differentiate into mature goblet cells, which provided a promising source of seed cells for conjunctival reconstruction. Furthermore, this system provides new insights for the clinical treatment of ocular surface diseases.
Novel technique for amniotic membrane transplantation for acute Stevens-Johnson syndrome/toxic epidermal necrolysis patients
2023, Heliyon
To report a novel technique to facilitate amniotic membrane transplantation (AMT) for acute stage Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN).
Laboratory investigation and retrospective, single-center case series.
The polylactic acid (PLA) amniotic fornical ring (AFR) have been successfully manufactured by three-dimensional (3D) printing technology for AMT. This study retrospectively analyzed the medical records of 5 SJS/TEN patients at the acute stage between 2019 and 2023. Patients were surgically treated with AFR or sutured amniotic membrane transplant (SAMT). Epidemiology, best-corrected visual acuity (BCVA), acute ocular severity score, operative duration, epithelial healing time, amniotic dissolution and follow-up time were evaluated.
Of all five patients, three patients (6 eyes) received AFR/AMT (Group A), and 2 patients (4 eyes) received SAMT (Group B). There were no significant differences between two groups in the mean preoperative days and vision changes. The mean operation duration was 11.7 ± 3.8 mins in group A. Compared with the SAMT (48.8 ± 5.3 mins), the operation duration was reduced by 76.02%. The mean times for epithelial healing were 32.5 ± 29.2 days in group A and 12.0 ± 0.0 days in group B. In addition, there were no significant side effects of 3D-printed sterile AFR on the eyes.
3D-printed PLA scaffolds could be used as an AFR device for acute SJS/TEN. In addition, personalized 3D-printed AFR is superior to conventional SAMT in operation duration.
Modified technique for sutureless amniotic membrane transplantation in acute Stevens-Johnson syndrome using fibrin sealant
2022, Ocular Surface
Analysis of different conditioned media secreted by limbal progenitor cells in the modulation of corneal healing
2022, Experimental Eye Research
Citation Excerpt :
A variety of pathological conditions affecting the ocular surface can partially or totally destroy the limbal repository epithelial SCs, giving rise to what is called a limbal stem cell deficiency (LSCD) (Deng et al., 2019). Among these causes, cicatricial keratoconjunctivitis – such as Stevens-Johnson syndrome, ocular cicatricial pemphigoid, and chemical burn stand out (Mondino and Brown, 1981; Solomon et al., 2002; Ma et al., 2016). The culture and subsequent ex vivo transplantation of limbal epithelial cells has been reported as an alternative source for reconstructing the ocular surface in patients with LSCD, with variable results (Lindberg et al., 1993).
Ex vivo cultivation and transplantation of limbal epithelial cells has been reported as an alternative source for ocular surface reconstruction. However, until now, the functional improvement of these patients is limited due to the low survival rate of the transplanted cells. Consequently, the clinical benefits of this therapeutic strategy are only temporary and can assign them to paracrine effects associated with the transplanted cells. With this background in mind, we aimed to analyze the effect of different conditioned media containing growth factors secreted by limbal progenitor cells on corneal epithelial healing, both in vitro and in vivo. Limbal tissue was used to obtain different conditioned media (CM). For the in vitro assay, corneal epithelial cells were treated with CM and the epithelial migration was analyzed. Growth factors in the CM were identified with ELISA and multiplex. For the in vivo assay in rats, total limbal stem cell deficiency (LSCD) was induced with an abrasive injury to the ocular surface, and the animals were treated with different CM. Clinical and histological analyses were performed. In the in vitro assay, treatment with limbal fibroblast (LF CM) was more effective compared to the other CM, and analysis revealed high concentrations of keratinocyte growth factor (KGF) and hepatocyte growth factor (HGF). In the in vivo assay, animals treated with LF CM showed epithelial defect improvement, maintenance of thickness, and decreased opacity and neovascularization. This treatment also allowed better ocular surface tissue organization when compared to the other treatments. The in vitro and in vivo experiments showed better outcomes in the corneal wound healing for the LF CM treatment. The high concentrations of KGF and HGF, linked to epithelial cell migration and proliferation, may correlate to the best results found in this treatment.
Vulvovaginal and ocular involvement and treatment in female patients with Stevens–Johnson syndrome and toxic epidermal necrolysis: A review
2021, International Journal of Women's Dermatology
Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are serious adverse cutaneous drug reactions, characterized by epidermal detachment and mucous membrane involvement. SJS/TEN is more common in female patients, with unique findings in the ocular and vulvar regions. Early recognition and intervention, as well as long-term follow-up, are crucial to prevent devastating scarring and sequelae. This review examines the vulvar and ocular manifestations of SJS/TEN and describes the current treatment recommendations for female patients, requiring close consultation and collaboration among dermatology, ophthalmology, and gynecology.

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: Financial support: None.

: The authors have no commercial or proprietary interest in any concept or product discussed in this article.

: Single-copy reprint requests to: Iason S. Mantagos, MD (address below).

^∗: Drs. Ma and Thanos contributed equally to this work.

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Innovative Techniques and TechnologyA Novel Technique for Amniotic Membrane Transplantation in Patients with Acute Stevens-Johnson Syndrome

Abstract

Introduction

Section snippets

Description of the Technique

Outcome Data

Discussion

Conclusion

Am J Ophthalmol

Am J Ophthalmol

J Clin Epidemiol

Ophthalmology

Ophthalmology

Surv Ophthalmol

Innovative Techniques and Technology
A Novel Technique for Amniotic Membrane Transplantation in Patients with Acute Stevens-Johnson Syndrome