Role of amniotic membrane transplantation for conjunctival reconstruction in ocular-cicatricial pemphigoid

doi:10.1016/S0161-6420(02)01892-4

Ophthalmology

Volume 110, Issue 3, March 2003, Pages 474-480

Presented in part as a poster at the annual meeting of the Association for Research in Vision and Ophthalmology, Fort Lauderdale, Florida, April 29–May 4, 2001.

https://doi.org/10.1016/S0161-6420(02)01892-4 Get rights and content

Abstract

Purpose

To evaluate the role and the effectiveness over time of amniotic membrane transplantation (AMT) as a first-step procedure to treat conjunctival reconstruction in late-stage ocular-cicatricial pemphigoid (OCP).

Design

Prospective interventional noncomparative case series.

Participants

Nine eyes (9 patients) with advanced OCP.

Methods

Preoperatively, the ocular surface conditions were evaluated by immunohistochemistry of conjunctival biopsy and impression cytology specimens. The amniotic membrane was obtained during cesarean section from women who were 39 weeks pregnant and seronegative for human immunodeficiency virus, hepatitis B and C, and syphilis; it was processed, histologically tested, and stored at −80° C. After scar tissue was removed, the preserved amniotic membrane was placed over the cornea, the bulbar, and tarsal conjunctiva, and was secured with 8-0 Vicryl sutures to the conjunctival edges and the deep fornices with double-armed 6-0 silk sutures. In 2 cases a double layer of amniotic membrane was transplanted. All patients received immunosuppressive systemic therapy and preservative-free tear substitutes and steroids topically for at least 6 months. During follow-up (average, 48 weeks; range, 28–96 weeks), a new standardized method was used to evaluate the fornix depth, and impression cytology testing was performed and conjunctival inflammation recorded and used as parameters for monitoring disease activity.

Main outcome measures

Symblepharon, increased inferior fornix depth, presence of conjunctival goblet cells, and the degree of conjunctival inflammation.

Results

The conjunctival surface was free from symblepharon in all subjects for the first 16 weeks. At the week 28 examination, a small area of symblepharon was present in four eyes (44.4%). The depth of the fornix was significantly (P < 0.0001, analysis of variance) improved at weeks 4, 16, and 28. The normal conjunctival epithelium with goblet cells was restored in 6 of 9 eyes (66.7%) at the week 4 examination and in 4 eyes (44.4%) at the week 28 examination. Conjunctival inflammation was clinically but not statistically reduced. The visual acuity improved in 5 subjects.

Conclusions

AMT can be a first-step procedure for ocular surface reconstruction in OCP, but its effectiveness deteriorates slightly over time.

Section snippets

Patients

We performed conjunctival reconstruction with AMT on 9 eyes of 9 subjects (4 females, 5 males; average age, 72 ± 9.4; range, 56–87 years) with late-stage OCP classified according to the classification of Mondino and Brown1, 3 (Table 1). Consecutive subjects were enrolled from among patients seeking consultation at the Anterior Surface Diseases Center of the Department of Neurologic and Visual Sciences of the University of Genoa and treated from February 1999 through March 2000. The diagnosis of

Results

The patient demographic data are shown in Table 1. At surgery, the subjects were classified according to Mondino and Brown’s classification1, 3 as follows: 1 subject had stage II disease, 5 stage III, and 3 had ankyloblepharon in both eyes and were classified as stage IV (Fig 1). The visual acuity was light perception in 5 subjects (55.5%), and hand motions and 20/200 in two subjects each (22.2%). Symblepharon was observed in all subjects, with entropion in 66.6% of cases. All subjects had

Discussion

Conjunctival reconstruction in late-stage OCP is important but difficult to achieve. In this study we demonstrated the efficacy of AMT in (1) restoring a physiologic conjunctival epithelium, (2) restoring and maintaining the fornix depth, and (3) reducing the ocular surface inflammation from a clinical standpoint. Furthermore, we described the effects of AMT over time: the fornix depth and the conjunctival inflammation had a typical course with maximum improvement occurring after 4 weeks and a

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This result indicates the heterogeneity in mechanical properties of conjunctival epithelial microenvironments and that a relatively soft niche may be favored by resident CjSCs. Various types of substrates, including 2D substrates such as and engineered gelatin membrane as well as 3D matrixes composed of compressed collagen and synthetic polymers have been reported to support ex vivo or in vitro culture of conjunctival epithelial cells [3,15,26,38,74]. However, the expansion of CjSCs has not been well addressed.
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The primary functions of the conjunctiva embody ocular surface protection and the maintenance of the tear film equilibrium. Severe conjunctival defects such as symblepharon may impair the integrity of ocular surface and cause loss of visual functions. Here we report the use of a decellularized porcine conjunctiva (DPC) for conjunctival reconstruction in rabbit models and in clinic. Our results show that the major xenoantigens are efficiently removed, while abundant matrix components and integrated microstructures are well preserved in the DPC. These characteristics provide mechanical support and favorable histocompatibility for repairing damaged conjunctiva. The DPC application has demonstrated enhanced transplant stability and improved epithelial regeneration in severe ocular surface damage comparing to those of amniotic membrane (AM), the most frequently applied matrix for ocular surface reconstruction nowadays. In order to test the DPC performance in clinic, three patients with pterygium and one patient with symblepharon underwent transplant with DPC. The grafts in all cases were completely re-epithelized and no graft melt or fibroplasia were observed. These results suggest that the strategy we developed is feasible and effective for conjunctival reconstruction and ocular surface repair.
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Such limitations necessitate development of efficient alternatives like bioengineered scaffolds that can have stroma-like structure similar to AM, promote epithelialization while not transmitting allogenic-related diseases. The results of animal study of several synthetic materials including collagen-glycosaminoglycan (CG) copolymer [9], poly (lactide-co-glycolide) (PLGA) [8], vitrified collagen [12], and cultured membranes [30,33] have been promising in terms of successful re-epithelialization, decreasing scar formation and fornix foreshortening [13,18,19]. However, they still have limitations like undesirable transparency, elasticity, and thickness [8–10].
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Role of amniotic membrane transplantation for conjunctival reconstruction in ocular-cicatricial pemphigoid☆

Abstract

Purpose

Design

Participants

Methods

Main outcome measures

Results

Conclusions

Section snippets

Patients

Results

Discussion

Ophthalmology

Am J Ophthalmol

Am J Ophthalmol

Lancet

Am J Ophthalmol

Ophthalmology

Ophthalmology

Am J Ophthalmol

Surv Ophthalmol

Ophthalmology

Am J Ophthalmol

Ophthalmology

Am J Ophthalmol

Ophthalmology

Placenta

J Cataract Refract Surg

Cicatricial pemphigoid

Trans Am Ophthalmol Soc

Immunosuppressive therapy for progressive ocular cicatricial pemphigoid

Ophthalmology

Conjunctival goblet cell density in normal subjects and dry eye syndromes

Invest Ophthalmol