Oral mucosal graft for chronic cicatricial conjunctivitis

Systemic immunosuppressants are not required because the graft is autologous.

Thomas John

A healthy ocular surface is of paramount importance in the preservation of vision. Compromised tear function, conjunctival cicatrization and limbal stem cell deficiency can individually or in combination affect the overall health of the ocular surface and have an adverse effect on the level of visual acuity and the quality of vision. When medical measures fail to manage ocular surface disease, surgical intervention may be the only route to restore the ocular surface and preserve vision.

Conditions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, ocular cicatricial pemphigoid and bilateral alkali burn can result in chronic cicatricial conjunctivitis that often progresses to bilateral stem cell deficiency with conjunctival scarring, eyelid abnormalities, keratinization of the ocular surface, adverse corneal effects and dryness of the ocular surface. Because the native tissue is lost or damaged in such disease states, there is a need for alternative tissue to line the ocular surface. A variety of surgical techniques have been described in the literature, including limbal allograft transplantation, ex vivo expansion of human limbal epithelial stem cells and autologous cultivated oral mucosal epithelial transplantation. New directions in the quest for an ideal tissue reconstruction have led to exploration of the potential use of hair follicle-derived stem cells and cell delivery with fixed amniotic membrane.

In this column, Dr. Huang describes the surgical technique of oral mucosal grafting in the treatment of chronic cicatricial conjunctivitis.

Thomas John, MD
OSN Surgical Maneuvers Editor

Keratolimbal allografts can be used to restore the limbal stem cells to promote corneal epithelial differentiation; however, prolonged systemic immunosuppression is needed to prevent rejection of limbal allografts. Unaffected autologous mucosal membrane of oral or nasal origin contains mucin-producing goblet cells. These tissues can be considered an alternative source for conjunctival replacement to resurface the keratinized or scarred bulbar conjunctiva for better ocular surface lubrication or to resurface the tarsal conjunctiva to restore the foreshortened fornix or lid malpositioning.

Surgical technique

A prerequisite for successful autologous mucosal grafting is adequate suppression of the underlying ocular surface inflammation (Figure 1); as such, the procedure is usually unsuccessful during the acute phase of a cicatricial conjunctivitis with active and severe inflammation. Upon adequate control of inflammation, the dense corneal pannus or conjunctival scars can be excised from the ocular surface, and the symblepharon or lid adhesions can be lysed via careful dissection with respect to the tissue plane (Figure 2). If the bulbar conjunctiva appears to be wet and free of keratinization or epidermalization, it can be used to restore the tarsal conjunctiva during fornix reconstruction to minimize the need for ectopic mucosal tissue. After the release of symblepharon and lysis of the adherent conjunctival tissue from the corneal surface, the underlying corneal surface and bulbar sclera are relatively unaffected (Figure 3). Oral mucosal membrane can generally be obtained from the inner lip or buccal surface. Superficial oral mucosa can be ballooned by infiltrating the tissue with 1 mL to 2 mL of 1% Xylocaine (lidocaine HCl, AstraZeneca) with 1:2000 epinephrine to allow easier separation from the submucosal tissues (Figure 4). A thin oral mucosal layer can be dissected manually or with the assistance of a mucotome. Homeostasis of the oral surface can be achieved by placement of strips of petrolatum gauze.

Figure 1. A successful autologous mucosal graft requires adequate suppression of the underlying ocular surface inflammation.

Figure 2. Careful dissection with respect to the tissue plane to excise the dense corneal pannus. Images: Huang AJW, John T

Figure 3. After excision of the ocular surface scar tissue and pannus, the underlying corneal surface and bulbar sclera are relatively unaffected.

Figure 4. Infiltration of the superficial oral mucosa with 1 mL to 2 mL of 1% Xylocaine with 1:2000 epinephrine to allow easier separation from the submucosal tissues.

Figure 5. Fibrin tissue adhesive is used to attach the mucosal graft to the tarsus.

Figure 6. A conformer is placed to maintain the upper and lower fornices.

Figure 7. At 2 weeks postop, the conformer is in place. The cornea has only mild stromal opacity and is devoid of surface scar tissue and pannus.

For fornix reconstruction, the host tarsal conjunctiva is first removed up to the mucocutaneous junction, and any adhesion to the globe is released by blunt dissection. The freshly harvested oral mucosa is placed on the denuded tarsal plate and fibrin tissue adhesive (Tisseel, Baxter) can be used to attach the mucosal graft to the tarsus (Figure 5). Gentle ironing with a muscle hook ensures a flat mucosal surface with proper adhesion. Additional 9-0 monofilament Vicryl sutures can be used to secure the free graft borders to the deep fornix and mucocutaneous junction. A symblepharon ring or conformer is then placed on the ocular surface to maintain the upper and lower fornices (Figure 6). Postoperatively, topical corticosteroids and prophylactic antibiotic ointments are used on the ocular surface as well as the oral donor site. The conformer is usually left in place for 2 to 3 weeks, until the oral mucosal graft heals and adheres properly.

Because the procedure is an autologous graft in nature, systemic immunosuppressants are not required. The tissue, which has a stiffer consistency and is much thicker than typical amniotic membrane, usually heals without significant inflammation. The bare sclera is usually re-epithelialized by the oral mucosa or remaining conjunctiva, with eventual conjunctival ingrowth onto the denuded corneal surface after several months. In general, oral mucosa does not readily assume the flexible conjunctival characteristics and remains more boggy and inflamed than the native conjunctiva (Figure 7). However, it does provide adequate lubrication for the ocular surface or proper tissue strength of the tarsal conjunctiva.

Indications

In contrast to the thin amniotic membrane, oral mucosa tends to be less ideal for the replacement of bulbar conjunctiva. Because oral mucosa remains vascularized and will not support corneal epithelial differentiation, the procedure is primarily indicated for mucosal replacement or fornix reconstruction. While a large surface area of oral mucosa can be obtained, it may not be sufficient to cover extensive ocular surface defect. Combined use of oral mucosa and commercial amniotic membrane can be considered for advanced cicatricial conjunctivitis. Nonetheless, neither tissue will provide limbal stem cells to maintain corneal epithelial lineage. Residual compromised ocular surface due to limbal stem cell deficiency usually needs to be further addressed because the procedure does not provide an adequate source of limbal stem cells.

References:

• Kim JH, Chun YS, Lee SH, et al. Ocular surface reconstruction with autologous nasal mucosa in cicatricial ocular surface disease. Am J Ophthalmol. 2010;149(1):45-53.
• Meyer-Blazejewska EA, Call MK, Yamanaka O, et al. From hair to cornea: toward the therapeutic use of hair follicle-derived stem cells in the treatment of limbal stem cell deficiency. Stem Cells. 2011;29(1):57-66.
• Nakamura T, Takeda K, Inatomi T, Sotozono C, Kinoshita S. Long-term results of autologous cultivated oral mucosal epithelial transplantation in the scar phase of severe ocular surface disorders [published online ahead of print Nov. 19, 2010]. Br J Ophthalmol. doi:10.1136/bjo.2010.188714.
• Nassiri N, Pandya HK, Djalilian AR. Limbal allograft transplantation using fibrin glue. Arch Ophthalmol. 2011;129(2):218-222.
• Shore JW, Foster CS, Westfall CT, Rubin PA. Results of buccal mucosal grafting for patients with medically controlled ocular cicatricial pemphigoid. Ophthalmology. 1992;99(3):383-395.
• Wan P, Wang X, Ma P, et al. Cell delivery with fixed amniotic membrane reconstructs corneal epithelium in rabbits with limbal stem cell deficiency. Invest Ophthalmol Vis Sci. 2011;52(2):724-730.

• Thomas John, MD, is a clinical associate professor at Loyola University at Chicago and is in private practice in Oak Brook, Tinley Park and Oak Lawn, Ill. He can be reached at 708-429-2223; fax: 708-429-2226; email: tjcornea@gmail.com.
• Andrew J.W. Huang, MD, MPH, is a professor of ophthalmology and visual sciences at Washington University School of Medicine in St. Louis. He can be reached at email: huanga@vision.wustl.edu.
• Disclosures: Dr. John has no relevant financial interests. Dr. Huang is a consultant for Allergan but has no relevant financial interests.