Modified tectonic keratoplasty with minimal corneal graft for corneal perforation in severe Stevens - Johnson syndrome: a case series study
© Wang et al.; licensee BioMed Central Ltd. 2014
Received: 24 January 2014
Accepted: 22 July 2014
Published: 8 August 2014
Corneal perforation in severe Stevens-Johnson syndrome (SJS) presenting great therapeutic difficulties, the imperative corneal transplantation always result in graft failure and repeated recurrence of perforation. The aim of this study was to evaluate the effectiveness of a modified small tectonic keratoplasty (MSTK) with minimal corneal graft in the management of refractory corneal perforation in severe SJS.
Refractory corneal perforations in ten patients (10 eyes) with severe SJS were mended with a minimal corneal patch graft, under the guidance of anterior chamber optical coherence tomography, combined with conjunctival flap covering. The outcome measures included healing of the corneal perforation, survival of the corneal graft and conjunctival flap, relevant complications, and improvement in visual acuity.
Corneal perforation healed, and global integrity was achieved in all eyes. No immune rejection or graft melting was detected. Retraction of conjunctival flap occurred in one eye, which was treated with additional procedure. Visual acuity improved in six eyes (60%), unchanged in three eyes (30%) and declined in one eye (10%).
The MSTK combined with conjunctival flap covering seems to be effective for refractory corneal perforation in severe SJS.
KeywordsCorneal transplantation Corneal perforation Stevens-Johnson syndrome Conjunctival flap
Severe Stevens-Johnson syndrome (SJS) usually affects the eyes with extensive area of necrosis of the ocular surface, which could result in corneal ulcer or even perforation [1–3]. Because of severe dry eye, limbal stem cell deficiency, persistent inflammation, trichiasis and symblepharon that result from the ocular surface cicatrization [4, 5], corneal perforation in these patients is usually refractory. Amniotic membrane transplantation (AMT), conjunctival flaps, and bandage contact lens seems does not work well [6–8]. In most cases, corneal transplantation has to be resort to for tectonic reasons.
Orthotopic corneal transplantation is commonly used in treating corneal perforation. But in eyes with severe ocular surface disorders, persistent epithelial defects can lead to graft melting, repeated recurrence of perforation or even loss of vision . Even though temporary success can be achieved in a few cases, long-term immunosuppressive drug administration has to be dependent on, and the graft still faces the risk of failure and other post-operative complications following orthotopic penetrating keratoplasty [1, 10]. Hence, preservation of the globe is the main objective of corneal transplantation for severe SJS, and visual rehabilitation becomes an important but secondary objective.
Small corneal graft has been successfully used in treating peripheral corneal perforations as it faces less risks of graft failure [11–14]. Portnoy et al. mentioned in a review that an appropriate size corneal graft could be used to patch the corneal lesions, and then the graft was covered with a conjunctival flap. But no details of the technique was described, and the long-term results were uncertain . In severe dry eye, small grafts still face the challenge of melting and recurrence of corneal perforation . To further facilitate survival of small corneal graft so that it could be successfully applied to the management of corneal perforation in eyes with severe SJS, we contrived to minimize the size of corneal graft and a conjunctival flap was used in a combined procedure. We report here our first experience in a small series of cases.
The study was approved by the Institutional Review Board of Shandong Eye Hospital and was conducted in accordance with the principles of the Declaration of Helsinki. Possible benefits and risks were explained to all patients, and informed consent was obtained.
The medical records of ten patients (10 eyes), with refractory corneal perforations resulting from severe SJS, who were treated with modified small tectonic keratoplasty (MSTK) combined with conjunctival flap covering were retrospectively reviewed. All the perforations were conducted at Shandong Eye Hospital of Shandong Eye Institute between July 2008 and June 2011. The diagnosis of SJS was mainly based on a history of severe inflammation of the oral, dermal, and tracheal mucous membranes after taking medicine or having an infection . Corneal perforations were confirmed by fluorescent stream tests. The size of corneal perforations and the surrounding corneal lesions was measured by slit-lamp microscopy or high-definition optical coherence tomography (HD-OCT, Carl Zeiss AG, Dublin, USA). All eyes underwent corneal scraping with care under a surgical microscope and topical anesthesia. The biopsy specimens were gram stained and examined under a microscope for possible bacterial and fungal infections. As aqueous leakage could disturb the results of the Schirmer test, it was performed on the fellow eye in all patients. Localization of corneal perforation, synechiae, flat anterior chamber, and visual acuity before surgery were also recorded.
All the patients were immediately administered with ofloxacin eyedrops (Santen, Osaka, Japan) twice per hour at the first presentation. Combined MSTK and conjunctival flap covering was performed within 24 hours. The resected tissues were subjected for etiological examination.
Patient demographics, pre- and postoperative data, and follow-up
Schirmer test (mm)
Localization of ulcer
Activity of SJS
Prior corneal surgical procedures (times)
AMT(2), CP (1)
AMT(1), CP (1)
AMT(1), LK (3)
LK (2), PK (1)
Size of corneal lesion (mm)
4.0 × 5.5
6.0 × 7.5
4.5 × 7.0
4.5 × 5.75
5.0 × 6.0
3.5 × 5.0
3.0 × 5.5
3.5 × 5.75
4.0 × 6.5
3.25 × 4.0
Size of perforation (mm)
Size of corneal graft (mm)
Preoperative IOP (mmHg)
Final IOP (mmHg)
The bulbar conjunctiva near corneal lesions with good elasticity and rich blood vessels was selected as the donor site of conjunctival flap. After subconjunctival injection of 0.5 to 1 mL of 2% lidocaine hydrochloride, a double pedicle conjunctival flap, 1 mm wider than the corneal lesion, was obtained 2 mm away from the limbus (Figure 2E and E’). A thin fascia under the conjunctival flap was preserved to avoid injury to conjunctival vessels during separation. Meanwhile, the preserved fascia may also promote tight adhesion of the conjunctival flap to corneal lesions. The conjunctival flap was fully separated toward both ends until it could be pulled to the corneal lesions without tension, and the eyeball could move freely towards all directions. Finally, the conjunctival flap was rotated to cover the entire corneal lesions. A 10–0 monofilament nylon suture was used to secure the flap with a certain tension (Figure 2F and F’). Any effusion beneath the conjunctival flap should be drive out with a muscle hook so that the flap could closely attach to corneal lesions.
Postoperative treatment and follow-up
Postoperatively, all patients were given intravenous hydrocortisone (2 mg/kg) daily for 3 days. TobraDex eyedrops (Alcon, Fort Worth, TX) and 1% cyclosporine A (North China Pharmaceutical Group, Shijiazhuang, China) were administered four times daily for the first month and tapered thereafter. Preservative-free artificial tears were administered 6 ~ 8 times daily according to the ocular surface conditions.
The patients were followed up weekly for 4 weeks and monthly or bimonthly thereafter. Visual acuity, slit lamp appearance, and intraocular pressure (IOP) were evaluated. All complications were recorded and disposed. Surgical success was defined as healing of the ulcer and perforation, and survival of the conjunctival and corneal grafts. Failure was defined as corneal graft melting, recurrence of an ulcer or perforation in the original position.
SPSS 16.0 was used for statistical analysis. The change in BCVA was analyzed using the Wilcoxon signed-rank test. P values of less than 0.05 were considered statistically significant.
The mean follow-up period was 21.1 ± 11.8 (SD) months (range, 6 to 38 months). Corneal perforations were healed, and the integrity of the globes was restored in all patients (Table 1). No pathogens were detected in any of the corneal scrapings for bacterial and fungal culture.
The conjunctival flap showed good adhesion to corneal lesions in 9 patients (patients 1–5, 7–10) during the follow-up period. A progressive regression of conjunctival flap was observed at 1 month after surgery, and the conjunctival flap became semi-transparent when healing of the corneal lesions was completed (Figure 3B). In one patient (patient 6), the conjunctival flap slipped off the corneal lesion and was difficult to be reset to the corneal surface because of poor flexibility associated with an anamnesis of ocular alkali burn. To promote corneal epithelial repair and prevent corneal graft autolysis, conjunctival flap resuture combined with tarsorrhaphy was performed. The corneal lesions were then healed completely.
Visual outcomes and IOP
Visual acuity was improved in 6 eyes (60%), unchanged in 3 eyes (30%), and declined in one eye (10%) at the final follow-up. There was a significant difference between the preoperative and postoperative visual acuities (P = 0.043). The IOP of all the patients was within the normal range throughout the study period.
Because of prolonged ocular surface morbidities, corneal perforations in severe SJS still face great challenge of recurrence, and the final visual function is always pessimistic. In this series of 10 patients, the corneal perforations were successfully repaired with MSTK and conjunctival flap in 9 patients. Tarsorrhaphy was required for remedial reason in one patient with conjunctival flap failure to adhere to the corneal lesion. All corneal grafts remained stable during the follow-up of no less than 1 year, and improved vision was acquired in more than 50% of the cases.
Efficacy of AMT in treating small corneal perforation has been well established but unable to promote corneal stability in patients with severe corneal thinning . Also, because the amniotic membrane cannot control corneal melting effectively in dry eyes , it does not seem to work well in patients with SJS [6, 10], which was further confirmed in 6 patients in this study. Conjunctival flaps could be used for small eccentric corneal perforations , but could not seal large corneal perforations associated with corneal melting because the leap would continue under the flap [19, 20]. Things were the same for 7 patients in this study. Tissue adhesives are effective for corneal perforations in a diameter of less than 2 mm but not for those chronic, deep ulcers, and the toxicity may worsen inflammatory reaction .
Traditional orthotopic PK, using a large-diameter graft, could achieve comparable anatomical and functional success in treating corneal perforation. But in patients with severe SJS, the corneal grafts are facing high risk of immune rejection, persistent epithelial defection, infection, graft melting, and resultant recurrence of corneal perforation . Tugal-Tutkun et al. reported PK, with grafts of 7.5 mm to 14 mm, for cicatrizing conjunctival diseases in 13 eyes, among which three out of four grafts in patients with SJS failed and required additional procedures . Theoretically, the smaller the size of a corneal graft, the greater is the chance of its survival. Soong et al. reported 3 cases of fistulous wound leaks after cataract surgery successfully treated with small diameter corneal grafts for tectonic reasons . Similar procedures were performed by Chern in treating various peripheral corneal disorders with small-diameter, round, eccentric PK . We previously modified this technique by preserving the deep stroma, Descemet’s membrane, and the endothelium of the corneal bed as much as possible, so that glycerin-cryopreserved grafts could be used with ultimate transparency . But all the corneal grafts used in the reported cases had the same size as corneal lesions, and all the eyes had a relative fertile ocular surface. The single case with ocular surface disorder reported by Chern et al. developed epithelial keratopathy and required further treatment . In this study, two patients had been treated with repeated small corneal graft transplantation, but both failed in graft melting and recurrence of corneal lesions. Therefore, small corneal grafts in patients with severe ocular disorders still risk graft failure.Corneal perforations in SJS are usually developed from corneal melting, and there is commonly an irregular corneal lesion, much larger than corneal perforation, which is usually apparent on HD-OCT examination (Figure 1A). If corneal grafts are prepared according to the corneal ulcer, certainly much larger than the perforation, the risk of graft failure would inevitably increase. In view of the characteristics of corneal perforation in SJS, we hypothesized that the diameter of corneal graft could be further reduced just to repair the perforation. In our experience, grafts can be well sutured as long as the thickness of the edge of the recipient bed is more than two-thirds of the cornea. Hence, instead of trying to cover the entire ulcer, we selected a trephine according to the shortest path through the central ulcer in which the remaining stromal thickness was more than two-thirds of the cornea (Figure 1B and C). In this study, all the 10 corneal grafts were successfully transplanted to the recipients, which indicate the feasibility of corneal transplantation with a reduced-size corneal graft.
Due to the fact that the corneal graft was much smaller than the ulcer, a ‘ditch’ was left around the graft (Figure 1C*). The epithelium of the recipient was expected to step across the ditch to cover the graft, which was a difficult task in the eye with severe ocular surface disorder. To prevent secondary infection and to enable repair of the ditch between the graft and the corneal bed, an effective epithelial barrier must be provided. Also, a sufficient source of nutrients was necessary to ensure the survival of corneal graft. AMT, with the function of promoting epithelialization and decreasing inflammation, neovascularization and fibrosis , was a potential selection. But its function would disappear with the amniotic membrane melting within one month after transplantation. Tarsorrhaphy could improve re-epithelialization and prevent corneal melting , but it is not acceptable for most patients for poor cosmetic appearance. Moreover, it could interfere with the observation of corneal lesions. So tarsorrhaphy was selected only when there were no other choices. Conjunctival flap, rich in blood vessels, is effective in treating refractory corneal ulcers. Although cosmetic appearance was poor over a period of time after surgery, the conjunctival flap would have a marked regression after healing of corneal lesions , and there is not any difference between conjunctival flap blood vessels and corneal neovascular results from severe SJS. Ultimately, the cosmetic appearance and impairment of corneal clarity after conjunctival flap covering are acceptable for most patients. Therefore, in this study, conjunctival flap was used for protective reasons. No one complained about the cosmetic appearance of conjunctival flap.
In this case series, MSTK combined with conjunctival flap achieved favorable effects. The success of this combined procedure may be attributed to the following aspects. First, the corneal graft was quite small, which resulted in a lower risk of immune rejection and melting. Second, the corneal graft restored the integrity of the eye and added a rigid barrier between the aqueous humor and the conjunctival flap, which facilitated adherence of conjunctival flap to the corneal lesions. Third, the conjunctival flap helped to prevent secondary infection by covering the space around the small-diameter corneal graft. Fourth, the flap aided in the absorption of necrotic tissues and promoted vascularization of the wounded cornea , thus preventing graft melting and the extension of remaining ulcers. In the only case with conjunctival flap failure, corneal epithelial reconstruction was delayed, and an additional procedure was required, which indicates the importance of conjunctival flap in this combined procedure.
Due to the complexity of corneal perforations in SJS, most patients may have poor visual acuity after treatment, and additional treatment for improving eyesight can be performed. Moreover, conjunctival flaps could not be obtained for protective necessities in patients who do not have enough healthy conjunctivas. Hence, permanent tarsorrhaphy would eventually be resorted to.
In summary, combined MSTK and conjunctival flap covering is effective in treating corneal perforations in SJS. The eye globe could achieve tectonic integrity with a minimal corneal allograft under the protection of conjunctival flap, and the vision could be partly restored. This combined procedure might also be considered for the treatment of refractory corneal perforations associated with other severe systemic immune diseases.
The authors thank Ms. Ping Lin for her editorial assistance.
This study was supported by the Taishan Scholar Program, Jinan, China (no.: ts20081148) and the National Natural Science Foundation of China, Beijing, China (81170815).
- Isawi H, Dhaliwal DK: Corneal melting and perforation in Stevens Johnson syndrome following topical bromfenac use. J Cataract Refract Surg. 2007, 33: 1644-1646. 10.1016/j.jcrs.2007.04.041.PubMedView Article
- Sachdev R, Bansal S, Sinha R, Sharma N, Titiyal JS: Bilateral microbial keratitis in highly active antiretroviral therapy-induced Stevens-Johnson syndrome and toxic epidermal necrolysis: a case series. Ocul Immunol Inflamm. 2011, 19: 343-345. 10.3109/09273948.2011.601389.PubMedView Article
- Lau B, Mutyala D, Dhaliwal D: A case report of doxycycline-induced Stevens-Johnson syndrome. Cornea. 2011, 30: 595-597.PubMed
- Arstikaitis MJ: Ocular aftermath of Stevens–Johnson syndrome. Arch Ophthalmol. 1973, 90: 376-379. 10.1001/archopht.1973.01000050378008.PubMedView Article
- Saito T, Nishida K, Sugiyama H, Yamato M, Maeda N, Okano T, Tano Y: Abnormal keratocytes and stromal inflammation in chronic phase of severe ocular surface diseases with stem cell deficiency. Br J Ophthalmol. 2008, 92: 404-410. 10.1136/bjo.2007.127738.PubMedView Article
- Hick S, Demers PE, Brunette I, La C, Mabon M, Duchesne B: Amniotic membrane transplantation and fibrin glue in the management of corneal ulcers and perforations: a review of 33 cases. Cornea. 2005, 24: 369-377. 10.1097/01.ico.0000151547.08113.d1.PubMedView Article
- Yagci A: Update on peripheral ulcerative keratitis. Clin Ophthalmol. 2012, 6: 747-754.PubMedPubMed CentralView Article
- Maeno A, Naor J, Lee HM, Hunter WS, Rootman DS: Three decades of corneal transplantation: indications and patient characteristics. Cornea. 2000, 19: 7-11. 10.1097/00003226-200001000-00002.PubMedView Article
- Tugal-Tutkun I, Akova YA, Foster CS: Penetrating keratoplasty in cicatrizing conjunctival diseases. Ophthalmology. 1995, 102: 576-585. 10.1016/S0161-6420(95)30980-3.PubMedView Article
- Md Noh UK, Then KY: Spontaneous bilateral corneal perforation in stevens- johnsons syndrome-a challenge in management. Malays J Med Sci. 2013, 20: 84-87.PubMedPubMed Central
- Soong HK, Meyer RF, Wolter JR: Fistula excision and peripheral grafts in the treatment of persistent limbal wound leaks. Ophthalmology. 1988, 95: 31-36. 10.1016/S0161-6420(88)33227-6.PubMedView Article
- Chern KC, Meisler DM, Wilson SE, Macsai MS, Krasney RH: Small-diameter, round, eccentric penetrating keratoplasties and corneal topographic correlation. Ophthalmology. 1997, 104: 643-647. 10.1016/S0161-6420(97)30258-9.PubMedView Article
- Shi W, Liu M, Gao H, Li S, Wang T, Xie L: Penetrating keratoplasty with small-diameter and glycerin-cryopreserved grafts for eccentric corneal perforations. Cornea. 2009, 28: 631-637. 10.1097/ICO.0b013e318191b857.PubMedView Article
- Soong HK, Meyer RF, Sugar A: Small, overlapping tectonic keratoplasty involving graft-host junction of penetrating keratoplasty. Am J Ophthalmol. 2000, 129: 465-467. 10.1016/S0002-9394(99)00413-4.PubMedView Article
- Portnoy SL, Insler MS, Kaufman HE: Surgical management of corneal ulceration and perforation. Surv Ophthalmol. 1989, 34: 47-58. 10.1016/0039-6257(89)90129-X.PubMedView Article
- Harr T, French LE: Orphanet J Rare Dis. Toxic epidermal necrolysis and Stevens-Johnson syndrome. Orphanet J Rare Dis. 2010, 5: 39-10.1186/1750-1172-5-39.PubMedPubMed CentralView Article
- Prabhasawat P, Tesavibul N, Komolsuradej W: Single and multilayer amniotic membrane transplantation for persistent corneal epithelial defect with and without stromal thinning and perforation. Br J Ophthalmol. 2001, 85: 1455-1463. 10.1136/bjo.85.12.1455.PubMedPubMed CentralView Article
- Gomes JA, Santos MS, Ventura AS, Donato WB, Cunha MC, Höfling-Lima AL: Amniotic membrane with living related corneal limbal/conjunctival allograft for ocular surface reconstruction in Stevens-Johnson syndrome. Arch Ophthalmol. 2003, 121: 1369-1374. 10.1001/archopht.121.10.1369.PubMedView Article
- Bhatt PR, Lim LT, Ramaesh K: Therapeutic deep lamellar keratoplasty for corneal perforations. Eye (Lond). 2007, 21: 1168-1173. 10.1038/sj.eye.6702428.View Article
- Jhanji V, Young AL, Mehta JS, Sharma N, Agarwal T, Vajpayee RB: Management of corneal perforation. Surv Ophthalmol. 2011, 56: 522-538. 10.1016/j.survophthal.2011.06.003.PubMedView Article
- Weiss JL, Williams P, Lindstrom RL, Doughman DJ: The use of tissue adhesive in corneal perforations. Ophthalmology. 1983, 90: 610-615. 10.1016/S0161-6420(83)34508-5.PubMedView Article
- Nobe JR, Moura BT, Robin JB, Smith RE: Results of penetrating keratoplasty for the treatment of corneal perforations. Arch Ophthalmol. 1990, 108: 939-941. 10.1001/archopht.1990.01070090041035.PubMedView Article
- Khokhar S, Natung T, Sony P, Sharma N, Agarwal N, Vajpayee RB: Amniotic membrane transplantation in refractory neurotrophic corneal ulcers: a randomized, controlled clinical trial. Cornea. 2005, 24: 654-660. 10.1097/01.ico.0000153102.19776.80.PubMedView Article
- Gundersen T: Conjunctival flaps in the treatment of corneal disease with reference to a new technique of application. AMA Arch Ophthalmol. 1958, 60: 880-888. 10.1001/archopht.1958.00940080900008.PubMedView Article
- The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2415/14/97/prepub
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.