Submandibular Gland Transfer for Severe Xerophthalmia

Randal C. Paniello, MD

Objective: To report early clinical experience INTRODUCTION with a new microvascular reconstructive procedure Xerophthalmia, sometimes referred to as keratocon- for patients with severe xerophthalmia. Study Design: junctivitis sicca (KCS), is the clinical condition of severe Retrospective clinical series. Methods: Patients with dryness of the surface of the eye. It may occur in a variety severe xerophthalmia were referred for treatment af- of clinical settings, as summarized in Table I. Chronic ter having exhausted all conventional means of treat- xerophthalmia can progress to corneal ulceration, eventu- ment. The ipsilateral submandibular gland was trans- ally leading to visual loss. In more severe cases, corneal ferred to the temporal fossa, as described by Macleod ulceration can progress to an infection or a ruptured globe, et al., and revascularized using the superficial tempo- potentially resulting in blindness or loss of the eye. ral artery and appropriate vein(s). The submandibu- Patients with xerophthalmia typically complain of lar duct was directed to the superolateral fornix so significant discomfort in the eyes. They may describe the that the saliva produced moistened the eye. Results sensation of eyelid closure as feeling like sandpaper rub- and complications were reviewed. Results: Seven microvascular submandibular gland transfer proce- bing across their eyes. Problems with turned-in eyelashes dures were performed in five patients, ages 6 to 54. are common. Some patients develop photophobia and keep The etiology of severe xerophthalmia was Stevens- their eyes closed most of the time, in part because opening Johnson syndrome in four and chemical burn in one. the eyes leads to pain or soreness. Follow-up time was 4 to 20 months. Successful trans- One of the common causes of severe xerophthalmia is fer with revascularization was achieved in six of Stevens-Johnson syndrome (SJS), also called erythema seven (86%) cases. Schirmer’s test scores improved multiforme major. SJS is an immune-complex mediated hypersensitivity reaction that affects the skin and mucus .(005. ؍ from 1.3 pretransfer to 8.1 posttransfer (P Patients experienced symptomatic relief within 1 membranes. Blindness from involvement of the cornea and month, and the microenvironment of the eye surface anterior uvea occurs in 3% to 10% of patients with SJS. improved enough to make them candidates for visual Treatment for early KCS involves administration of restorative eye surgery. There were no major compli- artificial tears, but as the condition progresses, the need cations. Conclusions: Microvascular submandibular for exogenous moisture becomes too frequent to be practi- gland transfer is an effective approach for correc- cal, with some patients using eye drops every 2 to 5 min- ting severe xerophthalmia. The procedure should be utes throughout the day. Ophthalmic ointments can be within the skills of any reconstructive microsurgeon. effective but often blur the vision. Punctal plugs may be This procedure offers a unique opportunity for oto- placed in the lacrimal apparatus to block the drainage of laryngologist–head and neck reconstructive sur- any tears that may be present but have limited benefit, geons to help restore vision to this unfortunate group and eventually the puncta become dilated so that plugging of patients. Key Words: Xerophthalmia, submandibular gland, microvascular free tissue transfer, kerato- no longer works. The management of dry eyes was sum- 1 conjunctivitis sicca, Stevens-Johnson syndrome. marized recently by Gilbard. Laryngoscope, 117:40–44, 2007 Ophthalmologists may be able to repair the damaged cornea using a corneal transplant; however, the transplanted cornea is likely to fail if the surface of the eye remains too dry. An appropriate healing environment for From the Department of Otolaryngology–Head and Neck Surgery, Washington University School of Medicine, St. Louis, Missouri, U.S.A. a new cornea may also require preliminary transplanta- Editor’s Note: This Manuscript was accepted for publication Septem- tion of stem cells, but this procedure also requires correc- ber 14, 2006. tion of the dry condition. A scleral lens may restore some Presented at the Annual Meeting of the Triological Society, Chicago, vision to severely damaged corneas but cannot be used Illinois, U.S.A., May 21, 2006. without adequate moisture present. Send correspondence to Dr. Randal Paniello, Washington University School of Medicine, Department of Otolaryngology–Head and Neck Sur- In 1991, MacLeod and Robbins2 reported their expe- gery, 660 S. Euclid Avenue, CB 8115, St. Louis, MO 63110, U.S.A. E-mail: rience treating patients with severe xerophthalmia using [email protected] a microvascular free tissue transfer of the submandibular DOI: 10.1097/01.mlg.0000246953.44163.81 gland (SMG) to the temporal fossa, bringing its salivary

Laryngoscope 117: January 2007 Paniello: Submandibular Gland Transfer for Severe Xerophthalmia 40 very superficial. If the STA is confirmed to be of adequate caliber TABLE I. to use for microvascular anastomosis, the procedure continues. Causes of Xerophthalmia. A typical incision is used to harvest the ipsilateral SMG. Stevens-Johnson syndrome The facial artery is divided superior to the gland, and care is Vitamin A deficiency taken to dissect and preserve every small vein on the gland surface. Typically, these veins coalesce into larger veins suitable Sjogren’s disease for microvascular anastomosis. The submandibular duct (Whar- Congenital absence of lacrimal gland ton’s) is cannulated with a lacrimal probe. The ampulla of the Trauma with scarring duct is released from the floor of mouth witha1to2mmcuff of Chemical burn mucosa, and the duct is dissected through the muscular sling Radiation using both transoral and transcervical approaches. This dissection is tedious because it is imperative that the duct be preserved Systemic lupus erythematosus to its maximum length. At this point, the gland may be rotated Rheumatoid arthritis inferolaterally on its vascular pedicle (Fig. 1A). Microvascular Scleroderma clamps are place on the vessels, and the gland is removed for Sarcoidosis transfer (Fig. 1B). Amyloidosis A portion of the temporalis muscle is removed to create a space for gland transfer while preserving the vessels (Fig. 1C). A Hypothyroidism tunnel is created from this fossa, over the orbital rim to the superolateral conjunctiva, by blunt dissection. The gland is placed in the fossa with the duct directed anteriorly and the vessels aligned. Microvascular anastomoses are then performed. output to the corner of the eye. Larger series were re- The venous anastomosis may be into the superficial temporal ported more recently by other groups. This procedure vein, if it is large enough, or a vein graft into a neck vein may be clearly falls within the skills of the head and neck recon- used. The facial artery is usually a bit larger than the STA, but structive surgeon but has not received much attention in the mismatch can be managed with interrupted sutures. The the United States. This report is intended to introduce microvascular clamps are removed, allowing reflow into the this concept to the Laryngoscope readership and to report gland, and it is irrigated with warm saline. the author’s early experience with it. An incision is made in superolateral fornix of the conjunctiva, and the duct is passed through the tunnel with the help of a METHODS tendon passer (Fig. 1, C and D). The mucosal cuff is sutured to the Five patients with severe xerophthalmia were referred for conjunctiva with fast absorbing gut suture. If the mucosal cuff SMG transfer (SMFTx). The patient characteristics are given in was inadequately preserved, the end of the duct may be incised Table II. The ages ranged from 6 to 48 (mean 28.8) years. Four of and the duct marsupialized as it is sutured in place. A Crawford the five patients had been the victims of SJS; the other patient tube is inserted in the duct to prevent stenosis. A suture is placed had suffered a thermal burn to the eyes in a workplace accident. through the gland superiorly to support it in the fossa against All patients had been managed with artificial tears, ophthalmo- gravity. Drains are placed, and the wounds are closed. logic ointments, and punctal plugs without success. The patients were typically using eye drops every 5 to 10 minutes throughout Postoperative Management the day when awake. Two of the patients had already had one eye Standard postoperative wound care and Doppler monitoring enucleated and were functionally blind on the remaining side; the is performed as with other free tissue transfers. The function of other three were functionally blind or nearly blind bilaterally. the gland may be evaluated using technecium-99 pertechnetate scintigraphy, typically performed on postoperative day 5; this Surgical Procedure radionucleide has affinity for salivary and thyroid tissue. Eye The location of the superficial temporal artery (STA), in- care with drops continues on an as-needed basis, the frequency of cluding its anterior and posterior branches, is identified with a administration diminishing as the gland output increases. Doppler probe and marked. A curvilinear incision is made in the Salivary-lacrimal flow was measured using a 2 minute Schirmer’s anterior temporal region, creating an inferiorly based scalp flap test, and results were compared with a paired t test. over the anterior temporalis muscle, exposing these vessels. Cau- tion is needed during flap elevation because the vessels may be RESULTS The submandibular free tissue transfers were successful in six of seven (86%) cases. The facial artery was TABLE II. anastomosed to the STA in all cases without the need for Patient Characteristics. an interposition graft. The venous outflow was directed directly into the superficial temporal vein in six cases, and Pre-Rx Vision Status a vein graft was used into the external jugular vein in two Patient Duration No. Age Sex Etiology (yr) Right Left cases (1 patient had both). For patient 3 (the young girl), only very small veins were found on the gland at harvest 1 29 M SJS 22 Blind Prosthesis of her second side (case 5). Although the microvascular 2 32 M Chemical 10 Blind Blind burn anastomoses were successful, there was obvious venous congestion, and the initial salivary flow from the duct 3 6 F SJS 3.5 Near-blind Near-blind tapered off to a minimal rate. This case was counted as a 4 29 M SJS 23 Blind Prosthesis failure. 5 48 M SJS 3 Near-blind Blind The Schirmer’s test results are given in Table III, SJS ϭ Stevens-Johnson syndrome. showing improvement from 1.3 mm preoperatively to 8.1

Laryngoscope 117: January 2007 Paniello: Submandibular Gland Transfer for Severe Xerophthalmia 41 Fig. 1. (A) Submandibular gland (SMG) dissected, duct released, still pedicled on facial vessels. (B) SMG ready for free tissue transfer. Duct is approximately 5 cm long. (C) Portion of temporalis muscle removed; revascularized gland in place; duct lies atop skin flap; tendon passer in tunnel to assist with transfer of duct to corner of eye. (D) Duct in position for suturing to superolateral fornix; extra length after passing. mm postoperatively (P ϭ .005). The mean follow-up was The clinical outcomes are also shown in Table III. 11.9 (range, 4–20) months. The patients experienced Two of the eyes improved enough to tolerate a scleral lens, symptomatic improvement with restored moisture to the a type of large contact lens. Two of the patients were eye within days of the procedure; the salivary lacrimal cleared by their ophthalmologist to undergo implantation flow then increased over the next 1 to 2 months. of an artificial lens (Alphacor Technology Inc., Sunnyvale, There were no major complications. One patient had CA). The eye with the most severe damage has now been an immediate postoperative neck hematoma, which was cleared for repopulation of the surface with transplanted explored and treated without consequence. There were no stem cells. wound infections or healing problems. One patient devel- The cosmetic results of the wound healing were very oped a buccal mucous retention cyst on the operated side, acceptable, similar to those obtained after parotidectomy. which was removed without difficulty. The removal of the temporalis muscle minimized the Patient 5 had moderate “salivary epiphora” starting bulge caused by the implantation of the gland, and after on postoperative day 2; this excessive flow tapered off by the temporal hair grew back, the remaining bulge was day 7. This degree of salivary flow was not seen when he imperceptible. returned for the procedure on the second side. The results of the scintigraphy were interesting. Four One patient reported that his need for supplemental of the seven transferred glands showed significant uptake artifical tears decreased from an average of 64 squeeze in the new location (Fig. 2), clearly indicating viable vials per day to 1 to 2 vials per day after the procedure. grafts. One gland showed no uptake, yet subsequently, the Three of the patients found that they could “milk” a little patient clearly experienced clinical benefit from the pro- extra saliva from the duct by pressing on the temporal cedure. One patient with clinical benefit had no uptake in region when they felt the need for more moisture. either SMG or in either parotid gland. Three patients with

TABLE III. Results of Seven Microvascular Submandibular Gland Transfer Procedures.

Schirmer’s Test

Case No. Patient/Side Preoperative Postoperative Follow-Up (mo) Clinical Status 1 1/R 0 7 20 Scleral lens, learning to read 2 2/L 1 6.5 17 First stage lens surgery successful 3 3/R 0 15 14 In school, can see chalkboard 4 4/R 3 9 11 Alphacor lens implant planned 5 3/L 0 2 9 Frequent drops still required 6 5/R 1 9 8 Can read clock, recognize faces 7 5/L 4 8 4 Stem cell transplant planned

Schirmer’s test improvement, P ϭ .005.

Laryngoscope 117: January 2007 Paniello: Submandibular Gland Transfer for Severe Xerophthalmia 42 Fig. 2. Postoperative technecium-99 scintigraphy from patient 1. Uptake is seen in thyroid glands, parotid glands, left submandibular gland (SMG) in place, and right SMG in temporal fossa. benefit had repeat scans 4 to 12 months postoperatively; gland as a separate procedure. This problem was not two showed reduced activity in the transferred gland, and observed in the small series reported here. The trans- one showed increased activity. It was concluded that a ferred SMG is not expected to be innervated; thus, the positive scan can be interpreted as demonstrating viabil- salivary flow occurs at a random, unstimulated, basal flow ity of the transferred gland, but a negative scan cannot be rate that appears to be about the right amount for natu- interpreted as showing nonviability. Thus, the role of scin- rally moistening the eye in most cases. There is a possi- tigraphy after this procedure is not well defined. bility of sympathetic neural ingrowth from the lacrimal nerve, but this should not be expected. Patients also DISCUSSION should not experience epiphora in response to olfactory The intent of microvascular SMGTx is to relieve stimuli. symptoms associated with severe KCS and to improve the Geerling et al.12 argue that although this is a complex environment of the eye surface to avoid enucleation, halt and possibly expensive procedure, the improvement in loss of vision, and improve the chance for corrective eye quality of life and the savings for items such as guard dogs surgery to be successful. In this initial cohort of seven eyes more than offset the costs. This involved procedure should in five patients, these goals appear to have been met. not be undertaken lightly, however; the author has used Improvement in vision without ophthalmologic surgery is this procedure only as a “last resort,” such as with the SJS not generally expected, but it was experienced in three of patients reported in this series.13 As noted, two of the the seven eyes treated in this series. The technical de- patients had already lost one eye; a third patient under- mands of this procedure should be well within the skills of went “emergency” corneal transplant on one eye just to any head and neck reconstructive surgeon who regularly protect the eye while awaiting the improvement expected performs free tissue transfers; no special training is from this procedure so that a more permanent eye proce- required. dure could be undertaken. Larger series of microvascular SMGTx have been This procedure would be much easier to perform if reported by other groups. Macleod et al.2,3 originally revascularization were not required. Liu et al.14 have reported 12 gland transfers in 8 patients. This work followed their series of experiments in rabbits demon- studied this question in a rat model. After 3 months, the strating the feasibility of the procedure.4,5 Geerling et nonvascularized transferred SMGs appeared to have nor- al.6,7 have reported their results with 31 patients un- mal histology and reinnervation, and the eyes were not dergoing this procedure. Continued long-term salivary dry compared with controls. The small size of the rat SMG flow from the glands was found in 87% of cases. On the may make it more likely to survive without revasculariza- basis of examinations of the eye surface and measure- tion than larger human glands, but this finding deserves ment of salivary outflow, they report success in 18 of 27 additional study. patients with at least 1 year follow-up. Jia et al.8 re- Some patients with severe KCS are not candidates ported success in six transfers in five patients. Yu et for microvascular SMGTx because their underlying dis- al.9–11 initially reported 33 of 38 (87%) surviving micro- ease also affects the SMG (e.g., Sjogren’s syndrome). For vascular SMG transfers, then 59 of 68 (87%) surviving these patients, the possibility of allotransplantation of the transfers in a later paper. SMG has also been explored by Ge et al.15 The miniature A common finding among the two larger series is a swine model enabled successful transfer, but all glands subgroup of patients who have excessive flow, resulting in experienced acute rejection by 5 days. Allotransplanta- salivary epiphora. This was reported in 10 of 31 (32%) and tion would introduce new issues of immune suppression 8 of 38 (21%) of patients, respectively.7,10 This problem into the discussion, and the salivary glands are highly was successfully managed by removing a portion of the immunogenic.

Laryngoscope 117: January 2007 Paniello: Submandibular Gland Transfer for Severe Xerophthalmia 43 CONCLUSION tis sicca. 2 year outcome. Ophthalmologe 1998;95:257–265. Microvascular SMGTx can be used to restore mois- 7. Sieg P, Geerling G, Kosmehl H, et al. Microvascular subman- ture to severely dry eyes, improving the microenviron- dibular gland transfer for severe cases of keratoconjunctivitis sicca. Plast Reconstr Surg 2000;106:554–562. ment of the cornea. This improvement can prevent loss of 8. Jia G, Wang Y, Lu L, et al. Reconstructive lacrimal gland with the eye and can possibly make these patients, who are free submandibular gland transfer for management of xe- often blind, eligible for additional ophthalmologic inter- rophthalmia. Zhonghua Yan Ke Za Zhi 1998;34:388–390. ventions to restore sight. The procedure is successful in a 9. Yu G, Zhu Z, Mao C, et al. Microvascular submandibular gland high percentage of patients and can be performed by most transfer for severe keratoconjunctivitis sicca: operation key points, prevention and management of complications. reconstructive microsurgeons. Zhonghua Kou Qiang Yi Xue Za Zhi 2002;37:353–355. 10. Yu GY, Zhu ZH, Mao C, et al. Microvascular autologous sub- BIBLIOGRAPHY mandibular gland transfer in severe cases of keratoconjunc- 1. Gilbard JP. The diagnosis and management of dry eyes. Oto- tivitis sicca. Int J Oral Maxillofac Surg 2004;33:235–239. laryngol Clin North Am 2005;38:871–885. 11. Mao C, Zhang L, Yu GY, et al. Management of blood vessels 2. MacLeod AM, Robbins SP. Submandibular gland transfer in in the vascularized autogenous submandibular gland the correction of dry eye. AustNZJOphthalmol 1992;20: transfer for severe keratoconjunctivitis sicca. Zhonghua 99–103. Kou Qiang Yi Xue Za Zhi 2005;40:370–372. 3. Macleod A, Kumar PA, Hertess I, Newing R. Microvascular 12. Geerling G, Liu CS, Collin JR, Dart JK. Costs and gains of submandibular gland transfer; an alternative approach for complex procedures to rehabilitate end stage ocular sur- total xerophthalmia. Br J Plast Surg 1990;43:437–439. face disease. Br J Ophthalmol 2002;86:1220–1221. 4. Kumar PA, Macleod AM, O’Brien BM, et al. Microvascular 13. Letko E, Papaliodis DN, Papaliodis GN, et al. Stevens-Johnson submandibular gland transfer for the management of xe- syndrome and toxic epidermal necrolysis: a review of the rophthalmia; an experimental study. Br J Plast Surg 1990; literature. Ann Allergy Asthma Immunol 2005;94:419–436. 43:431–436. 14. Liu WC, Hsu WM, Lee SM, et al. Transplantation of the 5. Kumar PA, Hickey MJ, Gurusinghe CJ, O’Brien BM. Long term autologous submandibular gland to the lacrimal basin in results of submandibular gland transfer for the management rats. Ophthalmic Res 2004;36:195–199. of xerophthalmia. Br J Plast Surg 1991;44:506–508. 15. Ge XY, Yu GY, Cai ZG, Mao C. Establishment of submandib- 6. Geerling G, Sieg P, Meyer C, et al. Transplantation of autolo- ular gland allotransplantation model in miniature swine. gous submandibular glands in very severe keratoconjunctivi- Chin Med J (Engl) 2006;119:482–487.

Laryngoscope 117: January 2007 Paniello: Submandibular Gland Transfer for Severe Xerophthalmia 44