Superior limbic keratoconjunctivitis can be treated with liquid nitrogen cryotherapy

Thomas John

Superior limbic keratoconjunctivitis is an ocular surface disease that usually comprises a triad of superior bulbar conjunctival inflammation, an adjacent epithelial keratitis and an upper tarsal conjunctival papillary hypertrophy.

It was initially described by Thygeson and Kimura in 1963 and was later named superior limbic keratoconjunctivitis (SLK) by Theodore. Although the exact pathophysiology has not been fully elucidated, mechanical trauma to the epithelium has been theorized as a causative factor. It has been associated with thyroid abnormalities, and more than half of SLK patients have been reported to have dry eyes. Rarely, ocular surface squamous neoplasia can masquerade as SLK. More recently, overexpression of matrix metalloproteinase-1 and matrix metalloproteinase-3 has been detected in SLK, so a matrix metalloproteinase imbalance may play a role in SLK. Also, increased mast cell numbers have been detected in some SLK specimens. The clinical features and wide array of treatment options for SLK are described below with differing medical and surgical outcomes.

In this column, Dr. Fraunfelder describes a surgical technique using liquid nitrogen cryotherapy to treat SLK. This Surgical Maneuvers column represents one of a series of applications for the use of cryotherapy for ocular surface disease.

Thomas John, MD
OSN Surgical Maneuvers Editor

by Frederick W. Fraunfelder, MD

The etiology of SLK is a subject of some debate; however, many researchers believe there is a mechanism leading to soft tissue microtrauma between the superior palpebral and superior bulbar conjunctival surfaces from normal repetitive eye blinking in susceptible individuals. Others have postulated an insufficient local tear supply. Regardless of etiology, a multitude of treatments are suggested for SLK, including thermocautery, chemocautery, conjunctival resection, punctal occlusion, topical application of autologous serum, topical cyclosporine A, topical ketotifen fumarate, bandage contact lenses, topical lodoxamide tromethamine, botulinum toxin and topical vitamin A eye drops. The fact that there are so many treatments frequently means that no single treatment is adequate and that the disease is a result of a combination of factors, including dry eyes, mechanical trauma, local inflammation and the effect of Graves’ disease on the eyes.

The diagnosis of SLK can sometimes be difficult. SLK can be unilateral or bilateral and present with ocular burning, foreign body sensation, ocular pain, epiphora, photophobia, blepharospasm and sometimes decreased vision. Some patients have mucus discharge and corneal filaments. On examination, the superior conjunctiva is found to be inflamed and red with fine punctate staining by rose bengal of the upper cornea, superior limbus and adjacent conjunctiva (Figure 1). Filaments are sometimes present at the superior limbus, with some patients exhibiting pseudoptosis. There is usually a fine papillary reaction of the upper eyelid palpebral conjunctiva, as well (Figure 2). Patients who present with symptoms and signs of SLK are frequently tested for abnormalities in thyroid function.

Figure 1. Superior limbic keratoconjunctivitis (Patient 2, Table).

Figure 2. Fine papillary reaction on palpebral conjunctiva in SLK (Patient 4, Table). Images: Fraunfelder FW

If conservative management with artificial tears, topical ocular steroids or ocular lodoxamide is not beneficial, liquid nitrogen cryotherapy can be performed using a Brymill E tip spray (0.013-inch aperture; Brymill Cryogenic Systems) with a double freeze-thaw technique. This can be achieved on an outpatient basis in clinic using topical proparacaine for anesthesia. A Weck-Cel sponge can also be soaked in proparacaine and held over the superior conjunctiva and limbus area for 30 seconds for additional anesthesia. Care is taken to create a chalk-white appearance before the thaw, which usually requires 1 to 2 seconds of freezing. The superior limbus and inflamed conjunctiva were treated in this manner, and the process is repeated after a thaw of 5 to 8 seconds. After the procedure, patients can use ofloxacin eye drops four times daily for 3 days. Post-procedure visits should be at intervals of 1 day, 2 weeks, 3 months, 6 months and yearly thereafter.

From a published case series, four patients, all women, with a median age of 64 ± 13 years (range: 51 to 78 years), were treated with liquid nitrogen cryotherapy for SLK (Table 1). Three of the four patients had bilateral disease, and two had associated thyroid disorders. Resolution of symptoms and signs occurred within 2 weeks in all cases. The SLK recurred in two of four patients and three of seven eyes. Median length of follow-up was 10 ± 6 months (range: 7 to 21 months). No eyes required a third cryospray treatment in this case series. Average time to recurrence was 3.6 months in the three eyes re-treated with cryotherapy. Patient 2 is pictured in Figure 3 before cryotherapy and 1 year after cryotherapy for SLK. Vision was the same in all patients before and after cryotherapy.

Figure 3. Superior bulbar conjunctiva in a patient with SLK before and 1 year after cryotherapy (Patient 2, Table).

The microtrauma hypothesis provides a likely explanation for SLK and also for the effectiveness of cryotherapy. One of the mainstays of treatment for this disease is chemocautery, usually with a silver nitrate solution or silver nitrate stick applied to the superior conjunctiva. Another common treatment is conjunctival resection. Both of these treatments essentially remove the theoretically redundant superior conjunctiva from the surface of the globe. Therefore, the chronic microtrauma from repetitive blinking does not occur.

Liquid nitrogen cryotherapy acts in the same way; it removes the redundant superior conjunctiva by causing a scar similar to that produced by chemocautery to form between the superior bulbar conjunctiva and the underlying Tenon’s capsule and sclera.

In the seven eyes of four patients in this series (Table), the effects of liquid nitrogen cryospray appeared to last for months without adverse ocular side effects. In three of seven eyes, disease recurred after a single cryotherapy treatment, but there were no recurrences after repeat cryotherapy. The published literature has a paucity of reports on recurrence of SLK, and the recurrence varies depending upon the type of treatment. Passons and Wood performed conjunctival resection for SLK and had recurrence in two of 10 patients. Ohashi and colleagues treated SLK with vitamin A eye drops with benefit in 10 of 12 patients. Udell and colleagues used thermocautery in the treatment of SLK, with recurrent disease in five of 11 patients. It is hoped that the effects of cryotherapy will be permanent, and if the mechanical theory of microtrauma is correct, then the scarring formed from cryospray to the surface of the globe should last permanently.

References:

• Donshik PC, Collin HB, Foster CS, Cavanagh HD, Boruchoff SA. Conjunctival resection treatment and ultrastructural histopathology of superior limbic keratoconjunctivitis. Am J Ophthalmol. 1978;85(1):101-110.
• Fraunfelder FW. Liquid nitrogen cryotherapy of superior limbic keratoconjunctivitis. Am J Ophthalmol. 2009;147(2):234-238.
• Goto E, Shimmura S, Shimazaki J, Tsubota K. Treatment of superior limbic keratoconjunctivitis by application of autologous serum. Cornea. 2001;20(8):807-810.
• Sun YC, Hsiao CH, Chen WL, Hu FR. Overexpression of matrix metalloproteinase-1 (MMP-1) and MMP-3 in superior limbic keratoconjunctivitis. Invest Ophthalmol Vis Sci. 2011;52(6):3701-3705.
• Udell IJ, Kenyon KR, Sawa M, Dohlman CH. Treatment of superior limbic keratoconjunctivitis by thermocauterization of the superior bulbar conjunctiva. Ophthalmology. 1986;93(2):162-166.
• Watson S, Tullo AB, Carley F. Treatment of superior limbic keratoconjunctivitis with a unilateral bandage contact lens. Br J Ophthalmol. 2002;86(4):485-486.
• Wright P. Superior limbic keratoconjunctivitis. Trans Ophthalmol Soc U K. 1972;92:555-560.

• Frederick W. Fraunfelder, MD, is a professor of ophthalmology and director of cornea and refractive surgery at Casey Eye Institute. He can be reached at Casey Eye Institute, 3375 SW Terwilliger Blvd., Portland, OR 97239-4197; 503- 494-4318; fax: 503-418-2284; email: eyedrug@ohsu.edu.
• Edited by Thomas John, MD, clinical associate professor at Loyola University at Chicago and 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.
• Disclosures: Dr. Fraunfelder’s research was supported in part by an unrestricted grant to Casey Eye Institute from Research to Prevent Blindness. Dr. John has no relevant financial disclosures.