Case report: Superior limbic keratoconjunctivitis

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Superior limbic keratoconjunctivitis (SLK) involves inflammation of the upper bulbar and palpebral conjunctiva. One proposed mechanism includes mechanical microtrauma at the superior limbus and bulbar conjunctiva interface. Here, we report a case of SLK treated with complete ocular lavage facilitated by an irrigating eyelid retractor (Rinsada).

Case presentation

Figure 1. Superior bulbar conjunctiva of patient with significant vascular dilation and injection on day of presentation. (Images courtesy of Shelby Brogdon, OD.)

A 53-year-old man presented with grittiness and irritation in both eyes, along with watering and burning. The patient reported that his symptoms were worse upon waking in the morning and late in the evenings, and he noticed his right eye symptoms were worse. At-home treatment included preservative-
free artificial tears multiple times per day, along with gel drops at bedtime. A review of systems was negative for recent trauma, hot or cold sensations, and increased thirst, anxiety, or hair loss. Examination on presentation revealed superior conjunctival injection on both bulbar and palpebral conjunctiva, mobile superior conjunctiva, 1 to 2+ staining of the superior cornea, and decreased tear breakup time (Figure 1). The remainder of the patient’s exam was unremarkable. Based on these findings, a diagnosis of SLK was made. Given the mechanical hypothesis underlying SLK pathophysiology, a complete ocular lavage was attempted using an irrigating eyelid retractor to deliver 0.9% normal saline to the palpebral conjunctiva, bulbar conjunctiva, and conjunctival fornix simultaneously. The patient was discharged with a prescription for lifitegrast 5% ophthalmic solution (Xiidra; Bausch + Lomb) to be administered 2 times per day and perfluorohexyloctane ophthalmic solution (Meibo; Bausch + Lomb) to be administered 4 times per day. The patient was also educated to continue with preservative-free tears and gel drops at bedtime.

Figure 2. Improved conjunctiva appearance with reduced vascular congestion 10 days post complete ocular lavage. (Images courtesy of Shelby Brogdon, OD.)

The patient returned for a follow-up appointment 10 days later, with improvements in burning, watering, and irritation. Examination revealed reduced conjunctival and corneal staining, improved tear breakup time, and decreased conjunctival injection (Figure 2). The patient continued with the current treatment plan and was to return to the clinic in 2 weeks for follow-up. Amniotic membrane and intense pulsed light (IPL) treatments will be considered for concurrent ocular surface disease.

Discussion

SLK is an ocular surface disease that was first described in 1963 by Frederick H. Theodore, MD. It is characterized by chronic inflammation affecting the superior limbus and bulbar conjunctiva, predominantly seen in women aged 30 to 55 years. Although it typically affects both eyes, one eye may exhibit more severe symptoms. Common symptoms include irritation, burning, redness, foreign body sensation, and sensitivity to light (photophobia). On examination, there is traditionally marked inflammation of the upper tarsal and bulbar conjunctiva, fluorescein staining of the cornea and upper limbus, positive staining with lissamine green or rose bengal of the superior bulbar conjunctiva adjacent to the limbus, proliferation and redundancy of superior limbic conjunctiva, and filament formation in the limbal area and upper cornea.¹

The exact cause of SLK remains unclear, though mechanical, infectious, and immunological factors have been suggested. Autoimmune and viral etiologies have been previously proposed; however, cultures and light microscopy have effectively made these hypotheses less likely.² One prominent theory, proposed by Theodore, suggests that SLK develops from chronic friction between the superior bulbar and tarsal conjunctiva due to excessive laxity.¹ However, like previous theories, this hypothesis lacks sufficient compelling evidence to establish itself as the definitive underlying mechanism in SLK pathogenesis.³

SLK has been associated with thyroid dysfunction in up to 30% of patients.^3-5 Additionally, there is an established link between SLK and ocular graft-vs-host disease, although its true incidence remains uncertain.⁶ Keratoconjunctivitis sicca has also been noted to coexist in 25% of patients with SLK.^1,2,5

Histopathological studies of SLK-affected conjunctiva typically reveal epithelial cell keratinization with dyskeratosis, acanthosis, and nuclear balloon degeneration. Microscopic analysis often demonstrates stromal infiltration by polymorphonuclear leukocytes, plasma cells, mastocytes, and lymphocytes.^7,8 Watanabe et al identified decreased levels of mucinlike glycoprotein through immunofluorescence staining of keratinized superior bulbar conjunctival epithelium, which normalized after treatment with topical vitamin A or a bandage contact lens compared with normal controls.⁹ Matsuda et al observed abnormal differentiation and hyperproliferation of conjunctival epithelium associated with elevated expression of cytokeratins 10, 13, and 14, as well as proliferating cell nuclear antigen. They also noted increased levels of TGF-β2 and tenascin, both of which can be induced by mechanical trauma, thus supporting the hypothesis of microtrauma as a potential trigger for SLK.^10,11

Treatment options for SLK include both surgical and nonsurgical approaches. Historically, silver nitrate had been used along the superior palpebral conjunctiva with symptom relief 4 to 6 weeks post treatment course. Other surgical interventions include conjunctival resection and cryotherapy, which aim to address the underlying inflammation. Nonsurgical therapies focus on reducing mechanical friction and irritation of the ocular surface. These may include using artificial tears, autologous serum eye drops (auto-SEDs), topical vitamin A, punctal occlusion, topical immunomodulators, pressure patching, and therapeutic bandage contact lenses.

Current literature on SLK management highlights the limited use of combined therapies, such as bandage contact lenses and topical steroids, topical tacrolimus,¹² topical rebamipide,¹³ topical cyclosporine A 0.5%,¹⁴ ketotifen fumarate,¹⁵ auto-SEDs,¹⁶ cromolyn sodium,¹⁷ and lodoxamide tromethamine.¹⁸ Other options include IPL and botulinum toxin injection into the Riolan muscle,¹⁹ as well as supratarsal triamcinolone injection.²⁰

In our case, we elected to try high-pressure irrigation of normal saline directed at the palpebral conjunctiva and fornix with the irrigating eyelid retractor. The irrigating eyelid retractor is a single-use, sterile medical device that consists of acrylonitrile butadiene styrene plastic. The device is indicated for the removal of irritants from the ocular surface in humans. The irrigating eyelid retractor has 5 distal ports: 2 aim high-pressure fluid at the palpebral conjunctiva, 2 aim at the bulbar conjunctiva, and 1 aims at the conjunctival fornix.²¹ We thought this high-pressure irrigation may help alleviate the microtrauma located at the superior bulbar conjunctiva and palpebral conjunctiva interface. Previous research has illustrated that this high-pressure irrigation can effectively reduce inflammatory load on the ocular surface, specifically MMP-9 in the tear film.^21,22

The patient’s clinical improvement 1 week post treatment was surprising for us, as, empirically, topical steroid alone is insufficient to resolve SLK. The high-pressure directed irrigation seems to have improved the signs and symptoms of SLK. Further work and investigation will be necessary to better understand how this high-pressure targeted lavage of the ocular surface can be of benefit to ocular surface homeostasis.

References:

1. Theodore FH. Superior limbic keratoconjunctivitis. Eye Ear Nose Throat Mon. 1963;42:25-28.

2. Eiferman RA, Wilkins EL. Immunological aspects of superior limbic keratoconjunctivitis. Can J Ophthalmol. 1979;14(2):85-87.

3. Hu Z, Terveen DC, Beebe JD, Goins KM. Superior limbic keratitis. EyeRounds.org. October 28, 2016. Accessed August 25, 2024. https://eyerounds.org/cases/245-superior-limbic-keratitis.html.

4. Wright P. Superior limbic keratoconjunctivitis. Trans Ophthalmol Soc UK (1962). 1972;92:555-560.

5. 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. doi:10.1016/s0002-9394(14)76673-5

6. Sivaraman KR, Jivrajka RV, Soin K, et al. Superior limbic keratoconjunctivitis-like inflammation in patients with chronic graft-versus-host disease. Ocul Surf. 2016;14(3):393-400. doi:10.1016/j.jtos.2016.04.003

7. Priyambada P, Mohapatra S, Harshavardhan VK, Mohanty S. Efficacy of 2% rebamipide eyedrops in patients with superior limbic keratoconjunctivitis. Sch J Appl Med. 2017;5(9): 3733-3737. doi:10.36347/sjams.2017.v05i09.046

8. Sun YC, Hsiao CH, Chen WL, Wang IJ, Hou YC, Hu FR. Conjunctival resection combined with tenon layer excision and the involvement of mast cells in superior limbic keratoconjunctivitis. Am J Ophthalmol. 2008;145(3):445-452. doi:10.1016/j.ajo.2007.10.025

9. Watanabe H, Maeda N, Kiritoshi A, Hamano T, Shimomura Y, Tano Y. Expression of a mucin-like glycoprotein produced by ocular surface epithelium in normal and keratinized cells. Am J Ophthalmol. 1997;124(6):751-757. doi:10.1016/S0002-9394(14)71691-5

10. Matsuda A, Tagawa Y, Matsuda H. TGF-beta2, tenascin, and integrin beta1 expression in superior limbic keratoconjunctivitis. Jpn J Ophthalmol. 1999;43(4):251-256. doi:10.1016/S0021-5155(99)00021-0

11. Matsuda A, Tagawa Y, Matsuda H. Cytokeratin and proliferative cell nuclear antigen expression in superior limbic keratoconjunctivitis. Curr Eye Res. 1996;15(10):1033-1038. doi:10.3109/02713689609017652

12. Shoughy SS. Topical tacrolimus in anterior segment inflammatory disorders. Eye Vis (Lond). 2017;4:7. doi:10.1186/s40662-017-0072-z

13. Takahashi Y, Ichinose A, Kakizaki H. Topical rebamipide treatment for superior limbic keratoconjunctivitis in patients with thyroid eye disease. Am J Ophthalmol. 2014;157(4):807-812.e2. doi:10.1016/j.ajo.2013.12.027

14. Perry HD, Doshi-Carnevale S, Donnenfeld ED, Kornstein HS. Topical cyclosporine A 0.5% as a possible new treatment for superior limbic keratoconjunctivitis. Ophthalmology. 2003;110(8):1578-1581. doi:10.1016/S0161-6420(03)00538-4

15. Udell IJ, Guidera AC, Madani-Becker J. Ketotifen fumarate treatment of superior limbic keratoconjunctivitis. Cornea. 2002;21(8):778-780. doi:10.1097/00003226-200211000-00009

16. Goto E, Shimmura S, Shimazaki J, Tsubota K. Treatment of superior limbic keratoconjunctivitis by application of autologous serum. Cornea. 2001;20(8):807-810. doi:10.1097/00003226-200111000-00006

17. Confino J, Brown SI. Treatment of superior limbic keratoconjunctivitis with topical cromolyn sodium. Ann Ophthalmol. 1987;19(4):129-131.

18. Grutzmacher RD, Foster RS, Feiler LS. Lodoxamide tromethamine treatment for superior limbic keratoconjunctivitis. Am J Ophthalmol. 1995;120(3):400-402. doi:10.1016/s0002-9394(14)72177-4

19. Chun YS, Kim JC. Treatment of superior limbic keratoconjunctivitis with a large-diameter contact lens and botulium toxin A. Cornea. 2009;28(7):752-758. doi:10.1097/ICO.0b013e3181967006

20. Shen YC, Wang CY, Tsai HY, Lee YF. Supratarsal triamcinolone injection in the treatment of superior limbic keratoconjunctivitis. Cornea. 2007;26(4):423-426. doi:10.1097/ICO.0b013e318030d23

21. Mayer N, Kondapalli SSA, Venkateswaran N, Saeed HN. The efficacy of an irrigating eyelid retractor-facilitated ocular rinse on MMP-9 expression and dry eye disease. Adv Ophthalmol Pract Res. 2024;4(3):142-146. doi:10.1016/j.aopr.2024.05.002

22. Kim A, Postnikoff CK, Nichols KK. Non pharmaceutical eye wash may reduce matrix metalloprotease-9 (MMP-9) in dry eye. Invest Ophthalmol Vis Sci. 2020;61(7):100.