Approach Considerations

Superior limbic keratoconjunctivitis (SLK) has been associated with thyroid dysfunction, therefore, investigations into thyroid function, including thyroid-stimulating hormone (TSH), free thyroxine (T4), thyroid-stimulating immunoglobulin, or TSH–binding inhibitory immunoglobulin, may be appropriate. An endocrinologist consultation should be obtained to aid in this workup.

To evaluate for and/or rule out dry eye syndrome, which is often present with superior limbic keratoconjunctivitis (SLK), the Schirmer test, measurement of tear lake, and tear breakup time are used to evaluate for.

The following laboratory studies and tests should be considered:

Slit-lamp examination
Fluorescein and lissamine green staining or rose Bengal staining
Schirmer test
Thyroid function test
Autoimmune markers (anti-Ro [SS-A] and anti-La [SS-B] antibodies and cyclic citrullinated-peptide antibodies)

Histologic Findings

Surgical specimens taken from patients with superior limbic keratoconjunctivitis (SLK) who had not received treatment with silver nitrate demonstrate abnormal limbic epithelium with keratinized epithelial cells with dyskeratosis and acanthosis and balloon degeneration of some nuclei. The intracellular accumulation of glycogen in the epithelial cells of tissue sections of the bulbar conjunctiva has been documented. The conjunctival stroma demonstrates edema without significant inflammatory cellular infiltrate. In specimens obtained after silver nitrate treatment, significant numbers of inflammatory cells, including plasma cells, neutrophils, and lymphocytes, also are found in the epithelium and stroma.

Immunohistochemical pathologic examination of the abnormal conjunctiva in superior limbic keratoconjunctivitis demonstrates a lack of the typical mosaic pattern of the epithelium in the resulting keratinized cells before the patient undergoes treatment and upregulation of transforming growth factor-beta 2 and tenascin.^[14]In separate studies, increased expression of proliferating cell nuclear antigens and altered expression of cytokines,^[15]as well as the presence of involucrin,^[16]was shown. More recently, heightened levels of matrix metalloproteinases 1 and 3 have been detected in specimens with the clinical manifestations of SLK.^[17]

In vivo laser scanning confocal microscopy has been used to aid in the diagnosis and grading of severity of the unique manifestations of SLK.^[18]

Treatment & Management

Thygeson P, Kimura SJ. Chronic conjunctivitis. Trans Am Acad Ophthalmol Otolaryngol. 1963 Jul-Aug. 67:494-517. [QxMD MEDLINE Link].
Tenzel RR. Comments on superior limbic filamentous keratitis: II. Arch Ophthalmol. 1968 Apr. 79(4):508. [QxMD MEDLINE Link].
Corwin ME. Superior limbic keratoconjunctivitis. Am J Ophthalmol. 1968 Aug. 66(2):338-40. [QxMD MEDLINE Link].
Smolin G, Thoft RA. Superior limbic keratoconjunctivitis. In: Ostler HB, ed. The Cornea. 2nd ed. 1987. 1:296-9.
Stenson S. Superior limbic keratoconjunctivitis associated with soft contact lens wear. Arch Ophthalmol. 1983 Mar. 101(3):402-4. [QxMD MEDLINE Link].
Theodore FH. Comments on findings of elevated protein-bound iodine in superior limbic keratoconjunctivitis: I. Arch Ophthalmol. 1968 Apr. 79 (4):508. [QxMD MEDLINE Link].
Cher I. Superior limbic keratoconjunctivitis: multifactorial mechanical pathogenesis. Clin Experiment Ophthalmol. 2000 Jun. 28(3):181-4. [QxMD MEDLINE Link].
Sheu MC, Schoenfield L, Jeng BH. Development of superior limbic keratoconjunctivitis after upper eyelid blepharoplasty surgery: support for the mechanical theory of its pathogenesis. Cornea. 2007 May. 26(4):490-2. [QxMD MEDLINE Link].
Cher I. Blink-related microtrauma: when the ocular surface harms itself. Clin Experiment Ophthalmol. 2003 Jun. 31(3):183-90. [QxMD MEDLINE Link].
Espana EM, Shah S, Santhiago MR, Singh AD. Graft versus host disease: clinical evaluation, diagnosis and management. Graefes Arch Clin Exp Ophthalmol. 2013 May. 251 (5):1257-66. [QxMD MEDLINE Link].
Sun YC, Hsiao CH, Chen WL, et al. Conjunctival resection combined with tenon layer excision and the involvement of mast cells in superior limbic keratoconjunctivitis. Am J Ophthalmol. 2008 Mar. 145(3):445-452. [QxMD MEDLINE Link].
Sun YC, Liou HM, Shen EP, Hu FR. Stem Cell Factor and Thymic Stromal Lymphopoietin Overexpression With Correlation to Mast Cells in Superior Limbic Keratoconjunctivitis. Cornea. 2015 Nov. 34 (11):1487-92. [QxMD MEDLINE Link].
Zoroquiain P, Sanft DM, Esposito E, Cheema D, Dias AB, Burnier MN Jr. High Inflammatory Infiltrate Correlates With Poor Symptomatic Improvement After Surgical Treatment for Superior Limbic Keratoconjunctivitis. Cornea. 2018 Apr. 37 (4):495-500. [QxMD MEDLINE Link]. [Full Text].
Matsuda A, Tagawa Y, Matsuda H. TGF-beta2, tenascin, and integrin beta1 expression in superior limbic keratoconjunctivitis. Jpn J Ophthalmol. 1999 Jul-Aug. 43(4):251-6. [QxMD MEDLINE Link].
Matsuda A, Tagawa Y, Matsuda H. Cytokeratin and proliferative cell nuclear antigen expression in superior limbic keratoconjunctivitis. Curr Eye Res. 1996 Oct. 15(10):1033-8. [QxMD MEDLINE Link].
Saika S, Minamide A, Tanaka T, et al. Expression of involucrin by ocular surface epithelia of patients with benign and malignant disorders. Curr Eye Res. 2000 Nov. 21(5):877-85. [QxMD MEDLINE Link].
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 May. 52(6):3701-5. [QxMD MEDLINE Link].
Kojima T, Matsumoto Y, Ibrahim OM, Sato EA, Dogru M, Tsubota K. In vivo evaluation of superior limbic keratoconjunctivitis using laser scanning confocal microscopy and conjunctival impression cytology. Invest Ophthalmol Vis Sci. 2010 Aug. 51(8):3986-92. [QxMD MEDLINE Link].
Udell IJ, Kenyon KR, Sawa M, et al. Treatment of superior limbic keratoconjunctivitis by thermocauterization of the superior bulbar conjunctiva. Ophthalmology. 1986 Feb. 93(2):162-6. [QxMD MEDLINE Link].
Fraunfelder FW. Liquid nitrogen cryotherapy of superior limbic keratoconjunctivitis. Am J Ophthalmol. 2009 Feb. 147(2):234-238.e1. [QxMD MEDLINE Link].
Azari AA, Rapuano CJ. Autologous serum eye drops for the treatment of ocular surface disease. Eye Contact Lens. 2015 May. 41 (3):133-40. [QxMD MEDLINE Link].
Kojima T, Higuchi A, Goto E, Matsumoto Y, Dogru M, Tsubota K. Autologous serum eye drops for the treatment of dry eye diseases. Cornea. 2008 Sep. 27 Suppl 1:S25-30. [QxMD MEDLINE Link].
Chun YS, Kim JC. Treatment of superior limbic keratoconjunctivitis with a large-diameter contact lens and Botulium Toxin A. Cornea. 2009 Aug. 28(7):752-8. [QxMD MEDLINE Link].
Rodriguez-Garcia A, Macias-Rodriguez Y, Gonzalez-Gonzalez JM. Efficacy and safety of 0.1% lodoxamide for the long-term treatment of superior limbic keratoconjunctivitis. Int Ophthalmol. 2017 Jun 10. [QxMD MEDLINE Link].
Kymionis GD, Klados NE, Kontadakis GA, Mikropoulos DG. Treatment of superior limbic keratoconjunctivitis with topical tacrolimus 0.03% ointment. Cornea. 2013 Nov. 32(11):1499-501. [QxMD MEDLINE Link].
Shen YC, Wang CY, Tsai HY, et al. Supratarsal triamcinolone injection in the treatment of superior limbic keratoconjunctivitis. Cornea. 2007 May. 26(4):423-6. [QxMD MEDLINE Link].
Takahashi Y, Ichinose A, Kakizaki H. Topical rebamipide treatment for superior limbic keratoconjunctivitis in patients with thyroid eye disease. Am J Ophthalmol. 2014 Apr. 157 (4):807-812.e2. [QxMD MEDLINE Link].
Passons GA, Wood TO. Conjunctival resection for superior limbic keratoconjunctivitis. Ophthalmology. 1984 Aug. 91(8):966-8. [QxMD MEDLINE Link].
Kheirkhah A, Casas V, Esquenazi S, et al. New surgical approach for superior conjunctivochalasis. Cornea. 2007 Jul. 26(6):685-91. [QxMD MEDLINE Link].
Donshik PC, Collin HB, Foster CS, et al. Conjunctival resection treatment and ultrastructural histopathology of superior limbic keratoconjunctivitis. Am J Ophthalmol. 1978 Jan. 85(1):101-10. [QxMD MEDLINE Link].
Goto E, Shimmura S, Shimazaki J, et al. Treatment of superior limbic keratoconjunctivitis by application of autologous serum. Cornea. 2001 Nov. 20(8):807-10. [QxMD MEDLINE Link].
Yang HY, Fujishima H, Toda I, et al. Lacrimal punctal occlusion for the treatment of superior limbic keratoconjunctivitis. Am J Ophthalmol. 1997 Jul. 124(1):80-7. [QxMD MEDLINE Link].
Mondino BJ, Zaidman GW, Salamon SW. Use of pressure patching and soft contact lenses in superior limbic keratoconjunctivitis. Arch Ophthalmol. 1982 Dec. 100(12):1932-4. [QxMD MEDLINE Link].
Watson S, Tullo AB, Carley F. Treatment of superior limbic keratoconjunctivitis with a unilateral bandage contact lens. Br J Ophthalmol. 2002 Apr. 86(4):485-6. [QxMD MEDLINE Link].
Gris O, Plazas A, Lerma E, Güell JL, Pelegrín L, Elíes D. Conjunctival resection with and without amniotic membrane graft for the treatment of superior limbic keratoconjunctivitis. Cornea. 2010 Sep. 29(9):1025-30. [QxMD MEDLINE Link].
Ahn JM, Choi CY, Seo KY. Surgical approach with high-frequency radiowave electrosurgery for superior limbic keratoconjunctivitis. Cornea. 2014 Feb. 33(2):210-4. [QxMD MEDLINE Link].
Sahin A, Bozkurt B, Irkec M. Topical cyclosporine a in the treatment of superior limbic keratoconjunctivitis: a long-term follow-up. Cornea. 2008 Feb. 27(2):193-5. [QxMD MEDLINE Link].
Confino J, Brown SI. Treatment of superior limbic keratoconjunctivitis with topical cromolyn sodium. Ann Ophthalmol. 1987 Apr. 19(4):129-31. [QxMD MEDLINE Link].
Grutzmacher RD, Foster RS, Feiler LS. Lodoxamide tromethamine treatment for superior limbic keratoconjunctivitis. Am J Ophthalmol. 1995 Sep. 120(3):400-2. [QxMD MEDLINE Link].
Moshirfar M, Khalifa YM, Kuo A, Davis D, Mamalis N. Ocular surface squamous neoplasia masquerading as superior limbic keratoconjunctivitis. Middle East Afr J Ophthalmol. 2011 Jan. 18(1):74-6. [QxMD MEDLINE Link]. [Full Text].
Ohashi Y, Watanabe H, Kinoshita S, et al. Vitamin A eyedrops for superior limbic keratoconjunctivitis. Am J Ophthalmol. 1988 May 15. 105(5):523-7. [QxMD MEDLINE Link].
Perry HD, Doshi-Carnevale S, Donnenfeld ED, et al. Topical cyclosporine A 0.5% as a possible new treatment for superior limbic keratoconjunctivitis. Ophthalmology. 2003 Aug. 110(8):1578-81. [QxMD MEDLINE Link].
Bron AJ, de Paiva CS, Chauhan SK, Bonini S, Gabison EE, Jain S, et al. TFOS DEWS II pathophysiology report. Ocul Surf. 2017 Jul. 15 (3):438-510. [QxMD MEDLINE Link].
Sivaraman KR, Jivrajka RV, Soin K, Bouchard CS, Movahedan A, Shorter E, et al. Superior Limbic Keratoconjunctivitis-like Inflammation in Patients with Chronic Graft-Versus-Host Disease. Ocul Surf. 2016 Jul. 14 (3):393-400. [QxMD MEDLINE Link].

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Author

Jean Deschênes, MD, FRCSC Professor, Research Associate, Director, Uveitis Program, Department of Ophthalmology, McGill University Faculty of Medicine; Senior Ophthalmologist, Clinical Director, Department of Ophthalmology, Royal Victoria Hospital, Canada

Jean Deschênes, MD, FRCSC is a member of the following medical societies: American Academy of Ophthalmology, Association for Research in Vision and Ophthalmology, Canadian Medical Association, Canadian Ophthalmological Society, International Ocular Inflammation Society, Quebec Medical Association

Disclosure: Nothing to disclose.

Coauthor(s)

Jia Yue You, MDCM Resident Physician, Department of Ophthalmology, McGill University Faculty of Medicine, Canada

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Christopher J Rapuano, MD Professor, Department of Ophthalmology, Sidney Kimmel Medical College of Thomas Jefferson University; Director of the Cornea Service, Wills Eye Hospital

Christopher J Rapuano, MD is a member of the following medical societies: American Academy of Ophthalmology, American Ophthalmological Society, American Society of Cataract and Refractive Surgery, Contact Lens Association of Ophthalmologists, Cornea Society, Eye Bank Association of America, International Society of Refractive Surgery

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: AAO; OMIC; American Society of Ophthalmic Trauma (ASOT); Avellino, Baxis; Bio-Tissue; Celularity; Dompe; Emmecell; Glaukos; Kala; Oyster Point; Sun Ophthalmics; Tarsus; TearLab<br/>Serve(d) as a speaker or a member of a speakers bureau for: Glaukos; Dompe; Bio-Tissue<br/>Received research grant from: Glaukos<br/>Received income in an amount equal to or greater than $250 from: AAO; OMIC; Baxis; Bio-Tissue; Cellularity; Dompe; Glaukos; Kala; Sun Ophthalmics; TearLab<br/>stock options for: RPS, Fount Bio.

Chief Editor

Hampton Roy, Sr, MD † Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences

Hampton Roy, Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, Pan-American Association of Ophthalmology

Disclosure: Nothing to disclose.

Additional Contributors

James H Oakman, Jr, MD Partner, Southern Eye Center, Augusta, Georgia

James H Oakman, Jr, MD is a member of the following medical societies: Association of American Physicians and Surgeons, Georgia Medical Society, Georgia Society of Ophthalmology, Georgia Society of the American College of Surgeons, American Academy of Ophthalmology, American Society of Cataract and Refractive Surgery

Disclosure: Nothing to disclose.

Susan Ruyu Qi University of Montreal Faculty of Medicine, Canada

Disclosure: Nothing to disclose.

Sections Superior Limbic Keratoconjunctivitis (SLK)
Overview
Presentation
DDx
Workup
Treatment
Medication
References

Superior Limbic Keratoconjunctivitis (SLK) Workup

Approach Considerations

Histologic Findings

References

Tables

Contributor Information and Disclosures

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