Skip to main content
Top
Published in: International Ophthalmology 3/2018

01-06-2018 | Original Paper

Efficacy and safety of 0.1% lodoxamide for the long-term treatment of superior limbic keratoconjunctivitis

Authors: Alejandro Rodriguez-Garcia, Yolanda Macias-Rodriguez, Jose M. Gonzalez-Gonzalez

Published in: International Ophthalmology | Issue 3/2018

Login to get access

Abstract

Purpose

To report the therapeutic efficacy and safety of topical 0.1% lodoxamide in the long-term treatment of superior limbic keratoconjunctivitis.

Methods

Sixty-seven eyes of 34 patients with active SLK were studied. Therapeutic response was analyzed according to modified-Ohashi parameters. All eyes were treated with 0.1% lodoxamide twice daily, and those with moderate or severe inflammation received a short course (7–14 days) of 0.1% fluorometholone acetate at presentation and during a relapse. Patients were evaluated at regular intervals and followed up for ≥3 months on continuous therapy. Primary endpoints included inflammatory response; rates of inflammatory control and remission; relapses while on therapy or on remission; and therapeutic failure rate.

Results

The mean follow-up time on lodoxamide therapy was 15.3 months. The majority of eyes (82.0%) achieved control of inflammation in a mean time of 2.2 months. Of these, 42 (76.3%) eyes remained under control while on therapy for 13.8 months. There was a significant improvement of SLK-related signs by the third month on therapy (p < 0.05). A total of 24 (35.8%) eyes achieved remission. Relapses presented in 12 (18.0%) treated eyes and in 4 (16.6%) eyes on remission. Only 5 (7.4%) eyes failed to respond to therapy. In the majority of cases (95.3%), lodoxamide 0.1% was well tolerated and minor adverse effects not requiring stopping the medication were reported in only 4.7% of patients.

Conclusions

Lodoxamide 0.1% is an efficacious therapeutic alternative for the treatment of active and chronic SLK. This medication has proved to be safe and well tolerated.
Literature
2.
go back to reference Theodore FH (1963) Superior limbic keratoconjunctivitis. Eye Ear Nose Throat 42:25–28 Theodore FH (1963) Superior limbic keratoconjunctivitis. Eye Ear Nose Throat 42:25–28
3.
go back to reference Wright P (1972) Superior limbic keratoconjunctivitis. Trans Ophthalmol Soc UK 92:555–560PubMed Wright P (1972) Superior limbic keratoconjunctivitis. Trans Ophthalmol Soc UK 92:555–560PubMed
5.
go back to reference Theodore FH, Ferry AP (1970) Superior limbic keratoconjunctivitis: clinical and pathologic correlations. Arch Ophthalmol 84:481–484CrossRefPubMed Theodore FH, Ferry AP (1970) Superior limbic keratoconjunctivitis: clinical and pathologic correlations. Arch Ophthalmol 84:481–484CrossRefPubMed
6.
go back to reference Mendoza-Adam G, Rodriguez-Garcia A (2013) Superior limbic keratoconjunctivitis (SLK) and its association to systemic diseases. Rev Mex Oftalmol 87:93–99 Mendoza-Adam G, Rodriguez-Garcia A (2013) Superior limbic keratoconjunctivitis (SLK) and its association to systemic diseases. Rev Mex Oftalmol 87:93–99
7.
go back to reference Kadrmas EF, Bartley GB (1995) Superior limbic keratoconjunctivitis: a prognostic sign for severe Grave´s ophthalmopathy. Ophthalmology 102:1472–1475CrossRefPubMed Kadrmas EF, Bartley GB (1995) Superior limbic keratoconjunctivitis: a prognostic sign for severe Grave´s ophthalmopathy. Ophthalmology 102:1472–1475CrossRefPubMed
8.
go back to reference Cher I (2000) Superior limbic keratoconjunctivitis: multifactorial mechanical pathogenesis. Clin Exp Ophthalmol 28:181–184CrossRefPubMed Cher I (2000) Superior limbic keratoconjunctivitis: multifactorial mechanical pathogenesis. Clin Exp Ophthalmol 28:181–184CrossRefPubMed
9.
go back to reference Eiferman RA, Wilkins EL (1979) Immunological aspects of superior limbic keratoconjunctivitis. Can J Ophthalmol 14:85–87PubMed Eiferman RA, Wilkins EL (1979) Immunological aspects of superior limbic keratoconjunctivitis. Can J Ophthalmol 14:85–87PubMed
10.
go back to reference Sun YC, Hsiao CH, Chen WL, Wang IJ, Hou YC, Hu FR (2008) Conjunctival resection combined with Tenon layer excision and the involvement of mast cells in superior limbic keratoconjunctivitis. Am J Ophthalmol 145:445–452CrossRefPubMed Sun YC, Hsiao CH, Chen WL, Wang IJ, Hou YC, Hu FR (2008) Conjunctival resection combined with Tenon layer excision and the involvement of mast cells in superior limbic keratoconjunctivitis. Am J Ophthalmol 145:445–452CrossRefPubMed
11.
go back to reference Goto E, Shimmura S, Shimazaki J, Tsubota K (2001) Treatment of superior limbic keratoconjunctivitis by application of autologous serum. Cornea 20:807–810CrossRefPubMed Goto E, Shimmura S, Shimazaki J, Tsubota K (2001) Treatment of superior limbic keratoconjunctivitis by application of autologous serum. Cornea 20:807–810CrossRefPubMed
12.
go back to reference Ohashi Y, Watanabe H, Kinoshita S, Hosotani H, Umemoto M, Manabe R (1998) Vitamin-A eye drops for superior limbic keratoconjunctivitis. Am J Ophthalmol 105:523–527CrossRef Ohashi Y, Watanabe H, Kinoshita S, Hosotani H, Umemoto M, Manabe R (1998) Vitamin-A eye drops for superior limbic keratoconjunctivitis. Am J Ophthalmol 105:523–527CrossRef
13.
go back to reference Donshik PC, Collin HB, Foster CS, Cavanagh HD, Boruchoff SA (1978) Conjunctival resection treatment and ultrastructural histopathology of superior limbic keratoconjunctivitis. Am J Ophthalmol 85:101–110CrossRefPubMed Donshik PC, Collin HB, Foster CS, Cavanagh HD, Boruchoff SA (1978) Conjunctival resection treatment and ultrastructural histopathology of superior limbic keratoconjunctivitis. Am J Ophthalmol 85:101–110CrossRefPubMed
14.
go back to reference Passons GA, Wood TO (1984) Conjunctival resection for superior limbic keratoconjunctivitis. Ophthalmology 91:966–968CrossRefPubMed Passons GA, Wood TO (1984) Conjunctival resection for superior limbic keratoconjunctivitis. Ophthalmology 91:966–968CrossRefPubMed
15.
go back to reference Udell IJ, Kenyon KR, Sawa M, Dohlman CH (1986) Treatment of superior limbic keratoconjunctivitis by thermocauterization of the superior bulbar conjunctiva. Ophthalmology 93:162–166CrossRefPubMed Udell IJ, Kenyon KR, Sawa M, Dohlman CH (1986) Treatment of superior limbic keratoconjunctivitis by thermocauterization of the superior bulbar conjunctiva. Ophthalmology 93:162–166CrossRefPubMed
16.
go back to reference Mondino BJ, Zaidman GW, Salamon SW (1982) Use of pressure patching and soft contact lenses in superior limbic keratoconjunctivitis. Arch Ophthalmol 100:1932–1934CrossRefPubMed Mondino BJ, Zaidman GW, Salamon SW (1982) Use of pressure patching and soft contact lenses in superior limbic keratoconjunctivitis. Arch Ophthalmol 100:1932–1934CrossRefPubMed
17.
go back to reference Yang HY, Fujishima H, Toda I, Shimazaki J, Tsubota K (1997) Lacrimal punctal occlusion for the treatment of superior limbic keratoconjunctivitis. Am J Ophthalmol 124:80–87CrossRefPubMed Yang HY, Fujishima H, Toda I, Shimazaki J, Tsubota K (1997) Lacrimal punctal occlusion for the treatment of superior limbic keratoconjunctivitis. Am J Ophthalmol 124:80–87CrossRefPubMed
18.
go back to reference Kabat AG (1998) Lacrimal occlusion therapy for the treatment of superior limbic keratoconjunctivitis. Optom Vis Sci 75:714–718CrossRefPubMed Kabat AG (1998) Lacrimal occlusion therapy for the treatment of superior limbic keratoconjunctivitis. Optom Vis Sci 75:714–718CrossRefPubMed
19.
go back to reference Shen YC, Wang CY, Tsai HY, Lee YF (2007) Supratarsal triamcinolone injection in the treatment of superior limbic keratoconjunctivitis. Cornea 26:423–426CrossRefPubMed Shen YC, Wang CY, Tsai HY, Lee YF (2007) Supratarsal triamcinolone injection in the treatment of superior limbic keratoconjunctivitis. Cornea 26:423–426CrossRefPubMed
20.
go back to reference Fraunfelder FW (2009) Liquid nitrogen cryotherapy of superior limbic keratoconjunctivitis. Am J Ophthalmol 147:234–238CrossRefPubMed Fraunfelder FW (2009) Liquid nitrogen cryotherapy of superior limbic keratoconjunctivitis. Am J Ophthalmol 147:234–238CrossRefPubMed
21.
go back to reference Chun YS, Kim JC (2014) Treatment of superior limbic keratoconjunctivitis using botulinum toxin A. Korean J Optom Vis SCi 13:46–52 Chun YS, Kim JC (2014) Treatment of superior limbic keratoconjunctivitis using botulinum toxin A. Korean J Optom Vis SCi 13:46–52
22.
go back to reference Liu J, Sheha H, Fu Y, John T, Tseng SC (2011) A new surgical approach of amniotic membrane transplantation for superior limbic keratoconjunctivitis. Techn Ophthalmol 9:41–43CrossRef Liu J, Sheha H, Fu Y, John T, Tseng SC (2011) A new surgical approach of amniotic membrane transplantation for superior limbic keratoconjunctivitis. Techn Ophthalmol 9:41–43CrossRef
23.
go back to reference Gris O, Plazas A, Lerma E, Güell JL, Pelegrín L, Elíes D (2010) Conjunctival resection with and without amniotic membrane graft for the treatment of superior limbic keratoconjunctivitis. Cornea 29:1025–1030CrossRefPubMed Gris O, Plazas A, Lerma E, Güell JL, Pelegrín L, Elíes D (2010) Conjunctival resection with and without amniotic membrane graft for the treatment of superior limbic keratoconjunctivitis. Cornea 29:1025–1030CrossRefPubMed
24.
go back to reference Ahn JM, Choi CY, Seo KY (2014) Surgical approach with high-frequency radiowave electrosurgery for superior limbic keratoconjunctivitis. Cornea 33:210–214CrossRefPubMed Ahn JM, Choi CY, Seo KY (2014) Surgical approach with high-frequency radiowave electrosurgery for superior limbic keratoconjunctivitis. Cornea 33:210–214CrossRefPubMed
25.
go back to reference Kim WS, Wee SW, Kim JC (2014) Two cases of superior limbic keratoconjunctivitis treated with bevacizumab and triamcinolone injection. J Korean Ophthalmol Soc 55:443–448CrossRef Kim WS, Wee SW, Kim JC (2014) Two cases of superior limbic keratoconjunctivitis treated with bevacizumab and triamcinolone injection. J Korean Ophthalmol Soc 55:443–448CrossRef
26.
go back to reference Sanchez JC, Mesa D, Avendafio E (2013) Superior limbic keratoconjunctivitis. In: Benitez del Castillo JM, Lemp MA (eds) Ocular surface disorders, vol 25. JP Medical, LTD, New Delhi, pp 215–219 Sanchez JC, Mesa D, Avendafio E (2013) Superior limbic keratoconjunctivitis. In: Benitez del Castillo JM, Lemp MA (eds) Ocular surface disorders, vol 25. JP Medical, LTD, New Delhi, pp 215–219
27.
go back to reference Bonini S, Schiavone M, Bonini S, Magrini L, Lischetti P, Lambiase A, Bucci MG (1997) Efficacy of lodoxamide eye drops on mast cells and eosinophils after allergen challenge in allergic conjunctivitis. Ophthalmology 104:849–853CrossRefPubMed Bonini S, Schiavone M, Bonini S, Magrini L, Lischetti P, Lambiase A, Bucci MG (1997) Efficacy of lodoxamide eye drops on mast cells and eosinophils after allergen challenge in allergic conjunctivitis. Ophthalmology 104:849–853CrossRefPubMed
28.
go back to reference Yanni JM, Weimer LK, Glaser RL, Lang LS, Robertson SM, Spellman JM (1993) Effect of lodoxamide on in vitro and in vivo conjunctival immediate hypersensitivity responses in rats. Int Arch Allergy Immunol 101:102–106CrossRefPubMed Yanni JM, Weimer LK, Glaser RL, Lang LS, Robertson SM, Spellman JM (1993) Effect of lodoxamide on in vitro and in vivo conjunctival immediate hypersensitivity responses in rats. Int Arch Allergy Immunol 101:102–106CrossRefPubMed
29.
go back to reference Caldwell DR, Verin P, Hartwich-Young R (1992) Efficacy and safety of lodoxamide 0.1% versus cromolyn sodium 4% in patients with vernal keratoconjunctivitis. Am J Ophthalmol 113:632–637CrossRefPubMed Caldwell DR, Verin P, Hartwich-Young R (1992) Efficacy and safety of lodoxamide 0.1% versus cromolyn sodium 4% in patients with vernal keratoconjunctivitis. Am J Ophthalmol 113:632–637CrossRefPubMed
30.
go back to reference Denis D, Bloch-Michel E, Verin P, Sebastiani A, Tazartes M, Helleboid L, Di Giovanni A, Lecorvec M (1998) Treatment of common ocular allergic disorders; a comparison of lodoxamide and NAAGA. Br J Ophthalmol 82:1135–1138CrossRefPubMedPubMedCentral Denis D, Bloch-Michel E, Verin P, Sebastiani A, Tazartes M, Helleboid L, Di Giovanni A, Lecorvec M (1998) Treatment of common ocular allergic disorders; a comparison of lodoxamide and NAAGA. Br J Ophthalmol 82:1135–1138CrossRefPubMedPubMedCentral
31.
go back to reference Grutzmacher RD, Foster RS, Feiler LS (1995) Lodoxamide tromethamine treatment for superior limbic keratoconjunctivitis. Am J Ophthalmol 120:400–402CrossRefPubMed Grutzmacher RD, Foster RS, Feiler LS (1995) Lodoxamide tromethamine treatment for superior limbic keratoconjunctivitis. Am J Ophthalmol 120:400–402CrossRefPubMed
32.
go back to reference Khalil M, Malik TG, Munawar S (2013) Use of silver nitrate in superior limbic keratoconjunctivitis. Pak J Ophthalmol 29:181–182 Khalil M, Malik TG, Munawar S (2013) Use of silver nitrate in superior limbic keratoconjunctivitis. Pak J Ophthalmol 29:181–182
33.
go back to reference Takahashi Y, Ichinose A, Kakizaki H (2014) Topical rebamipide treatment for superior limbic keratoconjunctivitis in patients with thyroid eye disease. Am J Ophthalmol 157:807–812CrossRefPubMed Takahashi Y, Ichinose A, Kakizaki H (2014) Topical rebamipide treatment for superior limbic keratoconjunctivitis in patients with thyroid eye disease. Am J Ophthalmol 157:807–812CrossRefPubMed
34.
go back to reference Yokoi N, Komuro A, Maruyama K, Tsuzuki M, Miyajima S, Kinoshita S (2003) New surgical treatment for superior limbic keratoconjunctivitis and its association with conjunctivochalasis. Am J Ophthalmol 135:303–308CrossRefPubMed Yokoi N, Komuro A, Maruyama K, Tsuzuki M, Miyajima S, Kinoshita S (2003) New surgical treatment for superior limbic keratoconjunctivitis and its association with conjunctivochalasis. Am J Ophthalmol 135:303–308CrossRefPubMed
35.
go back to reference Sun YC, Hsiao CH, Chen WL, Hu FR (2011) Overexpression of matrix metalloproteinase-1 (MMP-1) and MMP-3 in superior limbic keratoconjunctivitis. Invest Ophthalmol Vis Sci 52:3701–3705CrossRefPubMed Sun YC, Hsiao CH, Chen WL, Hu FR (2011) Overexpression of matrix metalloproteinase-1 (MMP-1) and MMP-3 in superior limbic keratoconjunctivitis. Invest Ophthalmol Vis Sci 52:3701–3705CrossRefPubMed
36.
go back to reference Li DQ, Meller D, Liu Y, Tseng SC (2000) Overexpression of MMP-1 and MMP-3 by cultured conjunctivochalasis fibroblasts. Invest Ophthalmol Vis Sci 41:404–410PubMed Li DQ, Meller D, Liu Y, Tseng SC (2000) Overexpression of MMP-1 and MMP-3 by cultured conjunctivochalasis fibroblasts. Invest Ophthalmol Vis Sci 41:404–410PubMed
37.
go back to reference Matsuda A, Tagawa Y, Matsuda H (1996) Cytokeratin and proliferative cell nuclear antigen expression in superior limbic keratoconjunctivitis. Curr Eye Res 15:1033–1038CrossRefPubMed Matsuda A, Tagawa Y, Matsuda H (1996) Cytokeratin and proliferative cell nuclear antigen expression in superior limbic keratoconjunctivitis. Curr Eye Res 15:1033–1038CrossRefPubMed
38.
go back to reference Matsuda A, Tagawa Y, Matsuda H (1999) TGF-beta2, tenascin, and integrin beta1 expression in superior limbic keratoconjunctivitis. Jpn J Ophthalmol 43:251–256CrossRefPubMed Matsuda A, Tagawa Y, Matsuda H (1999) TGF-beta2, tenascin, and integrin beta1 expression in superior limbic keratoconjunctivitis. Jpn J Ophthalmol 43:251–256CrossRefPubMed
39.
go back to reference Kinet JP (2007) The essential role of mast cells in orchestrating inflammation. Immunol Rev 217:5–7CrossRefPubMed Kinet JP (2007) The essential role of mast cells in orchestrating inflammation. Immunol Rev 217:5–7CrossRefPubMed
40.
go back to reference Greiner JV, Peace DG, Baird RS, Allansmith MR (1985) Effects of eye rubbing on the conjunctiva as a model of ocular inflammation. Am J Ophthalmol 100:45–50CrossRefPubMed Greiner JV, Peace DG, Baird RS, Allansmith MR (1985) Effects of eye rubbing on the conjunctiva as a model of ocular inflammation. Am J Ophthalmol 100:45–50CrossRefPubMed
41.
go back to reference Murphy GF, Austen KF, Fonferko E, Sheffer AL (1987) Morphologically distinctive forms of cutaneous mast cell degranulation induced by cold and mechanical stimuli: an ultrastructural study. J Allergy Clin Immunol 80:603–611CrossRefPubMed Murphy GF, Austen KF, Fonferko E, Sheffer AL (1987) Morphologically distinctive forms of cutaneous mast cell degranulation induced by cold and mechanical stimuli: an ultrastructural study. J Allergy Clin Immunol 80:603–611CrossRefPubMed
42.
go back to reference Allakhverdi Z, Comeau MR, Jessup HK (2007) Thymic stromal lymphopoietin is released by human epithelial cells in response to microbes, trauma, or inflammation and potently activates mast cells. J Exp Med 204:253–258CrossRefPubMedPubMedCentral Allakhverdi Z, Comeau MR, Jessup HK (2007) Thymic stromal lymphopoietin is released by human epithelial cells in response to microbes, trauma, or inflammation and potently activates mast cells. J Exp Med 204:253–258CrossRefPubMedPubMedCentral
43.
go back to reference Sun YC, Liou HM, Shen EP, Hu FR (2015) Stem cell factor and thymic stromal lymphopoietin overexpression with correlation to mast cells in superior limbic keratoconjunctivitis. Cornea 34:1487–1492CrossRefPubMed Sun YC, Liou HM, Shen EP, Hu FR (2015) Stem cell factor and thymic stromal lymphopoietin overexpression with correlation to mast cells in superior limbic keratoconjunctivitis. Cornea 34:1487–1492CrossRefPubMed
44.
go back to reference Confino J, Brown SI (1987) Treatment of superior limbic keratoconjunctivitis with topical cromolyn sodium. Ann Ophthalmol 19:129–131PubMed Confino J, Brown SI (1987) Treatment of superior limbic keratoconjunctivitis with topical cromolyn sodium. Ann Ophthalmol 19:129–131PubMed
45.
go back to reference Udell IJ, Guidera AC, Madani-Becker J (2002) Ketotifen fumarate treatment of superior limbic keratoconjunctivitis. Cornea 21:778–780CrossRefPubMed Udell IJ, Guidera AC, Madani-Becker J (2002) Ketotifen fumarate treatment of superior limbic keratoconjunctivitis. Cornea 21:778–780CrossRefPubMed
46.
go back to reference Mantelli F, Santos MS, Petitti T, Sgrulletta R, Cortes M, Lambiase A, Bonini S (2007) Systematic review and meta-analysis of randomised clinical trials on topical treatments for vernal keratoconjunctivitis. Br J Ophthalmol 91:1656–1661CrossRefPubMedPubMedCentral Mantelli F, Santos MS, Petitti T, Sgrulletta R, Cortes M, Lambiase A, Bonini S (2007) Systematic review and meta-analysis of randomised clinical trials on topical treatments for vernal keratoconjunctivitis. Br J Ophthalmol 91:1656–1661CrossRefPubMedPubMedCentral
47.
go back to reference Sahin A, Bozkurt B, Irkec M (2008) Topical cyclosporine-A in the treatment of superior limbic keratoconjunctivitis: a long-term follow-up. Cornea 27:193–195CrossRefPubMed Sahin A, Bozkurt B, Irkec M (2008) Topical cyclosporine-A in the treatment of superior limbic keratoconjunctivitis: a long-term follow-up. Cornea 27:193–195CrossRefPubMed
48.
go back to reference Perry HD, Doshi-Carnevale S, Donnenfeld ED, Kornstein HS (2003) Topical cyclosporine A 0.5% as a possible new treatment for superior limbic keratoconjunctivitis. Ophthalmology 110:1578–1581CrossRefPubMed Perry HD, Doshi-Carnevale S, Donnenfeld ED, Kornstein HS (2003) Topical cyclosporine A 0.5% as a possible new treatment for superior limbic keratoconjunctivitis. Ophthalmology 110:1578–1581CrossRefPubMed
49.
go back to reference Kymionis GD, Klados NE, Kontadakis GA, Mikropoulos DG (2013) Treatment of superior limbic keratoconjunctivitis with topical tacrolimus 0.03% ointment. Cornea 32:1499–1501CrossRefPubMed Kymionis GD, Klados NE, Kontadakis GA, Mikropoulos DG (2013) Treatment of superior limbic keratoconjunctivitis with topical tacrolimus 0.03% ointment. Cornea 32:1499–1501CrossRefPubMed
50.
go back to reference Whitcup SM, Chan CC, Luyo DA, Bo P, Li Q (1996) Topical cyclosporine inhibits mast cell-mediated conjunctivitis. Invest Ophthalmol Vis Sci 37:2686–2693PubMed Whitcup SM, Chan CC, Luyo DA, Bo P, Li Q (1996) Topical cyclosporine inhibits mast cell-mediated conjunctivitis. Invest Ophthalmol Vis Sci 37:2686–2693PubMed
Metadata
Title
Efficacy and safety of 0.1% lodoxamide for the long-term treatment of superior limbic keratoconjunctivitis
Authors
Alejandro Rodriguez-Garcia
Yolanda Macias-Rodriguez
Jose M. Gonzalez-Gonzalez
Publication date
01-06-2018
Publisher
Springer Netherlands
Published in
International Ophthalmology / Issue 3/2018
Print ISSN: 0165-5701
Electronic ISSN: 1573-2630
DOI
https://doi.org/10.1007/s10792-017-0588-1

Other articles of this Issue 3/2018

International Ophthalmology 3/2018 Go to the issue