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Advances in Therapy
Published in: Advances in Therapy 4/2016

Open Access 01-04-2016 | Review

Impact of the Topical Ophthalmic Corticosteroid Loteprednol Etabonate on Intraocular Pressure

Authors: John D. Sheppard, Timothy L. Comstock, Megan E. Cavet

Published in: Advances in Therapy | Issue 4/2016

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Abstract

Corticosteroids are a mainstay therapeutic option for the treatment of ocular inflammation. However, safety remains a concern for clinicians, particularly with long-term use. Though highly effective at suppressing inflammatory and allergic responses, topical ophthalmic corticosteroids carry an inherent risk of side effects, including elevated intraocular pressure (IOP), a risk factor for the development of glaucoma. The corticosteroid loteprednol etabonate (LE) contains an ester rather than a ketone at the C-20 position, minimizing the potential for side effects, including IOP elevation. In early pivotal clinical trials of LE ophthalmic suspension for conjunctivitis (allergic, giant papillary), anterior uveitis, and post-operative inflammation, LE had minimal impact on IOP over short-term (<28 days) and long-term (≥28 days) use. Since then, new LE formulations—including a gel, an ointment, and a suspension of LE in combination with tobramycin—have become commercially available. Multiple studies evaluating the safety and efficacy of LE for inflammatory conditions have been reported, including those requiring longer-term treatment such as photorefractive keratectomy, corneal transplantation, and dry eye disease. We review the available published data on the effect of LE on IOP and report on the cumulative incidence of clinically significant IOP elevations (≥10 mm Hg from baseline) with short-term and long-term LE use. In all studies, LE consistently demonstrated a low propensity to elevate IOP, regardless of formulation, dosage regimen, or treatment duration, including in known steroid responders. The cumulative proportion of patients exhibiting clinically significant IOP increases was 0.8% (14/1725 subjects) in studies evaluating short-term LE treatment and 1.5% (21/1386 subjects) in long-term studies. Furthermore, use of LE was associated with significantly lower rates of IOP elevation ≥10 mm Hg as compared to prednisolone acetate or dexamethasone (when used in combination with tobramycin). The cumulative data to date substantiates a favorable IOP-safety profile for LE with both short-term and long-term use.
Literature
1.
2.
Gupte R, Muse GW, Chinenov Y, Adelman K, Rogatsky I. Glucocorticoid receptor represses proinflammatory genes at distinct steps of the transcription cycle. Proc Natl Acad Sci USA. 2013;110(36):14616–21.CrossRefPubMedPubMedCentral
3.
Rhen T, Cidlowski JA. Antiinflammatory action of glucocorticoids–new mechanisms for old drugs. N Engl J Med. 2005;353(16):1711–23.CrossRefPubMed
4.
Sendrowski DP JSD, Semes LP, Stern ME Anti-inflammatory Drugs. In: Bartlett JD, JS, editor. Clinical Ocular Pharmacology: Elsevier 2008;12:221–44.
5.
Bielory BP, Perez VL, Bielory L. Treatment of seasonal allergic conjunctivitis with ophthalmic corticosteroids: in search of the perfect ocular corticosteroids in the treatment of allergic conjunctivitis. Curr Opin Allergy Clin Immunol. 2010;10(5):469–77.CrossRefPubMed
6.
Leonardi A. The central role of conjunctival mast cells in the pathogenesis of ocular allergy. Curr Allergy Asthma Rep. 2002;2(4):325–31.CrossRefPubMed
7.
McGhee CN, Dean S, Danesh-Meyer H. Locally administered ocular corticosteroids: benefits and risks. Drug Saf. 2002;25(1):33–55.CrossRefPubMed
8.
Pavesio CE, Decory HH. Treatment of ocular inflammatory conditions with loteprednol etabonate. Br J Ophthalmol. 2008;92(4):455–9.CrossRefPubMed
9.
Kersey JP, Broadway DC. Corticosteroid-induced glaucoma: a review of the literature. Eye (Lond). 2006;20(4):407–16.CrossRefPubMed
10.
11.
Razeghinejad MR, Myers JS, Katz LJ. Iatrogenic glaucoma secondary to medications. Am J Med. 2011;124(1):20–5.CrossRefPubMed
12.
Pleyer U, Ursell PG, Rama P. Intraocular pressure effects of common topical steroids for post-cataract inflammation: are they all the same? Ophthalmol Ther. 2013;2(2):55–72.CrossRefPubMedPubMedCentral
13.
Cantrill HL, Palmberg PF, Zink HA, Waltman SR, Podos SM, Becker B. Comparison of in vitro potency of corticosteroids with ability to raise intraocular pressure. Am J Ophthalmol. 1975;79(6):1012–7.CrossRefPubMed
14.
Armaly MF. Statistical attributes of the steroid hypertensive response in the clinically normal eye. I. The demonstration of three levels of response. Invest Ophthalmol. 1965;4:187–97.PubMed
15.
Becker B. Intraocular pressure response to topical corticosteroids. Invest Ophthalmol. 1965;4:198–205.PubMed
16.
17.
Chang DF, Tan JJ, Tripodis Y. Risk factors for steroid response among cataract patients. J Cataract Refract Surg. 2011;37(4):675–81.CrossRefPubMed
18.
Shukla D, Vidhya N, Prasad NM, Mahalakshmi R, Kolluru C, Krishnadas R. Evaluation of patient age as a risk factor for intraocular pressure elevation after intravitreal triamcinolone. Am J Ophthalmol. 2007;144(3):453–4.CrossRefPubMed
19.
Spaeth GL, Monteiro de Barros DS, Fudemberg SJ. Visual loss caused by corticosteroid-induced glaucoma: how to avoid it. Retina. 2009;29(8):1057–61.CrossRefPubMed
20.
Tripathi RC, Parapuram SK, Tripathi BJ, Zhong Y, Chalam KV. Corticosteroids and glaucoma risk. Drugs Aging. 1999;15(6):439–50.CrossRefPubMed
21.
22.
Bodor N. Designing safer ophthalmic drugs by soft drug approaches. J Ocul Pharmacol. 1994;10(1):3–15.CrossRefPubMed
23.
Bodor N, Buchwald P. Ophthalmic drug design based on the metabolic activity of the eye: soft drugs and chemical delivery systems. AAPS J. 2005;7(4):E820–33.CrossRefPubMedPubMedCentral
24.
Druzgala P, Hochhaus G, Bodor N. Soft drugs—10. Blanching activity and receptor binding affinity of a new type of glucocorticoid: loteprednol etabonate. J Steroid Biochem Mol Biol. 1991;38(2):149–54.CrossRefPubMed
25.
Druzgala P, Wu WM, Bodor N. Ocular absorption and distribution of loteprednol etabonate, a soft steroid, in rabbit eyes. Curr Eye Res. 1991;10(10):933–7.CrossRefPubMed
26.
A double-masked, placebo-controlled evaluation of 0.5% loteprednol etabonate in the treatment of postoperative inflammation. The Loteprednol Etabonate Postoperative Inflammation Study Group 2. Ophthalmology. 1998;105(9):1780–6.
27.
Controlled evaluation of loteprednol etabonate and prednisolone acetate in the treatment of acute anterior uveitis. Loteprednol Etabonate US Uveitis Study Group. Am J Ophthalmol. 1999;127(5):537–44.
28.
Asbell P, Howes J. A double-masked, placebo-controlled evaluation of the efficacy and safety of loteprednol etabonate in the treatment of giant papillary conjunctivitis. CLAO J. 1997;23(1):31–6.PubMed
29.
Dell SJ, Lowry GM, Northcutt JA, Howes J, Novack GD, Hart K. A randomized, double-masked, placebo-controlled parallel study of 0.2% loteprednol etabonate in patients with seasonal allergic conjunctivitis. J Allergy Clin Immunol. 1998;102(2):251–5.CrossRefPubMed
30.
Dell SJ, Shulman DG, Lowry GM, Howes J. A controlled evaluation of the efficacy and safety of loteprednol etabonate in the prophylactic treatment of seasonal allergic conjunctivitis. Loteprednol Allergic Conjunctivitis Study Group. Am J Ophthalmol. 1997;123(6):791–7.CrossRefPubMed
31.
Friedlaender MH, Howes J. A double-masked, placebo-controlled evaluation of the efficacy and safety of loteprednol etabonate in the treatment of giant papillary conjunctivitis. The Loteprednol Etabonate Giant Papillary Conjunctivitis Study Group I. Am J Ophthalmol. 1997;123(4):455–64.CrossRefPubMed
32.
Shulman DG, Lothringer LL, Rubin JM, et al. A randomized, double-masked, placebo-controlled parallel study of loteprednol etabonate 0.2% in patients with seasonal allergic conjunctivitis. Ophthalmology. 1999;106(2):362–9.CrossRefPubMed
33.
Stewart R, Horwitz B, Howes J, Novack GD, Hart K. Double-masked, placebo-controlled evaluation of loteprednol etabonate 0.5% for postoperative inflammation. Loteprednol Etabonate Post-operative Inflammation Study Group 1. J Cataract Refract Surg. 1998;24(11):1480–9.CrossRefPubMed
34.
Novack GD, Howes J, Crockett RS, Sherwood MB. Change in intraocular pressure during long-term use of loteprednol etabonate. J Glaucoma. 1998;7(4):266–9.CrossRefPubMed
35.
36.
Amon M, Busin M. Loteprednol etabonate ophthalmic suspension 0.5%: efficacy and safety for postoperative anti-inflammatory use. Int Ophthalmol. 2012;32(5):507–17.CrossRefPubMedPubMedCentral
37.
Coffey MJ, Decory HH, Lane SS. Development of a non-settling gel formulation of 0.5% loteprednol etabonate for anti-inflammatory use as an ophthalmic drop. Clin Ophthalmol. 2013;7:299–312.PubMedPubMedCentral
38.
Lane SS, Holland EJ. Loteprednol etabonate 0.5% versus prednisolone acetate 1.0% for the treatment of inflammation after cataract surgery. J Cataract Refract Surg. 2013;39(2):168–73.CrossRefPubMed
39.
Bannale SG, Pundarikaksha HP, Sowbhagya HN. A prospective, open-label study to compare the efficacy and the safety of topical loteprednol etabonate and topical flurbiprofen sodium in patients with post-operative inflammation after cataract extraction. J Clin Diagn Res. 2012;6(9):1499–503.PubMedPubMedCentral
40.
Holzer MP, Solomon KD, Sandoval HP, Vroman DT. Comparison of ketorolac tromethamine 0.5% and loteprednol etabonate 0.5% for inflammation after phacoemulsification: prospective randomized double-masked study. J Cataract Refract Surg. 2002;28(1):93–9.CrossRefPubMed
41.
Mifflin MD, Leishman LL, Christiansen SM, Sikder S, Hsu M, Moshirfar M. Use of loteprednol for routine prophylaxis after photorefractive keratectomy. Clin Ophthalmol. 2012;6:653–9.CrossRefPubMedPubMedCentral
42.
Erdurmus M, Cohen EJ, Yildiz EH, et al. Steroid-induced intraocular pressure elevation or glaucoma after penetrating keratoplasty in patients with keratoconus or Fuchs dystrophy. Cornea. 2009;28(7):759–64.CrossRefPubMed
43.
Holland EJ, Djalilian AR, Sanderson JP. Attenuation of ocular hypertension with the use of topical loteprednol etabonate 0.5% in steroid responders after corneal transplantation. Cornea. 2009;28(10):1139–43.CrossRefPubMed
44.
Bartlett JD, Horwitz B, Laibovitz R, Howes JF. Intraocular pressure response to loteprednol etabonate in known steroid responders. J Ocul Pharmacol. 1993;9(2):157–65.CrossRefPubMed
45.
The definition and classification of dry eye disease: report of the Definition and Classification Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf. 2007;5(2):75–92.
46.
47.
48.
Pflugfelder SC, Maskin SL, Anderson B, et al. A randomized, double-masked, placebo-controlled, multicenter comparison of loteprednol etabonate ophthalmic suspension, 0.5%, and placebo for treatment of keratoconjunctivitis sicca in patients with delayed tear clearance. Am J Ophthalmol. 2004;138(3):444–57.CrossRefPubMed
49.
Villani E, Garoli E, Termine V, Pichi F, Ratiglia R, Nucci P. Corneal confocal microscopy in dry eye treated with corticosteroids. Optom Vis Sci. 2015;92(9):e290–5.CrossRefPubMed
50.
Boynton GE, Raoof D, Niziol LM, Hussain M, Mian SI. Prospective randomized trial comparing efficacy of topical loteprednol etabonate 0.5% versus cyclosporine-A 0.05% for treatment of dry eye syndrome following hematopoietic stem cell transplantation. Cornea. 2015;34(7):725–32.CrossRefPubMed
51.
Sheppard JD, Scoper SV, Samudre S. Topical loteprednol pretreatment reduces cyclosporine stinging in chronic dry eye disease. J Ocul Pharmacol Ther. 2011;27(1):23–7.CrossRefPubMed
52.
Sheppard JD, Donnenfeld ED, Holland EJ, et al. Effect of loteprednol etabonate 0.5% on initiation of dry eye treatment with topical cyclosporine 0.05%. Eye Contact Lens. 2014;40(5):289–96.CrossRefPubMed
53.
Jung HH, Ji YS, Sung MS, Kim KK, Yoon KC. Long-Term outcome of treatment with topical corticosteroids for severe dry eye associated with Sjogren’s syndrome. Chonnam Med J. 2015;51(1):26–32.CrossRefPubMedPubMedCentral
54.
Lee H, Chung B, Kim KS, Seo KY, Choi BJ, Kim TI. Effects of topical loteprednol etabonate on tear cytokines and clinical outcomes in moderate and severe meibomian gland dysfunction: randomized clinical trial. Am J Ophthalmol. 2014;158(6):1172–83 e1.CrossRefPubMed
55.
Gong L, Sun X, Qu J, et al. Loteprednol etabonate suspension 0.2% administered QID compared with olopatadine solution 0.1% administered BID in the treatment of seasonal allergic conjunctivitis: a multicenter, randomized, investigator-masked, parallel group study in Chinese patients. Clin Ther. 2012;34(6):1259–72 e1.CrossRefPubMed
56.
Ilyas H, Slonim CB, Braswell GR, Favetta JR, Schulman M. Long-term safety of loteprednol etabonate 0.2% in the treatment of seasonal and perennial allergic conjunctivitis. Eye Contact Lens. 2004;30(1):10–3.CrossRefPubMed
57.
Oner V, Turkcu FM, Tas M, Alakus MF, Iscan Y. Topical loteprednol etabonate 0.5% for treatment of vernal keratoconjunctivitis: efficacy and safety. Jpn J Ophthalmol. 2012;56(4):312–8.CrossRefPubMed
58.
Berdy GJ, Stoppel JO, Epstein AB. Comparison of the clinical efficacy and tolerability of olopatadine hydrochloride 0.1% ophthalmic solution and loteprednol etabonate 0.2% ophthalmic suspension in the conjunctival allergen challenge model. Clin Ther. 2002;24(6):918–29.CrossRefPubMed
59.
Lu E, Fujimoto LT, Vejabul PA, Jew RL. Steroid-induced ocular hypertension with loteprednol etabonate 0.2%—a case report. Optometry. 2011;82(7):413–20.CrossRefPubMed
60.
Holland EJ, Bartlett JD, Paterno MR, Usner DW, Comstock TL. Effects of loteprednol/tobramycin versus dexamethasone/tobramycin on intraocular pressure in healthy volunteers. Cornea. 2008;27(1):50–5.CrossRefPubMed
61.
Thanathanee O, Sriphon P, Anutarapongpan O, et al. A randomized controlled trial comparing dexamethasone with loteprednol etabonate on postoperative photorefractive keratectomy. J Ocul Pharmacol Ther. 2015;31(3):165–8.CrossRefPubMed
62.
Rhee SS, Mah FS. Comparison of tobramycin 0.3%/dexamethasone 0.1% and tobramycin 0.3%/loteprednol 0.5% in the management of blepharo-keratoconjunctivitis. Adv Ther. 2007;24(1):60–7.CrossRefPubMed
63.
White EM, Macy JI, Bateman KM, Comstock TL. Comparison of the safety and efficacy of loteprednol 0.5%/tobramycin 0.3% with dexamethasone 0.1%/tobramycin 0.3% in the treatment of blepharokeratoconjunctivitis. Curr Med Res Opin. 2008;24(1):287–96.CrossRefPubMed
64.
Chen M, Gong L, Sun X, et al. A multicenter, randomized, parallel-group, clinical trial comparing the safety and efficacy of loteprednol etabonate 0.5%/tobramycin 0.3% with dexamethasone 0.1%/tobramycin 0.3% in the treatment of Chinese patients with blepharokeratoconjunctivitis. Curr Med Res Opin. 2012;28(3):385–94.CrossRefPubMed
65.
66.
Kwok AK, Lam DS, Ng JS, Fan DS, Chew SJ, Tso MO. Ocular-hypertensive response to topical steroids in children. Ophthalmology. 1997;104(12):2112–6.CrossRefPubMed
67.
Ohji M, Kinoshita S, Ohmi E, Kuwayama Y. Marked intraocular pressure response to instillation of corticosteroids in children. Am J Ophthalmol. 1991;112(4):450–4.CrossRefPubMed
68.
Comstock TL, Paterno MR, Bateman KM, Decory HH, Gearinger M. Safety and tolerability of loteprednol etabonate 0.5% and tobramycin 0.3% ophthalmic suspension in pediatric subjects. Paediatr Drugs. 2012;14(2):119–30.CrossRefPubMed
69.
Comstock TL, Paterno MR, Singh A, Erb T, Davis E. Safety and efficacy of loteprednol etabonate ophthalmic ointment 0.5% for the treatment of inflammation and pain following cataract surgery. Clin Ophthalmol. 2011;5:177–86.PubMedPubMedCentral
70.
Nguyen HT, Samudre SS, Lattanzio FA, Williams PB, Sheppard JD. Loteprednol etabonate (Lotemax 0.5%) reduces inflammatory response associated with pterygium progression. Invest Ophthalmol Vis Sci. 2008;49(13):6027.
71.
Sheppard JD, Mansur A, Comstock TL, Hovanesian JA. An update on the surgical management of pterygium and the role of loteprednol etabonate ointment. Clin Ophthalmol. 2014;8:1105–18.CrossRefPubMedPubMedCentral
72.
Fong R, Leitritz M, Siou-Mermet R, Erb T. Loteprednol etabonate gel 0.5% for postoperative pain and inflammation after cataract surgery: results of a multicenter trial. Clin Ophthalmol. 2012;6:1113–24.CrossRefPubMedPubMedCentral
73.
Rajpal RK, Roel L, Siou-Mermet R, Erb T. Efficacy and safety of loteprednol etabonate 0.5% gel in the treatment of ocular inflammation and pain after cataract surgery. J Cataract Refract Surg. 2013;39(2):158–67.CrossRefPubMed
74.
Abessi B, Schultze RL, Eden RA, Brooksby LM. Comparison of efficacy of difluprednate 0.05% and loteprednol gel 0.5% after cataract surgery. In: Paper presented at: American cataract and refractive surgery annual symposium and congress (ASCRS). 2015.
75.
Salinger CL, Gordon M, Jackson MA, Perl T, Donnenfeld E. A retrospective analysis of the postoperative use of loteprednol etabonate gel 0.5% following laser-assisted in situ keratomileusis or photorefractive keratectomy surgery. Clin Ophthalmol. 2015;9:2089–97.PubMedPubMedCentral
76.
Price MO, Feng MT, Scanameo A, Price FW Jr. Loteprednol etabonate 0.5% gel vs. prednisolone acetate 1% solution after descemet membrane endothelial keratoplasty: prospective randomized trial. Cornea. 2015;34(8):853–8.CrossRefPubMed
77.
Williams J, Evans D, Torkildesn G, Sheppard J. Safety and efficacy of Lotemax gel compared to Restasis in the treatment of inflammation associated with dry eye disease. In: Paper presented at Annual Meeting of American Academy of Optometry. 2014;Program Number 145034.
Metadata
Title
Impact of the Topical Ophthalmic Corticosteroid Loteprednol Etabonate on Intraocular Pressure
Authors
John D. Sheppard
Timothy L. Comstock
Megan E. Cavet
Publication date
01-04-2016
Publisher
Springer Healthcare
Published in
Advances in Therapy / Issue 4/2016
Print ISSN: 0741-238X
Electronic ISSN: 1865-8652
DOI
https://doi.org/10.1007/s12325-016-0315-8

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