Table 1.

Study design and key results from clinical trials of LE/T

Study	Design (country)	Treatments and duration	Efficacy findings	Safety findings
				IOP	Other
Blepharokeratoconjunctivitis—adults
White et al. [24]	Multicenter, randomized, investigator-masked trial (US)	2 weeks of treatment with:  LE/T QID (n = 138)  DM/T QID (n = 138)	Mean (SD) change from baseline in composite signs and symptoms at day 15 (LE/T vs DM/T): − 15.2 (7.3) vs − 15.6 (7.7); P = NS Investigator global assessment of cured (Grade 0; LE/T vs DM/T) at day 3 (2.2% vs 0.7%), day 7 (20.1%; vs 16.5%), and day 15 (43.6%; vs 40.9%); P = NS for all time points	Mean (SD) IOP change (LE/T vs DM/T) from baseline to day 7 (− 0.1 [2.2] mm Hg vs 0.6 [2.3] mm Hg, P = 0.04), day 15 (− 0.1 [2.4] mm Hg vs 1.0 [3.0] mm Hg, P = 0.01), and overall (1.6 mm Hg vs 2.3 mm Hg, P = 0.02) ↑IOP (≥ 10 mm Hg): LE/T, n = 0; DM/T, n = 1 (0.7%)	≥ 1 ocular AE (LE/T vs DM/T): 2.9% vs 6.5%  LE/T: allergic conjunctivitis, eye irritation, eye pain, ↑IOP (1 subject each)  DM/T: ↓ lacrimation, foreign body sensation (1 subject each); punctate keratitis (2 subjects); ↑IOP (5 subjects) No serious ocular AEs  ≥ 1 nonocular AE (LE/T vs DM/T): 2.9% vs 2.9% Discontinuation due to AEs:  LE/T: 1 subject (headache)  DM/T: 1 subject (allergic conjunctivitis) No clinically meaningful changes in VA or biomicroscopy findings
Chen et al. [25]	Multicenter, randomized, investigator-masked trial (China)	2 weeks of treatment with:  LE/T QID (n = 180)  DM/T QID (n = 177)	Significant (P < 0.01) improvement from baseline to day 15 in composite signs and symptoms in both treatment groups Mean (SD) change from baseline in composite signs and symptoms at day 15 (LE/T vs DM/T): –  11.6 (4.6) vs − 12.4 (4.7); P = NS	Mean IOP change (LE/T vs DM/T) from baseline to day 3 (0.61 mm Hg vs 0.6 1.15 mm Hg, P = 0.02), day 7 (0.61 mm Hg vs 1.73 mm Hg, P < 0.01), and day 15 (1.33 mm Hg vs 2.43 mm Hg, P < 0.01) ↑IOP (≥ 10 mm Hg): LE/T, n = 6 (3.4%); DM/T, n = 13 (7.3%); P = NS One eye in the DM/T group had IOP ≥ 30 mm Hg	≥ 1 ocular AE (LE/T vs DM/T): 13.0% vs 23.2%  LE/T: dryness, bacterial keratitis, pain after application, superficial punctate keratitis (1 subject each), instillation site stinging (3 subjects), ↑IOP > 5 mm Hg (16 subjects)  DM/T: instillation site stinging (5 subjects), ↑IOP (36 subjects)  ≥ 1 nonocular AE (LE/T vs DM/T): 2.2% vs 1.7% No serious AEs Discontinuation due to AEs:  LE/T: 4 subjects (headache)  DM/T: 7 subjects No differences between groups in VA or biomicroscopy findings
Rhee and Mah [21]	Single-center, randomized, double-masked trial (US)	3–5 days of treatment with:  LE/T BID (n = 20)  DM/T BID (n = 20)	Severity scores (lower is better) after 3–5 days of treatment (LE/T vs DM/T):  Blepharitis: 1.35 vs 0.9 (P = 0.02) Discharge: 0.6 vs 0.2 (P = 0.03)  Conjunctivitis: 0.6 vs 0.15 (P = 0.01)  Total ocular surface: 3.4 vs 1.8 (P = 0.01) No significant difference between groups in corneal punctate epithelial keratopathy scores	No differences between groups in IOP findings (mean IOP similar before and after treatment in both groups) No ↑IOP (≥ 10 mm Hg)	No AEs reported No clinically meaningful changes in VA
Blepharitis—pediatric
Comstock et al. [26]	Multicenter, randomized, double-masked trial (US)	Warm compresses BID plus:  LE/T QID week 1, BID week 2 (n = 72)  Vehicle QID week 1, BID week 2 (n = 36)	Efficacy findings ambiguous due to improvements in all treatment groups and use of warm compresses throughout the study	No significant differences between groups on day 1, day 8, or day 15 of treatment No ↑IOP (≥ 10 mm Hg)	≥ 1 ocular AE (LE/T vs vehicle): 4.2% vs 5.6%  LE/T: Meibomian gland dysfunction, corneal staining (1 subject each), conjunctivitis (2 subjects)  Vehicle: Meibomian gland dysfunction, erythema of eyelid, eyelid edema (1 subject each) No significant differences between treatments in proportions of subjects with any specific ocular AE No serious ocular AEs  ≥ 1 nonocular AE (LE/T vs vehicle): 8.3% vs 5.6% Discontinuation due to AEs: 1 subject in LE/T group (rash) No clinically meaningful changes in VA in either treatment group or between treatment groups
Blepharoconjunctivitis—pediatric
Comstock et al. [26]	Multicenter, randomized, double-masked trial (US)	2 weeks of treatment with:  LE/T QID (n = 34)  LE 0.5% QID (n = 35)  Tobramycin 0.3% QID (n = 34)  Vehicle QID (n = 34)	Efficacy findings ambiguous due to improvements in all treatment groups	IOP not evaluated	≥ 1 ocular AE (LE/T vs LE vs tobramycin vs vehicle): 2.9% vs 11.4% vs 0.0% vs 0.0%  LE/T: eye pain (1 subject)  LE: eye pain, conjunctivitis, eye discharge, eye inflammation (1 subject each) No serious ocular AEs  ≥ 1 nonocular AE (LE/T vs LE vs tobramycin vs vehicle): 5.9% vs 17.1% vs 17.6% vs 15.2% Discontinuation due to AEs: 1 subject in the tobramycin group (respiratory distress) No clinically meaningful changes in VA in either treatment group or between treatment groups
Healthy volunteers
Holland et al. [23]	Multicenter, randomized, double-masked trial (US)	4 weeks of:  LE/T QID (n = 156)  DM/T QID (n = 150)	Efficacy not evaluated	Significant ↑IOP observed at all visits from day 3 to day 29 with DM/T (P < 0.01); no significant ↑IOP with LE/T at any visit ↑IOP significantly greater with DM/T vs LE/T at every study visit ↑IOP (≥ 10 mm Hg): LE/T, n = 3 (2.0%); DM/T, n = 11 (7.5%); P = 0.03	≥ 1 ocular AE (LE/T vs DMT): 14.7% vs 12.0%  LE/T: lacrimation increased, foreign body sensation in eyes, allergic conjunctivitis, corneal erosion (3 subjects each)  DM/T: lacrimation increased (1 subject), iridocyclitis, iritis (3 subjects each) ↑IOP reported as an AE for 3 (1.9%) subjects in LE/T group vs 13 (8.7%) in DM/T group (P < 0.01) Sinus headache occurred in 5 subjects in DM/T group (3.3%) vs none in LE/T group (P = 0.03) Reductions in VA of ≥ 2 lines from baseline observed in 14 (4.6%) eyes in LE/T group vs 23 (7.8%) in DM/T group; significant difference at day 3 only (0.6% vs 3.4%, P = 0.02) No clinically significant changes in biomicroscopy or undilated direct ophthalmoscopy results

AE adverse event, BID twice daily, DM/T dexamethasone 0.1%/tobramycin 0.3%, IOP intraocular pressure, LE loteprednol etabonate, LE/T loteprednol etabonate 0.5%/tobramycin 0.3%, NS not significant, QID 4 times daily, SD standard deviation, VA visual acuity