Table 1.

Summary of studies using LIF for the treatment of dry eye

Reference	Evidence leveli	n	Population	Dose/treatment length	Efficacy		Side effects
					LIF vs control	LIF vs baseline*
Semba et al150	Level 1A Phase II, multicenter, randomized, double-blind, vehicle-controlled study	230	Americans ≥18 years old with the following: • Established history of bilateral dry eye • Use or desire to use AT substitute in the past 6 months • Conjunctival redness in any eye • CSS ≥2 in any eye • Schl >1 and <10 in any eye • BCVA ≥0.7 logMAR in both eyes • CAE-induced increase in ICSS >1 point in designated eye • CAE-induced increase in ODS >1 point in designated eye	LIF 0.1%, 1%, 5% vs vehicle twice daily for 84 days with CAE for 90 minutes at days 14, 42, and 84 of treatment	LIF better: Signs: ICSS (84 days with 1% and 5% LIF), Schl (14 days with 5% LIF) Symptoms: OSDI (14 days in all, 84 days with 1% LIF) VR-OSDI (14 and 84 days with 1% and 5% LIF), VAS (84 days, burning/stinging only) No difference: VAS, TBUT, conjSS, blink rate, ODS	Symptoms: ODS, VAS-EDS, VAS (photophobia)	• Instillation site irritation • Mild and transient
Sheppard et al151	Level 1A Phase III, multicenter, randomized, double-blind, vehicle-controlled study	588	Americans ≥18 years old with the following: • Established history of bilateral dry eye • Use or desire to use AT substitute in the past 6 months • Conjunctival redness in any eye • CSS ≥2 in any eye • Schl >1 and <10 in any eye • BCVA ≥0.7 logMAR in both eyes • CAE-induced increase in ICSS ≥1 point in designated eye • Intra-CAE ODS ≥3 or ≥4 if baseline pre-CAE was 3	LIF 5% vs vehicle twice daily for 84 days. No CAE during treatment	LIF better: Signs: ICSS (84 days), SCSS (84 days), CSS (84 days), nasal conjSS (14 and 84 days), conjSS (14 and 84 days) Symptoms: ODS (84 days), VAS-EDS (42 and 84 days) No difference: Schl, VR-OSDI, OSDI, VAS	Signs: Schl	• Instillation site irritation and discomfort, mild to moderate, transient • Dysgeusia
Tauber et al152	Level 1A Phase III, multicenter, randomized, double-blind, vehicle-controlled study	718	Americans ≥18 years old with the following: • Self-reported history of dry eye • AT use within 30 days • BCVA ≥0.7 logMAR in both eyes • CSS ≥2 in ≥1 eye region, CRS ≥1 in ≥1 eye • VAS-EDS ≥40 • Schl ≥1 and ≤10 in designated eye • ICSS ≥0.5 in designated eye	LIF 5% vs vehicle twice daily for 84 days	LIF better: Signs: None Symptoms: VAS-EDS (14, 42, and 84 days), ODS (84 days), VAS-eye discomfort score (84 days) No difference: ICSS, TCSS, nasal conjSS	Signs: ICSS, nasal conjSS, TCSS	• Instillation site irritation • Eye irritation • Blepharitis • Reduced visual acuity and blurred vision
Holland et al153	Level 1A Phase III, multicenter, randomized, double-blind, vehicle-controlled study	711	Americans ≥18 years old with the following: • Self-reported history of dry eye • AT use within 30 days • BCVA ≥0.7 logMAR in both eyes • CSS ≥2 in ≥1 region in ≥1 eye, CRS ≥1 in ≥1 eye • VAS-EDS ≥40 in both eyes • Schl ≥1 and ≤10 in designated eye • ICSS ≥0.5 in designated eye	LIF 5% vs vehicle at twice daily for 84 days	LIF better: Signs: ICSS (84 days, ad hoc analysis) Symptoms: VAS-EDS (14, 42, and 84 days), VAS (itching, foreign body sensation, eye discomfort only at 42 days) No difference: ODS, VAS (burning, photophobia, pain)		• Instillation site irritation • Instillation site reaction • Dysgeusia • Mostly mild to moderate

Notes:

ⁱEach study has been categorized from Level 1 through 4 as follows: Level 1A- a randomized, double-masked design; Level 1B- a randomized, double-masked design, with weak patient masking due to significant variations in treatment vs placebo side effect profiles; Level 2A- randomized, single-masked design; Level 2B- a randomized, single-masked design, with weak masking due to significant variations in treatment vs placebo side effect profiles; Level 3- randomized, non-masked; Level 4- nonrandomized, non-masked. Primary end points are shown in bold, while secondary end points are shown in italics.

^*Signs and symptoms are listed where the LIF group had improved parameters compared to baseline but not compared to control.

Abbreviations: AT, artificial tears; BCVA, best-corrected visual acuity; CAE, controlled adverse environment; conjSS, conjunctival staining score; CRS, conjunctival redness score; CSS, corneal staining score; ICSS, inferior corneal staining score; LIF, lifitegrast; logMAR, log of minimum angle of resolution; ODS, ocular discomfort score; OSDI, Ocular Surface Disease Index; SCSS, superior corneal staining score; Schl, Schirmer’s without anesthesia; TBUT, tear breakup time; TCSS, total corneal staining score; VAS, visual analog scale; VAS-EDS, visual analog scale eye dryness score; VR-OSDI, vision-related subscale score of OSDI.