. 2024 Jun 15;13(8):2083–2123. doi: 10.1007/s40123-024-00976-1

Table 2.

Summary of RCTs evaluating LipiFlow to treat MGD

Author/design/country	Patients (eyes)/age, mean (SD)	Last FU	Study arms	MG function Mean (SD)	Patient-reported outcomes Mean (SD)	NIKBUT/TBUT Mean (SD)	Staining	Overall conclusion and safety
Meng 2023 [22] Prospective, randomized, observer-masked China	N = 50 patients with MGD; LF: N = 25 patients (50 eyes), 58 (12) years; CL: N = 25 patients (50 eyes), 58 (12) years	3 months	Single 12-min LF Tx CL: Lid warming BID with EyeGiene Insta-Warmth patch and massage for 2 weeks	MGSS LF:8.8 (2.2) CL: 9.5 (3.1) MGYLS LF: 3.7 (0.85) CL: 4.1 (1.1)	MGSS LF:12.8 (3.9)* CL: 10.2 (3.3) MGYLS LF:5.5 (1.2)*† CL: 4.4 (1.2)	SPEED LF: 7.1 (2.7) CL: 7.2 (2.2)	SPEED LF: 3.8 (1.5)*† CL: 6.6 (2.8)	TBUT LF: 2.3 (0.96) CL: 2.7 (1.4)	TBUT LF: 5.6 (2.2)† CL: 4.0 (1.9)	Corneal LF: 2.8 (1.8) CL: 2.2 (1.3)	Corneal LF: 1.2 (1.2)* CL: 1.2 (1.2)	LF Tx can ameliorate subjective systems of MGD and markedly improve MG function for at least 3 months. Safety NR
Wesley 2022 [23] Prospective, randomized, multicenter, assessor-masked, parallel group USA	N = 236 patients with MGD; LF: 117 patients (234 eyes), 56 (14) years; iLUX: N = 119 (238 eyes), 58 (13) years	12 months	Single 12-min LF Tx Single Tx Systane iLux Dry Eye System thermal pulsation Note: LF was the control	MGSS LF: 6.5 (3.8) iLux: 6.6 (3.7)	MGSS LF: 23.4 (11.4) iLux: 22.9 (11.3)	IDEEL-SB LF: 57.2 (14.6) iLux: 55.8 (15.9)	IDEEL-SB LF: 36.0 (18.1) iLux: 34.4 (16.7)	NIKBUT LF: 8.0 (3.0) iLux: 8.0 (3.0)	NIKBUT LF: 10.1 (4.0) iLux: 10.7 (4.6)	Corneal LF: 1.9 (2.4) iLux: 2.1 (2.9)	Corneal LF: 0.6 (1.2) iLux: 0.7 (1.5)	iLux was noninferior to LF AEs None No significant biomicroscopy findings
Holland 2022 [24] Randomized single-masked, multicenter, non-inferiority, post-market USA	N = 235 patients with DED and MGD, LF:120 patients (240 eyes), 55 (15) years TearCare: 115 patients (230 eyes), 57 (14) years	1 month	Single 12-min LF Tx Single 15-min Tx with TearCare	NR	NR	OSDI LF:51.7 (15.3) TearCare: 51.7 (14.8) SANDE LF:77.2 (15.8) TearCare: 70.6 (16.8)	OSDI LF:27.1 (19.0)* TearCare: 22.6 (17.2)§ SANDE LF:34.0 (28.1) TearCare: 29.4 (26.6)*	NR	NR	NR	NR	LF and the TearCare consistently improved DED symptoms. Safety NR
Li 2021 [25] Prospective, randomized, observer-masked China	N = 54 patients with MGD (108 eyes), LF:54 eyes, 42 (11) years MiboFlo: 54 eyes, 44 (11) years	2 months after first Tx	Single 12-min LF Tx MiboFlo ThermoFlo Tx, three 10-min Tx, each 2 weeks apart. Tx was instantly followed by eyelid compression Note: LF was the control	MGSS LF: 11.0 (3.8) MiboFlo: 9.2 (3.7) MGYLS LF: 8.4 (3.7) MiboFlo: 8.7 (3.6)	MGSS LF: 4.8 (2.2)* MiboFlo: 4.8 (2.2)* MGYLS LF: 2.9 (2.8)* MiboFlo: 5.1 (2.3)*	OSDI LF: 46.1 (17.7) MiboFlo: 44.3 (1.0)	OSDI LF: 30.6 (19.9)* MiboFlo: 28.7 (18.2)*	NIKBUT LF: 5.8 (3.0) MiboFlo: 6.4 (3.5)	NIKBUT LF: 5.9 (2.7) MiboFlo: 6.0 (2.7)	Corneal LF: 0.38 (0.63) MiboFlo: 0.16 (0.43)	Corneal LF: 0.18 (0.50) MiboFlo: 0.02 (0.15)	OSDI, MGYLS, and MGSS improved from BL in both groups, and improvements were maintained at 2 months AEs None No safety-related changes in IOP or VA
Gupta 2022 [26] Randomized, masked, multicenter, controlled USA	N = 141 patients with DED; LF:72 patients (136 eyes), 52 (15) years; TearCare: 69 patients (134 eyes), 56 (14) years	1 month	Single 12-min LF Tx Single 15-min Tx with TearCare plus MGX Note: LF was the control	MGSS LF:6.29 TearCare: 6.54 MGYLS LF:5.62 TearCare: 5.42	MGSS LF:17.38* TearCare: 17.74* MGYLS LF:9.93* TearCare: 9.76*	OSDI LF:51.1 TearCare: 52.9 SANDE LF:73.2 TearCare: 68.4	OSDI LF:27.7* TearCare: 24.2* SANDE LF:33.8* TearCare: 30.1*	TBUT LF:4.49 TearCare: 4.62	TBUT LF:7.08* TearCare: 7.64*	Corneal LF:2.51 TearCare: 2.51 Conjunct LF:4.85 TearCare: 4.08	Corneal LF:1.93 TearCare: 2.25* Conjunct LF:4.07 TearCare: 3.43*	TearCare was as effective as LF at alleviating signs and symptoms of DED Device-related AEs LF: N = 4 (N = 1 blepharitis, N = 2 foreign body sensation, and N = 1 severe eye dryness) TearCare: N = 3 (N = 1 SPK, N = 1 chalazion, N = 1 blepharitis)
Booranapong 2020 [27] Prospective, observer-masked, randomized, controlled Thailand	N = 28 patients with moderate MGD (56 eyes), 54 (14) years; LF: 28 eyes; CL: contralateral eye (28 eyes)	6 months	Single 12-min LF Tx CL: warm compress for 5 min BID for 3 months	MGYLS LF: 2.6 (2.8) CL: 2.5 (2.3)	MGYLS LF: 3.1 (2.1) CL: 2.7 (2.2)	SPEED LF: 9.5 (4.5) CL: 9.2 (4.4)	SPEED LF: 7.8 (5.3)* CL: 7.9 (5.8)	NR	NR	NR	NR	Both Tx relieved symptoms AEs LF: N = NR (device-related AE of eye discomfort/pain among patients with small eyes, narrow palpebral fissure, or deep-set eyes)
Tauber 2020 [28] Randomized open-label, controlled, multicenter USA	N = 142 patients with DED and MGD, 55 (15) years LF: 70 patients (140 eyes), age NR; iLUX: N = 71 (142 eyes), age NR	1 month	Single 12-min LF Tx Single Tx Systane iLux Dry Eye System thermal pulsation Note: LF was the control in this study	MGSS LF OD: 6.2 (4.9) LF OS: 6.4 (4.4) iLux OD: 6.0 (3.7) iLux OS: 5.9 (4.1)	MGSS LF OD: 24.3 (11.2) * LF OS: 23.3 (11.9) * iLux OD: 23.2 (12.1)* iLux OS: 23.8 (11.4)*	OSDI LF: 50.6 (18.7) iLux: 50.7 (18.6)	OSDI LF: 22.6 (19.8) * iLux: 19.5 (17.0)*	TBUT LF OD: 3.9 (2.0) LF OS: 3.8 (2.0) iLux OD: 3.9 (1.9) iLux OS: 3.7 (1.8)	TBUT LF OD: 6.6 (3.2) * LF OS: 6.5 (3.1) * iLux OD: 6.7 (3.7)* iLux OS: 6.5 (3.6)*	Corneal LF OD: 2.0 (2.2) LF OS: 2.5 (2.6) iLux OD: 2.1 (2.2) iLux OS: 2.3 (2.2)	Corneal LF OD: 0.9 (1.6) * LF OS: 1.2 (1.6) * iLux OD: 1.5 (2.4)* iLux OS: 1.4 (2.2)*	Both Tx had significant improvements in MG function and symptoms Device-related AEs LF: N = 0 iLux: N = 4 patients (N = 2 burning sensations without skin findings and N = 1 petechial hemorrhaging in lower lids, N = 1 transient decrease in BSCVA with findings consistent with exposure keratitis). No other abnormal findings
Tauber 2020 [33] Single-center, 6-week, prospective, randomized, single-masked (investigator) USA	N = 50 patients with inflammatory MGD; LF: N = 25 patients (25 eyes), 67 (9) years; Liftegrast: N = 25 patients (25 eyes), 64 (8) years	42 days	Single 12-min LF Tx plus warm compress/lid compression BID Lifitegrast ophthalmic solution 5% BID plus warm compress/ lid compression BID for 42 days	MGSS LF: 1.8 (0.55) Lifitegrast: 2.1 (0.49) MG patency LF: 5.4 (2.1) Lifitegrast: 4.8 (2.9)	MGSS LF: 1.9 (0.81) Lifitegrast: 1.8 (0.97) MG patency LF: 5.3 (2.6) Lifitegrast: 6.1 (2.8)	VAS Dryness LF: 1.9 (0.83) Lifitegrast: 2.4 (0.70)	VAS Dryness LF: 1.4 (0.71) Lifitegrast: 1.4 (0.91)†	NR	NR	Corneal LF: 0.84 (0.85) Lifitegrast: 1.5 (1.0)	Corneal LF: 0.96 (0.98) Lifitegrast: 1.0 (1.3)†	Lifitegrast significantly improved symptoms and signs compared with LF AEs None
Ambaw 2020 [81] Single-center, investigator-masked interventional Singapore	N = 53 patients, LF: 35 patients (70 eyes); CL: 18 patients (36 eyes)	3 months	Single 12-min LF Tx CL: eyelid warming (warm towel, Blephasteam or Eyegiene) 3x/day for 3 months	NR	NR	NR	NR	NR	NR	NR	NR	Both Tx reduced pro-inflammatory molecules generated by lipoxygenase and oxidative stress
He 2018 [29] Single-blind, prospective, open-label, randomized, controlled China	N = 50 patients with MGD (100 eyes); LF: N = 25 patients (50 eyes), 40 (12) years; CL: N = 25 patients (50 eyes), 38 (12) years	3 months	Single 12-min LF Tx 15-min Tx with warm eye patch (EyeGiene Insta-Warmth) 1x/day for 2 weeks in office	MGYLS LF: 3.6 (3.8) CL: 4.2 (3.9)	MGYLS LF: 19.7 (1.0)* CL: 16.2 (10.8)	OSDI LF: 55.0 (18.0) CL: 47.3 (18.1)	OSDI LF: 27.5 (18.1)† CL: 34.2 (19.8)	TBUT LF: 6.9 (4.3) CL: 26.3 (6.2)	TBUT LF: 8.4 (3.7)*† CL: 19.0 (9.9)	Corneal + Conjunct LF:2.5 (0.8) CL: 2.5 (0.9)	Corneal + Conjunct LF:2.1 (0.3)*† CL: 2.3 (0.7)	Both LF and CL were effective at treating MGD. However, LF Tx was more effective and achieved better 3 months long-term efficacy than CL AEs None. No change in IOP
Blackie 2018 [34] Prospective, open-label, randomized, crossover, multicenter USA and Canada	N = 55 patients, contact lens wearer; LF: N = 29 patients (58 eyes), 40 (13) years CL: N = 26 patients (52 eyes), 44 (16) years; CO: N = 25 patients (50 eyes) in CL who were CO to LF	3 months; CO: 1 month	Single 12-min LF Tx plus blinking exercises for 1 month post-Tx to foster healthy blinking habits CL: untreated	MGSS LF: 8.0 (3.5) CL: 8.2 (4.2) MGYLS LF: 1.9 (1.6) CL: 2.1 (1.7)	MGSS LF: 20.4 (9.1)† CL: 9.6 (5.7) CO: 22.4 (9.4)† MGYLS LF: 7.1 (3.6)† CL: 2.5 (2.2) CO: 7.9 (3.6)†	SPEED LF: 14.5 (4.8) CL: 15.3 (4.5) OSDI LF: 39.6 (16.4) CL: 40.8 (20.3)	SPEED LF: 6.1 (4.6)† CL: 14.5 (5.3) CO: 7.4 (5.0)† OSDI LF: 13.4 (15.5)† CL: 37.5 (23.8) CO: 13.8 (11.2)†	TBUT LF: 4.8 (2.7) CL: 4.6 (2.0)	TBUT LF: 6.5 (4.0)† CL: 4.3 (1.7) CO: 5.3 (2.4)†	Conjunct LF: 3.5 (3.0) CL: 4.3 (3.6)	Conjunct LF: 3.4 (3.3)† CL: 5.6 (4.5) CO: 3.6 (3.7)	LF Tx improved signs and symptoms of DED and increased mean comfortable contact wearing time by 4 h, approximately doubling the comfortable wearing time, and was sustained for 3 months AEs None related to LF. N = 11 AEs unrelated LF (N = 5 ocular, N = 6 systemic). Slit-lamp findings not considered AEs were observed immediately after LF: eyelid edema, conjunctival edema, conjunctival hyperemia/injection, petechiae, and SPK and were transient and did not require Tx
Hagen 2018 [30] Prospective, randomized, parallel group, single-masked USA	N = 28 patients with moderate-to-severe MGD (50 eyes); LF: N = 14 patients (26 eyes), 52 (6) years; Doxy: N = 14 patients (24 eyes), 50 (14) years	3 months	Single 12-min LF Tx Oral doxy daily for 3 months (100 mg BID for the first 14 days and 100 mg 1x/day for days 15–90)	MGYLS LF:4.0 (1.5) Doxy: 4.6 (1.4)	MGYLS LF: 7.7 (5.5)* Doxy:10.6 (6.0)*	SPEED LF: 11.0 (3.3) Doxy: 13.4 (4.2)	SPEED LF: 5.4 (2.2)† Doxy: 9.4 (5.5)	TBUT LF:6.3 (2.0) Doxy: 6.9 (2.6)	TBUT LF: 8.4 (1.8)* Doxy: 7.6 (2.0)	Corneal LF: 0.4 (0.5) Doxy: 0.2 (0.4) Conjunct LF: 1.7 (1.9) Doxy: 2.4 (1.9)	Corneal LF:0.1 (0.3)* Doxy: 0.1 (0.3) Conjunct LF: 0.6 (0.8)* Doxy: 1.1 (1.5)*	LF was significantly more effective than doxy at treating signs and symptoms of MGD and was a favorable alternative to doxy AEs LF: N = 0 Doxy: N = 2 (stomach upset/intolerance)
Yeo 2016 [82] Singapore	N = 90 patients, LF: 24 patients (48 eyes) Hot towel: N = 22 patients (44 eyes), EyeGiene: N = 22 patients (44 eyes); Blephasteam: N = 22 patients (44 eyes)	3 months	Single 12-min LF Tx Details of other Tx NR	NR	NR	NR	NR	NR	NR	NR	NR	LF Tx significantly reduced tear evaporation rate
Finis 2014 [31] Prospective, randomized, crossover, observer-masked Germany This is a long-term FU of Finis 2014 [32]	N = 26 patients with MGD (52 eyes), 50 (22) years; LF: N = 17 patients (34 eyes), 45 (23) years; CL: N = 9 patients (18 eyes) with CL for 3 months prior to LF	6 months post-LF	Single 12-min LF Tx CL: Lid warming BID and massage for 3 months	MGYLS LF: 2.9 (1.6)	MGYLS LF: 6.4 (4.6)*	OSDI LF: 42 (19) SPEED LF: 16 (7) CL: 15.9 (6.6) CO: 14.7 (7.7)	OSDI LF: 33 (21)* SPEED LF: 12 (7)* CL: 14.7 (7.1) CO: 12.6 (6.5)	TBUT LF: 9.5 (8.7)	TBUT LF: 10.0 (6.7)	Corneal + Conjunct LF: 2.0 (2.0)	Corneal + Conjunct LF: 2.4 (2.3)	LF reduces subjective symptoms and objective measures of MGD over 6 months but has no effect on atrophy of MG as visualized by meibography. Safety NR
Finis 2014 [32] Prospective, randomized, crossover, observer-masked Germany	N = 31 patients with MGD; LF: N = 17 patients (34 eyes), 45 (23) years; CL: N = 14 patients, (28 eyes) 50 (19) years After completing the initial study, 9 CL patients (18 eyes) completed a 3-month CO with LF	3 months	Single 12-min LF Tx CL: Lid warming BID and massage for 3 months	MGYLS LF: 2.5 (1.4) CL: 2.1 (1.3) CO: 4.1 (2.5)	MGYLS LF: 5.5 (3.6)* CL: 4.6 (3.8)* CO:5.8 (3.2)	OSDI LF: 46.2 (14.8) CL: 40.1 (16.7) CO: 39.7 (26.3) SPEED LF: 16.8 (5.6) CL: 15.9 (6.6) CO: 14.7 (7.7)	OSDI LF: 34.6 (19.6)* CL: 40.0 (23.4) CO: 32.8 (24.4) SPEED LF: 14.5 (7.2) CL: 14.7 (7.1) CO: 12.6 (6.5)	NIBUT LF: 7.9 (8.5) CL: 7.7 (6.1) CO: 6.7 (6.1)	NIBUT LF: 9.9 (7.0) CL: 7.5 (6.1) CO: 7.3 (5.1)	Corneal + Conjunct LF: 2.6 (2.4) CL:1.9 (2.4) CO: 1.4 (1.4)	Corneal + Conjunct LF: 3.5 (2.7) CL:1.1 (1.4) CO: 3.0 (2.2)	Single LF Tx was at least as effective as a 3-month BID lid margin hygiene regimen. Safety NR
Baumann 2014 [35] Single-center, prospective, randomized France	N = 30 patients with moderate-to-severe DED and MGD; LF: N = 15 patients (30 eyes), 65 (12) years; CL: N = 15 patients (30 eyes), 65 (11) years	3 months	Single 12-min LF Tx plus blinking exercises CL: MeiboPatch heat mask for 10 min and massage for 10 min 1x/day for 3 months plus blinking exercises	MGYLS LF: 3.3 (1.7) CL: 5.7 (3.2)	MGYLS LF: 8.5 (2.4)* CL: 9.4 (4.3)*	OSDI LF: 51.0 (20.8) CL: 42.9 (20.3) SPEED LF: 16.5 (4.6) CL: 13.5 (3.1)	OSDI LF: 27.0 (17.6)* CL: 23.5 (15.3)* SPEED LF: 8.0 (5.3)* CL: 8.9 (5.2)*	TBUT LF: 4.5 (2.3) CL: 5.2 (2.2)	TBUT LF: 6.8 (2.5)* CL: 6.9 (2.2)*	Corneal + conjunct LF: 1.0 (1.1) CL:1.8 (1.2)	Corneal + conjunct LF: 0.4 (0.8)* CL:0.7 (0.7)*	LF Tx is highly effective in treating MGD. The results for 3 months of CL Tx were excellent, but not convenient for the patient Randomized but MGD more severe in LF group at BL Safety NR
Lane 2012 [14] Randomized, controlled, open-label, crossover, multicenter USA	N = 139 patients with MGD; LF: N = 69 patients (138 eyes), age NR; CL: N = 70 patients (140 eyes), age NR; CO: N = 68 patients (136 eyes) in CL group who were CO to LF	LF: 1 month; CL: 2 weeks; CO: 2 weeks	Single 12-min LF Tx CL: Warm compress (iHeat) for 5 min/day for 2 weeks	MGSS LF: 6.3 (3.5) CL: 5.6 (3.9) MGYLS LF: 0.6 (0.9) CL: 0.4 (0.8)	MGSS LF: 14.3 (8.7) at 2 weeks†; 16.7 (8.7) at 1 month CL: 6.1 (5.6) CO: 11.7 (7.3)† MGYLS LF: 2.0 (2.9) at 2 weeks†; 2.6 (3.6) at 1 month CL: 0.5 (1.1) CO: 1.2 (1.9)†	SPEED LF: 14.3 (4.8) CL: 14.8 (4.8) OSDI LF: 32.0 (20.0) CL: 34.7 (19.6)	SPEED LF: 8.1 (5.5) at 2 weeks†; 7.6 (5.8) at 1 month CL: 11.2 (5.4) CO: 7.9 (5.6)† OSDI LF: 17.3 (17.2) at 2 weeks†; 16.6 (18.1) at 1 month CL: 26.9 (18.2) CO: 21.0 (18.3)†	TBUT LF: 5.5 (2.9) CL: 5.4 (3.5)	TBUT LF: 6.9 (5.0) at 2 weeks†; 7.4 (5.5) at 1 month CL: 5.3 (3.5) CO: 6.3 (4.7)†	Corneal LF: 2.2 (2.2) Conjunct LF: 1.3 (2.1)	Corneal LF: 1.5 (1.7) at 1 month* Conjunct LF: 1.6 (2.5) at 1 month*	LF Tx improved signs and symptoms over 1 month The safety profile of LF Tx reflects a low occurrence of non-serious, transient side effects that resolve quickly and do not require medical treatment AEs LF: N = 4 (N = 3 eyelid pain, N = 1 conjunctival vascular injection) CL: N = 2 (burning) Mean discomfort score during LF Tx was 1.4 (scale 0–10). Slit-lamp findings not considered AEs most frequently were trace to mild conjunct injection, hyperemia, or redness; and trace or mild petechial hemorrhages on the eyelid or conjunct immediately or 1 day post-Tx, which fully resolved by the 2-week visit without Tx. No changes in the intraocular findings except for 1 case of posterior vitreous floaters unrelated to device

Author/design/country

Patients (eyes)/age, mean (SD)

Last FU

Study arms

MG function
Mean (SD)

Patient-reported outcomes
Mean (SD)

NIKBUT/TBUT
Mean (SD)

Staining

Overall conclusion and safety

Pre

Post

Pre

Post

Pre

Post

Pre

Post

Meng 2023 [22]

Prospective, randomized, observer-masked

China

N = 50 patients with MGD;

LF: N = 25 patients (50 eyes), 58 (12) years;

CL: N = 25

patients (50 eyes), 58 (12) years

3 months

Single 12-min LF Tx

CL: Lid warming BID with EyeGiene Insta-Warmth patch and massage for 2 weeks

MGSS

LF:8.8 (2.2)

CL: 9.5 (3.1)

MGYLS

LF: 3.7 (0.85)

CL: 4.1 (1.1)

MGSS

LF:12.8 (3.9)*

CL: 10.2 (3.3)

MGYLS

LF:5.5 (1.2)*†

CL: 4.4 (1.2)

SPEED

LF: 7.1 (2.7)

CL: 7.2 (2.2)

SPEED

LF: 3.8 (1.5)*†

CL: 6.6 (2.8)

TBUT

LF: 2.3 (0.96)

CL: 2.7 (1.4)

TBUT

LF: 5.6 (2.2)*†

CL: 4.0 (1.9)*

Corneal

LF: 2.8 (1.8)

CL: 2.2 (1.3)

Corneal

LF: 1.2 (1.2)*

CL: 1.2 (1.2)

LF Tx can ameliorate subjective systems of MGD and markedly improve MG function for at least 3 months.

Safety NR

Wesley 2022 [23]

Prospective, randomized, multicenter, assessor-masked, parallel group

USA

N = 236 patients with MGD;

LF: 117 patients (234 eyes), 56 (14) years;

iLUX: N = 119 (238 eyes), 58 (13) years

12 months

Single 12-min LF Tx

Single Tx Systane iLux Dry Eye System thermal pulsation

Note: LF was the control

MGSS

LF: 6.5 (3.8)

iLux: 6.6 (3.7)

MGSS

LF: 23.4 (11.4)

iLux: 22.9 (11.3)

IDEEL-SB

LF: 57.2 (14.6)

iLux: 55.8 (15.9)

IDEEL-SB

LF: 36.0 (18.1)

iLux: 34.4 (16.7)

NIKBUT

LF: 8.0 (3.0)

iLux: 8.0 (3.0)

NIKBUT

LF: 10.1 (4.0)

iLux: 10.7 (4.6)

Corneal

LF: 1.9 (2.4)

iLux: 2.1 (2.9)

Corneal

LF: 0.6 (1.2)

iLux: 0.7 (1.5)

iLux was noninferior to LF

AEs

None

No significant biomicroscopy findings

Holland 2022 [24]

Randomized single-masked, multicenter, non-inferiority, post-market

USA

N = 235 patients with DED and MGD, LF:120 patients (240 eyes), 55 (15) years

TearCare: 115 patients (230 eyes), 57 (14) years

1 month

Single 12-min LF Tx

Single 15-min Tx with TearCare

OSDI

LF:51.7 (15.3)

TearCare: 51.7 (14.8)

SANDE

LF:77.2 (15.8)

TearCare: 70.6 (16.8)

OSDI

LF:27.1 (19.0)*

TearCare: 22.6 (17.2)*§

SANDE

LF:34.0 (28.1)*

TearCare: 29.4 (26.6)*

LF and the TearCare consistently improved DED symptoms.

Safety NR

Li 2021 [25]

Prospective, randomized, observer-masked

China

N = 54 patients with MGD (108 eyes),

LF:54 eyes, 42 (11) years

MiboFlo: 54 eyes, 44 (11) years

2 months after first Tx

Single 12-min LF Tx

MiboFlo ThermoFlo Tx, three

10-min Tx, each 2 weeks apart. Tx was instantly followed by

eyelid compression

Note: LF was the control

MGSS

LF: 11.0 (3.8)

MiboFlo: 9.2 (3.7)

MGYLS

LF: 8.4 (3.7)

MiboFlo: 8.7 (3.6)

MGSS

LF: 4.8 (2.2)*

MiboFlo: 4.8 (2.2)*

MGYLS

LF: 2.9 (2.8)*

MiboFlo: 5.1 (2.3)*

OSDI

LF: 46.1 (17.7)

MiboFlo: 44.3 (1.0)

OSDI

LF: 30.6 (19.9)*

MiboFlo: 28.7 (18.2)*

NIKBUT

LF: 5.8 (3.0)

MiboFlo: 6.4 (3.5)

NIKBUT

LF: 5.9 (2.7)

MiboFlo: 6.0 (2.7)

Corneal

LF: 0.38 (0.63)

MiboFlo: 0.16 (0.43)

Corneal

LF: 0.18 (0.50)

MiboFlo: 0.02 (0.15)

OSDI, MGYLS, and MGSS improved from BL in both groups, and

improvements were maintained at 2 months

AEs

None

No safety-related changes in IOP or VA

Gupta 2022 [26]

Randomized, masked,

multicenter, controlled

USA

N = 141 patients with DED; LF:72 patients (136 eyes), 52 (15) years;

TearCare: 69 patients (134 eyes), 56 (14) years

1 month

Single 12-min LF Tx

Single 15-min Tx with TearCare plus MGX

Note: LF was the control

MGSS

LF:6.29

TearCare: 6.54

MGYLS

LF:5.62

TearCare: 5.42

MGSS

LF:17.38*

TearCare: 17.74*

MGYLS

LF:9.93*

TearCare: 9.76*

OSDI

LF:51.1

TearCare: 52.9

SANDE

LF:73.2

TearCare: 68.4

OSDI

LF:27.7*

TearCare: 24.2*

SANDE

LF:33.8*

TearCare: 30.1*

TBUT

LF:4.49

TearCare: 4.62

TBUT

LF:7.08*

TearCare: 7.64*

Corneal

LF:2.51

TearCare: 2.51

Conjunct

LF:4.85

TearCare: 4.08

Corneal

LF:1.93

TearCare: 2.25*

Conjunct

LF:4.07

TearCare: 3.43*

TearCare was as effective as LF at alleviating signs and symptoms of DED

Device-related AEs

LF: N = 4 (N = 1 blepharitis, N = 2 foreign body sensation, and N = 1 severe eye dryness)

TearCare: N = 3 (N = 1 SPK, N = 1 chalazion, N = 1 blepharitis)

Booranapong 2020 [27]

Prospective, observer-masked, randomized, controlled

Thailand

N = 28 patients with moderate MGD (56 eyes), 54 (14) years; LF: 28 eyes;

CL: contralateral eye (28 eyes)

6 months

Single 12-min LF Tx

CL: warm compress for 5 min BID for 3 months

MGYLS

LF: 2.6 (2.8)

CL: 2.5 (2.3)

MGYLS

LF: 3.1 (2.1)

CL: 2.7 (2.2)

SPEED

LF: 9.5 (4.5)

CL: 9.2 (4.4)

SPEED

LF: 7.8 (5.3)*

CL: 7.9 (5.8)

Both Tx relieved symptoms

AEs

LF: N = NR (device-related AE of eye discomfort/pain among

patients with small eyes, narrow palpebral fissure, or deep-set eyes)

Tauber 2020 [28]

Randomized open-label, controlled, multicenter

USA

N = 142 patients with DED and MGD, 55 (15) years

LF: 70 patients (140 eyes), age NR;

iLUX: N = 71 (142 eyes), age NR

1 month

Single 12-min LF Tx

Single Tx Systane iLux Dry Eye System thermal pulsation

Note: LF was the control in this study

MGSS

LF OD: 6.2 (4.9)

LF OS: 6.4 (4.4)

iLux OD: 6.0 (3.7)

iLux OS: 5.9 (4.1)

MGSS

LF OD: 24.3 (11.2) *

LF OS: 23.3 (11.9) *

iLux OD: 23.2 (12.1)*

iLux OS: 23.8 (11.4)*

OSDI

LF: 50.6 (18.7)

iLux: 50.7 (18.6)

OSDI

LF: 22.6 (19.8) *

iLux: 19.5 (17.0)*

TBUT

LF OD: 3.9 (2.0)

LF OS: 3.8 (2.0)

iLux OD: 3.9 (1.9)

iLux OS: 3.7 (1.8)

TBUT

LF OD: 6.6 (3.2) *

LF OS: 6.5 (3.1) *

iLux OD: 6.7 (3.7)*

iLux OS: 6.5 (3.6)*

Corneal

LF OD: 2.0 (2.2)

LF OS: 2.5 (2.6)

iLux OD: 2.1 (2.2)

iLux OS: 2.3 (2.2)

Corneal

LF OD: 0.9 (1.6) *

LF OS: 1.2 (1.6) *

iLux OD: 1.5 (2.4)*

iLux OS: 1.4 (2.2)*

Both Tx had significant improvements in MG function and symptoms

Device-related AEs

LF: N = 0

iLux: N = 4 patients (N = 2 burning sensations without skin findings and N = 1 petechial hemorrhaging in lower lids, N = 1 transient decrease in BSCVA with findings consistent with exposure keratitis). No other abnormal findings

Tauber 2020 [33]

Single-center, 6-week, prospective, randomized, single-masked (investigator)

USA

N = 50 patients with inflammatory MGD;

LF: N = 25 patients (25 eyes), 67 (9) years;

Liftegrast: N = 25 patients (25 eyes), 64 (8) years

42 days

Single 12-min LF Tx plus warm compress/lid compression BID

Lifitegrast ophthalmic

solution 5% BID plus warm compress/ lid compression BID for 42 days

MGSS

LF: 1.8 (0.55)

Lifitegrast: 2.1 (0.49)

MG patency

LF: 5.4 (2.1)

Lifitegrast: 4.8 (2.9)

MGSS

LF: 1.9 (0.81)

Lifitegrast: 1.8 (0.97)

MG patency

LF: 5.3 (2.6)

Lifitegrast: 6.1 (2.8)

VAS Dryness

LF: 1.9 (0.83)

Lifitegrast: 2.4 (0.70)

VAS Dryness

LF: 1.4 (0.71)

Lifitegrast: 1.4 (0.91)†

Corneal

LF: 0.84 (0.85)

Lifitegrast: 1.5 (1.0)

Corneal

LF: 0.96 (0.98)

Lifitegrast: 1.0 (1.3)†

Lifitegrast significantly improved symptoms and signs compared with LF

AEs

None

Ambaw 2020 [81]

Single-center, investigator-masked interventional

Singapore

N = 53 patients, LF: 35 patients (70 eyes);

CL: 18 patients (36 eyes)

3 months

Single 12-min LF Tx

CL: eyelid warming (warm towel, Blephasteam or Eyegiene) 3x/day for 3 months

Both Tx reduced pro-inflammatory molecules generated by lipoxygenase and oxidative stress

He 2018 [29]

Single-blind, prospective, open-label, randomized, controlled

China

N = 50 patients with MGD (100 eyes);

LF: N = 25 patients (50 eyes), 40 (12) years;

CL: N = 25 patients (50 eyes), 38 (12) years

3 months

Single 12-min LF Tx

15-min Tx with warm eye patch (EyeGiene Insta-Warmth) 1x/day for 2 weeks in office

MGYLS

LF: 3.6 (3.8)

CL: 4.2 (3.9)

MGYLS

LF: 19.7 (1.0)*

CL: 16.2 (10.8)

OSDI

LF: 55.0 (18.0)

CL: 47.3 (18.1)

OSDI

LF: 27.5 (18.1)*†

CL: 34.2 (19.8)*

TBUT

LF: 6.9 (4.3)

CL: 26.3 (6.2)

TBUT

LF: 8.4 (3.7)*†

CL: 19.0 (9.9)

Corneal +

Conjunct

LF:2.5 (0.8)

CL: 2.5 (0.9)

Corneal +

Conjunct

LF:2.1 (0.3)*†

CL: 2.3 (0.7)

Both LF and CL were effective at treating MGD. However, LF Tx was more effective and achieved better 3 months long-term efficacy than CL

AEs

None. No change in IOP

Blackie 2018 [34]

Prospective, open-label, randomized, crossover, multicenter

USA and Canada

N = 55 patients, contact lens wearer;

LF: N = 29 patients (58 eyes), 40 (13) years

CL: N = 26 patients (52 eyes), 44 (16) years;

CO: N = 25 patients (50 eyes) in CL who were CO to LF

3 months; CO:

1 month

Single 12-min LF Tx plus blinking exercises for 1 month post-Tx to foster healthy blinking habits

CL: untreated

MGSS

LF: 8.0 (3.5)

CL: 8.2 (4.2)

MGYLS

LF: 1.9 (1.6)

CL: 2.1 (1.7)

MGSS

LF: 20.4 (9.1)†

CL: 9.6 (5.7)

CO: 22.4 (9.4)†

MGYLS

LF: 7.1 (3.6)†

CL: 2.5 (2.2)

CO: 7.9 (3.6)†

SPEED

LF: 14.5 (4.8)

CL: 15.3 (4.5)

OSDI

LF: 39.6 (16.4)

CL: 40.8 (20.3)

SPEED

LF: 6.1 (4.6)†

CL: 14.5 (5.3)

CO: 7.4 (5.0)†

OSDI

LF: 13.4 (15.5)†

CL: 37.5 (23.8)

CO: 13.8 (11.2)†

TBUT

LF: 4.8 (2.7)

CL: 4.6 (2.0)

TBUT

LF: 6.5 (4.0)†

CL: 4.3 (1.7)

CO: 5.3 (2.4)†

Conjunct

LF: 3.5 (3.0)

CL: 4.3 (3.6)

Conjunct

LF: 3.4 (3.3)†

CL: 5.6 (4.5)

CO: 3.6 (3.7)

LF Tx improved signs and symptoms of DED and increased mean comfortable contact wearing time by 4 h, approximately doubling the comfortable wearing time, and was sustained for 3 months

AEs

None related to LF. N = 11 AEs unrelated LF (N = 5 ocular, N = 6 systemic). Slit-lamp findings not considered AEs were observed immediately after LF: eyelid edema, conjunctival edema, conjunctival hyperemia/injection, petechiae, and SPK and were transient and did not require Tx

Hagen 2018 [30]

Prospective, randomized, parallel group, single-masked

USA

N = 28 patients with moderate-to-severe

MGD (50 eyes);

LF: N = 14 patients (26 eyes), 52 (6) years;

Doxy: N = 14 patients (24 eyes), 50 (14) years

3 months

Single 12-min LF Tx

Oral doxy daily for 3 months (100 mg BID for the first 14 days and 100 mg 1x/day for days 15–90)

MGYLS

LF:4.0 (1.5)

Doxy: 4.6 (1.4)

MGYLS

LF: 7.7 (5.5)*

Doxy:10.6 (6.0)*

SPEED

LF: 11.0 (3.3)

Doxy: 13.4 (4.2)

SPEED

LF: 5.4 (2.2)*†

Doxy: 9.4 (5.5)*

TBUT

LF:6.3 (2.0)

Doxy: 6.9 (2.6)

TBUT

LF: 8.4 (1.8)*

Doxy: 7.6 (2.0)

Corneal

LF: 0.4 (0.5)

Doxy: 0.2 (0.4)

Conjunct

LF: 1.7 (1.9)

Doxy: 2.4 (1.9)

Corneal

LF:0.1 (0.3)*

Doxy: 0.1 (0.3)

Conjunct

LF: 0.6 (0.8)*

Doxy: 1.1 (1.5)*

LF was significantly more effective than doxy at treating signs and symptoms of MGD and was a favorable alternative to doxy

AEs

LF: N = 0

Doxy: N = 2 (stomach upset/intolerance)

Yeo 2016 [82]

Singapore

N = 90 patients,

LF: 24 patients (48 eyes)

Hot towel: N = 22 patients (44 eyes), EyeGiene: N = 22 patients (44 eyes); Blephasteam: N = 22 patients (44 eyes)

3 months

Single 12-min LF Tx

Details of other Tx NR

LF Tx significantly reduced tear evaporation rate

Finis 2014 [31]

Prospective, randomized, crossover,

observer-masked

Germany

This is a long-term FU of Finis 2014 [32]

N = 26 patients with MGD (52 eyes), 50 (22) years;

LF: N = 17 patients (34 eyes), 45 (23) years;

CL: N = 9 patients (18 eyes) with CL for 3 months prior to LF

6 months post-LF

Single 12-min LF Tx

CL: Lid warming BID and massage for 3 months

MGYLS

LF: 2.9

(1.6)

MGYLS

LF: 6.4

(4.6)*

OSDI

LF: 42 (19)

SPEED

LF: 16 (7)

CL: 15.9 (6.6)

CO: 14.7 (7.7)

OSDI

LF: 33 (21)*

SPEED

LF: 12 (7)*

CL: 14.7 (7.1)

CO: 12.6 (6.5)

TBUT

LF: 9.5 (8.7)

TBUT

LF: 10.0 (6.7)

Corneal +

Conjunct

LF: 2.0 (2.0)

Corneal +

Conjunct

LF: 2.4 (2.3)

LF reduces subjective symptoms and

objective measures of MGD over 6 months but has no effect on atrophy of MG as visualized by meibography.

Safety NR

Finis 2014 [32]

Prospective, randomized, crossover,

observer-masked

Germany

N = 31 patients with MGD;

LF: N = 17 patients (34 eyes), 45 (23) years;

CL: N = 14

patients, (28 eyes) 50 (19) years

After completing the initial

study, 9 CL patients (18 eyes)

completed

a 3-month CO

with LF

3 months

Single 12-min LF Tx

CL: Lid warming BID and massage for 3 months

MGYLS

LF: 2.5

(1.4)

CL: 2.1 (1.3)

CO: 4.1

(2.5)

MGYLS

LF: 5.5

(3.6)*

CL: 4.6

(3.8)*

CO:5.8

(3.2)

OSDI

LF: 46.2 (14.8)

CL: 40.1 (16.7)

CO: 39.7 (26.3)

SPEED

LF: 16.8 (5.6)

CL: 15.9 (6.6)

CO: 14.7 (7.7)

OSDI

LF: 34.6 (19.6)*

CL: 40.0 (23.4)

CO: 32.8 (24.4)

SPEED

LF: 14.5 (7.2)

CL: 14.7 (7.1)

CO: 12.6 (6.5)

NIBUT

LF: 7.9 (8.5)

CL: 7.7 (6.1)

CO: 6.7 (6.1)

NIBUT

LF: 9.9 (7.0)

CL: 7.5 (6.1)

CO: 7.3 (5.1)

Corneal + Conjunct

LF: 2.6 (2.4)

CL:1.9 (2.4)

CO: 1.4 (1.4)

Corneal +

Conjunct

LF: 3.5 (2.7)

CL:1.1 (1.4)

CO: 3.0 (2.2)

Single LF Tx was at least as effective

as a 3-month BID lid margin hygiene regimen.

Safety NR

Baumann 2014 [35]

Single-center, prospective, randomized

France

N = 30 patients with moderate-to-severe DED and MGD;

LF: N = 15 patients (30 eyes), 65 (12) years;

CL: N = 15 patients (30 eyes), 65 (11) years

3 months

Single 12-min LF Tx plus blinking exercises

CL: MeiboPatch heat mask for 10 min and massage for 10 min 1x/day for 3 months plus blinking exercises

MGYLS

LF: 3.3

(1.7)

CL: 5.7 (3.2)

MGYLS

LF: 8.5

(2.4)*

CL: 9.4 (4.3)*

OSDI

LF: 51.0 (20.8)

CL: 42.9 (20.3)

SPEED

LF: 16.5 (4.6)

CL: 13.5 (3.1)

OSDI

LF: 27.0 (17.6)*

CL: 23.5 (15.3)*

SPEED

LF: 8.0 (5.3)*

CL: 8.9 (5.2)*

TBUT

LF: 4.5 (2.3)

CL: 5.2 (2.2)

TBUT

LF: 6.8 (2.5)*

CL: 6.9 (2.2)*

Corneal +

conjunct

LF: 1.0 (1.1)

CL:1.8 (1.2)

Corneal + conjunct

LF: 0.4 (0.8)*

CL:0.7 (0.7)*

LF Tx is highly effective in treating MGD. The results for 3 months of CL Tx were excellent, but not convenient for the patient

Randomized but MGD more severe in LF group at BL

Safety NR

Lane 2012 [14]

Randomized, controlled, open-label, crossover, multicenter

USA

N = 139 patients with MGD;

LF: N = 69 patients (138 eyes), age NR;

CL: N = 70 patients (140 eyes), age NR;

CO: N = 68 patients (136 eyes) in CL group who were CO to LF

LF: 1 month; CL: 2 weeks; CO: 2 weeks

Single 12-min LF Tx

CL: Warm compress (iHeat) for 5 min/day for 2 weeks

MGSS

LF: 6.3 (3.5)

CL: 5.6 (3.9)

MGYLS

LF: 0.6 (0.9)

CL: 0.4 (0.8)

MGSS

LF: 14.3 (8.7) at 2 weeks*†;

16.7 (8.7) at 1 month*

CL: 6.1 (5.6)

CO: 11.7 (7.3)†

MGYLS

LF: 2.0 (2.9) at 2 weeks*†;

2.6 (3.6) at 1 month*

CL: 0.5 (1.1)

CO: 1.2 (1.9)†

SPEED

LF: 14.3 (4.8)

CL: 14.8 (4.8)

OSDI

LF: 32.0 (20.0)

CL: 34.7 (19.6)

SPEED

LF: 8.1 (5.5) at 2 weeks*†;

7.6 (5.8) at 1 month *

CL: 11.2 (5.4)

CO: 7.9 (5.6)†

OSDI

LF: 17.3 (17.2) at 2 weeks*†;

16.6 (18.1) at 1 month *

CL: 26.9 (18.2)

CO: 21.0 (18.3)†

TBUT

LF: 5.5 (2.9)

CL: 5.4 (3.5)

TBUT

LF: 6.9 (5.0) at 2 weeks*†;

7.4 (5.5) at 1 month *

CL: 5.3 (3.5)

CO: 6.3 (4.7)†

Corneal

LF: 2.2 (2.2)

Conjunct

LF: 1.3 (2.1)

Corneal

LF: 1.5 (1.7) at 1 month*

Conjunct

LF: 1.6 (2.5) at 1 month*

LF Tx improved signs and symptoms over 1 month

The safety profile of LF Tx reflects a low occurrence of non-serious, transient side effects that resolve quickly and do not require medical treatment

AEs

LF: N = 4 (N = 3 eyelid pain, N = 1 conjunctival vascular injection)

CL: N = 2 (burning)

Mean discomfort score during LF Tx was 1.4 (scale 0–10). Slit-lamp findings not considered AEs most frequently were trace to mild conjunct injection, hyperemia, or redness; and trace or mild petechial hemorrhages on the eyelid or conjunct immediately or 1 day post-Tx, which fully resolved by the 2-week visit without Tx. No changes in the intraocular findings except for 1 case of posterior vitreous floaters unrelated to device

Units of measure are as follows: IDEEL-SB = points, score 0–100; MGSS = points, score 0–45; MGYLS = number of functional glands; NIKBUT = seconds; OSDI = points, score 0–100; SANDE = visual analog scale score, 0–100; SPEED = points, score 0–28; staining = scale score; TBUT = seconds; VAS = scale score

Treatment manufacturers are as follows: Blephasteam (Laboratoires Thea, Clermont-Ferrand, France); EyeGiene^® Insta-Warmth™ patch (Eyedetec Medical Inc, Danville, CA); iHeat (manufacturer unknown); Lifitegrast ophthalmic solution 5% (Xiidra; Shire, Lexington, MA); MeiboPatch^® heat mask (Butterflies Eyecare, Banbury, UK); MiboFlo ThermoFlo (Mibo Medical, Dallas, TX); Systane iLux Dry Eye System thermal pulsation (Alcon, Ft Worth, Tx); TearCare (Sight Sciences, Menlo Park, CA)

AEs adverse events, BID 2 times per day, BL baseline, CL control, CO crossover group, conjunct conjunctiva, DED dry eye disease, doxy doxycycline, FU follow-up, IDEEL-SB Impact of Dry Eye on Everyday Life—Symptom Bother, IOP intraocular pressure, LF LipiFlow, MG meibomian glands, MGD meibomian gland dysfunction, MGSS meibomian gland secretion score (secretion quality), MGX manual gland expression, MGYLS meibomian glands yielding liquid secretion (glands with secretion capacity), min minutes, NIKBUT noninvasive keratograph break-up time, NR not reported, OD right eye, OS left eye, OSDI ocular surface disease index, pre pretreatment, post post-treatment, SANDE Symptom Assessment in Dry Eye, SD standard deviation, SPEED standard patient evaluation of eye dryness, SPK superficial punctate keratitis, TBUT tear break-up time, Tx treatment, VA visual acuity, VAS visual analog scale

¹Data only presented in a figure. We did not extrapolate the data from the figure to avoid presenting estimated data

^*P < 0.05 vs. baseline

^†P < 0.05 vs. control

^§P < 0.05 vs. comparator