Advice

Evidence review

Evidence review

Clinical and technical evidence

Regulatory bodies

One adverse event report was listed on the US Food and Drug Administration (FDA) Manufacturer and User Device Facility Experience (MAUDE) database.

One person suffered a corneal abrasion 5 days after having treatment with the LipiFlow system. No permanent impairment was sustained. The manufacturer stated the injury could not be attributed to the device given the time delay between the treatment and the injury (MAUDE Adverse Event Report: TearScience LipiFlow thermal pulsation system).

A search of the Medicines and Healthcare Products Regulatory Agency (MHRA) website revealed no manufacturer Field Safety Notices or Medical Device Alerts for this device.

Clinical evidence

The evidence on the use of the LipiFlow system is provided by 2 randomised controlled trials, for which 3 additional follow‑up publications have been reported, and 1 clinical feasibility study. These studies are described below.

Randomised controlled trials

Lane et al. (2012) conducted a multicentre study in the USA, comparing the safety and effectiveness of the LipiFlow system with the iHeat warm compress. iHeat warm compresses are single‑use, chemically‑activated, warm compresses that deliver heat to the outer eyelids and surrounding tissue. In the study 139 people with meibomian gland dysfunction (MGD) were randomised into a LipiFlow therapy group (n=69) and a control group (iHeat, n=70). The LipiFlow intervention was administered in a single, 12‑minute session and the iHeat warm compresses were applied in daily 5‑minute sessions for 2 weeks. Follow‑up was at 1 day (LipiFlow group only), 2 weeks (LipiFlow and control groups) and 4 weeks (LipiFlow group only) post treatment. The control group then crossed over to have LipiFlow therapy, and follow‑up data were recorded at 1 day and 2 weeks after this treatment. Statistically significant increases in both meibomian gland secretions and tear break‑up time (TBUT), and statistically significant reductions in dry eye symptoms, were observed in the LipiFlow therapy group from baseline to follow‑up. The crossover group also showed similar statistically significant improvements in mean meibomian gland secretions and TBUT and significant reductions in dry eye symptoms after they had LipiFlow therapy. Patient‑reported pain and discomfort scores during and after treatment were statistically significantly higher in the LipiFlow treatment group compared with the iHeat warm compresses group. A summary of these results is reported in tables 1 and 2.

Two additional publications (Greiner 2012, 2013) report longer‑term outcomes from the same group of people treated in the Lane et al. (2012) study, with 9‑ and 12‑month follow‑up respectively. Data were collected from people who had had LipiFlow treatment (n=21 at 9 months and n=18 at 12 months). At both additional follow‑up points, the statistically significant reductions in dry eye symptoms compared with baseline (originally observed by Lane et al. 2012) were sustained, as were the significant increases in meibomian gland secretions and TBUT. A summary of Greiner (2012 and 2013) is reported in tables 3 and 4.

Finis et al. (2014a) conducted a randomised controlled trial in Germany, comparing 1 single LipiFlow treatment with twice‑daily application of heat and massage to the eyelids for 3 months. People with MGD (n=31) were randomised into a LipiFlow treatment group (n=17) and a control group (n=14). Both groups were studied at baseline and with 1‑ and 3‑month follow‑up. The control group then crossed over to LipiFlow therapy and were studied at baseline and 1‑ and 3‑month follow‑up. Treatment with LipiFlow demonstrated non‑inferiority compared with twice‑daily warming and massage of the eyelids, in respect to dry eye symptoms, TBUT, tear osmolarity, lipid layer thickness, tear meniscus height, ocular surface staining, lid margin parallel conjunctival folds and number of expressible meibomian glands. A summary of these results is reported in tables 5 and 6.

An additional publication (Finis et al. 2014b) reported 6‑month follow‑up data from the original study by Finis et al. (2014a). People who had LipiFlow treatment (n=26), including those from the crossover group (n=9), were included. Subjective dry eye symptoms were statistically significantly improved from baseline as were lipid layer thickness, the number of expressible meibomian glands, lid margin parallel conjunctival folds and bulbar redness. In addition, treatment with LipiFlow demonstrated no effect on meibomian gland atrophy. A summary of Finis et al. (2014b) is reported in table 7.

Clinical feasibility study

Friedland et al. (2011) conducted a multicentre, prospective, clinical feasibility study in the USA comparing LipiFlow with heated manual expression of the meibomian glands. The authors studied 14 people at baseline and at 1 day, 1 week, 1 month and 3 months after the treatment. All 14 people had a single 12‑minute session of LipiFlow in both eyes. Immediately after receiving LipiFlow treatment, each person received further treatment in 1 randomly selected eye using an alternative manual heated expression device, which was not named in the study. Results demonstrated LipiFlow statistically significantly improved dry eye symptoms and objective meibomian gland functionality outcomes during the 3‑month study period compared with baseline. No statistically significant differences were observed in any outcome measures between eyes that received LipiFlow therapy only versus those that received LipiFlow therapy and additional heated manual expression. Three adverse events were reported during the study and these were resolved without long‑term harm. A summary of these results is reported in table 8.

Table 1 Summary of the Lane et al. (2012) randomised controlled trial

Study component

Description

Objectives/hypotheses

To evaluate the safety and effectiveness of LipiFlow compared with the iHeat warm compresses for adults with MGD.

Study design

Prospective, open‑label, randomised, crossover multicentre clinical trial.

Setting

9 US based centres.

People were recruited between March and May 2009.

People in the study were followed‑up at:

  • 1 day, 2 and 4 weeks (LipiFlow cohort)

  • 2 weeks (iHeat warm compresses cohort)

  • 1 day and 2 weeks (crossover cohort).

Inclusion/exclusion criteria

Inclusion:

  • people aged 18 years or over

  • willingness to comply with the study procedures and follow‑up schedule

  • dry eye symptoms within 3 months of the baseline examination (SPEED score≥6)

  • evidence of meibomian gland obstruction (based on a total meibomian gland secretion score≤12 for 15 glands of the lower lid)

  • provided informed consent.

Exclusion:

  • evidence of coexisting ocular conditions (e.g. active ocular infection or inflammation in either eye)

  • ocular surgery or trauma within 3 months of the baseline examination

  • ocular surface abnormality potentially compromising corneal integrity

  • eyelid abnormalities affecting lid function

  • systemic disease resulting in dry eye

  • unwillingness to abstain from systemic medications known to cause dryness for the study duration

  • coexisting conditions that could interfere with the assessment of safety and effectiveness of the treatment (e.g. macular disease; women who were pregnant or nursing).

Outcomes

Primary:

  • meibomian gland assessment (gland secretions) and TBUT.

Secondary:

  • dry eye symptoms using SPEED and OSDI questionnaires.

Safety:

  • adverse events, ocular health examination, ocular surface staining, intraocular pressure, visual acuity, patient‑reported pain and discomfort scores (1–2, slight or transient awareness of pressure without pain; 3–4, moderate discomfort with minimal pain; 5–6, moderate pain; 7–8, severe pain; and 9–10, intolerable pain).

Statistical methods

Descriptive statistics were used to present data in the form of the mean and SD.

Paired 2‑tailed t‑tests were used to compare baseline and post‑treatment outcomes for each treatment group.

Two sample 2‑tailed t‑tests were used to compare the mean changes from baseline to 2 weeks between treatment groups.

Fischer's exact test was used to compare the incidence of device‑related adverse events between treatment groups.

All enrolled intention‑to‑treat patients (139 patients; 278 eyes) were analysed for safety and all eligible per‑protocol treated patients (133 patients; 266 eyes) were analysed for efficacy.

Significance was set at the 0.05 level.

Participants

All people in the study had to discontinue the use of systemic antihistamines or isotretinoin (Accutane) for at least 1 month, cyclosporine‑A (Restasis) for at least 2 months, and other dry eye or MGD‑related medication (e.g. antibiotics, non‑steroidal and anti‑inflammatory drugs, and corticosteroids) for at least 2 weeks, before the beginning of the study. People could not use this medication throughout the study duration.

A total of 139 people (278 eyes) were enrolled on the study and randomised into the following groups:

Group 1: had a single, 12‑minute treatment of LipiFlow; n=69 (138 eyes).

Group 2: had a 5‑minute iHeat warm compress treatment with instructions to perform the same treatment daily for 2 weeks; n=70 (140 eyes).

Group 3: crossed‑over to a single, 12‑minute treatment of LipiFlow; n=68 (136 eyes).

Results

Mean (±SD) meibomian gland secretion and TBUT significantly increased (p<0.0001) with LipiFlow from baseline to 2 and 4 weeks (meibomian gland secretion: baseline 6.3±3.5; 2 weeks 14.3±8.7; 4 weeks 16.7±8.7 and TBUT: baseline 5.5±2.9; 2 weeks 6.9±5.0; 4 weeks 7.4±5.5).

There was no significant difference in mean (±SD) meibomian gland secretion (p=0.3214) and TBUT (p=0.6492) with iHeat warm compresses (meibomian gland secretion: baseline 5.6±3.9; 2 weeks 6.1±5.6 and TBUT: baseline 5.4±3.5; 2 weeks 5.3±3.5).

The use of LipiFlow resulted in a reduction in dry eye symptoms, which was higher compared with the reduction in dry eye symptoms attributed to the use of iHeat warm compresses (SPEED, p<0.0001; OSDI, p<0.0004).

The crossover group demonstrated similar significant improvement in mean meibomian gland secretion (p<0.0001), TBUT (p=0.0027) and dry eye symptoms (SPEED, p<0.0001; OSDI, p<0.0002) 2 weeks post‑treatment with the LipiFlow.

There was no significant difference between groups in the incidence of non‑serious, device‑related adverse events (p=0.4455).

Self‑reported pain and discomfort scores during and after treatment were significantly higher in the LipiFlow treatment group compared with the iHeat warm compresses group (p<0.0001).

Conclusions

The LipiFlow system was significantly more effective than iHeat warm compresses. Results support its safety and effectiveness in the treatment of MGD and dry eye symptoms. However, people in the study experienced greater pain and discomfort with the use of the LipiFlow system.

Abbreviations: MGD, meibomian gland dysfunction; OSDI, ocular surface disease index; SD, standard deviation; SPEED, standard patient evaluation of eye dryness; TBUT, tear break‑up time.

Table 2 Summary of the Lane et al. (2012) randomised controlled trial

LipiFlow

Daily warm compresses

Analysis

Randomised

n=69 (138 eyes)

n=70 (140 eyes)

Efficacy

n=65 (130 eyes)

n=68 (136 eyes)

Primary outcome:

  • MG gland secretion score

  • TBUT(seconds)

MG secretion (mean score[±SD])

  • Baseline 6.3 (3.5)

  • 2 weeks 14.3 (8.7)

  • 4 weeks 16.7 (8.7)

TBUT (mean time [±SD])

  • Baseline 5.5 (2.9)

  • 2 weeks 6.9 (5.0)

  • 4 weeks 7.4 (5.5)

MG secretion (mean score[±SD])

  • Baseline 5.6 (3.9)

  • 2 weeks 6.1 (5.6)

TBUT (mean time [±SD])

  • Baseline 5.4 (3.5)

  • 2 weeks 5.3 (3.5)

  • p<0.0001

  • p=0.0017

Secondary outcome:

SPEED questionnaire score

Mean score (±SD)

  • Baseline 14.3 (4.8)

  • 2 weeks 8.1 (5.5)

  • 4 weeks 7.6 (5.8)

Mean score (±SD)

  • Baseline 14.8 (4.8)

  • 2 weeks 11.2 (5.4)

  • p<0.0001

Secondary outcome:

OSDI questionnaire score

Mean score (±SD)

  • Baseline 32.0 (20.0)

  • 2 weeks 17.3 (17.2)

  • 4 weeks 16.6 (18.1)

Mean score (±SD)

  • Baseline 34.7 (19.6)

  • 2 weeks 26.9 (18.2)

  • p=0.0004

Safety

n=69

n=70

Abbreviations: MG, meibomian gland; OSDI, ocular surface disease index; SD, standard deviation; SPEED, standard patient evaluation of eye dryness; TBUT, tear break‑up time.

Table 3 Summary of the Greiner (2012) follow‑up report to Lane et al. (2012)

Study component

Description

Objectives/hypotheses

To evaluate the effect of a single treatment with LipiFlow on signs of MGD and dry eye symptoms over a 9‑month period.

Study design

Follow‑up to the prospective, open‑label, randomised, crossover multicentre clinical trial (Lane et al. 2012).

Setting

The original setting from Lane et al. (2012):

9 US centres.

Participants were recruited between March and May 2009.

Study participants were followed‑up at:

  • 1 day, 2 and 4 weeks (LipiFlow cohort)

  • 2 weeks (iHeat warm compress cohort)

  • 1 day and 2 weeks (cross‑over cohort).

Inclusion/exclusion criteria

As stated in Lane et al. (2012) study (see table 1).

Outcomes

Primary:

  • meibomian gland assessment (gland secretions) and TBUT.

Secondary:

  • dry eye symptoms using SPEED and OSDI questionnaires.

Statistical methods

Descriptive statistics were used to present data in the form of mean and SD.

ANOVA and post‑hoc analysis using Bonferroni correction was used to assess statistical changes in TBUT, meibomian gland secretions and dry eye symptoms over time (baseline and 1 month follow‑up [data from original study by Lane et al. 2012] to 9 month follow‑up).

Significance was set at the 0.05 level.

Participants

A total of 21 participants (42 eyes) were followed‑up to 9 months from the original study (Lane et al. 2012): n=21; 5 men and 16 women, mean (±SD) age=62.2±12.1, all of white origin.

Results

Mean (±SD) meibomian gland secretion scores improved significantly (p<0.0001) from baseline (4.4±4.0) to 1 month follow‑up (11.3±6.2) and this improvement was maintained, with no significant regression (p>0.05), at 9 months (11.7 ± 5.9).

Mean (±SD) TBUT significantly increased (p<0.001) from baseline (4.8±3.2) to 1 month follow‑up (9.6±7.6) and this improvement was maintained with no significant regression (p>0.05) at 9 months (7.1±5.6).

Mean OSDI score (±SD) significantly improved (p<0.0005) from baseline (23.4±14.4) to 1 month follow‑up (10.9±13.1) and this improvement was maintained at 9 months (12.4±15.3), with no significant difference observed (p>0.05).

Mean SPEED scores (±SD) significantly improved (p<0.0001) from baseline (12.9±4.0) to 1 month (6.3±5.4) and this improvement was maintained at 9 months (6.2±7.1), with no significant difference observed (p>0.05).

Conclusions

A single 12‑minute LipiFlow treatment results in up to 9 months of sustained improvement of meibomian gland function, TBUT and dry eye symptoms.

Abbreviations: ANOVA, analysis of variance; MGD, meibomian gland dysfunction; OSDI, ocular surface disease index; SD, standard deviation; SPEED, standard patient evaluation of eye dryness; TBUT, tear break‑up time.

Table 4 Summary of the Greiner (2013) follow‑up report to Lane et al. (2012)

Study component

Description

Objectives/hypotheses

To determine the 1‑year post‑treatment dry eye status of participants with MGD and dry eye symptoms after having a single LipiFlow.

Study design

Follow‑up to the prospective, open‑label, randomised, crossover multicentre clinical trial.

Setting

The original setting from Lane et al. (2012; table 1):

9 US centres.

This study recruited participants between March and May 2009.

Study participants were followed‑up at:

  • 1 day, 2 and 4 weeks (LipiFlow cohort)

  • 2 weeks (iHeat WC cohort)

  • 1 day and 2 weeks (crossover cohort).

Inclusion/exclusion criteria

As stated in Lane et al. (2012) study (see table 1).

Outcomes

Primary:

  • meibomian gland assessment (gland secretions) and TBUT.

Secondary:

  • dry eye symptoms using SPEED and OSDI questionnaires.

Statistical methods

Descriptive statistics were used to present data in the form of mean and SD.

ANOVA and post‑hoc analysis using Bonferroni correction was used to assess statistical changes in TBUT, meibomian gland secretions and dry eye symptoms over time (baseline and 1 month [data from original study by Lane et al. 2012] to 12 months).

Significance was set at the 0.05 level.

Participants

A total of 18 participants (36 eyes) were followed‑up to 12 months from the original study (Lane et al. 2012):

n=18; 2 men and 14 women, mean (±SD) age=63.2±12.1, all of white origin.

Results

Mean (±SD) meibomian gland secretion scores improved significantly (p<0.0005) from baseline (4.0±3.4) to 1 month follow‑up (11.3±4.7) and this improvement was maintained with no significant regression (p>0.05) at 12 months (7.3±4.6).

Mean (±SD) TBUT significantly increased (p<0.001) from baseline (4.9±3.0) to 1 month follow‑up (9.5±6.9). There was a significant decrease (p>0.05) in mean TBUT from 1‑month (9.5±6.9) to 12 month follow‑up (6.0±4.4).

Mean OSDI symptoms score (±SD) significantly improved (p<0.0005) from baseline (22.2±14.2) to 1 month follow‑up (8.5±7.5) and this improvement was maintained at 12 month follow‑up (12.4±14.6) with no significant difference observed (p>0.05).

Mean SPEED scores (±SD) significantly improved (p<0.0005) from baseline (12.9±3.8) to 1 month follow‑up (6.4±5.5) and this improvement was maintained at 12 month follow‑up (6.3±5.5), with no significant difference observed (p>0.05).

Conclusions

A single 12‑minute treatment with the LipiFlow system offers an effective treatment for evaporative dry eye and MGD resulting in significant and sustained improvement in signs and symptoms for up to 1 year.

Abbreviations: ANOVA, analysis of variance; MGD, meibomian gland dysfunction; OSDI, ocular surface disease index; SD, standard deviation; SPEED, standard patient evaluation of eye dryness; TBUT, tear break‑up time.

Table 5 Summary of the Finis et al. (2014a) randomised controlled trial

Study component

Description

Objectives/hypotheses

To compare the effectiveness of a single LipiFlow treatment with lid warming and massage in patients with MGD.

Study design

Single‑blinded, prospective, crossover, randomised trial.

Setting

German centre.

People were recruited between April 2012 and June 2013.

People in the study were followed up at 1 and 3 months.

Inclusion/exclusion criteria

Inclusion:

  • 18 years or over

  • provided informed consent

  • needed treatment for MGD (defined by SPEED score ≥8, LLT≤61 nm and expressible meibomian glands≤4).

Exclusion:

  • used systemic medication with tetracycline derivatives, antihistamines, isotretinoin or nutritional supplements for MGD (beginning less than 3 months before baseline examination)

  • used topical cyclosporine‑A or steroids (beginning less than 1 month before baseline examination)

  • ocular surgery or trauma less than 3 months before baseline examination

  • evidence of any eyelid abnormalities

  • evidence of systemic diseases resulting in dry eye.

Outcomes

Primary:

  • subjective dry eye symptoms (OSDI and SPEED questionnaires).

Secondary:

  • TBUT, tear osmolarity, LLT, tear meniscus height, ocular surface staining, lid margin parallel conjunctival folds, number of expressible meibomian glands.

Statistical methods

Descriptive statistics were used to present data in the form of the mean and SD.

A power analysis was performed using G*Power 3.

ANOVA and Bonferroni post hoc tests were used to compare values between time points (non‑significant values were given as exact p values of Fisher's post hoc test).

Wilcoxon signed rank tests were used to compare relative changes between treatment groups.

Student t‑tests were used to compare baseline values between treatment groups.

Kolmogorov–Smirnov tests were used for normality; Pearson's linear correlation coefficient was used for normally distributed data and Spearman's linear correlation coefficient was calculated for non‑normally distributed values.

Significance was set at the 0.05 level.

Participants

A total of 31 people were enrolled on the study and randomised into the following groups:

Group 1: single, 12‑minute treatment of LipiFlow; n=17, 5 men and 12 women, mean (±SD) age=45±23.

Group 2: twice‑daily lid warming and massage treatment; n=14, 4 men and 10 women, mean (±SD) age=50±19.

Group 3: crossed‑over to a single, 12‑minute treatment of LipiFlow; n=14, 4 men and 10 women, mean (±SD) age=50±19.

Results

Both mean (±SD) OSDI and SPEED scores were significantly improved (p<0.01 and p<0.05 respectively) at 1 month follow‑up (OSDI=30.9±20.8 and SPEED=12.7±7.9) compared to baseline (OSDI=46.2±14.8 and SPEED=16.8±5.6) with LipiFlow treatment.

Mean (±SD) OSDI scores were significantly improved (p<0.01) from baseline to 3‑month follow‑up (34.6±19.6) with the LipiFlow treatment, however there was no difference (p=0.055) in mean (±SD) SPEED score between baseline and 3‑month follow‑up (14.5±7.2).

No significant differences were observed in mean OSDI or SPEED scores with the control treatment group.

Mean (±SD) number of expressible glands significantly increased (p<0.01 and p<0.01) from baseline (2.5±1.4) to 1‑month (5.9±3.5) and 3‑month follow‑up (5.5±3.6) with LipiFlow treatment.

Mean (±SD) number of expressible glands significantly increased (p<0.05 and p=0.0326) from baseline (2.1±1.3) to 1‑month (4.9±4.0) and 3‑month follow‑up (4.6±3.8) with the control treatment.

Mean (±SD) TBUT significantly improved (p<0.05) from baseline (6.7±6.1) to 1‑month follow‑up (11.6±5.8) with the crossover treatment group, however there was no significant difference observed at 3 months.

No other significant differences were observed.

Conclusions

Results show that a single LipiFlow treatment is non‑inferior to a 3‑month, twice‑daily lid warming and massage regime for MGD.

Abbreviations: ANOVA, analysis of variance; LLT, lipid layer thickness; MGD, meibomian gland dysfunction; OSDI, ocular surface disease index; SD, standard deviation; SPEED, standard patient evaluation of eye dryness; TBUT, tear break‑up time.

Table 6 Summary of the Finis et al. (2014a)

LipiFlow

Twice‑daily warming and massage

Analysis

Randomised

n=17 (34 eyes)

n=14 (28 eyes)

Efficacy

n=17

n=14

Primary outcome:

OSDI questionnaire score

Mean score (±SD)

  • Baseline 46.2 (14.8)

  • 1 month 30.9 (20.8)

  • 3 months 34.6 (19.6)

Mean score (±SD)

  • Baseline 40.1 (16.7)

  • 1 month 35.6 (20.9)

  • 3 months 40.0 (23.4)

  • p>0.05

  • p>0.05

  • p>0.05

Secondary outcome:

LLT (nm)

Mean height (±SD)

  • Baseline 43.4 (9.9)

  • 1 month 48.8 (15.5)

  • 3 months 47.4 (16.7)

Mean height (±SD)

  • Baseline 44.1 (7.9)

  • 1 month 46.9 (25.7)

  • 3 months 46.4 (20.8)

  • p>0.05

  • p>0.05

  • p>0.05

Secondary outcome:

Tear film osmolarity (mOsm/l)

Mean osmotic concentration (±SD)

  • Baseline 301.5 (11.4)

  • 1 month 301.0 (10.2)

  • 3 months 307.1 (14.0)

Mean osmotic concentration (±SD)

  • Baseline 296.7 (10.2)

  • 1 month 298.3 (12.3)

  • 3 months 303.7 (8.1)

  • p>0.05

  • p>0.05

  • p>0.05

Safety

n=17

n=17

Patients reporting serious adverse events

Not reported

Not reported

Abbreviations: LLT, lipid layer thickness; OSDI, ocular surface disease; SD standard deviation.

Table 7 Summary of the Finis et al. (2014b) follow‑up report to Finis et al. (2014a)

Study component

Description

Objectives/hypotheses

To evaluate the 6‑month effect of a single LipiFlow treatment and implications of meibomian gland atrophy on treatment efficacy 6 months after application.

Study design

Follow‑up study to the single‑blinded, prospective, crossover, randomised trial (Finis et al. 2014a).

Setting

The original setting from Finis et al. (2014a; table 5):

Europe based centre.

People were recruited between April 2012 and June 2013.

Study patients were followed‑up at:

  • 1 and 3 months (LipiFlow group)

  • 1 and 3 months (lid warming and massage group)

  • 1 and 3 months (crossover group).

Inclusion/exclusion criteria

As stated in Finis et al. (2014a) (see table 5).

Outcomes

Primary:

  • subjective dry eye symptoms (OSDI and SPEED questionnaires).

Secondary:

  • TBUT, tear osmolarity, LLT, tear meniscus height, meibography, bulbar redness, ocular surface staining, LIPCOF and number of expressible meibomian glands.

Statistical methods

Descriptive statistics were used to present data in the form of the mean and SD.

Paired t‑tests were used to analyse the changes between time points.

Heteroscedastic t‑tests were used to analyse the changes between different subgroups.

Significance was set at the 0.05 level.

Participants

A total of 26 people (52 eyes) were studied and completed the 6‑month follow‑up: mean (±SD) age=50±22 years, 7 men and 19 women.

Results

Mean (±SD) OSDI scores significantly improved (p<0.005) from baseline (42±19) to 6‑month follow‑up (33±21).

Mean (±SD) SPEED scores significantly improved (p<0.001) from baseline (16±7) to 6‑month follow‑up (12±7).

Mean (±SD) LLT significantly improved (p=0.014) from baseline (44.0±15.6) to 6‑month follow‑up (51.3±20.4).

Mean (±SD) number of expressible glands significantly improved (p<0.0001) from baseline (2.9±1.6) to 6‑month follow‑up (6.4±4.6).

Mean (±SD) LIPCOF significantly improved (p=0.04) from baseline (2.3±1.0) to 6‑month follow‑up (2.0±0.9).

Mean (±SD) bulbar redness significantly improved (p=0.0001) from baseline (1.4±0.5) to 6‑month follow‑up (1.2±0.5).

No other significant differences were observed.

Conclusions

This study demonstrated that a single LipiFlow treatment reduces subjective symptoms and objective dry eye parameters in people with MGD over 6 months but has no effect on atrophy of meibomian glands.

Abbreviations: ANOVA, analysis of variance; LIPCOF, lid margin parallel conjunctival folds; LLT, lipid layer thickness; MGD, meibomian gland dysfunction; OSDI, ocular surface disease index; SD, standard deviation; SPEED, standard patient evaluation of eye dryness; TBUT, tear break‑up time.

Table 8 Summary of the Friedland et al. (2011) clinical feasibility study

Study component

Description

Objectives/hypotheses

To evaluate LipiFlow for obstructive MGD.

Study design

Multicentre, prospective, clinical feasibility study.

Setting

US based centres.

This study recruited people in June 2008.

People in the study were followed‑up at 1 day, 1 week, 1 month and 3 months.

Inclusion/exclusion criteria

Inclusion:

  • 18 years or older

  • provided informed consent

  • willingness and ability to return for all study follow‑ups

  • dry eye symptoms for more than 3 months (SPEED score≥6) and previous diagnosis of moderate‑to‑severe dry eye

  • regular use of artificial tears, lubricants or rewetting drops in both eyes

  • obstructed meibomian gland (presence or absence of secretions expressed.

Exclusion:

  • individuals who had either changed the dosing of systemic or ophthalmic medication less than 30 days prior to screening

  • individuals unable or unwilling to remain on a stable dosing regimen for the duration of the study

  • ocular surgery, trauma or herpetic keratitis less than 3 months before baseline examination

  • evidence of chronic or recurrent eye inflammation or infection

  • pregnant women, nursing or not utilising adequate birth control measures

  • evidence of systemic diseases resulting in dry eye

  • using topical or systemic medications known to cause eye dryness

  • using another investigational device or agent within 30 days of study participation.

Outcomes

  • Meibomian gland assessment (the meibomian gland secretion score and the number of meibomian glands yielding liquid secretion, lower eyelid)

  • objective dry eye tests (TBUT and corneal fluorescein staining)

  • subjective dry eye symptoms (SPEED and OSDI questionnaires)

  • ocular health examination (anterior segment and retina evaluation and intraocular pressure measurement)

  • discomfort/pain evaluation (during and after treatment).

Statistical methods

Descriptive statistics were used to present data in the form of the mean and SD.

ANOVA with post‑hoc Bonferroni corrections were used to determine significant changes due to the treatment between visits (time) and between treatment groups.

Significance was set at the 0.05 level.

Participants

A total of 14 people (28 eyes) were enrolled: mean age (±SD)=54.2±9.6 (range=37–72) years, 4 men and 10 women.

One eye from each person was randomly selected to undergo additional manual heated expression with another treatment device:

Group 1: LipiFlow only, n=14 (14 eyes).

Group 2: LipiFlow and heated manual expression, n=14 (14 eyes).

Results

The mean meibomian gland secretion score, TBUT, corneal staining score, number of meibomian glands yielding liquid secretion and symptom scores all improved significantly from baseline to 1 week (all p<0.05) for both treatment groups. This was maintained at 3‑month follow‑up.

There was no statistically significant difference in any outcomes measured between the treatment groups (LipiFlow versus LipiFlow + heated manual expression).

The mean (SD±) discomfort/pain score reported during the treatment with LipiFlow=2.4±1.6 compared with 3.7±1.5 (LipiFlow + heated manual expression; p=0.003).

Three adverse events were reported:

  • One person reported a high discomfort score causing treatment to be stopped.

  • One person developed a chalazion on the upper lid (not recorded at baseline). It completely resolved within a month of therapy.

  • One person complained of a gritty sensation and irritation in the right eye and lump on the right lower eyelid, 3 weeks post‑therapy. The condition completely resolved within a month of therapy.

Conclusions

A single 12‑minute session of LipiFlow per eye was highly effective in treating obstructive MGD and dry eye symptoms for the 3‑month study period.

Abbreviations: ANOVA, analysis of variance; MGD, meibomian gland dysfunction; OSDI, ocular surface disease index; SD, standard deviation; SPEED, standard patient evaluation of eye dryness; TBUT, tear break‑up time.

Recent and ongoing studies

Seven ongoing clinical trials involving LipiFlow have been identified. Two of these are described as currently active:

  • NCT02102464: Treatment of meibomian gland dysfunction and dry eye in contact lens wearers.

  • NCT01808560: Treatment of meibomian gland dysfunction prior to cataract surgery.

The remaining five trials are listed as having been completed:

  • NCT01769105: Comparison of LipiFlow‑treatment and a standard lid hygiene regime.

  • NCT01202747: Evaluation of screening methods for treatment of meibomian gland dysfunction.

  • NCT01521507: Randomized controlled trial of long‑term treatment effectiveness for meibomian gland dysfunction (MGD) and dry eye.

  • NCT01683318: Treatment of meibomian gland dysfunction.

  • NCT01787942: Investigating abnormal lipid layer thickness in blepharoplasty patients.

Costs and resource consequences

If the LipiFlow system were to be adopted in the NHS, it could potentially help people with meibomian gland dysfunction (MGD). Marketing of the LipiFlow system to the NHS has only recently begun, and this system is not thought to be currently in use in any NHS centres. The potential NHS use for this system is difficult to estimate from MGD prevalence data as alternative treatment options, such as warm compresses or lid massage, are available at little or no cost to the NHS. Therefore, the LipiFlow system would represent a significant additional cost to current services and this may limit uptake. According to the manufacturer, the device is being used by several private healthcare providers.

There would be no need to change the way in which current services are organised or delivered. No other additional facilities or technologies are needed alongside the technology.

No published evidence on resource consequences for the LipiFlow system was identified in the systematic review of evidence.

Strengths and limitations of the evidence

Neither Lane et al. (2012) nor Finis et al. (2014a) reported their method of randomisation. Therefore it is unclear if the randomisation methods could have influenced the outcomes in either study. Both studies, however, benefited from crossover trial designs. Two potentially confounding issues arise with crossover study designs: the order in which the person has each intervention can affect the outcomes, and a carry‑over effect from the previous intervention can affect the results of the second intervention. The latter can be mitigated by a 'wash‑out period' (Louis et al. 1984). In both of these studies the people in the crossover group received LipiFlow therapy after the control therapy, but neither study reported a 'wash‑out period'. It is unclear how the crossover design may have influenced the Lane et al. (2012) and Finis et al. (2014a) studies.

The study by Finis et al. (2014a) was the only included study to perform a power calculation and adapt the sample size to reflect its findings. A minimum sample size was calculated as n=7 so the authors increased their sample size to n=15. However, they conceded that they lost people to follow‑up and that further increasing their sample size may have increased the number of outcomes that reached significance (particularly at 3 months). In their follow‑up publication (Finis et al. 2014b), data were collected for a sample size above the n=7 initially intended.

Neither Lane et al. (2012) nor Friedland et al. (2011) reported a power calculation. However, Lane et al. (2012) studied a much larger sample size (n=139, randomised into 2 cohorts) than Finis et al. (2014a) or Friedland et al. (2011). Consequently, it is unclear whether these studies were adequately powered to detect any differences in the primary and secondary outcomes reported by the authors.

The study by Finis et al. (2014a) was 'single‑blinded', meaning that the investigators were blinded from the intervention during the data collection phase. However, people were aware which therapy group they were assigned to and this may have introduced performance bias. The studies by Lane et al. (2012) and Friedland et al. (2011) were 'open‑label' studies, meaning that neither the investigators nor the people involved were blinded to the assigned therapy groups. This also may have introduced performance bias. However, this limitation is not specific to these trials because, although blinding of the operator is standard practice for studies involving drugs, it is often not feasible in studies involving medical devices.

In addition, another source of potential performance bias is the mode of treatment. Both Lane et al. (2012) and Finis et al. (2014a) compared LipiFlow with a mode of treatment that required substantial compliance in the home (daily and twice‑daily interventions respectively). Neither study reported compliance rates therefore it is unclear if this affected the study outcomes.

All studies included in this briefing compared the same intervention, namely, a single 12‑minute session with the LipiFlow system. All studies reported a consistent temperature of the activator and duration of therapy. However, only Finis et al. (2014a) reported which pressure cycle they used in their study. TearScience state that it is possible to modify the pressure cycle but both Lane et al. (2012) and Friedland et al. (2011) fail to report which cycle was used.

In an effort to reduce bias both Lane et al. (2012) and Friedland et al. (2011) performed their studies in multiple centres. The former used 9 different centres across the USA and the latter used 2 separate centres, also across North America. Finis et al. (2014a) failed to report if they incurred additional bias with or without the use of the use of multiple centres. None of the studies included in this briefing took place in the UK, and so the generalisability of the results to the NHS is unclear.

Finally, the studies by Lane et al. (2012) and Friedland et al. (2011) were funded by the manufacturer, TearScience, which has the potential for introducing bias in the reporting of outcomes.