Ophthalmol Ther (2023) 12:2427–2439
https://doi.org/10.1007/s40123-023-00740-x
ORIGINAL RESEARCH
Preoperative Treatment of Meibomian Gland
Dysfunction with a Vectored Thermal Pulsation
System Prior to Extended Depth of Focus IOL
Implantation
Cynthia Matossian . Daniel H. Chang . Jeffrey Whitman .
Thomas E. Clinch . Jerry Hu . Leilei Ji . David Murakami .
Ying Wang . Caroline A Blackie
Received: April 5, 2023 / Accepted: May 18, 2023 / Published online: June 15, 2023
Ó The Author(s) 2023
ABSTRACT
Introduction: Patients implanted with a range-
of-vision intraocular lens (IOL) (multifocal or
extended depth of focus, EDOF) may be more
susceptible to visual disturbances from poor tear
film quality, and prophylactic treatment of
meibomian gland dysfunction (MGD) has been
recommended. The purpose was to evaluate
whether vectored thermal pulsation (Lipi-
FlowTM) treatment prior to cataract surgery with
a range-of-vision IOL safely improves postoper-
ative outcomes.
Methods: This is a prospective, randomized,
open-label, crossover, multicenter study of
patients with mild-to-moderate MGD and
C. Matossian (&)
Matossian Eye Associates, 3096 Comfort Road, New
Hope, Doylestown, PA, USA
e-mail: CMatossianMD@icloud.com
D. H. Chang
Empire Eye and Laser Center, Bakersfield, CA, USA
J. Whitman
Key-Whitman Eye Center, Dallas, TX, USA
T. E. Clinch
Eye Doctors of Washington, Chevy Chase, MD, USA
J. Hu
Texas Eye and Laser Center, Hurst, TX, USA
L. Ji
D. Murakami
Y. Wang
C. A. Blackie
Johnson & Johnson Surgical Vision, Inc., Irvine, CA,
USA
cataract. The test group underwent LipiFlow
treatment prior to cataract surgery and
implantation of an EDOF IOL, while the control
group did not. Both groups were evaluated
3 months postoperatively, after which the con-
trol group received LipiFlow treatment (cross-
over). The control group was re-evaluated
4 months postoperatively.
Results: A total of 121 subjects were random-
ized, with 117 eyes in the test group and 115
eyes in the control group. At 3 months after
surgery, the test group had a significantly
greater improvement from baseline in total
meibomian gland score compared with the
control group (P = 0.046). At 1 month after
surgery, the test group had a significant
decrease in corneal (P = 0.04) and conjunctival
(P = 0.002) staining compared to the control
group. At 3 months after surgery, the test group
had significantly lower incidence of being
bothered by halos compared with the control
group (P = 0.019). The control group had a sig-
nificantly lower incidence of being bothered by
multiple or double vision compared with the
test group (P = 0.016). After crossover, patients
had significant improvement in vision
(P = 0.03) and total meibomian gland score
(P \ 0.0001). No safety concerns or relevant
safety findings were uncovered.
Conclusion: Presurgical LipiFlow treatment of
patients implanted with range-of-vision IOLs
improved meibomian gland function and post-
operative ocular surface health. This supports
2428
guidelines recommending proactive diagnosis
and management of MGD in patients with cat-
aracts to improve patient experience.
Trial Registration: The study was registered on
www.clinicaltrials.gov (NCT03708367).
Keywords: Cataract; Extended depth of focus;
LipiFlow; Meibomian gland dysfunction; Ocular
surface disease; Tecnis IOL; Vectored thermal
pulsation
Key Summary Points
Why carry out this study?
Patients requiring cataract surgery can
have meibomian gland dysfunction
(MGD) without presenting with dry eye
symptoms.
Failure to address ocular surface disease
(OSD) preoperatively could lead to
refractive misses, fluctuating vision,
induced higher-order aberrations,
bothersome ocular symptoms, and new or
worse OSD symptoms postoperatively.
This is the first study to evaluate the effect
of treating MGD with a vectored thermal
pulsation system (LipiFlow) prior to
cataract removal and implantation of a
range-of-vision IOL.
What was learned from this study?
This study shows measurable positive
impact of LipiFlow treatment on visual
symptoms in patients implanted with
range-of-vision IOLs.
The use of LipiFlow before cataract surgery
could optimize patient expectations from
range-of-vision IOLs.
This study validates the recommendations
of recent clinical consensus guidelines to
proactively diagnose and treat ocular
surface disease, even in the absence of dry
eye symptoms, in patients with a cataract
prior rather than post cataract surgery.
Ophthalmol Ther (2023) 12:2427–2439
INTRODUCTION
Meibomian gland dysfunction (MGD) is defined
as chronic diffuse abnormality of the meibo-
mian glands (MG) and characterized by termi-
nal duct obstruction and/or changes in
glandular secretion [1]. MGD reduces availabil-
ity of meibum to the lid margin and tear film.
Thus, MGD can alter the tear film, causing eye
irritation, inflammation, dry eye, and ocular
surface disease (OSD) [1]. MG function and a
healthy lipid layer are vital for ocular surface
health [2].
Aging is associated with alterations in MG
secretions with or without ocular symptoms or
OSD diagnosis [3–5]. Accordingly, asymp-
tomatic dry eye disease and OSD occur in up to
60–80% of patients presenting for cataract sur-
gery [6]. Gupta et al. reported that 57% of
patients presenting for cataract surgery had no
previous diagnosis of OSD, but 81% had at least
one abnormal tear film test, suggesting that
OSD is often overlooked/underdiagnosed in this
population [6]. This is a concern because
abnormal tear film and/or corneal surface can
cause errors in presurgical keratometric and
topographic measurements [7, 8]. This can lead
to IOL calculation errors, refractive misses,
residual ametropia, and ultimately dissatisfac-
tion in postoperative outcomes [6, 8]. A survey
of clinicians reported that more than 90% of
respondents felt that mild-to-moderate dry eye
affected post-cataract surgery satisfaction [8].
Thus, MGD and OSD of any severity can lead to
suboptimal visual outcomes after cataract
surgery.
The American Society of Cataract and
Refractive Surgery (ASCRS) conducted a survey
of its membership and learned of educational
gaps related to managing OSD in patients
undergoing cataract and refractive surgery. The
ASCRS Cornea Clinical Committee published
guidelines, and recommends identifying and
treating OSD prior to cataract surgery regardless
of the presence of symptoms [8]. The Commit-
tee acknowledges that addressing OSD preop-
eratively can be cumbersome; however, they
state that ‘‘its importance cannot be underesti-
mated.’’ The committee concluded that failure
Ophthalmol Ther (2023) 12:2427–2439 2429

to address OSD preoperatively could lead to METHODS

refractive misses, fluctuating vision, induced
higher-order aberrations, and new or worse OSD Study Design and Patients
symptoms postoperatively [8]. Further, the
committee recommends that any case of OSD,
This was a prospective, randomized, open-label,
whether visually significant or not, should be
crossover multicenter study conducted at five
prophylactically treated to prevent postopera-
study sites in the USA. Prior to cataract surgery,
tive worsening.
the test group underwent LipiFlow treatment
The commonly recommended treatment of
while the control group did not. Three months
MGD is a twice-daily regimen of warm com-
postoperatively, both groups were evaluated for
presses and lid hygiene/massage. However,
clinical outcomes; then the control group
elderly patients often have poor compliance
received LipiFlow treatment as the crossover
with these at-home treatments, and effective
group. The control group was then evaluated at
manual gland expression can be difficult [8]. An
4 months after surgery (1 month post LipiFlow
alternate treatment is vectored thermal pulsa-
treatment) for clinical outcomes. The study
tion (LipiFlowTM; Johnson & Johnson Vision,
protocol was reviewed and approved by Salus
Irvine, CA, USA), which applies constant heat
Institutional Review Board in accordance with
and a sequence of pressure pulsations to evac-
the Declaration of Helsinki and the Interna-
uate static oils from the upper and lower MGs
tional Council for Harmonization Guideline for
simultaneously and to improve glandular flow.
Good Clinical Practice. All patients provided
The temperature safely and effectively heats the
written informed consent and HIPAA regula-
gland contents without causing thermal injury
tions were followed. The study was registered on
[2, 9]. Prior clinical studies demonstrate safety,
www.clinicaltrials.gov (NCT03708367).
effectiveness, and clinical utility of treatment
Included patients were adults at least
with the LipiFlow in patients with MGD and dry
22 years of age with bilateral mild to moderate
eye symptoms [10–12]. LipiFlow is more effec-
MGD (defined as a score of 15 or less on a scale
tive than the commonly recommended treat-
of 0 to 45), none to moderate dry eye symptoms
ment and the effectiveness is rapid, only
bilaterally [defined as total score 0 to 15 on the
requiring a single 12-min in-office procedure
standard patient evaluation of eye dryness
[2, 12–14]. As opposed to manual gland
(SPEED) questionnaire], and scheduled for
expression, LipiFlow causes an awareness of
bilateral cataract surgery with Tecnis Symfony
pressure without causing pain [13].
IOL implantation. Key exclusion criteria were
According to the ASCRS consensus guideli-
irregular corneal astigmatism; pupil or zonular
nes, patients implanted with range-of-vision
abnormalities; having a systemic disease that
IOLs (i.e., multifocal or extended depth of
causes dry eye; unwillingness/inability to
focus, EDOF) may be more susceptible to visual
abstain from using systemic antihistamines,
disturbances from poor tear film or other OSDs
systemic medications known to cause dryness,
and preoperative optimization of the tear film is
or prescription medications to treat MGD or dry
valuable [8, 15]. Hence, we hypothesized that
eye; having prior intraocular, oculoplastic, cor-
preoperative treatment of MGD with a vectored
neal, or refractive surgery procedure; having
thermal pulsation system would help promote
ocular trauma, ocular infection, recurrent/ac-
better postsurgical meibomian gland function,
tive ocular inflammation, or punctal plugs or
and improve ocular health and visual quality.
occlusion; eyelid abnormalities that affect lid
Thus, the purpose of this study was to evaluate
function; having moderate to severe (grade 2–4)
whether LipiFlow treatment prior to cataract
allergic, vernal, or giant papillary conjunctivitis;
surgery with TecnisTM SymfonyTM EDOF IOL
and pregnant or breast feeding.
implantation in patients with mild-to-moderate
MGD safely improves postoperative outcomes.
2430
Study Procedures
Patients were randomized 1:1 to receive the
LipiFlow treatment preoperatively (test group)
or after the 3-month postoperative visit (control
group). Treatment with the LipiFlow system was
conducted per the LipiFlow System Instructions
for Use [16]. Patients were instructed on how to
perform blinking exercises for 1 month after
LipiFlow treatment to facilitate the flow of oils
from the MGs into the tear film. Patients were
instructed not to use any MGD or dry eye pre-
scription medications or other treatments dur-
ing the study (except over-the-counter artificial
tears, ocular lubricants, ointments, emollients,
or omega-3 dietary supplements). Except for
LipiFlow treatment, no other MGD or dry eye
treatment was prescribed or administered to
patients throughout the study. Two to
four weeks prior to cataract surgery, the test
group received preoperative LipiFlow treatment
according to manufacturer’s instructions and as
reported by others [13, 16]. All subjects in both
arms had bilateral cataract surgery via standard
small-incision phacoemulsification and
implantation of the Tecnis Symphony Non-
Toric or Toric Extended Range of Vision IOL
(Models ZXR00, ZXT150, ZXT225, ZXT300, and
ZXT375).
The test and control groups were examined
preoperatively to establish a baseline, and study
assessments were collected at 1 and 3 months
after surgery. The control group was also
examined 1 month following the
crossover/postoperative LipiFlow treatment
(= 4-month postoperative visit). The following
were assessed: visual acuity, manifest refraction
spherical equivalent (MRSE), contrast acuity,
visual symptoms via the Patient-Reported
Visual Symptom Questionnaire (PRVSQ),
biomicroscopic slit-lamp findings, ocular/visual
symptom assessment (non-directed, sponta-
neous), corneal surface staining via fluorescein
dye, conjunctival staining via lissamine green
dye, complications, and adverse events (AEs).
MG function was measured on the basis of
secretion characterization via an MG Evaluator
diagnostic instrument (Johnson & Johnson
Vision, Irvine, CA) as described in the manu-
facturer’s instructions [17] and slit-lamp. Gland
Ophthalmol Ther (2023) 12:2427–2439
function was scored 0 = no secretion to
3 = clear liquid oil secretion, and the sum of
scores for 15 glands in the lower eyelid was used
to calculate the total MG secretion score (higher
score indicates better gland function). Meibo-
mian glands yielding liquid secretion (MGYLS)
is a measure of gland expressibility, and was
calculated as the count of the number of 15
glands with grade 2 or 3 function (total score
range 0–15, and the higher the number the
better the MG function). Tear breakup time
(TBUT) was measured as an average of three
measures, with a higher number indicating
better tear film stability. Eyelid margin was
evaluated via slit lamp or digital images from
LipiViewTM II Ocular Surface Interferometer
(Johnson & Johnson Vision, Irvine, CA) digital
imaging. The frequency and severity of dry eye
symptoms were assessed via the SPEED ques-
tionnaire, with frequency scored 0 = never to
3 = constant and severity scored 0 = no prob-
lems to 4 = intolerable. The maximum SPEED
score was 28 points, and a lower total score
indicated less frequent/less severe symptoms.
Although the study was not masked, to main-
tain consistency, one individual at each site
conducted all study-related vision testing.
Outcome Measures and Data Analysis
The co-primary effectiveness endpoints were (1)
mean monocular uncorrected distance visual
acuity (UCDVA) at 3 months after surgery; (2)
rate of refractive predictability at 3 months after
surgery; (3) rate of bothersome ocular symp-
toms (PRVSQ) at 3 months after surgery; and (4)
the mean change in total MG score in the test
group compared to the control group from
baseline to 1 month after surgery. In addition,
the mean change from baseline to 1 month
after surgery was evaluated for MGYLS, ocular
surface stain grade, TBUT, and eyelid margin
evaluation. The mean change from baseline to
3 months after surgery was evaluated for SPEED
score and total MG score. In the control group,
the change from 3 to 4 months after surgery
(i.e., before vs. after crossover) was evaluated for
UCDVA, BCDVA, total MG score, and total
Ophthalmol Ther (2023) 12:2427–2439 2431

Table 1 Demographics
Parameter Test group (N = 59) Control group (N = 58) Total (N = 117) P value
Age (years)
Mean ± SD 65.1 ± 7.5 65.2 ± 8.0 65.2 ± 7.7 0.970
Range 39, 79 48, 84 39, 84
Sex, n (%)
Male 25 (42.2) 23 (39.7) 48 (41.0) 0.852
Female 34 (57.6) 35 (60.3) 69 (59.0)
Race, n (%)
White (Caucasian) 48 (81.4) 42 (72.4) 90 (76.9) 0.559
Asian (including Indian) 3 (5.1) 4 (6.9) 7 (6.0)
Black or African American 8 (13.6) 12 (20.7) 20 (17.1)
N number of patients in treatment group, n number of patients in specified category, SD standard deviation
Percentages are calculated as (n/N) 9 100. P value is for test vs. control group

SPEED score. Safety was assessed by monitoring RESULTS

AEs and medical/lens findings.
The sample size determination was based on
the primary endpoint of UCDVA. There was
90% power to detect a 1-line or greater differ-
ence in mean UCDVA between the test and
control groups with 55 subjects in each group.
This assumed one-sided two-sample t test with
an alpha of 0.05 and standard deviation of 1.6
lines. Considering a 20% screen failure/dropout
rate, 69 subjects per group were planned for
enrollment. No more than 30% of enrolled
subjects with no dry eye symptoms were per-
mitted at each site. Continuous and categorical
variables were summarized with descriptive
statistics and frequencies and percentages. The
mean change in total MG score was compared
between groups at 1 month after surgery. All
other key study endpoints were evaluated at
3 months after surgery. Additional endpoints
were evaluated at 1 and 3 months after surgery,
and at 4 months after surgery for the crossover
control group only. Missing data were not
imputed. Statistically significant difference was
recorded when P B 0.05. Data were analyzed
using SAS (v9.4, SAS Institute).
A total of 121 subjects were randomized, with
117 eyes treated in the test group and 115 eyes
treated in the control group. One subject in
each group was lost to follow-up. The demo-
graphics were similar between groups (Table 1).
The mean age of the total population was
65.2 ± 7.7 years, 59.0% (69/117) were women,
and 76.9% (90/117) were White.
Visual Outcomes
A comparison of the visual outcomes at
3 months is presented in Table 2. As expected,
the mean monocular UCDVA at 3 months was
not significantly different between groups (co-
primary endpoint). At the 3-month postopera-
tive visit, the test group had significantly better
mean monocular BCDVA than the control
group (P = 0.0495; - 0.03 ± 0.09 vs.
- 0.05 ± 0.08 logMAR, respectively), while the
mean binocular BCDVA was similar between
groups. The rate of refractive predictability (i.e.,
within 0.50 D and 1.00 D of target refraction) at
3 months was similar between groups, and both
groups had mean achieved MRSE of - 0.24 D at
2432 Ophthalmol Ther (2023) 12:2427–2439

Table 2 Visual outcomes at 3 months after surgery

Parameter Test group (N = 116) Control group (N = 114) P value
Monocular UCDVA, n 116 114
Mean logMAR ± SD 0.08 ± 0.15 0.07 ± 0.13 0.416
95% CL for mean [0.06, 0.11] [0.04, 0.09]
Monocular BCDVA, n 116 114
Mean logMAR ± SD - 0.03 ± 0.09 - 0.05 ± 0.08 0.0495
95% CL for mean [- 0.05, - 0.01] [- 0.07, - 0.04]
Binocular BCDVA, n 58 57
Mean logMAR ± SD - 0.08 ± 0.08 - 0.10 ± 0.07 NA
95% CL for mean [- 0.10, - 0.06] [- 0.12, - 0.08]
Binocular contrast acuity, n 58 57
Mean logMAR ± SD 0.29 ± 0.15 0.29 ± 0.11 NA
95% CL for mean [0.25, 0.33] [0.26, 0.32]
Achieved MRSE 116 114
Mean ± SD - 0.24 ± 0.48 - 0.24 ± 0.35 NA
95% CI [- 0.32, - 0.15] [- 0.31, - 0.18]
± 0.50 D of target, n (%) 85 (73.3) 94 (82.5) NA
95% CI [0.64, 0.81 [0.74, 0.89]
± 1.00 D of target, n (%) 109 (94.0) 112 (98.2) NA
95% CI [0.88, 0.98] [0.94, 1.00]
Percentages are calculated as (n/N) 9 100
Achieved MRSE = Postoperative MRSE - target MRSE
BCDVA best corrected distance visual acuity, CI confidence interval, CL confidence limit, MRSE manifest refraction
spherical equivalent, N number of patients in treatment group, n number of patients in specified category, NA not available,
SD standard deviation, UCDVA uncorrected distance visual acuity

3 months (co-primary endpoint). At the
3-month visit, contrast acuity was similar
between groups.
Ocular Symptoms
The rate of bothersome ocular symptoms is
presented in Table 3 (co-primary endpoint). The
test group had a significantly lower incidence of
being bothered by halos compared with the
control group (P = 0.019; 58.6% vs. 78.95%,
respectively). The control group had a signifi-
cantly lower incidence of being bothered by
multiple or double vision compared with the
test group (P = 0.016; 8.8% vs. 25.9%, respec-
tively). There were no significant differences
between groups in the following bothersome
symptoms: starbursts, sensitivity to light, glare
related to scattered light, and poor low-light
vision.
Ocular Surface Assessment
The total MG score change from baseline to the
1-month postoperative visit was not signifi-
cantly different between groups (co-primary
Ophthalmol Ther (2023) 12:2427–2439 2433

Table 3 PRVSQ rating at 3 months after surgery Table 4 Ocular surface assessment
Parameter Test Control P value Parameter Test group Control P value
group, group, group
n (%) n (%)
Total meibomian 114 114
Had halos over the 34 (58.62) 45 (78.95) 0.019 gland score
last 7 days change from
Were bothered by 23 (39.66) 28 (49.12) 0.307 baseline to
halos 1 month after
surgery, n
Had a lot of 4 (6.9) 7 (12.28) 0.326
difficulty with, or Mean ± SD 4.8 ± 8.2 3.9 ± 8.3 0.41
did not do 95% CL for [3.3, 6.3] [2.3, 5.4]
something, because mean
of halos
Total meibomian 114 114
Had multiple or 15 (25.86) 5 (8.77) 0.016 gland score
double vision over change from
the last 7 days baseline to
Were bothered by 11 (18.97) 4 (7.02) 0.057 3 months after
multiple or double surgery, n
vision Mean ± SD 7.3 ± 9.3 4.7 ± 10.1 0.046
Had a lot of 3 (5.17) 1 (1.75) 0.317 95% CL for [5.6, 9.1] [2.9, 6.6]
difficulty with, or mean
did not do
SPEED score 58 57
something, because
change from
of multiple or
baseline to
double vision
3 months after
Q questionPRVSQ Patient-Reported Visual Symptom surgery, n
Questionnaire
Mean ± SD - 2.1 ± 5.3 - 1.5 ± 5.6 0.60
95% CL for [- 3.5, [- 3.0, 0.0]
outcome, Table 4). However, at 3 months after mean - 0.7]
surgery, the test group had a significantly larger
improvement from baseline in total MG score CL confidence limit, n number of patients in specified
compared with the control group (P = 0.046; category, SD standard deviation, SPEED standard patient
7.3 ± 9.3 vs. 4.7 ± 10.1, respectively). The test evaluation of eye dryness
group had an improvement in SPEED outcomes
but was not statistically different from the
control group.
corneal and conjunctival staining compared to
the control group (corneal: P = 0.04;
Anterior Ocular Health - 0.57 ± 2.33 vs. 0.20 ± 3.19, respectively and
conjunctival: P = 0.002; - 1.2 ± 3.8 vs.
Table 5 summarizes the mean change from 0.45 ± 4.03, respectively). There were no sig-
baseline to 1 month after surgery in anterior nificant between-group differences in the mean
ocular health outcomes. At 1 month after sur- change in MGYLS, eyelid margin evaluation,
gery, the test group had a significant decrease in and TBUT at 1 month after surgery.
2434 Ophthalmol Ther (2023) 12:2427–2439

Table 5 Anterior ocular health scores: change from the 3-month visit (P = 0.03; 0.05 ± 0.12 vs.
baseline to 1 month after surgery 0.07 ± 0.13 logMAR, respectively), while
monocular and binocular BCDVA remained
Parameter Test group Control P value
group unchanged. The total MG score was signifi-
cantly improved at the 4-month visit compared
MGYLS, n 114 114 with the 3-month visit (P \ 0.0001, 16.1 ± 11.5
Mean ± SD 1.6 ± 3.1 1.1 ± 3.3 0.17 vs. 12.0 ± 10.6, respectively) and total SPEED
score improved at the 4-month visit compared
95% CL for [1.1, 2.2] [0.5, 1.7] with the 3-month visit; however, the difference
mean was not statistically significant.
Eyelid margin 114 114
evaluation, n Safety

Mean ± SD 0.0 ± 0.4 0.1 ± 0.5 0.89

Ocular serious AEs (SAEs) occurred in 1/59 sub-
95% CL for [0.0, 0.1] [0.0, 0.2] jects (1.7%) in the test group (cystoid macular
mean edema = 1 eye) and 4/58 subjects (6.9%) of the
control group (cystoid macular edema = 3 eyes,
TBUT, n 112 114
anterior capsular phimosis = 1 eye). None of the
Mean ± SD 0.69 ± 4.63 0.06 ± 3.67 0.26 ocular SAEs were related to the study devices.
The test group had no AEs; 12.1% (7/58) of the
95% CL for [- 0.18, 1.56] [- 0.62,
control group had AEs and all were categorized
mean 0.74]
as undesirable optical phenomena. Rates of
Degree of 116 114 anterior segment, anterior chamber, and poste-
corneal rior segment findings were similar between the
staining, n groups.

Mean ± SD - 0.57 ± 2.33 0.20 ± 3.19 0.04

95% CL for [- 1.00, [- 0.39, DISCUSSION
mean - 0.14] 0.79]
In patients with MGD, inflammation and other
Degree of 115 114 obvious signs of pathology may be absent; thus,
conjunctival MGD diagnosis may be overlooked [18]. Pro-
staining, n phylactic treatment of MGD is recommended
because there is an increased risk of worsening
Mean ± SD - 1.2 ± 3.8 0.45 ± 4.03 0.002
quality of MG secretions, decrease in meibum
95% CL for [- 1.90, [- 0.30, expressibility, and increase in dry eye symptoms
mean - 0.50] 1.20] after cataract surgery [6, 10, 19]. To our knowl-
edge, this is the first study to evaluate visual
CL confidence limit, MGYLS meibomian glands yielding outcomes and safety of treating MGD with a
liquid secretion, n number of patients in specified category, vectored thermal pulsation system prior to cat-
SD standard deviation, TBUT tear breakup time
aract removal and implantation of a range-of-
vision IOL. Results of the co-primary endpoints
show that LipiFlow treatment prior to cataract
Crossover Outcomes surgery with Symfony IOL implantation had no
negative impact on 3-month postoperative
objective visual outcome assessments. At
The outcomes in the control group after post-
3 months after surgery, there was no difference
operative LipiFlow treatment are summarized in
in mean monocular UCDVA between study and
Table 6. Monocular UCDVA significantly
control groups, and both groups achieved sim-
improved at the 4-month visit compared with
ilar MRSE. In addition, the control group had
Ophthalmol Ther (2023) 12:2427–2439 2435

Table 6 Outcomes in the control group after postoperative LipiFlow treatment (4-month visit)
Parameter 3 months 4 months Differencea
Monocular UCDVA, n 114 112
Mean ± SD 0.07 ± 0.13 0.05 ± 0.12 - 0.02 ± 0.08*
95% CL for mean [0.04, 0.09] [0.03, 0.08] [- 0.03, 0.0]
Monocular BCDVA, n 114 112
Mean ± SD - 0.05 ± 0.08 - 0.05 ± 0.08 0.0 ± 0.06
95% CL for mean [- 0.07, 0.04] [- 0.06, 0.03] [- 0.01, 0.02]
Binocular BCDVA, n 57 56
Mean ± SD - 0.01 ± 0.07 - 0.10 ± 0.07 0.0 ± 0.05
95% CL for mean [- 0.12, - 0.08] [- 0.12, - 0.08] [- 0.01, 0.01]
Total meibomian gland score, n 112 112 112
Mean ± SD 12.0 ± 10.6 16.1 ± 11.5 4.1 ± 11.0**
95% CL for mean [10.0, 14.0] [13.9, 18.2] [2.1, 6.2]
Total SPEED score 56 56 56
Mean ± SD 6.5 ± 5.1 5.3 ± 4.8 - 1.2 ± 5.6
95% CL for mean [5.1, 7.9] [4.0, 6.6] [- 2.7, 0.3]
Percentages are calculated as (n/N) 9 100. A higher total MG secretion score indicates better gland function. A lower total
SPEED score indicates less frequent/less severe symptoms
BCDVA best corrected distance visual acuity, CL confidence limit, N number of patients in treatment group, n number of
patients in specified category, SD standard deviation, SPEED standard patient evaluation of eye dryness, UCDVA uncor-
rected distance visual acuity
*P = 0.03, **P \ 0.0001
a
Difference = 4 months - 3 months

no notable change in MRSE from 3 to 4 months the difference between blur/shadowing of a

after receiving postoperative LipiFlow treat-
ment. However, there were notable differences
in the rate of subjective bothersome ocular
symptoms. Halos are the most frequently
reported ocular symptom after presbyopia-cor-
recting IOL implantation [20]. As anticipated,
the test group had a significantly lower inci-
dence of bothersome halos 3 months after sur-
gery, which may be attributed to a healthier tear
film post-LipiFlow treatment and less subse-
quent light scatter (i.e., fewer halos). In con-
trast, the control group reported a significantly
lower incidence of multiple or double vision
compared to the test group (Table 3). This
finding could be attributed to the difficultly
patients have in recognizing and understanding
letter and diplopia [21]. Shippman et al. repor-
ted that many patients who present with
symptoms of double vision do not have diplo-
pia [21]. Thus, it is possible that the patients
had difficulty interpreting the PRVSQ multi-
ple/double vision questions, and that the
patients did not have true diplopia. Although
25.86% of the test group reported multi-
ple/double vision over the last 7 days, PRVSQ
Q3E data revealed that only 5.17% of patients
reported that the multiple/double vision was
causing difficulty. This response was not sig-
nificantly different from the control group
(P = 0.317). This suggests that the patients
noticed the visual disturbance, but it did not
affect day-to-day activities.
2436
No safety concerns or relevant safety find-
ings were uncovered. Everything was routine
and as expected after cataract surgery. Both
groups had similar surgeries and postsurgery
treatment, so it would be expected that all eyes
have some surgery-induced dry eye [11, 22]. The
healing process varies between patients, and the
healing process affects dry eye and MGD.
One month after surgery may have been too
soon to examine changes in the eyelid margin,
total MG score, and MGYLS, thereby explaining
the lack of significant difference between
groups at this timepoint (Table 5). In contrast,
at 3 months, the test group had a significantly
larger improvement than the control group in
total MG score (Table 4). The improvements
from baseline in both SPEED scores and TBUT
were greater in the test group than the control
group; however, the between-group differences
were not statistically significant. This may be
attributed to either environmental factors [23],
which are known to impact tear film and drive
symptoms, or to the timepoint for evaluation.
Park et al. reported that a significant between-
group difference in TBUT following LipiFlow
and cataract surgery with a monofocal IOL was
not evident until 3 months postsurgery [19].
Despite the study limitation of evaluating the
anterior ocular health only at 1 month, the test
group had significantly less corneal and con-
junctival staining than the control group
(Table 5), which indicates that the test group
had a better ocular surface environment.
A study evaluating the effect of LipiFlow
treatment prior to cataract surgery with
implantation of a monofocal IOL concluded
that severity of MGD at baseline was correlated
with greater improvement in expressibility
(MGYLS) and quality of meibum at 3 months
after surgery [19]. It is noteworthy that our
study excluded patients with severe MGD,
whereas the Park et al. study did not. We simi-
larly demonstrated a significant improvement
in meibum quality at 3 months after surgery in
the test group, but the lack of significant dif-
ference in MGYLS in our study could be related
to the assessment at 1 month or that our study
population excluded patients with severe MGD.
The ASCRS Cornea Clinical Committee con-
cluded that ocular surface health cannot be
Ophthalmol Ther (2023) 12:2427–2439
maintained or rehabilitated in the absence of
healthy MG function because MGs are the
foundation of a healthy tear film, stable vision,
and ocular comfort [8]. Dissatisfaction with
visual outcomes following multifocal lens
implantation can be caused by dry eye [24]. The
ASCRS Committee concluded that patients who
are dissatisfied with their visual outcomes fol-
lowing a range-of-vision IOL implantation
should be examined and treated for OSD before
undergoing Nd:YAG capsulotomy or IOL
exchange [8]. Our data supports this suggestion;
patients in the crossover group who had MG
treatment after cataract surgery had significant
improvement in UCDVA and total MG score
(Table 6).
Optimal functioning of range-of-vision IOLs
requires best astigmatic correction because as
little as 0.50 D of astigmatism could result in
blurry vision, halos, and ghosting [25]. Unsta-
ble tear film affects the quality of optical surface
reflections from the cornea, which compro-
mises keratometry and can affect the accuracy
of measurement of the magnitude and axis of
astigmatism [25]. Matossian et al. evaluated
LipiFlow treatment prior to cataract surgery
with a monofocal IOL in patients with MGD-
associated dry eye. The study concluded that
stabilization of the tear film following LipiFlow
treatment altered the magnitude of astigma-
tism, emphasizing the importance of managing
dry eye prior to determining the surgical plan
for astigmatism management. This is especially
true when implanting a range-of-vision IOL.
This study has some limitations. The base-
line characteristic of having visually significant
OSD was not collected; thus, there was no sub-
group analysis evaluating patients who had
visually significant OSD versus visually non-
significant OSD. Possibly, the differences
between test and control groups may have been
larger if subgrouped by visually significant OSD.
One of the co-primary endpoints was an evalu-
ation of bothersome ocular symptoms as asses-
sed by the PRVSQ. However, PRVSQ was not
designed to evaluate patients after cataract sur-
gery. PRVSQ was self-administered by the
patients to minimize any effect of the doc-
tor–patient relationship. Some studies show
that improvement in meibomian function
Ophthalmol Ther (2023) 12:2427–2439
following LipiFlow may not be seen until sev-
eral months post-treatment and treatment may
improve over time [11, 12, 19]. In the present
study, 1 month was chosen as the primary
timepoint because postoperative drops were
discontinued at 1 month. Greater improve-
ments in MGD outcomes may have occurred
beyond the duration of assessment. Nonethe-
less, significantly less corneal and conjunctival
staining in the test group at 1 month indicates a
better ocular surface environment.
Despite the study limitations, the study has a
robust study design and demonstrates the value
of preoperative and postoperative LipiFlow
treatment. A benefit of the study design is that
not all patients had dry eye symptoms; there-
fore, the study included a mixed population (up
to 30% could be asymptomatic), which is rem-
iniscent of a real-world practice. Note that all
patients were assessed as having MGD in both
eyes as per the study protocol.
CONCLUSION
Presurgical LipiFlow treatment of patients
implanted with range-of-vision IOLs improved
meibomian gland function and improved post-
operative anterior ocular health. In addition,
LipiFlow treatment reduced postoperative
reports of halos and had measurable improve-
ments in visual acuity. These findings support
the ASCRS guidelines recommending the
proactive diagnosis and management of MGD
in patients with cataracts by assessing all pre-
operative patients for MGD and proactively
treating MGD prior to surgery to improve
patient experience. The use of LipiFlow before
cataract surgery could optimize patient satis-
faction from a range-of-vision IOL by producing
a healthier more stable tear film to better sup-
port range-of-vision IOL outcomes.
ACKNOWLEDGEMENTS
We thank the participants of this study.
2437
Funding. Sponsorship for this study was
funded by Johnson & Johnson Vision, Irvine,
CA, USA. The study sponsor funded the jour-
nal’s Rapid Service Fee.
Medical Writing/Editorial Assistance. Writ-
ing assistance was provided by Heather S. Oliff,
PhD of Science Consulting Group, LLC. Support
for this assistance was provided by Johnson &
Johnson Vision, Irvine, CA, USA.
Author Contributions. Study conception
and design was conducted by Caroline A Blackie
and Leilei Ji. Study conduct was performed by
Cynthia Matossian, Daniel H Chang, Jeffrey
Whitman, Thomas E Clinch, and Jerry Hu.
Material preparation and data analysis were
performed by Leilei Ji, David Murakami, Ying
Wang, and Caroline A Blackie. All authors
commented on all versions of the manuscript.
All authors read and approved the final
manuscript.
Prior Presentation. The data has been pre-
viously shared at the ASCRS annual meeting,
Las Vegas, NV, July 2021.
Disclosures. Cynthia Matossian has received
speaker honoraria from and is a consultant to
Johnson & Johnson Vision. Daniel H Chang has
received research grants and speaker honoraria
from and is a consultant to Johnson & Johnson
Vision. Jeffrey Whitman is a consultant to
Alcon Laboratories, Johnson & Johnson Vision,
and Bausch ? Lomb; received speaker honorar-
ium from Johnson & Johnson Vision and
Bausch ? Lomb; and received research grants
from Johnson & Johnson Vision, Alcon Labo-
ratories, Staar Surgical, RxSight, Allergan, and
BVI Medical. Thomas E Clinch has received
research grants from Alcon Laboratories and
Johnson & Johnson Vision; and speaker hono-
raria from Johnson & Johnson Vision, and is a
consultant to Johnson & Johnson Vision. Jerry
Hu is a consultant to and received research
grants from Johnson & Johnson Vision. Leilei Ji,
David Murakami, Ying Wang, and Caroline A
Blackie are employees of Johnson & Johnson
Surgical Vision Inc.
2438
Compliance with Ethics Guidelines. This
study was conducted in accordance with U.S.
Code of Federal Regulations, the Declaration of
Helsinki, ISO 14155 and all other applicable
laws and regulations. This study received
approval from Salus Institutional Review Board.
Data Availability. The data sets generated
during and/or analyzed during the current
study are available from the corresponding
author on reasonable request.
Open Access. This article is licensed under a
Creative Commons Attribution-NonCommer-
cial 4.0 International License, which permits
any non-commercial use, sharing, adaptation,
distribution and reproduction in any medium
or format, as long as you give appropriate credit
to the original author(s) and the source, provide
a link to the Creative Commons licence, and
indicate if changes were made. The images or
other third party material in this article are
included in the article’s Creative Commons
licence, unless indicated otherwise in a credit
line to the material. If material is not included
in the article’s Creative Commons licence and
your intended use is not permitted by statutory
regulation or exceeds the permitted use, you
will need to obtain permission directly from the
copyright holder. To view a copy of this licence,
visit http://creativecommons.org/licenses/by-
nc/4.0/.
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