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Contact Lens and Anterior Eye
journal homepage: www.elsevier.com/locate/clae
Effects of a sea buckthorn oil spray emulsion on dry eye
Petra Larmoa,⁎, Riikka Järvinenb, Jarmo Laihiab, Eliisa Löyttyniemic, Laura Maavirtad,
Baoru Yange, Heikki Kallioe, Minna Sandberg-Lalld
a Aromtech Ltd, Tornio, Finland
b Finnsusp Ltd, Lieto, Finland
c EL Statistics, Raisio, Finland
d Turun Silmäexpertit Ltd, Turku, Finland
e Food Chemistry and Food Development, Department of Biochemistry, University of Turku, Finland
A R T I C L E I N F O
Keywords:
Dry eye
Eyelid spray
Hyaluronic acid
Sea buckthorn oil
A B S T R A C T
Purpose: To investigate the effects of a sea buckthorn oil and sodium hyaluronate-containing eyelid spray
emulsion (SB spray) on dry eye.
Methods: A randomized controlled study was carried out. Adults (25–70 years) with Ocular Surface Disease
Index (OSDI)≥20 and moderate or severe dryness, burning or grittiness of the eyes were included. In study part
one (n= 2), SB spray was used on both closed eyelids four times in one day. In part two (n=10), SB spray was
used on one randomized eyelid, and a commercial reference spray on the other for nine days. In part three
(n=40), eyes were randomized to one eye receiving SB spray and an untreated control for 1.5 months. Dry eye
tests were carried out at baseline, during, and at the end of each study section. Symptoms were recorded in
questionnaires and daily logs.
Results: In part one, the SB spray was well tolerated. In part two, OSDI decreased significantly (P=0.022) in the
SB spray eye compared to the reference spray, indicating a beneficial effect on symptoms. In part three, OSDI in
the SB spray eye decreased significantly compared to the untreated control (P= 0.0007). The scores for dryness
at the study end were lower in the SB spray eye compared to control (P= 0.0070). Symptom sums and fre-
quencies of dryness (sum P=0.0046, frequency P= 0.0016) and watering (sum P=0.0003, frequency
P=0.013) in the daily logs were lower in the eye treated with SB spray.
Conclusions: SB spray on closed eyelids relieved the symptoms of dry eye.
1. Introduction
Dry eye is a multifactorial disease of the ocular surface character-
ized by loss of homeostasis of the tear film, and accompanied by ocular
symptoms [1]. There are two main mechanisms, which exist in a con-
tinuum and can reinforce each other. In evaporative dry eye, there is
excess water evaporation from the tear film due to an unstable or de-
ficient tear film lipid layer. In aqueous deficient dry eye, the lacrimal
secretion is reduced, most commonly due to inflammatory infiltration
of the lacrimal gland. Both mechanisms lead to hyperosmolarity of the
tear film, which induces inflammation and damage to the ocular sur-
face. The updated definition of dry eye includes contribution of neu-
rosensory abnormalities to the symptoms [1–3].
Dry eye is among the most common reasons for patients to seek
medical eye care. Prevalence ranging from 5 to 50% has been reported,
depending on the population and the definition used [2,4]. The best-
substantiated risk factors include aging, female sex, Asian ethnicity,
Sjögren’s syndrome, connective tissue diseases, and meibomian gland
dysfunction, along with several modifiable factors (e.g. computer use,
low environmental humidity, and certain medications) [4].
Dry eye can cause significant pain and limit everyday activities such
as reading and using a computer [4]. The condition is commonly
treated with artificial tears in an attempt to supplement the tear film.
Lipid-containing products are considered a good alternative to tradi-
tional water-based formulations because they more closely resemble the
composition of the tear film. During recent years, artificial tears
sprayed on closed eyelids have been introduced as alternatives to eye
drops [5,6]. The effects of oral sea buckthorn oil on dry eye have pre-
viously been investigated. Intake of 2 g sea buckthorn oil taken as four
capsules per day for three months improved tear osmolarity and
symptoms compared to placebo in a randomized, double-blind, pla-
cebo-controlled trial [7]. In the current study sea buckthorn oil was
https://doi.org/10.1016/j.clae.2018.11.011
Received 20 August 2018; Received in revised form 14 November 2018; Accepted 15 November 2018
⁎ Corresponding author at: Aromtech Ltd, Veturitallintie 1, 95410, Tornio, Finland.
E-mail address: petra.larmo@aromtech.com (P. Larmo).
Contact Lens and Anterior Eye xxx (xxxx) xxx–xxx
1367-0484/ © 2018 The Authors. Published by Elsevier Ltd on behalf of British Contact Lens Association. This is an open access article under the CC BY-NC-ND 
license (http://creativecommons.org/licenses/BY-NC-ND/4.0/).
Please cite this article as: Larmo, P., Contact Lens and Anterior Eye, https://doi.org/10.1016/j.clae.2018.11.011
used as an active ingredient of a topical spray emulsion. The objective
was to investigate the effects of this novel sea buckthorn oil - hyaluronic
acid eyelid spray emulsion (SB spray) on dry eye.
2. Materials and methods
2.1. Study design
A randomized, controlled study was carried out at a private eye
clinic Turun Silmäexpertit Ltd (Turku, Finland) between March and
June 2016. The protocol followed the principles of the Declaration of
Helsinki and was approved by the Ethics Committee of the Hospital
District of Southwest Finland, and Valvira - National Supervisory
Authority for Welfare and Health. This study was registered in clin-
icaltrials.gov (identifier NCT02683382).
The protocol consisted of three parts, each attended by different
participants (Fig. 1). In the first part, the safety and tolerability of SB
spray were monitored for one day, before proceeding to observation
periods of longer duration. The same tests and measurements were
carried out as in the following parts of the study. Detailed results are
not reported. In the second part, the eyes of each participant were
randomized, and SB spray was compared to a commercial reference for
nine days. In the third part, the effects of SB spray were compared to an
untreated control eye during a study period of 45 days. Study partici-
pants, and the optician performing the measurements and symptom
questionnaires at study visits were not blinded to the treatment. The
study ophthalmologist scoring the signs of irritation from photographs
taken at visits, did not know the treatment of the eye. The researchers
analysing the data and outcome knew which eyes belonged to the same
treatment but did not know what their treatment was.
2.2. Participants
The participants provided written informed consent, and they were
informed of their right to withdraw at any time without giving a reason.
Inclusion criteria were age 25–70 years, moderate or severe symptoms
of dryness, grittiness/foreign body sensation or burning of eyes, and
Ocular Surface Disease Index (OSDI) score ≥ 20. Exclusion criteria
were: serious eye disease, known hypersensitivity to ingredients of the
study sprays, or laser eye surgery within the previous 12 months.
Participants were instructed to avoid local eye-care products during the
study, and for at least five days prior to the beginning of the study.
Otherwise they were asked to continue their normal routines and use of
medication and personal care products, including eye cosmetics. The
participants were instructed to come to the study visits without eye
makeup or other eye-proximal cosmetics, including moisturizers.
2.3. Study products
The SB spray was an optically clear and preservative-free eyelid
spray microemulsion containing sea buckthorn seed oil (0.4%) and
hyaluronic acid (0.02%) as active ingredients in a hypo-osmolar and pH
neutral buffer (Aromtech Ltd, Tornio, Finland, and Finnsusp Ltd, Lieto,
Finland). The sea buckthorn seed oil, rich in α-linolenic acid (ALA,
18:3n-3) and linoleic acid (LA, 18:2n-6), was produced by supercritical
CO2 extraction with in-process control of oil colour (Aromtech Ltd).
Hyaluronic acid was in the form of sodium hyaluronate and produced
by bacterial fermentation. One dose of spray was administered to closed
eyelids four times/d (in the morning, twice during the day, and in the
evening).
The reference spray was a liposomal spray with soya lecithin
(Tearsagain Sensitive, Optima Medical Swiss AG, Zug, Switzerland). It
was administered to the closed eyelid four times/d (in the morning,
twice during the day, and in the evening) according to the manu-
facturer’s instructions. When applying the study spray(s), participants
were asked to protect the other eye with their palm to avoid cross-
contamination. For the visits following baseline assessment, partici-
pants were instructed to use the spray(s) about one hour before the
appointment.
2.4. Tests and symptom evaluations
Dry eye tests were performed at each visit (Fig. 1) as follows: Tear
osmolarity was measured using TearLab Osmolarity System (TearLab,
CA; mOsm/L [8,9]). Tear film stability was measured as tear film
breakup time (TBUT; seconds until breakup of fluorescein tear film
[8,10]). Tear fluid secretion was measured using phenol red thread tear
test (PRT) (Tianjin Jingming New Technological Development Co. Ltd,
China; length of wetting the thread, mm/20 s [8,11]). To investigate the
effect on skin around the eye, transepidermal water loss (TEWL), which
indicates the integrity of the permeability barrier, was measured with a
Vapometer device (Delfin Technologies Ltd, Kuopio, Finland; g/m2h
[12]). All measurements were performed in the same order and by the
same person throughout the study.
Signs of irritation (corneal epithelial inflammation/corrosion, dila-
tation of blood vessels in the bulbar conjunctiva, conjunctival chemosis,
dots on the margin of the cornea, oedema on the margin of the con-
junctiva/cornea, eyelid irritation, and other possible signs of irritation)
were evaluated and scored from photographs taken of the eyes and
eyelids at study visits (TRC-NW7SF Retinal Camera, Topcon
Corporation, Japan). The severity was scored, depending on the
symptom, on a 3 or 4-point scale, in which each symptom corresponded
to a verbal description (modified for this study from [13]).
Occurrence of dry eye symptoms was evaluated at each study visit
by OSDI questionnaire [14] separately for the left and right eye. The
questionnaire was translated into Finnish and modified for the study
protocol. In the visits following baseline, participants were asked to
report the symptoms experienced between the visits. Additionally, the
symptoms of dryness, grittiness/foreign body sensation or burning of
eyes were scored using a 4-point scale (0= no symptoms to 3= severe
symptoms). Adverse effects, effect on periocular and eyelid skin, other
user experience, and health and lifestyle information were monitored
by questionnaires. In the second and third parts of the study, partici-
pants also kept daily symptom logs, where symptoms were reported
using a 4-point scale (0= no symptoms to 3= severe symptoms).
2.5. Statistical analysis
Participants’ eyes were randomized to SB spray eye and reference
spray/control eye using randomly permuted blocks. Pre-study sample
size estimation was based on the assumption that in part three the SB
spray eye and the control eye would differ by one point or more
(standard deviation 1.5) in the severity scores for eye dryness, burning,
or grittiness/foreign body sensation. With a sample size of 40 partici-
pants, the study would have a power of 80% to detect the difference
between the SB spray and control assuming a dropout rate of 10% (two-
tailed tests, 0.05 significance level).
In the second and third parts of the study, the primary outcome was
the difference of change between the SB spray and reference spray/
control eye in OSDI, symptom scores at visits, TBUT, PRT, osmolarity,
and TEWL. When analysing whether the mean changes between the SB
Fig. 1. Study design. Different participants attended each part of the study.
P. Larmo et al. Contact Lens and Anterior Eye xxx (xxxx) xxx–xxx
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spray and reference spray/ control eye in OSDI, TBUT, osmolarity, or
TEWL differed, the analysis of repeated measures was used, with two
within-repeated factors: the eye and the visit. In this hierarchical linear
mixed model, the UN@CS co-variance structure was used. If the overall
significance level of the specific variables (time, time× treatment)
was< 0.05, pairwise comparisons, their estimates, and confidence in-
tervals were calculated for the differences at visits by using fitted means
of the model. If the treatment× time interaction was significant, con-
trasts were programmed between two time-points and treatments. The
normality assumption was tested visually together with Shapiro-Wilk
test using residuals. If skewness was observed in the distribution, a
square root transformation or a logarithm transformation was per-
formed. The PRT measurements did not follow a normal distribution,
and the comparison between treatment groups was made using the
Wilcoxon signed-rank test.
Due to the small number of participants in study part two; treatment
differences were not statistically analysed for the categorical variables
except for the signs of irritation. In study part three, differences in the
severity of symptoms, and in study parts two and three, signs of eye
irritation between treatment groups at different points in time were
analysed using the Stuart-Maxwell test or Wilcoxon signed-rank test.
The symptoms recorded in the logs (secondary outcome) were
compared between the SB spray and reference spray/ control eye using
the Wilcoxon signed-rank test. A symptom-sum variable was calculated
to indicate the severity of symptoms. The percentage of symptom days
was calculated for each symptom (percentage of days having a
symptom score ≥1).
A significance level of 0.05 was used (two-tailed test). All partici-
pants were included in the statistical analyses (intention to treat). The
software used was SAS® for Windows, version 9.4 (SAS Institute Inc,
NC).
3. Results
In the first part of the study, no signs of irritation or adverse effects
were observed (data not shown), and the study was continued to parts
two and three.
3.1. Compliance and participants
In the first part, both participants completed the study according to
the protocol. The majority of participants in the subsequent parts were
women over 40 years of age who did not wear contact lenses (Table 1).
In study part two, one participant dropped out because of an eye injury,
not related to the study. In the logs, all participants reported using the
SB and reference sprays as instructed for the majority of the study days.
One participant reported not using the sprays on the final study day. On
all other study days, all participants used at least part of the daily dose.
Compliance in using SB and reference sprays was very similar. None of
the participants reported using other local dry eye treatments during
the intervention. All participants came to the study visits wearing no
eye cosmetics.
Of the 45 participants beginning the third part of the study, 40
completed and attended the final visit. Two participants withdrew be-
cause they reported not benefitting from the SB spray. Other known
reasons for withdrawal were unrelated to the study product. According
to the logs, the SB spray was used according to the instructions on
97.6% of the days (median), and partly according to the instructions on
2.4% of the days. One participant reported the use of antihistamine eye
drops in addition to the SB spray during two days of the study. Five
participants reported the use of allergy or inflammation-relieving eye
drops on their control eye on one to five study days. All participants
followed the instruction not to wear eye cosmetics to the study visits.
3.2. Dry eye tests
In the second part of the study, the changes in tear film osmolarity
(P= 0.91) or TBUT (P=0.34) did not differ between the treatment
eyes (Table 2). PRT at any visit did not differ between the SB spray and
reference spray eyes (day 0, P= 0.66; day 1, P= 0.38; day 3, P=0.15;
day 9, P=0.56; Table 2).
In the final part of the study, tear film osmolarity (P=0.38) and
TBUT (P=0.11) did not differ between the SB spray and control eyes
(Table 3). Results of the PRT test did not differ between the SB spray
and control eyes at baseline (P=0.25) or the end of the study
(P= 0.74).
3.3. Dry eye symptoms
In the second part of the study, the mean change in OSDI differed
significantly between the SB spray eye and reference eye (Fig. 2;
treatment-by-time interaction, P=0.045). OSDI lowered significantly
more in the SB spray eye compared to the reference eye from baseline to
study day 9 (P=0.022, Fig. 2). Participants’ scores regarding their
experience of eye dryness, grittiness/ foreign body sensation or burning
at study visits indicated lowering trends in the severity of all symptoms
in both treatment eyes (data not shown). Symptom sums from the
whole study period (Supplementary Table 1) and proportion of
symptom days (Supplementary Table 2) calculated from the daily logs
did not differ significantly between the treatments. A beneficial trend
by SB spray compared to the reference (P= 0.094) was observed for
watering of eyes (Supplementary Tables 1 and 2).
In the third part, OSDI in the SB spray eye was significantly reduced
compared to the control eye with no treatment (P=0.0007; Fig. 3).
Participants’ experience of eye dryness score was significantly lower in
the SB spray eye compared to control at the study conclusion
(P= 0.0070; SupplementaryTable 3). The scores for grittiness/ for-
eign body sensation (P=0.11) and burning (P=0.11) did not differ
between the eyes (data not shown). Symptom sums of dryness
(P= 0.0046) and watering (P= 0.0003) from the logs were sig-
nificantly lower in the SB spray eye compared to control (Supple-
mentaryTable 4). Furthermore, the proportion of symptom days was
lower in the SB spray eye (dryness, P= 0.0016; watering, P=0.013;
Supplementary Table 5).
3.4. Skin
In the second part of the study, an overall increasing trend in skin
TEWL from baseline to end was observed from the mean 15 (SD 6) to 27
(SD 7) and 16 (SD 8) to 30 (SD 9) g/m2h in the SB and reference spray
eyes, respectively. The changes in TEWL did not differ between the
treatments (P=0.71; Supplementary Table 6). In both treatments the
experience of beneficial skin effects increased towards the end of the
study (Supplementary Table 7). At the final visit, 8 of the 10 parti-
cipants reported beneficial skin effects from SB spray and four partici-
pants from the reference spray. One person reported negative skin ef-
fects (feeling dryness) from the SB spray and three from the reference
spray.
In the third part of the study, the baseline TEWL levels were higher
compared to the baseline levels in the second part of the study, and
there was no major difference in TEWL between the baseline and the
Table 1
Baseline characteristics of participantsa.
Part two n=11 Part three n= 45
Women, n (%) 9 (82) 39 (87)
Age, years 53 (9) 60 (8)
Contact lens wearers, n (%) 2 (18) 0 (0)
Smokers, n (%) 2 (18) 5 (11)
Participants having an allergy, n (%) 4 (36) 19 (42)
a Values are means (SD), n (%).
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end of the study for either the SB spray-treated or control eye. Changes
in skin TEWL did not differ between the SB spray and the control eye
(P= 0.45; Supplementary Table 8). At the final study visit, 18 (46%)
of participants reported the spray had beneficial (e.g. hydrating, soft-
ening) effects on skin. Two participants (5%) felt negative skin effects.
3.5. Irritation
In the second part of the study, signs of corneal epithelial irritation/
corrosion were significantly more severe in the reference spray eye than
the SB spray eye after using the sprays for one day (P= 0.025;
Supplementary Table 9). However, the irritation score was generally
low, and lower at the last study visit compared to the baseline. After
using the sprays for three days, signs of eyelid irritation were more
severe in the SB spray eye compared to the reference spray (P= 0.046,
Supplementary Table 10). Mild or local scaling/ redness was observed
in five SB spray eyelids vs. one reference spray eyelid. At other visits,
the treatment effects did not differ. At the end of the treatment, the
number of participants not having signs of eyelid irritation was higher
in both treatment eyes, compared to baseline, indicating the safety of
the products. The other signs of eye irritation did not differ between the
treatments at any time point (data not shown). In the final part of the
study, none of the irritation signs differed significantly between SB
spray and control eyes at baseline or the end of the study (data not
shown).
3.6. Convenience of use
In the second part of the study, two participants used contact lenses.
Both reported that the SB and reference sprays improved lens comfort.
None of the participants felt that use of eye cosmetics affected the
convenience of use of either spray. One participant reported the re-
ference spray affecting the use of eye cosmetics. At the final study visit,
all ten participants wanted to continue the use of SB spray and six
participants wanted to continue the use of reference spray.
In the third part, all participants replying (n= 39) felt that use of
Table 2
Dry eye tests in study part two. Values are means (SD), or medians (Q1; Q3).
Day Osmolarity (mOsm/L)a TBUT (s)b PRT (mm/20 s)c
SB spray RF spray SB spray RF spray SB spray RF spray
0 288.6 (10.6) 287.0 (5.7) 4.9 (1.1) 5.2 (1.6) 2.0 (1.0; 5.0) 3.0 (1.0; 5.0)
1 286.4 (6.1) 286.2 (6.9) 4.7 (1.4) 4.7 (1.8) 2.0 (1.0; 3.0) 2.0 (1.0; 5.0)
3 288.7 (10.2) 286.0 (7.2) 6.2 (1.5) 5.3 (1.6) 2.0 (1.0; 3.0) 4.0 (2.0; 6.0)
9 288.1 (10.2) 286.0 (7.0) 6.0 (1.2) 5.9 (1.6) 2.5 (1.0; 3.0) 3.5 (1.0; 5.0)
a Sea buckthorn oil (SB) spray n=7–10, reference (RF) spray n=9–11.
b SB spray n=10–11, RF spray n=10–11.
c SB spray n= 10–11, RF spray n= 10–11.
Table 3
Dry eye tests in study part three. Values are means (SD), or medians (Q1; Q3).
Day Osmolarity (mOsm/L)a TBUT (s)b PRT (mm/20 s)c
SB spray Control SB spray Control SB spray Control
0 289.2 (9.9) 289.5 (9.3) 3.0 (1.6) 2.8 (1.4) 2.0 (1.0; 3.0) 2.0 (1.0; 3.0)
45 292.5 (8.8) 295.5 (17.4) 4.0 (1.7) 3.5 (2.2) 2.0 (1.0; 3.0) 2.0 (1.0; 3.0)
a Sea buckthorn oil (SB) spray n=39–41, Control n=38–42.
b SB spray n=40–45, Control n=40–45.
c SB spray n= 40–45, Control n= 40–45.
Fig. 2. OSDI scores in study part two. Values are estimates of the mean in the
OSDI statistical model. Error bars describe the 95% CI. For statistical analyses, a
square root transformation was performed on the data to fulfil the assumption
of normal distribution. Estimates in the figure are back-transformed values. Sea
buckthorn oil (SB) spray n= 10–11, reference (RF) spray n= 10–11. P-values
represent the difference in change from baseline between the treatments.
Fig. 3. OSDI scores in study part three. Values are estimates of the mean in the
OSDI statistical model. Error bars describe the 95% CI. For statistical analyses, a
square root transformation was performed on the data to fulfil the assumption
of normal distribution. Estimates in the figure are back-transformed values. Sea
buckthorn oil (SB) spray n=39–45, Control n=39-45. P-value represents the
difference in change from baseline between the treatments.
P. Larmo et al. Contact Lens and Anterior Eye xxx (xxxx) xxx–xxx
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eye cosmetics did not affect the convenience of using the SB spray. One
participant felt that SB spray affected the use of eye cosmetics by
causing mild running of make-up. At the last visit, 26 participants
(67%) would have liked to continue the use of SB spray.
4. Discussion
Beneficial effects were found with sea buckthorn oil and hyaluronic
acid-containing eyelid spray for the symptoms of dry eye. The im-
provement of dry eye symptoms was significant compared to a com-
mercial reference spray over a nine-day treatment period and when
compared to the untreated control eye over a 45-day treatment period.
Hyaluronic acid is a polysaccharide naturally found in the vitreous
body and extracellular matrix and commonly used in ophthalmologic
formulations [15]. It has a high water-binding capacity, and several
clinical studies have reported beneficial effects of hyaluronic acid, ty-
pically with ≥0.1% solutions, on signs and symptoms of dry eye and
ocular damage [6,16–19]. However, in spray formulations, the con-
centration is restricted to appreciably lower concentrations to obtain a
pleasant spray behavior on the eyelid.
Inflammation is an important contributor to dry eye [1,2]. Sea
buckthorn seed oil is rich in essential fatty acids ALA and LA. In hu-
mans, a proportion of ALA and LA can be converted to very long-chain
n-3 and n-6 fatty acids, respectively, in a series of enzyme catalysed
reactions. These are precursors for eicosanoids, biologically active lipid
mediators regulating inflammation. With the exception of dihomo-γ-
linolenic acid (20:3n-6) derivatives, the n-6 fatty acid-derived eicosa-
noids are generally considered pro-inflammatory, whereas eicosanoids
from n-3 fatty acids are anti-inflammatory or less inflammatory [20].
Very long-chain n-3 fatty acids are also precursors for resolvins and
protectins, contributing to the resolution of inflammation [21]. A
higher intake of n-3 fatty acids from the diet is associated with a lower
risk of dry eye in women [22]. Clinical interventions suggest attenua-
tion of dry eye by intake of combined LA and γ-linolenic acid (GLA,
18:3n-6) [23–27], n-3 fatty acids [28] and a combination of GLA and n-
3 fatty acids [29].
Topical application n-3 fatty acids (0.2%) in mice attenuated several
markers of dry eye-associated corneal damage, lipid peroxidation and
inflammation [30]. ALA (0.2%) in eye drops relieved corneal damage
and inflammation of dry eye in mice [31]. Topical ALA attenuated the
release of inflammatory cytokines in stimulated human corneal epi-
thelial cells via effects on the proinflammatory transcription factor
nuclear factor-κB pathway [32]. Thus, it is justified to speculate that at
least part of the clinical improvement observed in the present study
may derive from the local activity of the sea buckthorn oil fatty acids in
the SB spray.
Most previous studies of lipid-containing artificial tear sprays on
closed eyelids have focused on the effect of a single dose, whereas there
are fewer studies covering longer duration. The single-dose studies re-
port beneficial effects on TBUT, tear film lipid layer thickness or grade,
and subjective comfort from eyelid sprays containing phospholipids,
sodium hyaluronate, plant extracts, and/or isoflavonoids from 10 to
90min after application of the product [33–37]. Longer-term studies
(from two to four-weeks duration) of phospholipid-containing eyelid
sprays have reported beneficial effects on OSDI and markers of dry eye
[38], modest changes in tear film lipid classes [39] or beneficial trends
on TBUT and Schirmer test, but not significantly different compared to
untreated controls [40].
In this study, a significant decrease in dry eye symptoms measured
by OSDI was observed in response to SB spray compared to the re-
ference spray or untreated control. In both in study parts two and three
the effect on OSDI was in the range considered clinically important
[41]. The improving symptoms were also recorded in the daily logs,
whereas TBUT, PRT and tear osmolarity were not affected. These results
may have been affected by the fact that participants were advised to use
the study sprays about one hour before the scheduled study visits. The
time interval between the tests and the application of the product was
longer than in most similar studies published recently [33–37].
TEWL controlled by the stratum corneum, the outer layer of skin, is
commonly used as a measure of barrier function of the skin. If the skin
is damaged the barrier function is compromised and the TEWL in-
creases [42]. Previous studies on the lipid-containing eyelid emulsions
did not measure skin TEWL [33–40]. In this study the change in TEWL
did not differ between the SB and reference spray or control eyes. Oil in
water emulsions can improve stratum corneum hydration in healthy skin
without affecting TEWL. However, effects on TEWL commonly need a
more occluding film with water in oil emulsion [43] or pure plant oil
[44].
This study has limitations. Due to the sensory properties of sea
buckthorn oil an identical placebo was not possible to manufacture, and
the participants could not be blinded to the treatments. It cannot be
excluded that this may have affected the reporting of symptoms.
However, using a commercial reference spray instead of a placebo al-
lowed for a comparison between the SB spray and a spray with pre-
existing efficacy studies [33–35,37–40]. It was expected that the par-
ticipants’ knowledge of getting active treatments (placebo effect) would
be similar for the SB and reference sprays. It must also be acknowledged
that the effects of different treatments observed in the contralateral
eyes are not fully independent because of inter-eye signalling [45]. This
may have equalized the differences in OSDI, especially at the end of
part three, where the untreated eye showed only mild symptoms. On
the other hand, comparing different treatments in contralateral eyes
allows for less participant-related variation, and this design is com-
monly used to investigate dry eye treatments [33–35,37,46]. The in-
clusion criteria were experience of dry eye symptoms, and different dry
eye types were included. Based on the median TBUT, PRT and OSDI, the
participants at baseline had at least mild dry eye disease (TBUT < 10 s
[2,8], PRT < 10mm/20 s [8,11], OSDI≥ 13 [8,14]). Mean tear os-
molarities, however, were< 308 – 316 mOsm/L, commonly considered
as the threshold values indicative of dry eye [2,8,9,47]. The poor cor-
relation of the common diagnostic measures with symptoms of dry eye
is well known, and each test reflects different aspects of dry eye disease
[48].
In conclusion, a novel eyelid spray emulsion containing sea buck-
thorn oil and sodium hyaluronate relieved the symptoms of dry eye as
measured by OSDI, visit questionnaires and by daily symptom logs. The
beneficial effects were significant compared to a commercial reference
spray and compared to an untreated control eye. The spray was well
tolerated, and no significant adverse effects were observed.
Declaration of interest
Larmo P is an employee, and Kallio H is a partner of Aromtech Ltd
(Tornio, Finland), manufacturer of SB oil and spray. Järvinen R is a
partner and employee, Laihia J is an employee of Finnsusp Ltd (Lieto,
Finland), manufacturer of SB spray. Other authors: no conflicts of in-
terest.
Acknowledgements
Tuija Vaattovaara and Pia Sorsa are acknowledged for their con-
tribution in the study arrangements. This work was presented as an oral
congress presentation at the European Society of Ophthalmology
Congress, Barcelona, 10-13 June 2017. The study was supported by
Tekes - The Finnish Funding Agency for Technology and Innovation.
Appendix A. Supplementary data
Supplementary data associated with this article can be found, in the
online version, at https://doi.org/10.1016/j.clae.2018.11.011.
P. Larmo et al. Contact Lens and Anterior Eye xxx (xxxx) xxx–xxx
5
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