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Efficacy of Green Tea Extract for Treatment of Dry Eye and Meibomian Gland Dysfunction; A Double-blind Randomized Controlled Clinical Trial Study

Authors:

Abstract

Introduction: With an incidence rate of 9%, dry eye is a common problem of the ocular surface, especially in patients more than 40-year-old. Green tea extract has anti-oxidative, anti-bacterial, anti-androgen, and immunomodulatory properties. Aim: To evaluate the efficacy of green tea extract for treatment of patients with dry eye and Meibomian Gland Dysfunction (MGD). Materials and methods: In a double-blind randomized controlled clinical trial, 60 patients were selected within the age range of 30 to 70 years, and divided into two groups by blocked randomization method. Standard treatment included artificial tear eye drops, three times a day for a month for all patients. Topical green tea extract was prescribed three times a day for one month in one of the groups. All patients were evaluated at the beginning and end of the study for clinical symptoms based on the Ocular Surface Disease Index (OSDI) score, Schirmer's test, Tear Breakup Time (TBUT), corneal and conjunctival staining and meibum score. Results: The mean age of participants in the green tea and control group was 61 and 64 years respectively. In the green tea group, the mean score of clinical symptoms was 9±0.86 that improved to 4.86±0.55 after one month (p=0.002). Scores suggesting improvement of TBUTs and the health of meibomian glands were significantly higher in the green tea group (p=0.002). Furthermore, no side effects of the treatment were observed. Conclusion: Green tea extract is an effective, safe, and well-tolerated topical treatment for mild and moderate evaporative dry eyes and MGD.
Journal of Clinical and Diagnostic Research. 2017 Feb, Vol-11(2): NC05-NC08 55
DOI: 10.7860/JCDR/2017/23336.9426 Original Article
INTRODUCTION
With an incidence rate of 9%, dry eye syndrome is a common
condition that causes different amounts of discomfort and disability,
especially in patients over 40 years of age. It can result in visual
disturbance and instability in the tear film, due to the increase
of tear film osmolarity and inflammation of ocular surface, or the
overall lack of an appropriate and stable tear film [1,2].
A well-formed tear film is required for nourishing, lubricating, and
protecting the ocular surface. Tear film instability may be caused
by the dysfunction of any lachrymal or meibomian gland: eyelids,
cornea, conjunctiva, or the connecting neural reflex circles.
Dry eye has divided into two distinct etiological groups: Aqueous
Tear Deficiency (ATD) and evaporative dry eye. The first group is
further divided into Sjögren’s syndrome and non-Sjögren causes of
lachrymal gland dysfunction. The second group includes intrinsic
MGD and extrinsic causes (contact lens wear or ocular surface
diseases, such as allergy) [1,2].
MGD is characterized by a chronic abnormality in the meibomian
glands, which can be determined by way of an obstruction in its
terminal duct, qualitative and quantitative changes in secretion and
consecutive tear film instability, inflammation, and ocular surface
diseases. Meibomian gland secretions (consisting of different polar
and non-polar lipids) spread across the tear film and facilitate
slow evaporation of aqueous components, thereby, maintaining a
translucent optical surface. Thus, it can prevent any adhesion of
microbial agents and organic matter, such as dust and pollen [3]. A
high level of inflammatory mediators has also been identified in the
tear films of patients with MGD [4].
Various drugs and anti-inflammatory agents are used in the
treatment of dry eye and MGD, but due to the chronic nature of
dry eye, long-term treatment with drugs often leads to side-effects,
such as the incidence of glaucoma or cataract, in many patients.
Green tea exhibits anti-oxidative, anti-bacterial, anti-androgen
and immunomodulatory properties. One of the main components
extracted from green tea is Epigallocatechin Gallate (EGCG). The
substance has an inhibitory effect on inflammation, through the
suppression of IL-1, IL-6, MCP-1 and TNF-a and through inhibition
of NF-kBs activation. Ointment made from plant extracts is useful
in the treatment of impetigo contagiosa [5,6]. In addition, green tea
extract has been used in the treatment of acne vulgaris. Its effect on
acne vulgaris may be due to modulation in the androgenic activity;
however, this observation needs further evaluation [6]. Another use
of green tea is the safe, effective, and tolerable topical application
of 10% and 15% of sinecatechins ointment for anogenital warts
[7]. In addition, green tea has important benefits in reducing the
incidence of selenite cataract, which further indicates the anti-
cataract potential of green tea [8]. It was also found effective in
treatment of vernal keratoconjunctivitis by suppressing of TNF-a,
which plays an important role in causing allergic reactions [9].
Green tea seems to be potentially effective against UV damage
in cultured human retinal pigmented epithelial cells. This was
demonstrated by increased cell count and activity after UV
irradiation [10-12]. The same research was directed at cultured
human lens epithelium with the idea that green tea can support
lens epithelial cells against UV damage [13].
This study was conducted to assess the efficacy of green tea
extract in cases with dry eye and Meibomian Gland Dysfunction
(MGD).
MATERIALS AND METHODS
Study Design: For the double-blind randomized controlled clinical
trial, 60 patients were selected from February to April 2014, based
on the incidence rate of dry eye (9%) and an anticipated dropout
rate of 10%.
Keywords: Anti-bacterial, Anti-oxidative, Ocular surface, Schirmer test
Ophthalmology Section
Efficacy of Green Tea Extract for Treatment
of Dry Eye and Meibomian Gland
Dysfunction; A Double-blind Randomized
Controlled Clinical Trial Study
ABSTRACT
Introduction: With an incidence rate of 9%, dry eye is a common
problem of the ocular surface, especially in patients more than
40-year-old. Green tea extract has anti-oxidative, anti-bacterial,
anti-androgen, and immunomodulatory properties.
Aim: To evaluate the efficacy of green tea extract for treatment
of patients with dry eye and Meibomian Gland Dysfunction
(MGD).
Materials and Methods: In a double-blind randomized
controlled clinical trial, 60 patients were selected within the age
range of 30 to 70 years, and divided into two groups by blocked
randomization method. Standard treatment included artificial
tear eye drops, three times a day for a month for all patients.
Topical green tea extract was prescribed three times a day for
one month in one of the groups. All patients were evaluated at
the beginning and end of the study for clinical symptoms based
on the Ocular Surface Disease Index (OSDI) score, Schirmer’s
test, Tear Breakup Time (TBUT), corneal and conjunctival
staining and meibum score.
Results: The mean age of participants in the green tea and
control group was 61 and 64 years respectively. In the green
tea group, the mean score of clinical symptoms was 9±0.86
that improved to 4.86±0.55 after one month (p=0.002). Scores
suggesting improvement of TBUTs and the health of meibomian
glands were significantly higher in the green tea group (p=0.002).
Furthermore, no side effects of the treatment were observed.
Conclusions: Green tea extract is an effective, safe, and well-
tolerated topical treatment for mild and moderate evaporative
dry eyes and MGD.
MAHMOOD NEJABAT1, SALEHI ALI REZA2, MEHDI ZADMEHR3, MASOUD YASEMI YASEMI4, ZAHRA SOBHANI5
Mahmood Nejabat et al., Effect of Green Tea Extract on Dry Eye and MGD www.jcdr.net
Journal of Clinical and Diagnostic Research. 2017 Feb, Vol-11(2): NC05-NC08
66
Formula for calculating the sample size with prevalence rate of 9%
and a=5% and drop out 10% is: n= (Z1 – a/2)2 p (1-p)/d2=56
These patients were further divided into two equal groups by the
blocked randomization method. For all patients, scores of the right
eye were recorded for statistical analysis. The study has been
approved by the Ethics Committee of Shiraz University of Medical
Sciences and the patients have provided informed consent prior
to inclusion. Withdrawal from the study was allowed at any time
after following standard treatment.
The study was also registered to the Iranian Registry of Clinical
Trials (IRCT2014042117374N1). The inclusion criteria comprised
of mild-to-moderate dry eye and MGD. Exclusion criteria consisted
of the use of oral Tetracyclines and Corticosteroids up to three
months before start of the trial, and any ophthalmic medication
one month before the trial. Patients with other ocular surface
disorders (except MGD) such as corneal surface damage and eyelid
complications also fell within the exclusion criteria. In addition,
patients with any previous ocular surgery, history of topical ocular
drug allergy, use of medication to treat other ophthalmic conditions,
as well as those with severe MGD and dry eye requiring systemic
treatment, patients with nasolachrymal duct disorders, and those
undergoing pregnancy, lactation, and other systemic disorders
were excluded from the study. Standard treatment in the control
group included artificial-tear eyedrops thrice a day for one month.
In the intervention group, artificial tears were administered at the
same frequency, combined with topical green tea extract three
times a day for a month.
Preparation of the topical green tea extract: Firstly, fresh
leaves from the tip of the green tea plant stem were collected from
farms in the northern region of Iran. The leaves were then promptly
transferred and dried in a laboratory environ¬ment. The dried
leaves were gritted and the powder inserted in a sterile shaker to
achieve uniformity. Following this, it was extracted by a percolator
and hydro-alcoholic solution in 75°C for 72 hours. The extracts
were concentrated to up to 4.5% of the dry remains after filtration,
by a rotary device. It was then transferred to a refrigerator as a
source of drop preparation. All processes were completed under
sterile conditions. Each millilitre of the prepared extract was mixed
with 5 ml of distilled water and allotted in to 10 ml-eyedrop-bottles
for one week of usage by patients. After a week, the drop was
replaced and the process was continued for a month. All patients
were evaluated at the beginning and end of the study, under the
following parameters.
1) Ocular symptoms were evaluated based on a standard
questionnaire that included itching, burning sensation, reduced
vision, foreign body sensation, photophobia, and redness. The
response ‘0’ correlated to ‘never’, while a value of ’4’ referred to
‘all of the time’. Finally, scores from these seven symptoms were
summarized to arrive at a cumulative score of 28. For evaluation
purposes, the symptoms were classified as Never-0, Rarely-1,
Sometimes-2, Often-3, All of the time-4 [14].
2) Schirmer’s test [2,14] with anaesthesia was used to check for
tear production. Results below 10 mm were considered within the
dry eye category.
3) Tear film stability [2,14] was checked through TBUT. This was
done through fluorescein paper with one drop of saline solution
and without preservative material. If it lasted less than ten seconds,
the eye was considered dry.
4) Ocular surface health [14] was evaluated by staining the cornea
and conjunctiva with fluorescein [Table/Fig-1]. So, the cornea
was divided into five areas: central, superior, inferior, nasal, and
temporal {Grade 0 = no staining, Grade 1 = mild staining (micro-
punctate), Grade 2 = moderate staining (macropunctat), Grade
3 = severe staining (confluent macro-punctate)}. Eventually, the
scores of these items were added together to record a total of
15. For conjunctival staining, the conjunctiva is divided into six
areas: supranasal, inferonasal, centronasal, supratemporal,
inferotemporal, centrotemporal. {Grade 0 = no staining, Grade
1 = mild staining (micro-punctate), Grade 2 = moderate staining
(macro-punctate), Grade 3 = severe staining (confluent macro-
punctate)}. For evaluation of the scores, corneal and conjuctival
staining were classified as None-0, Mild-1, Moderate-2, and
Severe-3.
5) For evaluation of meibomian-gland health [14], the patient was
seated with the head resting comfortably on the slit lamp. Both
lower lids were examined with the slit lamp illumination and 10X
to 16X magnification. One sterile wooden-stemmed cotton-tipped
applicator was used to press the lids against the globe, right at the
margin, to express the gland contents [Table/Fig-2]. Meibomian
gland health was evaluated in terms of its orifice and quality of
sebum concentration {liquid (0), thick (1), granular (2), toothpaste
(3)}, and its colour {clear (0), yellow (0.5), white (1)}. For final
registration, scores of these items were added together.
Score
A
Quality
B
Colour
Liquid Thick Granular Toothpaste Clear Yellow White
Score 0 1 2 3 0 0.5 1
[Table/Fig-2]: Evaluation of Meibomian glands health based on its orifice and quality
of sebum, concentration and colour of discharge [2,6].
STATISTICAL ANALYSIS
Finally, the data was analysed with statistical package for social
science (SPSS-version 21) software, where it was presented as
mean ± standard deviation and percentages. Chi-square test was
used for comparison of data. Means between differences were
compared using Student’s t tests. Values of p less than 0.05 were
considered to be statistically significant.
RESULTS
Overall, 60 patients with impressions of mild-to-moderate dry eye
with MGD were evaluated in the study. Most of patients in the
green tea group (N=18) were female. Most patients in the control
group were also females (N=20). Participants in the green tea
group ranged from 30 to 70 years of age, with a mean age of
61 years. In the control group, participants were between 35 and
69 years, with a mean age of 64 years. At the baseline, patient
characteristics in both groups did not significantly differ [Table/
Fig-3]. The symptom scores of itching, burning, reduced vision,
foreign body sensation; pains, photophobia, and redness in the
green tea group were 9±0.86, which improved to 4.86±0.55 after
a month. For the control group, the scores were 9.03±0.75, which
improved to 6.63±0.46. The changes in the green tea group were
statistically significant as compared to the control (p=0.002).
Differences in the Schirmer’s test score as a measure of tear
production were not too significant between the two groups, both
at the baseline and the end of the study. Furthermore, changes in
[Table/Fig-1]: A. The five regions of the cornea were evaluated using fluorescein
staining. B. The six areas of conjunctiva were evaluated using Rose Bengal staining.
www.jcdr.net Mahmood Nejabat et al., Effect of Green Tea Extract on Dry Eye and MGD
Journal of Clinical and Diagnostic Research. 2017 Feb, Vol-11(2): NC05-NC08 77
Another interesting find was the significant improvement in both
TBUT and meibum quality in the green tea group, which suggests,
an enhancement in lipid layer and improvement in tear film
stability.
There was no statistically-significant increase in Schirmer scores for
either group. A number of probable causes could be responsible
for this, such as the dosing schedule, time and frequency of topical
administration, and the length of the study for patients with dry eye
syndrome.
Ocular surface health was assessed by corneal and conjunctival
fluorescein staining, but this did not deliver any statistically-
significant improvement in scores for both groups.
The absence of correlation between significant increases in OSDI
scores and the lack of significant improvement in staining in the
green tea group could be due to the short period of the study. In
addition, the use of Rose Bengal staining for conjunctiva could be
effective in yielding better results.
LIMITATION
Some of limitations of the study were poor cooperation from elderly
patients and the resulting difficulty in conducting and evaluating
the mentioned tests on them. In addition, many patients were
affected by anxiety due to the chronic nature of dry eye syndrome.
Continuing the study proved difficult for them, and these patients
were referred to a psychiatrist for simultaneous treatment of non-
pharmaceutical problems.
CONCLUSION
Our study shows that, green tea extract improves ocular
surface inflammation, TBUT and meibum score in patients with
evaporative dry eyes and MGD, based on the OSDI symptoms
questionnaire. Thus, this treatment can decrease the clinical signs
and inflammatory changes in evaporative dry eyes and MGD by
suppressing the inflammatory cytokine expression. Furthermore,
EGCG could be used therapeutically for the treatment of dry
eye and MGD. Additional studies are needed to establish the
favourable dosage of green tea extract. Our study shows that, the
most hopeful endpoints for further clinical trials would include dry
eye and MGD.
Financial support: This study was financially supported by Shiraz
University of Medical Sciences.
ACKNOWLEDGEMENTS
The study was completed with the support of Poostchi eye
research and traditional Persian Medicine Centres at the Shiraz
University of Medical Sciences, with research grant 5201. Finally,
we express our gratitude to all participants of the study.
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the score for each group at the baseline and end of the study were
not significant.
Significant improvement was seen in TBUT in the green tea group
at the end of study. In the control group, the change was not
significant. The difference between both groups was statistically
significant (p=0.001).
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in both groups. Besides, the difference in corneal fluorescein
staining scores between the two groups was not statistically
significant. Conjunctival staining scores were also not significantly
enhanced in both groups.
The health of meibomian glands and their secretions improved
in both the groups after a month. The average medium quality
significantly improved, and this difference between the two groups
was statistically significant (p=0.002). Changes from the baseline
in impartial clinical measures at the one-month time point, with
pertinent p-values for both groups, are summarized in [Table/
Fig-3].
DISCUSSION
Dry eye and MGD are the most common causes behind clinical
complaints in ophthalmology [1,15]. Inflammation of the meibomian
glands induces MGD, which in turn causes evaporative dry eye.
MGD may result in alteration of the tear film, symptoms of eye
irritation, and ocular surface diseases [15]. There are many drugs
and anti-inflammatory preparations used to counter this, but in
the long-term, the chronic nature of the problem can result in the
emergence of side-effects from conventional treatment [2,16].
So, green tea extract was evaluated as a potentially safe anti-
inflammatory agent. To determine the effect of green tea on MGD
and evaporative dry eye, we conducted a double-blind clinical
trial where patients were randomly assigned to either the green
tea group or the control group. The main parameters used to
evaluate the participants were Schirmer’s test, TBUT, corneal and
conjunctival staining, and meibum content, at a one-month time
point.
Evaluation of both groups at the baseline showed similar
characteristics. Overall, dry eye and MGD is seen more commonly
in women than men, and this was compatible with our study
results. Even though the mechanism of inflammation in men and
women is similar, the function and levels of androgens, which play
an important role in the function of meibomian glands, were not
alike.
We evaluated the symptoms of patients according to OSDI
scores. Patients in the green tea group had statistically-significant
improvement in their overall OSDI scores. Thus, the clinical score
could be used as a therapeutic determinant.
Variables
Green tea group Control group
Baseline One Month
Later Baseline One Month
Later p-Value*
Symptoms score
(0 to 28) 9±0.86 -4.1±2.27 9.03±0.75 -2.4±1.88 0.002
Schirmer test score
(mm) 8.2±0.30 0.4±0.72 8.16±0.29 0.3±0.91 0.641
Tear breakup time (s) 6.1±0.23 3.03±1.29 6.3±0.25 1.03±0.80 0.001
Corneal staining
score (0 to 15) 3.8±0.22 -0.13±0.73 4.06±0.20 +0.10±0.71 0.215
Conjunctival staining
score (0 to 18) 8.06±0.24 -0.16±0.69 7.56±0.25 -0.43±0.81 0.180
Meibum quality
score (0 to 4) 1.06±0.09 -0.35±0.26 1.03±0.09 -0.13±0.26 0.002
[Table/Fig-3]: Changes from baseline in the objective clinical measures after one
month from using green tea.
*The P-value is associated with comparing two groups of control and green tea one month later
using green tea.
Mahmood Nejabat et al., Effect of Green Tea Extract on Dry Eye and MGD www.jcdr.net
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PARTICULARS OF CONTRIBUTORS:
1. Poostchi Ophthalmology Research Center, Department of Ophthalmology, Shiraz, Iran.
2. Assistant Professor of Epidemiology, Research Center for Traditional Medicine and History of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
3. Poostchi Ophthalmology Research Center, Department of Ophthalmology, Shiraz, Iran.
4. Poostchi Ophthalmology Research Center, Department of Ophthalmology, Shiraz, Iran.
5. Department of Pharmacology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.
NAME, ADDRESS, E-MAIL ID OF THE CORRESPONDING AUTHOR:
Dr. Masoud Yasemi,
Poostchi Ophthalmology Research Center, Khalili Hospital, Shiraz-843-3233342, Iran.
E-mail: ophthalmology67@gmail.com.
FINANCIAL OR OTHER COMPETING INTERESTS: None.
Date of Submission: Aug 04, 2016
Date of Peer Review: Aug 29, 2016
Date of Acceptance: Oct 25, 2016
Date of Publishing: Feb 01, 2017
... 7,11,12 Regarding the key role of inflammation in DED pathogenesis, it has already been shown that oral or topical (intraocular) administration of natural antiinflammatory and anti-oxidant compounds extracted from medicinal herbs has a significant effect on the improvement of signs and symptoms of DED. 13 Based on common traditional Persian medical manuscripts, Persian practitioners paid a great deal of attention to herbal medicines for the treatment of DED. 14,15 Among these medicinal plants, violet, which is called 'Banafshah' in Persian, with its anti-inflammatory, diaphoretic, diuretic, emollient, expectorant, antipyretic and laxative effects, has been widely used for the treatment of whooping cough, jaundice and inflammatory eye diseases. ...
... These results are supported by previous studies that have demonstrated that anti-inflammatory agents can improve the signs and symptoms of DED. 34,35 However, in contrast to the present study, Nejabat et al. 13 did not show any significant differences in the Schirmer's test scores between the groups treated with a topical green tea extract (a natural anti-inflammatory agent) and the placebo, perhaps due to an unsuitable dosing schedule or the time and frequency of drug administration. In addition, the present results revealed a slight improvement in Schirmer's test scores of the AO and placebo groups after the trial. ...
... These results are in agreement with the results obtained in a recent study conducted by Nejabat et al., where the rate of improvement between the treatment and control groups was negligible. 13 Note that the corneal epithelium turnover is approximately 10 days. 37 It seems that the short duration of the study is a major factor in the incomplete remission of corneal epithelium healing. ...
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Introduction: Finding non-systemic antipyretic option in cancer patients who simultaneously receive several other drugs seems be logical. This study was designed to evaluate complementary therapy with Viola odorata L. oil for fever control in febrile neutropenic children. Methods and materials: In a randomized placebo controlled clinical trial, 41 febrile children were divided into two groups .Children in the active drug group received viola oil (20 drops) to be rubbed on the peripheral margin of the patient umbilicus. Primary outcome measure of the study was the mean axillary temperature in the 30, 60, and 240 minutes after the intervention. Results: The mean temperature reduced significantly in the viola group after 30 minutes of administration (p =0.005), while there was no significant change in the placebo group (p =1.00). The number of patients who received paracetamol as the rescue treatment was significantly lower in the viola group than that in the placebo group (5 vs. 17, p =0.001). Conclusion: The results of our study showed the safety and efficacy of complementary therapy with Viola odorata L. oil for fever control in febrile neutropenic children during hospital course.
... 7,11,12 Regarding the key role of inflammation in DED pathogenesis, it has already been shown that oral or topical (intraocular) administration of natural antiinflammatory and anti-oxidant compounds extracted from medicinal herbs has a significant effect on the improvement of signs and symptoms of DED. 13 Based on common traditional Persian medical manuscripts, Persian practitioners paid a great deal of attention to herbal medicines for the treatment of DED. 14,15 Among these medicinal plants, violet, which is called 'Banafshah' in Persian, with its anti-inflammatory, diaphoretic, diuretic, emollient, expectorant, antipyretic and laxative effects, has been widely used for the treatment of whooping cough, jaundice and inflammatory eye diseases. ...
... These results are supported by previous studies that have demonstrated that anti-inflammatory agents can improve the signs and symptoms of DED. 34,35 However, in contrast to the present study, Nejabat et al. 13 did not show any significant differences in the Schirmer's test scores between the groups treated with a topical green tea extract (a natural anti-inflammatory agent) and the placebo, perhaps due to an unsuitable dosing schedule or the time and frequency of drug administration. In addition, the present results revealed a slight improvement in Schirmer's test scores of the AO and placebo groups after the trial. ...
... These results are in agreement with the results obtained in a recent study conducted by Nejabat et al., where the rate of improvement between the treatment and control groups was negligible. 13 Note that the corneal epithelium turnover is approximately 10 days. 37 It seems that the short duration of the study is a major factor in the incomplete remission of corneal epithelium healing. ...
Article
Background Dry eye disease is a disorder of the tear film. In this study, the effect of Viola odorata L. oily extract was examined for the treatment of patients suffering from dry eye disease. Methods A randomised, double‐blind, placebo‐controlled study was designed. During the trial, Schirmer's test, tear breakup time, Oxford staining and the Ocular Surface Disease Index were assessed. Overall, 105 patients with dry eye symptoms between the ages of 18 and 60 years were allocated to the violet‐almond oil, almond oil and placebo (1% w/v hydroxypropyl methylcellulose solution) groups. The treatment and placebo were administered intranasally, two drops three times a day for one month. The patients were followed up for four weeks. A total of 91 patients (32, 29 and 30 in the violet‐almond oil, almond oil and placebo groups, respectively) completed the study. Results At baseline, there was no difference between the three groups in terms of demographic data and the measurement parameters. After the intervention, the results revealed that the Schirmer's score without local anaesthesia and the tear breakup time results significantly improved in the violet‐almond oil group. One‐way ANOVA indicated a significant improvement in the Schirmer's score, tear breakup time and Ocular Surface Disease Index of the treatment group, as compared with the other groups (p < 0.05). However, the obtained results did not present any significant mean difference between and within the groups of the Oxford staining grade (p > 0.05). Conclusions This trial showed that the intranasally administered V. odorata L. oily extract enhances tear production and improves tear film stability.
... However, 0.5% quercetin administered 4 times per day significantly restored the tear film after 3 days together with decreasing MMP-9, MMP-2, tumor necrosis factor α (TNF-α), intercellular adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1) [35]. Moreover, in a double-blind randomized controlled clinical trial with green tea extract (rich in polyphenols, mainly epigallocatechin gallate) topically applied for one month, no significant difference was observed in the restoration of tear film production and corneal and conjunctival staining [38]. Additionally, the patients were without any ophthalmic medication for at least one month before the study. ...
... Additionally, the patients were without any ophthalmic medication for at least one month before the study. Based on these results, it seems that polyphenols might not be very efficient in the restoration of tear film production, but rather in tear film stability [38]. ...
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Dry eye disease (DED) is a chronic debilitating ophthalmological disease with the current therapeutic options focused on the suppression of the symptoms. Among the possibilities of how to improve DED therapy, polyphenols have shown an enormous capacity to counteract DED functional changes. The study aimed to specifically target pathophysiological mechanisms by the addition of fisetin to the cyclosporine treatment protocol. We examined dog patients with DED on cyclosporine treatment that were administered 0.1% fisetin or fisetin-free eye drops. For the assessment of fisetin effects, tear film production and matrix metalloproteinase 9 (MMP-9) were studied in the tear film. Tear production was not recovered after 7 or 14 days (9.40 mm ± 6.02 mm, p = 0.47; 9.80 mm ± 6.83 mm, p = 0.53, respectively). MMP-9 levels significantly increased after 7 days and then dropped after 14 days (775.44 ng/mL ± 527.52 ng/mL, p = 0.05; 328.49 ng/mL ± 376.29 ng/mL, p = 1.00, respectively). Fisetin addition to cyclosporine DED treatment was not able to restore tear fluid production but influenced molecular pathological events through MMP-9.
... Tea (from Camellia sinensis) is one of the most widely consumed drinks worldwide. Green tea contains numerous polyphenols (collectively, 30% dry weight) including low molecular weight phenols (such catechins), which account for approximately 25% of the dry weight of green tea [173] to which antioxidant, immunomodulatory [174] and antiviral activities have been ascribed [175]. In addition, green tea has beneficial effects against degenerative diseases, oxidative stress and chronic diseases [176], and lipid profile [177]. ...
... In addition, green tea has beneficial effects against degenerative diseases, oxidative stress and chronic diseases [176], and lipid profile [177]. A 2017 double-blind placebo-controlled study into the efficacy of green tea in ameliorating dry eye and meibomian gland dysfunction due to its anti-oxidative, antibacterial, anti-androgen and immunomodulatory anti-inflammatory properties [174] reported significant improvement in TBUT, meibomian gland health and ocular comfort scores after one month. The authors suggest efficacy might be due to Epigallocatechin Gallate which exerts inhibitory effects on inflammation, through the suppression of IL-1, IL-6, MCP-1 and TNF-α and t NF-kB. ...
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Dry eye disease (DED) is one of the most frequent presentations to optometrists with over 16 million US adults (6.8% of adult population) diagnosed as having this disorder. The majority of associated marketed products offer relief from symptomatology but do not address aetiology. DED harbours many distinguishing features of a chronic inflammatory disorder. The recent explosion in human microbiome research has sparked interest in the ocular microbiome and its role in the preservation and extension of ocular surface health and in the contribution of the gut microbiome to chronic systemic inflammation and associated “Western life-style” diseases. With a significant lack of success for many patients using currently available DED treatments, in this era of the microbiome, we are interested in exploring potential novel therapies that aim to reconstitute healthy bacterial communities both locally and distally (in the gut) as a treatment for DED. Although this direction of investigation is in its infancy, burgeoning interest makes such a review timely. This paper considers a number of studies into the use functional foods and associated products to ameliorate dry eye.
... A possible reason is the lack of solid clinical trials demonstrating polyphenols therapeutic benefits. Polyphenols have shown significant potential against DED in many preclinical studies, but not enough clinical trials are actually performed [21,22]. It is fundamental to proceed with other clinical trials taking into account, to avoid the same trouble, the omega-3 results of the Dry Eye Assessment and Management (DREAM) study that stated " . . . ...
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The collection of studies in this Special Issue, “The Role of Antioxidant Molecules and Melatonin in Cellular Protection”, published in Antioxidants (accessed on 30 April 2021; https://www [...]
... Moreover, a double-blind randomized controlled clinical trial with 60 patients of dry eye and Meibomian Gland Dysfunction (MGD) showed that GTE improved the clinical symptoms, tear breakup time (TBUT), and the health of meibomian glands. No side effect of the treatment was observed (108). ...
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Ocular inflammation is a common complication of various eye diseases with wide consequences from irritations to potentially sight-threatening complications. Green tea is a popular beverage throughout the world. One of the proven health benefits of consuming green tea extract (GTE) is anti-inflammation. Catechins are the biologically active constituents of GTE. In in vitro and in vivo studies, GTE and catechins present inhibition of inflammatory responses in the development of ocular inflammation including infectious, non-infectious or autoimmune, and oxidative-induced complications. Research on the ocular inflammation in animal models has made significant progress in the past decades and several key disease mechanisms have been identified. Here we review the experimental investigations on the effects of GTE and catechins on various ocular inflammation related diseases including glaucoma, age-related macular degeneration, uveitis and ocular surface inflammation. We also review the pharmacokinetics of GTE constituents and safety of green tea consumption. We discuss the insights and perspectives of these experimental results, which would be useful for future development of novel therapeutics in human.
... Nejabat et al. [104] evaluated green tea extract rich in EGCG as topical DED treatment in a double-blind randomized controlled clinical trial with 60 patients involved. Patients followed the treatment for one month. ...
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Dry eye disease is a multifactorial pathology compromising the quality of life of patients, resulting in significant damage of the ocular surface and discomfort. The current therapeutical strategies are not able to definitively resolve the underlying causes and stop the symptoms. Polyphenols are promising natural molecules that are receiving increasing attention for their activity/effects in counteracting the main pathologic mechanisms of dry eye disease and reducing its symptoms. In the present review, a deep literature search focusing on the main polyphenols tested against dry eye disease was conducted, analyzing related in vitro, in vivo, and clinical studies to provide a comprehensive and current review on the state of the art. Polyphenols present multiple effects against dry eye diseases-related ocular surface injury. In particular, the observed beneficial effects of polyphenols on corneal cells are the reduction of the pathological processes of inflammation, oxidative stress, and apoptosis and modulation of the tear film. Due to numerous studies reporting that polyphenols are effective and safe for treating the pathological mechanisms of this ocular surface disease, we believe that future studies should confirm and extend the evidence of polyphenols efficacy in clinical practice against dry eye disease and help to develop new ophthalmic drug(s).
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Plant polyphenols and polyphenol-rich extracts are known to exhibit a wide range of anti-cancer, anti-inflammatory, anti-oxidative and pro-apoptotic properties, and may also suppress the development of many ophthalmological diseases. Dry eye disease is associated with disturbances of the tear film. Although synthetic drugs and artificial tears can be used to treat the disorder, their long-term use may cause many side effects. The etiology of dry eye syndrome is complex, but the disease is now recognized as being mainly associated with ocular surface inflammation and oxidative stress. This review highlights the impact of polyphenols (alone or mixed) on the inflammatory process contributed to the pathophysiology of dry eye syndrome and summarizes the scientific basis for this action. It also describes the preclinical development, pharmacological properties, clinical efficacy and safety of polyphenols.
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