Effect of a Natural Eye Drop, Made of Plantago Ovata Mucilage on Improvement of Dry Eye Symptoms: A Randomized, Double-Blind Clinical Trial

Document Type : Research article

Authors

1 Traditional Medicine Clinical Trial Research Center, Shahed University, Tehran, Iran.

2 Department of Iranian Traditional Medicine, School of Traditional Medicine, Tehran University of Medical Sciences, Tehran, Iran.

3 Department of Traditional Pharmacy, School of Traditional Medicine, Tehran University of Medical Sciences, Tehran, Iran.

4 Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran.

5 Department of Traditional Pharmacy, School of Traditional Medicine, Iran University of Medical Sciences, Tehran, Iran.

Abstract

This study was designed to evaluate efficacy of a natural eye drop made of Plantago ovata mucilage versus placebo to improve dry eye symptoms. In a Randomized, double-masked, placebo-controlled clinical trial, sixty dry eye patients with ocular symptom and total OSDI score≥12 were randomly assigned to receive either a natural ophthalmic drop, made of Plantago ovata mucilage or placebo 4 times a day for 6 weeks. Patients were evaluated at first, weeks 4 and 6 of treatment. Evaluations of efficacy and safety were conducted based on Ocular Surface Disease Index questionnaire, Noninvasive tear film break-up time (NI-BUT) with keratograph, Schirmer test without anesthesia, osmolarity test and by monitoring adverse events. After 6 weeks, the result showed significant improvement in total OSDI score within (p

Keywords


References
Lemp MA, Baudouin C, Baum J, Dogru M, Foulks

GN, Kinoshita S, Laibson P, McCulley J, Murube J and

Pflugfelder SC. The definition and classification of dry

eye disease: report of the definition and classification

subcommittee of the international dry
eye workshop
(2007).
Ocul. Surf. (2007) 5: 75-92.
Friedman NJ. Impact of dry eye disease and treatment

on quality of life
. Curr. Opin. Ophthalmol. (2010) 21:
310-6
.
Nichols KK. Patient-reported symptoms in dry dye

disease
. Ocul. Surf. (2006) 4: 137-45.
Grubbs Jr JR, Tolleson-Rinehart S, Huynh K and

Davis RM. A review of quality of life measures in dry

eye questionnaires
. Cornea (2014) 33: 215.
Miljanović B, Dana R, Sullivan DA and Schaumberg

DA. Impact of dry eye syndrome on vision-related

quality of life
. Am. J. Ophthalmol. (2007) 143: 409-15.
Uchino M and Schaumberg DA. Dry eye disease:

impact on quality of life and vision
. Curr. Ophthalmol.
Rep
. (2013) 1: 51-7.
Uchino M, Uchino Y, Dogru M, Kawashima M, Yokoi

N, Komuro A, Sonomura Y, Kato H, Kinoshita S

and Schaumberg DA. Dry eye disease and work

productivity loss in visual display users: the Osaka

study
. Am. J. Ophthalmol. (2014) 157: 294-300.
Yamada M, Mizuno Y and Shigeyasu C. Impact of dry

eye on work productivity
. Clinicoecon. Outcomes Res.
(2012) 4: 307-12
.
Ahn JM, Lee SH, Rim THT, Park RJ, Yang HS, im

Kim T, Yoon KC, Seo KY and Epidemiologic Survey

Committee of the Korean Ophthalmological Society.

Prevalence of and risk factors associated with dry eye:

the Korea national health and nutrition examination

survey 2010–2011
. Am. J. Ophthalmol. (2014) 158:
(1)

(2)

(3)

(4)

(5)

(6)

(7)

(8)

(9)

1205-14
.
Pflugfelder SC. Prevalence, burden, and

pharmacoeconomics of dry eye disease
. Am. J. Manag.
Care
(2008) 14: 102-6.
Bron AJ, Abelson MB, Ousler G, Pearce E, Tomlinson

A, Yokoi N, Smith JA, Begley C, Caffery B and

Nichols K. Methodologies to diagnose and monitor

dry eye disease
. Ocul. Surf. (2007) 5: 108-52.
Gumus K and Cavanagh DH. The role of inflammation

and antiinflammation therapies in keratoconjunctivitis

sicca
. Clin. Ophthalmol. (2009) 3: 57-67.
Pflugfelder SC, Tseng SC, Yoshino K, Monroy D,

Felix C and Reis BL. Correlation of goblet cell density

and mucosal epithelial membrane mucin expression

with rose bengal staining in patients with ocular

irritation
. Ophthalmology (1997) 104: 223-35.
Lee JH, Kim M, Im YS, Choi W, Byeon SH and Lee

HK. NFAT5 induction and its role in hyperosmolar

stressed human limbal
epithelial cells . Invest.
Ophthalmol. Vis. Sci
. (2008) 49: 1827-35.
Li DQ, Luo L, Chen Z, Kim HS, Song XJ and

Pflugfelder SC. JNK and ERK MAP kinases mediate

induction of IL-1beta, TNF-alpha and IL-8 following

hyperosmolar stress in
human limbal epithelial cells.
Exp. Eye Res
. (2006) 82: 588-96.
Li DQ, Chen Z, Song XJ, Luo L and Pflugfelder

SC. Stimulation of matrix metalloproteinases by

hyperosmolarity via a JNK pathway in human corneal

epithelial cells
. Invest. Ophthalmol. Vis. Sci . (2004)
45: 4302-11
.
Luo L, Li DQ, Corrales RM and Pflugfelder SC.

Hyperosmolar saline is a proinflammatory stress on

the mouse ocular surface
. Eye Contact Lens (2005)
31: 186-93
.
Management and therapy of dry eye disease: report

of the Management and Therapy Subcommittee of the

International Dry Eye WorkShop (2007)
. Ocul. Surf .
(2007) 5: 163-78
.
Dias DA, Urban S and Roessner U. A historical

overview of natural products in drug discovery
.
Metabolites
(2012) 2: 303-36.
Huynh TP, Mann SN and Mandal NA. Botanical

compounds: effects on major eye diseases
. J. Evid.
Based Complementary Altern. Med.
(2013) 2013:
549174
.
Lahlou M. The success of natural products in drug

discovery
. Pharmacol. Pharm. (2013) 4: 17.
Chan HC, Chang RCC, Ip AKC, Chiu K, Yuen WH,

Zee SY and So KF. Neuroprotective effects of
Lycium
barbarum Lynn
on protecting retinal ganglion cells
in an ocular hypertension model of glaucoma
. Exp.
Neurol
. (2007) 1: 269-73.
Falsini B, Piccardi M, Minnella A, Savastano C,

Capoluongo E, Fadda A, Balestrazzi E, Maccarone R

and Bisti S. Influence of
saffron supplementation on
retinal flicker sensitivity in early age-related macular

degeneration
. Invest. Ophthalmol. Vis. Sci . (2010) 51:
6118-24
.
Gupta SK, Kumar B, Nag TC, Agrawal SS, Agrawal

(10)

(11)

(12)

(13)

(14)

(15)

(16)

(17)

(18)

(19)

(20)

(21)

(22)

(23)

(24)
 
Haji-Ali-Nili N et al. / IJPR (2019), 18 (3): 1602-16111610
R, Agrawal P, Saxena R and Srivastava S.
Curcumin
prevents experimental diabetic retinopathy in rats

through its hypoglycemic, antioxidant, and anti-

inflammatory mechanisms
. J. Ocul. Pharmacol. Ther.
(2011) 27: 123-30
.
Kim NR, Kim JH and Kim CY. Effect of Korean red

ginseng
supplementation on ocular blood flow in
patients with glaucoma
. J. Ginseng Res . (2010) 34:
237–45.

Manikandan R, Thiagarajan R, Beulaja S, Sudhandiran

G and Arumugam M. Effect of
curcumin on selenite-
induced cataractogenesis in Wistar rat pups
. Curr. Eye
Res.
(2010) 35: 122-9.
Nair NK, Patel K and Gandhi T. Effect of aqueous

extract of
Embelica officinalis on selenite induced
cataract in rats
. Iran. J. Pharm. Res. (2010) 9: 147.
Paduch R and Woźniak A. The effect of
Lamium album
extract on cultivated human corneal epithelial cells

(10.014
pRSV-T). J. Ophthalmic. Vis. Res. (2015) 10:
229
.
Paduch R, Woźniak A, Niedziela P and Rejdak R.

Assessment of eyebright (
Euphrasia officinalis L. )
extract activity in relation to human corneal cells using

in-vitro
tests. Balkan Med. J. (2014) 31: 29.
Ritch R. Natural compounds: evidence for a protective

role in eye disease
. Can. J. Ophthalmol . (2007) 42:
425-38
.
Woźniak A and Paduch R.
Aloe vera extract activity on
human corneal cells
. Pharm. Biol. (2012) 50: 147-54.
Bae HW, Kim JH, Kim S, Kim M, Lee N, Hong S,

Seong GJ and Kim CY. Effect of Korean Red
Ginseng
supplementation on dry eye syndrome in glaucoma

patients–A randomized, double-blind, placebo-

controlled study
. J. Ginseng Res. (2015) 39: 7-13.
Barabino S, Rolando M, Nardi M, Bonini S, Aragona

P and Traverso CE. The effect of an artificial tear

combining hyaluronic acid and
tamarind seeds
polysaccharide in patients with moderate dry eye

syndrome: a new treatment for dry eye
. Eur. J.
ophthalmol
. (2013) 24: 173-8.
Choi W, Kim JC, Kim WS, Oh HJ, Yang JM, Lee JB

and Yoon KC. Clinical effect of antioxidant glasses

containing extracts of medicinal plants in
patients
with dry eye disease: a multi-center, prospective,

randomized, double-blind, placebo-controlled trial
.
PloS One
(2015) 10: e0139761.
Ansari A. Unani system of medicine and development

of its materia medica
. Iran. J . Pharm. Res. (2010) 3:
21-2
.
Hajimehdipoor H, Mortazavi SA, Dehpour A and

Hassanzadeh G.
Evaluation of the wound healing
activity of a traditional compound herbal product

using rat excision wound model
. Iran. J. Pharm. Res.
(2017
) 16: 153-63.
Pourahmad J. History of medical sciences in Iran
.
Iran. J. Pharm. Res.
(2010) 7: 93-9.
Ibn-e-Sina A.
Al-qanun fit-tib [The canon of medicine].
Alamle-al-Matbooat Institute, Beirut (2005).

Aghili Khorasani MH.
Makhzan-al-Advia [Source of
plants]
. Bavardaran, Tehran (2001).
Jorjani S.
Zhakhireh Kharazmshahi [Treasures of the
Khwarazm Shah]
. Ehya Teb Tabiee Institute, Qom
(2012).

Westerhof W, Das P, Middelkoop E, Verschoor J,

Storey L and Regnier C. Mucopolysaccharides from

psyllium
involved in wound healing. Drugs Exp. Clin.
Res
. (2000) 27: 165-75.
Singh B, Lal H, Pal L and Sharma V.
In-vitro
release profile of anti-ulcer drug rabeprazole from

biocompatible
psyllium-PVA hydrogels. J. Mater. Sci.
Mater. Med
. (2012) 23: 1021-32.
Hulbert D, Thorpe P, Winning A and Beckett M.

Fatal bronchospasm after oral ingestion of
isphagula.
Postgrad. Med. J
. (1995) 71: 305.
Cheng Y, Ohlsson L and Duan RD.
Psyllium and fat in
diets differentially affect the activities and expressions

of colonic sphingomyelinases and caspase in mice
. Br.
J. Nutr
. (2004) 91: 715-23.
Rodrı́guez-Cabezas M, Galvez J, Camuesco D,

Lorente M, Concha A, Martinez-Augustin O, Redondo

L and Zarzuelo A. Intestinal anti-inflammatory activity

of dietary fiber (
Plantago ovata seeds) in HLA-B27
transgenic rats
. Clin. Nutr. (2003) 22: 463-71.
Triantafyllidi A, Xanthos T,
Papalois A and
Triantafillidis JK. Herbal and plant therapy in patients

with inflammatory bowel disease
. Ann. Gastroenterol.
(2015) 28: 210
.
Yakoob J, Jafri W, Mehmood MH, Abbas Z and Tariq

K. Immunomodulatory effects of
psyllium extract on
helicobacter pylori interaction with gastric epithelial

cells.
J. Evid. Based Complementary Altern. Med.
(2016) 21: 18-24
.
Rahimi R, Shams-Ardekani MR and Abdollahi

M. A review of the efficacy of traditional Iranian

medicine for inflammatory bowel disease
. World J.
Gastroenterol
. (2010) 16: 4504-14.
United States Pharmacopeial Convention
. USP35
NF30, 2012: U. S. Pharmacopoeia National

Formulary
. United States Pharmacopeial (2011).
DuBois M. Colorimetric method for determination of

sugars
and related substances. Anal. Chem. (1956) 28:
350-6
.
Moss SE, Klein R and Klein BE. Prevalence of and

risk factors for dry eye syndrome
. Arch. Ophthalmol.
(2000) 118: 1264-8
.
Pflugfelder SC, Maskin SL, Erson B, Chodosh J,

Holland EJ
,De Paiva CS, Bartels SP, Micuda T,
Proskin HM and Vogel R. A randomized, double-

masked, placebo-controlled, multicenter comparison

of loteprednol etabonate ophthalmic suspension, 0.5%,

and placebo for treatment of keratoconjunctivitis

sicca in patients
with delayed tear clearance . Am. J.
Ophthalmol
. (2004) 138: 444-57.
Wadhwa J, Nair A and Kumria R. Potential of plant

mucilages in pharmaceuticals and therapy
. Curr. Drug
Deliv
. (2013) 10: 198-207.
Nayak AK, Pal D, Pany DR and Mohanty B.

Evaluation of
Spinacia oleracea L. leaves mucilage
(25)

(26)

(27)

(28)

(29)

(30)

(31)

(32)

(33)

(34)

(35)

(36)

(37)

(38)

(39)

(40)

(41)

(42)

(43)

(44)

(45)

(46)

(47)

(48)

(49)

(50)

(51)

(52)

(53)

(54)
 
Effect of Plantago Ovata on Dry Eye: RCT1611
as an innovative suspending agent
. J. Adv. Pharm.
Technol. Res
. (2010) 1: 338.
Niu L, Zhang S, Wu J, Chen L and Wang Y.

Upregulation of NLRP3 inflammasome in the tears

and ocular surface of dry eye patients
. PloS One
(2015) 10: e0126277
.
Uchino Y, Kawakita T, Ishii T, Ishii N and Tsubota

K. A new mouse model of dry eye disease: oxidative

stress affects functional decline in the lacrimal gland
.
Cornea
(2012) 31: 63-7.
Nakamura S, Shibuya M, Nakashima H, Hisamura

R, Masuda N, Imagawa T, Uehara M and Tsubota K.

Involvement of oxidative stress on corneal epithelial

alterations in a blink-suppressed dry eye
. Invest.
Ophthalmol. Vis. Sci
. (2007) 48: 1552-8.
(55)

(56)

(57)

Mizuno Y, Yamada M, Miyake Y and Dry Eye Survey

Group of the National Hospital Organization of Japan.

Association between clinical diagnostic tests and

health-related quality of life surveys in paients with

dry eye syndrome.
Jpn. J. Ophthalmol. (2010) 54:
259-65.

Nichols KK, Nichols JJ and Mitchell GL. The lack of

association between signs and symptoms in patients

with dry eye disease.
Cornea (2004) 23: 762-70.
Sullivan BD, Whitmer D, Nichols KK, Tomlinson

A, Foulks GN, Geerling G, Pepose JS, Kosheleff V,

Porreco A and Lemp MA.
An objective approach to
dry eye disease severity.
Invest. Ophthalmol. Vis. Sci.
(2010) 51: 6125-30