Professional Documents
Culture Documents
2 0 1 5;9 0(3):112118
ARCHIVOS DE LA SOCIEDAD
ESPAOLA DE OFTALMOLOGA
www.elsevier.es/oftalmologia
Original article
a r t i c l e
i n f o
a b s t r a c t
Article history:
Objective: To compare the efcacy of 3 treatment options in patients with chronic blepharitis.
(female 67%; mean age: 40.5 years) diagnosed with chronic blepharitis, in order to compare
the effectiveness of three treatment options. Group 1: eyelid hygiene with neutral shampoo
three times/day; group 2: neutral shampoo eyelid hygiene plus topical metronidazole gel
Keywords:
0.75% twice/day; group 3: neutral eyelid hygiene with shampoo plus neomycin 3.5% and
Chronic blepharitis
polymyxin 10% antibiotic ointment with 0.5% dexamethasone 3 times/day. The symptoms
Demodex folliculorum
and signs were assessed by assigning scores from 0: no symptoms and/or signs; 1: mild
Metronidazole gel
symptoms and/or signs, 2: moderate symptoms and/or signs; and 3: severe symptoms and/or
Eyelid hygiene
signs.
Neutral shampoo
Results: A signicant improvement was observed in the signs and symptoms in all 3 treatment groups. While groups 1 and 2 had more improvement in all variables studied (P < .05),
Group 3 showed no clinical improvement for itching (P = .16), dry eye (P = .29), eyelashes
falling (P = .16), and erythema at the eyelid margin (P = .29).
Conclusions: Shampoo eyelid hygiene neutral and neutral shampoo combined with the use of
metronidazole gel reported better hygiene results than neutral shampoo lid with antibiotic
ointment and neomycin and polymyxin dexamethasone.
Blefaritis crnica
crnica.
Demodex folliculorum
Gel de metronidazol
Corresponding author.
E-mail address: microbiologia@iics.una.py (M. Samudio).
113
a r c h s o c e s p o f t a l m o l . 2 0 1 5;9 0(3):112118
Higiene palpebral
Champ neutro
champ neutro 3 veces/da; grupo 2: higiene palpebral con champ neutro y gel tpico de
metronidazol al 0,75% 2 veces/da; grupo 3: higiene palpebral con champ neutro y pomada
antibitica de neomicina al 3,5% y polimixina al 10% con dexametasona al 0,5% 3 veces/da.
Los sntomas y signos fueron valorados asignndoles puntuaciones entre 0: sin sntomas ni
signos; 1: sntomas o signos leves; 2: sntomas o signos moderados y 3: sntomas o signos
severos.
Resultados: En los 3 grupos de tratamiento se observ mejora signicativa de los signos
y sntomas. Mientras que los grupos 1 y 2 presentaron una mayor mejora en todas las
variables estudiadas (p < 0,05), el grupo 3 no present mejora clnica para comezn (p = 0,16),
Introduction
Blepharitis is a very common disease in the ophthalmological practice. It normally courses chronically with intermittent
symptom exacerbations. Generally, it is classied as acute and
chronic, the former being caused by a bacterial infection and
the latter by the involvement of the Meibomium glands.1,2
Blepharitis is commonly associated to systemic diseases
such as rosaceae and seborrheic dermatitis. Some studies
relate it to the presence of Demodex folliculorum (D. folliculorum)
which perpetuates the inammatory process at the follicular
level.36
Even though the treatment of chronic blepharitis remains
controversial, neutral shampoo cleaning has been the most
widely accepted medical therapy in our environment, followed
by the use of antibiotic ointment with 3.5% neomycin and 10%
polymixin with 0.5% dexamethasone.7,8 Said combination is
used because it has demonstrated to produce improvements
for patients with acute conditions in clinical practice, although
the presence of corticoids inhibits chronic use of said ointment
due to its potential collateral effects. The use of ointments
based exclusively on antibiotics has not demonstrated to be
effective in the treatment of chronic blepharitis as it does
not address the root cause, to which we must add the toxicity of antibiotics which could give rise to undesirable side
effects. The application of 0.75% metronidazol topical gel has
demonstrated a signicant reduction symptom as well as a
50% reduction in infestation by D. folliculorum.9,10
Apparently, metronidazole reduces the hydrogen peroxide
and hydroxyl radical levels, both powerful oxidants which can
cause tissue damage. For this reason, its effects would the
mainly anti-inammatory instead of antimicrobial.9,10 The
majority of North American and European studies recommend
the use of 2% yellow mercury oxide for treating chronic blepharitis. However, this type of treatment is not affordable for
the majority of patients in our environment due to its cost.11
The internacional workshop for the treatment of Meibomium gland dysfunctions established a clinical classication system for assessing the severity of this dysfunction
and a treatment algorithm based on the stages of this disease. For stages 1 and 2, corresponding to asymptomatic
patients or those having very slight symptoms, it was recommended to optimize the working environment, increase
consumption of omega-3, carry out palpebral hygiene with
warm pads followed by massage and expression of Meibomium gland secretions. Stages 3 and 4, corresponding to
patients with moderate and notable symptoms, the same recommendations for phase 1 and 2 apply together with the use
of lubricants, topical acytromycin, oral tetracycline derivates
and anti-inammatory therapy for dry eye.1214
The majority of chronic blepharitis treatments have
demonstrated signicant reductions in the amount of infection by the parasite. However, the only treatment which was
able to diminish the D. folliculorum count to zero is tea tree oil
(Melaleuca alternifolia), a therapeutic mode which is not available in our environment.15,16
In our country, even though chronic blepharitis is diagnosed with relative frequency, no data has been published on
the medical therapy evaluations implemented for this disease,
which increases the importance of the present report. Accordingly, the objective of this study consisted in comparing the
efcacy of 3 treatment schemes applied for chronic blepharitis: (1) palpebral hygiene with neutral shampoo; (2) palpebral
hygiene with neutral shampoo and 0.75% metronidazole topical gel; and (3) palpebral hygiene with neutral shampoo and
3.5% neomycin antibiotic ointment and 10% polymixin with
0.5% dexamethasone, as well as assessing the clinical and
microbiological characteristics of patients with chronic blepharitis and clinical improvements 2 months after beginning
treatment between the various groups of the study.
114
a r c h s o c e s p o f t a l m o l . 2 0 1 5;9 0(3):112118
would not represent additional expenses for them. After signing the informed consent, samples were taken of the patients
and sent to the microbiology laboratory. The study protocol
was approved by the Ethics Committee for Research of the
institution.
Chronic blepharitis was dened by the presence of 3 or
more of the following characteristics. Burning feeling, foreign
body or irritation; sheathing of eyelashes, telangiectasia in the
palpebral edge, foamy secretion, slight or moderate papillary
hyperemia or hypertroa of the palpebral conjunctival or Meibomium glands. The study excluded patients with additional
acute or chronic ocular diseases (corneal, conjunctival, palpebral, lacrimal pathways), those with applied topical treatment
during the month before samples were taken or with oral
treatment involving metronidazole, isotretinoin or other medications which could interfere with the density of parasites, as
well as patients who did not return for the control examinations. The patients were recruited from the outpatient practice
of the aforementioned Ophthalmology Department and were
assigned randomly to the different groups.
Group 1: 15 patients who were treated with palpebral
hygiene with neutral shampoo 3 times a day; Group 2: 15
patients who were treated with palpebral hygiene with neutral
shampoo and topical gel 0.75% metronidazolee 2 times a day;
Group 3: 15 patients who were treated with palpebral hygiene
with neutral shampoo and 3.5% neomycin antibiotic ointment
and 10% polymixin with 0.5% dexamethasone 3 times a day.
Control visits were scheduled for day 15, 30 and 60 after establishing the treatment. In said visits, the appropriate variables
were measured.
Palpebral hygiene comprised cleaning both palpebral edges
with cotton swabs impregnated with neutral shampoo diluted
in water, followed by warm compresses and massage with
expression of the Meibomium gland points during 15 min.
A prearranged questionnaire was given to the patients
when taking the samples as well as 2 months after establishing treatment. The questionnaire included demographic
data (sex, age) and demographic data (dermatological diseases, symptoms and signs).
Due to the subjectivity involved in the assessment of symptoms and signs, a score of 0 to 3 was devised to measure
severity, considering 0 as no symptoms or signs; 1, slight
symptoms or signs; 2, moderate symptoms or signs; and
3, severe symptoms or signs. Subsequently, the score of each
variable was added up to obtain a mean value that was utilized
for the statistical analysis.
In order to determine the presence of causing agents, 6 eyelashes were removed from the eye of each individual which
exhibited more signs of chronic anterior or posterior blepharitis, alternating between the lower and upper eyelid. Said
eyelashes were placed in a recipient to which 10% potassium
hydroxide (KOH) was added for parasitologic and mycologic
analysis under microscope at 40. The palpebral edge of both
eyes was scraped with a kimura spatula to obtain samples
for bacteriological studies in 5% sheep blood agar in CO2 ;
the fungus culture was made in sabouraud agar. Isolation
and identication of germs was performed with conventional
microbiological methods.
The data were analyzed by means of the Epi-Info
2002 statistical application (CDC, Atlanta, United States).
Results
Overall, 45 subjects which fullled all the controls were
included in the study. As regards gender, the female sex (67%)
and city dwellers (69%). The mean age was of (range from
17 to 87 years). As regards personal pathological history, 7
patients (15.5%) referred dermatological history of rosaceae
(Table 1).
Of the 45 examined patients, parasitological and bacteriological isolation could be carried out in 28 (62.2%). Of these,
15 patients (54%) were positive for D. folliculorum. In turn, bacterial isolation was obtained in 26 patients (92.8%). As for
isolated bacteria, negative coagulase Staphylococcus was isolated in 21 patients (75%), Staphylococcus aureus in 3 (11%) and
Streptococcus pneumoniae in 2 (7%).
Table 2 shows the distribution of signs and symptoms
according to severity and average score. It can be seen that
the mean of the higher scores corresponded to burning (2.4),
sheathing of eyelashes (2.4), irritation (2.2), erythema or palpebral edema (2.2), hypertroa of the papilla or the Meibomium
gland (1.2), foreign body feeling (1.9), presence of scales or
crusts (1.9) and foamy secretion (1.9).
No signicant differences were found when comparing the
baseline average scores between the study groups in any of
the studied signs and symptoms (Table 3).
When comparing symptoms and signs between the different groups at baseline and at the end of the study,
improvements were observed in all study groups for all the
variables in groups 1 and 2. In group 3, no improvement was
observed in eyelashes (p = 0.527), or in telangiectasia at the
palpebral edge (p = 0.894) (Table 4).
Table 5 compares the average posttreatment scores of
patients for each variable of the study.
Fig. 1 shows the overall scores of signs and symptoms
before and after the treatment. Even though signicant reductions were observed in the 3 groups, group 3 exhibited the
lowest improvement.
In what concerns the effects of infestation by Demodex
sp. on the efcacy of the treatment, it was not possible to
reach a conclusion due to the small number of the sample.
It was observed that patients with Demodex sp. in the group
that was administered metronidazole exhibit greater improvement than those who did not have said parasite (Fig. 2).
Discussion
Chronic blepharitis is a worldwide public health problem due
to its high prevalence, chronicity and resistance to treatment.
As described above, there are multiple treatment options for
this multifactor disease although none has demonstrated
healing capacities. Recurrence rates are very high and treatments are generally lifelong.
Shulman et al.7 concluded that the combined use of 3.5%
neomycin and 10% polymixyn with 1% dexamethasone was
more efcient than the sole use of 1% dexamethasone for
115
a r c h s o c e s p o f t a l m o l . 2 0 1 5;9 0(3):112118
Sex
Female
Male
Mean age (range)
Age group
1739
4059
60
Group 1
n (%)
Group 2
n (%)
10
5
45 (3087)
8
7
34 (1772)
12
3
34 (2070)
30 (66)
15 (33)
34 (1787 years)
10
3
2
11
3
1
26 (58)
14 (31)
5 (11)
5
8
2
Group 3
n (%)
Total
n (%)
Origin
Urban
Rural
Pathological antecedents
DM
Allergy
Asthma
Acne
Rosaceae
Demodex folliculorum
31 (69)
14 (31)
1
1
2
0
3
6
1
2
1
1
0
3
0
2
0
2
4
6
2 (4.4)
3 (6.7)
3 (6.7)
3 (6.7)
7 (15.6)
15/28 (54.0)
n = 45.
Group 1: palpebral hygiene with neutral shampoo 3 times/day; Group 2: palpebral hygiene with neutral shampoo and topical 0.75% metronidazole
gel 2 times/day; Group 3: palpebral hygiene with neutral shampoo and antibiotic cream comprised of 3.5% neomycin and 10% polymixin with
0.5% dexamethasone 3 times/day.
bacterial control and symptom reduction in chronic blepharitis patients, although its prolonged use could have toxic effects
on the ocular surface due to the presence of neomycin sulfate.
Demmler8 compared the use of 2% mercury oxide and lindane, which is a neutral lotion for palpebral hygiene versus the
use of combined corticoids with antibiotics, demonstrating
higher reduction of Demodex in patients who applied the neutral lotion and 2% mercury oxide. However, patients reported
difculties in the application and toxicity of the mercury
oxide, which must be applied very carefully to avoid contact with conjunctival mucosa. In turn, Junk et al.9 reported
one case of symptom improvement in a patient with chronic
Burning
Sheathing of eyelashes
Itching
Erithema or palpebral edema
Hypertrophia of papilla or the Meibomium gland
Foreign body feeling
Presence of crusts or scale
Foamy secretion
Pruritus
Dry eye feeling
Fallen eyelashes
Telangiectasiae in the palpebral edge
Poliosis
Trichiasis
n = 45.
None
0
1
0
0
4
0
4
1
8
9
8
22
42
34
32
Slight
1
5
12
7
8
4
9
15
5
7
11
9
2
5
7
Moderate
2
12
18
23
19
18
18
16
17
20
19
8
1
6
5
Severe
3
Average score
27
15
15
14
23
14
13
15
9
7
6
0
0
1
2.4
2.4
2.2
2.2
2.1
1.9
1.9
1.9
1.6
1.6
1.0
0.1
0.1
0.1
116
a r c h s o c e s p o f t a l m o l . 2 0 1 5;9 0(3):112118
Table 3 Inter-group comparison of the baseline average scores on symptoms and signs of patients with chronic
blepharitis.
Symptoms/signs
Group 2
n = 15
Group 1
n = 15
Burning
Sheathing of eyelashes
Itching
Palpebral erythema or edema
Hypertrophia of the papilla or the Meibomium gland
Foreign body feeling
Presence of crusts or scale
Foamy secretion
Pruritus
Dry eye feeling
Fallen eyelashes
Telangiectasiae in the palpebral edge
Poliosis
Trichiasis
2.2
2.5
2.2
2.2
2.0
2.1
1.9
1.8
1.6
1.5
1.1
0.1
0.5
0.2
Group 3
n = 15
2.4
2.4
2.1
1.9
2.1
1.8
1.9
1.8
1.8
1.5
0.8
0.1
0.5
0.5
2.7
2.3
2.2
2.5
2.1
1.9
1.9
2.0
1.4
1.6
1.0
0.1
0.5
0.5
0.2
0.7
0.9
0.7
0.9
0.6
1.0
0.8
0.5
1.0
0.7
1.0
1.0
0.5
Group 1: palpebral hygiene with neutral shampoo 3 times/day; Group 2: palpebral hygiene with neutral shampoo and topical 0.75% metronidazole gel 2 times/day; Group 3: palpebral hygiene with neutral shampoo and 3.5% neomycin antibiotic ointment and 10% polymixin with 0.5%
dexamethasone 3 times/day.
p: KruskalWallis test.
In the present experimental study, signicant improvements were observed in the studied variables when comparing
baseline and the results of treatment after 2 months in the
3 groups of the study, matching several published studies58
in what concerns efcacy of each administered treatment. As
for the most effective treatment, it is concluded that treatments with nutrition pool 3 times a day and with nutrition
pool and 0.75% metronidazole topical gel twice a day one
of the treatments which exhibited the best improvement of
assessed symptoms and signs, similar to the results reported
by Czepita5 and Barnhorst,10 nding statistically signicant
values (p < 0.05) for all the studied variables. The treatment
Table 4 Inter-group comparison of the average scores on symptoms and signs of patients with chronic blepharitis
before and after treatment.
Symptoms/signs
Burning
Sheathing of eyelashes
Itching
Palpebral erythema or edema
Hypertrophia of the papilla or the Meibomium gland
Foreign body feeling
Presence of crusts or scale
Foamy secretion
Pruritus
Dry eye feeling
Fallen eyelashes
Telangiectasiae in palpebral edge
Poliosis
Trichiasis
Group 1
Pre
Post
2.2
2.5
2.2
2.2
2.0
2.1
1.9
1.8
1.6
1.5
1.1
0.1
0.5
0.2
0.3
0.3
0.5
0.6
0.6
0.3
0.7
0.5
0.2
0.4
0.6
0.0
0.4
0.1
Group 2
p
Pre
Post
<0.0001
<0.0001
<0.0001
<0.0001
<0.0001
<0.0001
<0.0001
<0.0001
<0.0001
<0.0001
0.0003
0.0234
0.0234
0.0234
2.4
2.4
2.1
1.9
2.1
1.8
1.9
1.8
1.8
1.5
0.8
0.1
0.5
0.5
0.7
0.9
0.5
0.9
0.6
0.5
0.5
0.5
0.2
0.7
0.3
0.1
0.2
0.2
Group 3
p
Pre
Post
<0.0001
<0.0001
<0.0001
<0.0001
<0.0001
<0.0001
<0.0001
<0.0001
<0.0001
<0.0001
<0.0001
0.0354
<0.0001
<0.0001
2.7
2.3
2.2
2.5
2.1
1.9
1.9
2.0
1.4
1.6
1.0
0.1
0.5
0.5
1.5
1.4
0.9
1.1
1.5
1.3
1.3
1.4
0.8
0.9
0.6
0.1
0.2
0.2
p
<0.0001
<0.0001
<0.0001
<0.0001
<0.0001
<0.0001
<0.0001
<0.0001
<0.0001
<0.0001
0.527
0.894
<0.0001
<0.0001
Group 1: palpebral hygiene with neutral shampoo 3 times/day; Group 2: palpebral hygiene with neutral shampoo and topical 0.75% metronidazole gel 2 times/day; Group 3: palpebral hygiene with neutral shampoo and 3.5% neomycin antibiotic ointment and 10% polymixin 0.5% with
dexamethasone 3 times/day.
Paired t test for comparing pre- and post-treatment.
117
a r c h s o c e s p o f t a l m o l . 2 0 1 5;9 0(3):112118
Table 5 Inter-group comparison of the average scores on symptoms and signs of patients with chronic blepharitis
2 months after treatment.
Symptoms/signs
Group 2
n = 15
Group 1
n = 15
Burning
Sheathing of eyelashes
Itching
Palpebral erythema or edema
Hypertrophia of the papilla or the Meibomium gland
Foreign body feeling
Presence of crusts or scale
Foamy secretion
Pruritus
Dry eye feeling
Fallen eyelashes
Telangiectasiae in the palpebral edge
Poliosis
Trichiasis
0.3
0.3
0.5
0.6
0.6
0.3
0.7
0.5
0.2
0.4
0.6
0.0
0.4
0.1
p*
Group 3
n = 15
0.7
0.9
0.5
0.9
0.6
0.5
0.5
0.5
0.2
0.7
0.3
0.1
0.2
0.2
1.5
1.4
0.9
1.1
1.5
1.3
1.3
1.4
0.8
0.9
0.6
0.1
0.2
0.2
<0.001
<0.001
0.161
0.296
<0.001
<0.001
0.002
0.002
<0.001
0.295
0.169
0.350
0.808
0.350
Group 1: palpebral hygiene with neutral shampoo 3 times/day; Group 2: palpebral hygiene with neutral shampoo and topical 0.75% metronidazol gel 2 times/day; Group 3: palpebral hygiene with neutral shampoo and 3.5% neomycin antibiotic cream and 10% polymixin with 0.5%
dexamethasone 3 times/day.
KruskalWallis test.
30
Total score
20
Treatment
10
Pre
Post
0
No. = 15
15
15
15
15
15
Study group
40
30
20
10
Demodex
Absence
Presence
10
No. = 3
Study group
118
a r c h s o c e s p o f t a l m o l . 2 0 1 5;9 0(3):112118
Funding
Financial support: Hannelore-Georg Zimmermann Foundation, Munich, Germany.
Conict of interest
No conict of interest has been declared by the authors.
references
5. Czepita D, Kuzna-Grygiel
W, Czepita M, Grobelny A. Demodex
folliculorum and Demodex brevis as a cause of chronic marginal
blepharitis. Ann Acad Med Stetin. 2007;53:637, discussion
67.
6. Liu J, Sheha H, Tseng SC. Pathogenic role of Demodex mites in
blepharitis. Curr Opin Allergy Clin Immunol. 2010;10:
50510.
7. Shulman DG, Sargent JB, Stewart RH, Mester U. Comparative
evaluation of the short-term bactericidal potential of a
steroid-antibiotic combination versus steroid in the
treatment of chronic bacterial blepharitis and conjunctivitis.
Eur J Ophthalmol. 1996;6:3617.
8. Demmler M, de Kaspar HM, Mhring C, Klauss V. Blepharitis.
Demodex folliculorum, associated pathogen spectrum and
specic therapy. Ophthalmologe. 1997;94:1916.
9. Junk AK, Lukacs A, Kampik A. Topical administration of
metronidazole gel as an effective therapy alternative in
chronic Demodex blepharitis: a case report. Klin Monatsbl
Augenheilkd. 1998;213:4850.
10. Barnhorst DA Jr, Foster JA, Chern KC, Meisler DM. The efcacy
of topical metronidazole in the treatment of ocular rosacea.
Ophthalmology. 1996;103:18803.
11. Rodrguez AE, Ferrer C, Ali JL. Chronic blepharitis and
Demodex. Arch Soc Esp Oftalmol. 2005;80. Madrid.
12. Geerling G, Tauber J, Baudouin C, Goto E, Matsumoto Y,
OBrien T, et al. The international workshop on Meibomian
gland dysfunction report of the subcommittee on
management and treatment of meibomian gland
dysfunction. Invest Ophthalmol Vis Sci. 2011;52:
205064.
13. Asbell PA, Stapleton FJ, Wickstrm K, Akpek EK, Aragona P,
Dana R, et al. The international workshop on meibomian
gland dysfunction: report of the clinical trials subcommittee.
Invest Ophthalmol Vis Sci. 2011;52:206585.
14. Nelson JD, Shimazaki J, Benitez-del-Castillo JM, Craig JP,
McCulley JP, Den S, et al. The international workshop on
meibomian gland dysfunction: report of the denition and
classication subcommittee. Invest Ophthalmol Vis Sci.
2011;52:19307.
15. Gao YY, di Pascuale MA, Li W, Baradaran-Rai A, Elizondo A,
Kuo CL, et al. In vitro and in vivo killing of ocular Demodex
by tea tree oil. Br J Ophthalmol. 2005;89:146873.
16. Koo H, Kim TH, Kim KW, Wee SW, Chun YS, Kim JC. Ocular
surface discomfort and Demodex: effect of tea tree oil eyelid
scrub in Demodex blepharitis. J Korean Med Sci.
2012;27:15749.