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Comparison of therapeutic effects of
topical azithromycin solution and systemic doxycycline on posterior blepharitis
Mehdi
Zandian1, Neda
Rahimian2, Sanaz Soheilifar3
1Department
of Ophthalmology, Faculty of Medicine, Hamadan
University of Medical sciences, Hamadan 6516836595, Iran
2Endocrine Research Center, Research Institute for Endocrine Sciences,
Shahid Beheshti University of Medical Sciences, Tehran 193954763, Iran
3Department
of Orthodontics, Faculty of Dentistry, Hamadan University of Medical
Sciences, Hamadan 6516836595, Iran
Correspondence to:
Sanaz Soheilifar. Tavoos Alley,
Andalib Avenue, Hamadan 6516836595, Iran. sanaz_soheilifar@yahoo.com
Received:
2015-03-14
Accepted: 2015-07-20
Abstract
AIM: To compare the effect of azithromycin
drop and doxycycline capsule on treatment of posterior blepharitis.
METHODS: Fifty patients (100
eyes) with moderate posterior blepharitis, randomly divided into two
therapeutic groups; all the patients got warm eyelid compress and massage three
times a day for 3wk. In
addition the first group got azithromycin 1% drop, twice daily for 1wk and then one drop daily for 2wk. The second group got oral doxycycline
100 mg daily for 3wk. At the
end of the research, patients’ signs and symptoms were compared together.
ANOVA, Chi-square and Mann-Whitney tests were
used for statistical analysis.
RESULTS:
Topical therapy with azithromycin and oral therapy with doxycycline relieved
signs and symptoms after 3wk. There were no significant differences between
symptoms healing rate and foreign body sensation healing in these two groups (P>0.05). However, azithromycin drop
was more effective in reduction of eye redness and doxycycline was more
effective in meibomian glands plugging healing and reducing the corneal
staining.
CONCLUSION:
Topical azithromycin could have similar effects as oral doxycycline on
posterior blepharitis in improving subjective symptoms. However, doxycycline can reduce objective signs
such as ocular surface staining and meibomian gland plugging more than
azithromycin.
KEYWORDS: blepharitis; azithromycin; doxycycline
DOI:10.18240/ijo.2016.07.14
Citation: Zandian
M, Rahimian N, Soheilifar S. Comparison of therapeutic effects of topical
azithromycin solution and systemic doxycycline on posterior blepharitis. Int J
Ophthalmol 2016;9(7):1016-1019
INTRODUCTION
Blepharitis or
eyelid margin inflammation is one of the most common ocular diseases
encountered by eye care professionals and is often characterized by
erythematous, thickened eyelid margins with dysfunctional meibomian glands and
accumulation of debris along the eyelid margin[1-4]. Common signs of chronic blepharitis are
conjunctival hyperemia, mucous secretion, meibomian gland dysfunction, and
superficial punctuate keratitis[3].
Patients with blepharitis usually complain of itching, foreign body sensation,
burning, dryness, and tearing[3]. American Academy of Ophthalmology classified
the disease as anterior or posterior blepharitis, according to whether it
primarily affects the lash-bearing region of the eyelids or meibomian gland
orifices, respectively[5].
However, it is clear that these classifications are not mutually exclusive and
are often observed together because of the proximity of the areas involved[5].
Management of
blepharitis may include daily eyelid cleansing methods and the use of
therapeutic agents that reduce infection and inflammation[6-7].
There are no established guidelines regarding therapeutic regimens but
antibiotics and topical corticosteroids can produce significant improvement in
signs and symptoms of blepharitis. In most cases subjective symptoms may
persist even when signs have been improved[7].
Systemic therapy
with low-dose doxycycline, a long-acting semi-synthetic tetracycline, has
become the treatment of choice for patients whose symptoms and signs are not
adequately controlled[3].
It has been used to treat ocular rosacea, improving irritation symptoms and
increasing tear film stability[8-9]. It
has also been used to treat corneal erosions[10-11].
Other than their antibacterial activity, tetracyclines have anti-inflammatory
and antiangiogenic properties.
In fact, these
compounds decrease the activity of phospholipase A2 and reduce the production
of interleukin IL-1α and tumor necrosis factor (TNF)-α
in corneal epithelium[12-14].
At high concentrations, tetracyclines inhibit staphylococcal exotoxin-induced
cytokines and chemokines[15].
Gastro-intestinal
effects including nausea, vomiting and diarrhea are the side effects of
tetracyclines and are common especially with high doses and most of them could
be attributed to iritation of the mucosa[16].
Doxycycline is
one of the most common causes of drug induced esophageal
ulcers[17].
Oral
azithromycin therapy improves the signs and symptoms associated with dry eyes[1,18]. It is believed that
systemic azithromycin penetrates into the ocular surface and remains at
therapeutic levels days after the cessation of the medication[19]. Azithromycin is
anti-inflammatory, inhibiting proinflammatory cytokines, and is potent against
Gram-negative microorganisms[20].
Clinical trials have identified topical azithromycin as a potentially effective
treatment for lid margin disease and meibomian gland dysfunction[21-23].
The aim of the
present study was to compare the therapeutic effects of topical azithromycin
and oral doxycycline on improving the signs and
symptoms of posterior blepharitis.
SUBJECTS AND METHODS
Fifty patients (26 men, 24 women) with
chronic blepharitis, 25-40 years old with the mean age of 33.88±9.03y were
included in this study and randomly divided into two groups. These two groups
were matched by sex and age. All of the patients instructed to use warm eyelid
compress and massage three times 1d for 3wk. In addition the first group received
azithromycin 1% drop (Azithromax, Sinadarou, Tehran,
Iran), twice daily for 1wk
and then one drop daily for 2wk. The second group received oral
doxycycline 100 mg (Doxycycline, Mahbandarou, Tehran, Iran) once daily for 3wk. All the experiments were approved by
the Ethics Committee in the Research Center of Hamadan University of Medical
Sciences and a written informed consent was obtained from every participant in
the study.
The patients were visited three times
(at the beginning of the study, 2 and 3wk after initiation of the treatment).
On each visit, conjunctival peripheral injection and corneal staining were
examined with slit lamp. Each of these features was graded based on area
involved from 1+ to 4+. For corneal staining, cornea
divided into four imaginary concentric cycles and staining of most peripheral
band recorded as 1+ and central
cycle as 4+. Furthermore bulbar conjunctiva imaginary
divided into four equal quadrants and grading was done based on the number of
involved quadrants. Subjective symptoms including itching, irritation and
lacrimation were recorded in a check list as 0 for no symptom and 2+ for severe
symptoms. In addition Schirmer I test (2min test without anesthesia) performed
in all of the patients, while
considering more than 10 mm tear production as normal[24]. The presence of foreign body sensation
and meibomian glands plugging were also determined for all of the patients in
every visit.
Statistical Analysis Analysis was
performed using the statistical package SPSS 16. ANOVA was used for comparing
the results of Schirmer test and Chi-square
test was used to compare signs and symptoms at different time intervals within
each group. Mann-Whitney test was
used for comparing sign and symptoms between the groups. The level of
significance for all tests was set at P<0.05.
RESULTS
All patients in the azithromycin group
completed the study and none of them experienced side effects; however 6 out of
25 patients in doxycycline group (24%) left the study. In the doxycycline group
6 out of 19 patients (31.5%) reported nausea and 2 patients (10.5%) complained
of vomiting and diarrhea. The results of this study showed that the reduction
of the signs and symptoms in the two groups was not affected by sex (P>0.05).
The results of ANOVA test showed that
Schirmer I test score did not change significantly at different intervals in
the two groups (Tables 1, 2).
Table 1 Schirmer test mean in azithromycin group, results
of ANOVA
Visits |
Mean |
SD |
P |
1st |
6.12 |
5.89 |
0.287 |
2nd |
7.12 |
6.51 |
|
3rd |
8.16 |
6.84 |
Table 2 Schirmer test mean
in doxycycline group, results of ANOVA
Visits |
Mean |
SD |
P |
1st |
9 |
5.64 |
0.246 |
2nd |
9.9 |
6.07 |
|
3rd |
11.04 |
6.48 |
The scores of subjective symptoms
including itching, irritation, lacrimation and the frequency of foreign body
sensation decreased significantly during the treatment time (P<0.05,
Tables 3, 4).
However no significant difference was found in the reduction of subjective
symptoms score and frequency of foreign body sensation from the 1st
to the 3rd visit between the groups (P>0.05, Tables 3, 4).
Table
3 Subjective symptoms scores in the groups
at different visits
Groups |
1st visit |
2nd visit |
3rd visit |
P (Chi-square) |
1st to 3rd visit difference |
P (Mann-Whitney) |
Azitromycin |
1.2 |
0.64 |
0.24 |
<0.01 |
0.96 |
0.701 |
Doxycycline |
0.96 |
0.58 |
0.32 |
<0.01 |
0.64 |
Table 4 Frequency of foreign body sensation in the groups
at different visits
Groups |
1st visit |
2nd visit |
3rd visit |
P (Chi-square) |
1st to 3rd visit difference |
P (Mann-Whitney) |
Azithromycin |
58% |
44% |
26% |
0.016 |
28% |
0.881 |
Doxycycline |
54% |
46% |
28% |
0.027 |
26% |
The mean score of peripheral injection
was improved significantly from the 1st to the 3rd visit
in the two groups. Furthermore the reduction of the peripheral injection score
in the azithromycin group was significantly more than the doxycycline group (P<0.05, Table 5).
Table 5 Peripheral injection scores in the two groups
Groups |
1st visit |
2nd visit |
3rd visit |
P (Chi-square) |
1st to 3rd visit difference |
P (Mann-Whitney) |
Azithromycin |
1.76 |
1.16 |
0.36 |
<0.01 |
1.4 |
0.041 |
Doxycycline |
1.54 |
1.24 |
0.26 |
0.001 |
1.28 |
The mean score of corneal staining was
improved significantly from the 1st to the 3rd visit in
the two groups. Furthermore the reduction of corneal staining score in the doxycycline
group was significantly more than the azithromycin group (P<0.05, Table 6).
Table 6 Corneal staining
scores in the two groups
Groups |
1st visit |
2nd visit |
3rd visit |
P (Chi-square) |
1st to 3rd visit difference |
P (Mann-Whitney) |
Azitromycin |
1.24 |
1.09 |
0.9 |
0.004 |
0.34 |
0.022 |
Doxycycline |
1.66 |
1.26 |
0.36 |
<0.01 |
1.3 |
The frequency of meibomian glands
plugging reduced significantly from the 1st to the 3rd visit
in the two groups. Furthermore the reduction of the meibomian glands plugging
frequency in the doxycycline group was significantly more than the azithromycin
group (P<0.05, Table 7).
Table
7 Meibomian glands plugging frequency in the two group
Groups |
1st visit |
2nd visit |
3rd visit |
P (Chi-square) |
1st to 3rd visit difference |
P (Mann-Whitney) |
Azitromycin |
96% |
68% |
32% |
<0.01 |
64% |
0.039 |
Doxycycline |
96% |
70% |
14% |
<0.01 |
82% |
DISCUSSION
In the present clinical trial it was
found that topical therapy
with azithromycin and systemic
treatment with doxycycline
relieved signs and symptoms of posterior blepharitis except for Schirmer I test
score. On the other hand, no significant differences was demonstrated in
improvment and healing of the subjective symptoms, including foreign body
sensation, itching, irritation and lacrimation between patients treated with
azithromycin ophthalmic solution and patients treated with doxycycline capsule.
However azithromycin ophthalmic solution led to more improvement in peripheral
injection than doxycycline capsule and doxycycline caused more improvement in
meibomian glands plugging and corneal staining than azithromycin.
Igami et al[25] in their clinical trial evaluated the effects of
oral azithromycin on posterior blepharitis. They
graded the subjective clinical outcomes and also performed tear break-up time,
Schirmer I test, corneal fluorescein staining score and rose bengal staining
score in all of the patients. They observed that all clinical outcome scores
showed statistically significant improvement after treatment with oral
azithromycin, except for eyelid swelling. On the other hand they found no
statistically significant improvement on average values of Schirmer I test, corneal fluorescein staining score, and
rose bengal staining score[25].
In the present study, azithromycin ophthalmic solution improved subjective
symptoms and no significant improvement was found in Schirmer I test, similar
to Igami et al's[25] study.
In our study
topical azithromycin instead of systemic azithromycin was used in order to
prevent potential systemic side effects associated with oral administration. In
addition consuming oral azithromycin could result in microbial resistance to
this antibiotic, especially for staphylococous species[26].
Iovieno et al[27] in their study on patients with chronic blepharitis
concluded that 4wk treatment with doxycycline significantly improved symptoms
and signs, similar to our study. Furthermore they found that this drug
decreases matrix metalloproteinase-9 activity and increase anti-lipase level in
tear film[27].
Foulks et al[15] compared biochemical features of meibomian gland
secretions and subjective symptoms of patients with meibomian gland dysfunction
who were treated with topical azithromycin and oral doxycycline. They resulted
that oral doxycycline treatment was slightly less effective in improving
foreign body sensation and the signs of plugging and secretion and found more
biochemical lipid quality improvement with azithromycin treatment[15]. However,
in the present study, oral doxycycline had slightly better effect on meibomian
glands plugging than topical azithromycin and no significant difference was
found in foreign body sensation in the two groups. This may be justified with
larger number of our cases and different treatment schedule and duration of
treatment compared to Foulks et al's[15] study.
Long half life
and low frequency of usage are advantages of using azithromycin[26], but azithromycin
solution is not available as a generic drug in our country, while doxycycline
is readily available and it may be considered a disadvantage of using
azithromycine solution.
From economic point
of view, the cost of using topical azithromycin 1%
(www.drugs.com/price-guide/azasite) for 14d
(Azasite, Inspire Pharmaceuticals, Whitehouse station, USA) is approximately
four times more than using doxycycline capsule 100 mg (Doxycycline Monohydrate,
Lupin Pharmaceuticals, Baltimore,
Maryland, USA) for 28d of
treatment in US market[28].
Topical
azithromycin could have similar effects as oral doxycycline on posterior
blepharitis in improving subjective symptoms, however doxycycline can reduce
objective signs such as ocular surface staining and meibomian gland plugging
more than azithromycin. Regarding the gastrointestinal complaints of the
patients treated with systemic doxycycline, azithromycin solution can be a
comparable choice with less systemic side effects in treatment of posterior
blepharitis.
ACKNOWLEDGEMENTS
Conflicts of Interest: Zandian M, None; Rahimian N, None; Soheilifar S, None.
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