JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS ORIGINAL ARTICLE

Volume 34, Number 4, 2018

ª Mary Ann Liebert, Inc.
DOI: 10.1089/jop.2017.0095

Comparison of the Clinical Efficacy of Topical

and Systemic Azithromycin Treatment
for Posterior Blepharitis

Elvin Yildiz,1,* Nursal Melda Yenerel,1,* Ayca Turan-Yardimci,2 Murat Erkan,3 and Pembegul Gunes3,*
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Abstract

Purpose: To compare the clinical efficacy of topical and oral azithromycin treatments for posterior blepharitis.
Methods: Both topical and oral treatment groups comprised 15 patients. In the topical group, azithromycin
15 mg/g ophthalmic solution (Azyter; Thea Pharmaceuticals, Clermont-Ferrand, France) was used twice a day
for 3 days and then once a day until the treatment completes a month. In the systemic treatment group,
azithromycin 250 mg tablets (Azitro; Deva Pharmaceuticals, Istanbul, Turkey) were used, 1 · 2 tablets (500 mg)
at the first day of treatment and then 1 · 1 tablet (250 mg) for 4 days. Three cycles of treatment with 5-day
intervals were completed. The ocular symptoms, eyelid margin sings, Ocular Surface Disease Index (OSDI),
tear film break-up time, corneal/conjunctival staining score, Schirmer test, and conjunctival brush cytology
were evaluated at baseline, 1, and 5 weeks after the end of treatment.
Results: Both topical azithromycin and oral azithromycin were found to be effective in improving the clinical
signs and symptoms of posterior blepharitis. The mean OSDI scores, lissamine green staining scores, and
Schirmer test results showed improvements after both topical and oral treatments. However, topical treatment
was shown to be associated with longer cytological improvements that persist at least 5 weeks and with better
stabilization of the tear film, which is well documented by showing longer tear film break up time (TFBUT) in
the topical treatment group.
Conclusions: Although both treatment methods are found to be effective, the results of topical treatment group
showed some superiority over those of systemic treatment group, which may be associated with a higher ocular
tissue concentration of azithromycin after topical administration.

Keywords: azithromycin, posterior blepharitis, meibomian gland dysfunction, dry eye

Introduction eye disease. According to the Dry Eye Workshop (DEWS)

P osterior blepharitis or meibomian gland dysfunction
(MGD) is a common clinical problem with a prevalence
of 39%–50%, according to the different studies.1–3 MGD is
characterized by lid margin hyperemia, crusting of the la-
shes, plugging of the meibomian gland orifices, and foamy
tears. MGD is often associated with the meibomian gland
terminal duct obstruction and alteration to the anatomy of
the meibomian glands and to their secretion.4,5 The condi-
tion usually results in alteration of the tear film, tear film
instability, symptoms of eye irritations, and evaporative dry
report, MGD is very likely the most frequent cause of dry
eye disease.6
Most cases of posterior blepharitis are associated with
low-grade infection and inflammation. Thus, the treatment
includes lid hygiene, warm compress, topical and systemic
antibiotics, and anti-inflammatory agents.7–11 Azithromycin,
a macrolide antibiotic, has a broad-spectrum antibacterial
effectiveness, including Haemophilus influenza, Staphylo-
coccus aureus, and Streptococcus pneumonia. Like other
macrolides, azithromycin has also anti-inflammatory activ-
ities.12,13 Recent studies showed a significant improvement

Departments of 1Ophthalmology and 3Pathology, Ministry of Health, Haydarpasa Numune Egitim ve Arastirma Hastanesi, Istanbul,
Turkey.
2
Ministry of Health, Tunceli State Hospital, Tunceli, Turkey.
*Associate professor.

1
 2 YILDIZ ET AL.
in the signs and symptoms associated with posterior ble-
pharitis after the use of azithromycin 1% ophthalmic solu-
tion.14,15 Spectroscopic measures of meibomian gland lipid
secretion showed significant improvement after topical azi-
thromycin therapy of MGD.16 This improvement is shown to
be associated with an increase in carotenoids in meibum after
azithromycin therapy.17 The use of systemic azithromycin in
the treatment of posterior blepharitis has been also shown to
be effective.18–20
To the best of our knowledge, the clinical efficacy of
topical and oral azithromycin treatments for posterior ble-
pharitis has not been compared before. For this reason, this
prospective, comparative study was designed to evaluate the
efficacy of topical azithromycin ophthalmic solution and oral
azithromycin for the treatment of posterior blepharitis. The
comprehensive evaluation included the changes in the ocular
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symptoms, eyelid margin sings, environmental triggers as
measured by Ocular Surface Disease Index (OSDI), tradi-
tional dry eye diagnostic tests, and conjunctival cytology.
Methods
Patient recruitment
This prospective, randomized, open-label study adhered
to the tenets of the Declaration of Helsinki and was ap-
proved by the Institutional Review Board of Ministry of
Health Haydarpasa Numune Training and Research Hospi-
tal, Istanbul, Turkey. Written informed consent was ob-
tained from each subject. Diagnosis of posterior blepharitis
was based on the formation of lid margin hyperemia, eyelid
debris, plugging of the meibomian gland orifices, and foamy
tears. Thirty patients with a diagnosis of posterior blephar-
itis were enrolled in the study between March 2016 and May
2016. Patients with any of the following were excluded from
the study: younger than 18 years of age, history of posterior
blepharitis treatment, including topical antibiotic ointments
or drops, topical anti-inflammatory drops, oral antibiotics
within the previous 6 months, history of ocular surgery
within the previous 6 months, history of ocular allergy,
presence of ocular inflammation, glaucoma, and history of
the use of systemic antibiotics for any reason within the
previous 6 months.
Evaluation of ocular symptoms, eyelid
margin sings, and OSDI questionnaire
The diagnosis of posterior blepharitis was based on the
presence of lid margin hyperemia, eyelid debris, plugging of
the meibomian gland orifices, and foamy tears. All eligible
patients were examined for baseline measurements. The
OSDI questionnaire was used in each subject to evaluate any
existing complaint related to dry eye. The OSDI was a 12-
item questionnaire, including 5 different levels of symptoms
and those were scored as 0 (none of the time), 1 (some of the
time), 2 (half of the time), 3 (most of the time), and 4 (all of
the time). The total OSDI score was calculated based on the
formula OSDI = [(sum of scores for all questions an-
swered) · 100]/[(total number of questions answered) · 4].
The symptoms and signs of MGD were evaluated and further
graded. Subjective symptoms such as itching and foreign body
sensation were questioned and graded as follows: 0, no
symptoms; 1, mild symptoms; 2, moderate symptoms; and 3
severe symptoms. Eyelid hyperemia was evaluated and graded
Table 1. Semiquantitative Cytological Scoring
Criteria Score
Cellularity 0: Abundant
1: Moderate
2: Scarce
Cell/cell contact 0: Associated cells
1: Associated cells and
isolated cells
2: Isolated cells only
Nucleus/cytoplasm ratio 0: ½
1: 1/3–1/4
2: >1/5
Goblet cell 0: Abundant (‡300)
1: Moderate (<300)
2: Scarce (<100)
3: Absent (<10)
Metaplasia 0: Absent
1: Incipient
2: Moderate
3: Advanced
as follows: 0, no signs; 1, mild signs (redness localized to a
small region of the lid margin or skin); 2, moderate signs
(redness of most of the lid margin); and 3, severe signs (marked
diffuse redness of both lid margins and skin). Eyelid debris was
evaluated and graded as follows: 0, no signs; 1, mild signs
(debris localized to a small region of the eyelid); 2, moderate
signs (debris localized to the most of the eyelid); and 3, severe
signs (marked debris of eyelid). Meibomian gland secretion
was evaluated and further graded as follows: 0, clear secretion;
1, cloudy secretion; 2, paste-like secretion; and 3, no express-
ible secretion.
Tear film break-up time, corneal/conjunctival
staining score, and Schirmer test
An impregnated fluorescein strip moistened with 1–2 drops
of sterile ocular irrigation solution was inserted into the lower
fornix. Two minutes after the application of fluorescein, the
tear film was examined under the cobalt blue filtered light of
the slit lamp microscope. Tear film break-up time (TBUT)
was the time interval between the last blink and the appear-
ance of the first random dry spot on the corneal surface (black
spot indicates the formation of dry area). The patients were
requested to blink several times and then keep their eyes
open. TBUT was measured 3 times and the mean value was
recorded. Corneal fluorescein staining was evaluated after
TBUT measurements. Lissamine green conjunctival staining
was evaluated after instillation of 10 mL of a 1% lissamine
green dye (Leiter’s Pharmacy, San Jose, CA). Corneal and
Table 2. Nelson Grading Based on the
Semiquantitative Cytological Scoring
Nelson grading Total score of cytological criteria
0 0–3
1 4–5
2 6–9
3 ‡10
 TOPICAL VS. SYSTEMIC AZITHROMYCIN FOR POSTERIOR BLEPHARITIS 3

FIG. 1. (A) In hypercellular smear, abundant cellularity (cellularity score; 0), cohesive cell clusters (cell to cell contact
score; 0), nucleus/cytoplasm ratio: 1/3 (score 1), moderate goblet cells (score 1), incipient squamous metaplasia (score 1)
(total score 3 = Nelson grade 0). (B) In normocellular smear, moderate cellularity (score 1), both cohesive cell clusters and
discohesive cells (cell to cell contact score; 1), nucleus/cytoplasm ratio: 1/3 (score 1), moderate goblet cells (score 1),
incipient squamous metaplasia (score 1) (total score 5 = Nelson grade 1). (C) In hypocellular smear, scarce cellularity (score
2), discohesive cells (cell to cell contact score; 2), nucleus/cytoplasm ratio: 1/3 (score 1), scarce goblet cells (score 2),
moderate squamous metaplasia (score 2) (total score 9 = Nelson grade 2).
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conjunctival staining pattern was graded according to the Statistical analysis

SICCA ocular staining score.21 Schirmer test was performed
after obtaining topical anesthesia with 0.5% proparacaine
hydrochloride. Standard Schirmer strips were placed into the
lower conjunctival sac at the junction of the lateral and
middle thirds, avoiding touching the cornea, and the length of
wetting strips in millimeters was recorded after 5 min.
Conjunctival brush cytology
Conjunctival brush cytology specimens were taken fol-
lowing topical anesthesia with 0.5% proparacaine and cen-
tral upper bulbar conjunctiva was used for sampling.
Conjunctiva was scraped by rotating the Cytobrush-S
(Medscand AB, Malmö, Sweden) 360. The brushes were
placed in PreservCyt solution and the containers were sha-
ken to detach the cells from the brush. The suspended cells
in the container were fixed in the ThinPrep processor ac-
cording to the manufacturer’s directions and ThinPrep slides
were obtained at the end of the procedure. Goblet cell
number and Nelson grade were determined for each sample.
To determine goblet cells per slide, periodic-acid Schiff
staining was performed. Goblet cells were counted using a
200 · magnification. Five cytological criteria derived from
the grading system described by Nelson et al. were used.22
A numerical value was assigned to each of these criteria
according to the magnitude (Table 1). The sum of the values
supplied by each of the 5 criteria (overall score) determined
the Nelson grading for each eye (Table 2) (Fig. 1). All ex-
aminations were performed by the same cytopathologist
(P.G.) who was unaware of the group assignment.
After the baseline evaluation, patients were randomly
assigned to treatment groups. In the topical azithromycin
group, azithromycin 15 mg/g ophthalmic solution (Azyter;
Thea Pharmaceuticals, Clermont-Ferrand, France) was used
twice a day for 3 days and then once a day until the treat-
ment completes a month. In the systemic treatment group,
azithromycin 250 mg tablets (Azitro; Deva Pharmaceuticals,
Istanbul, Turkey) were used, 1 · 2 tablets (500 mg) at the
first day of treatment and then 1 · 1 tablet (250 mg) for
4 days. Three cycles of treatment with 5-day intervals were
completed. Warm compress, once a day, was recommended
to all study subjects. All tests were repeated 1 week after
discontinuation of treatment and 4 weeks after the second
visit (5 weeks after the end of treatment).
Number Cruncher Statistical System (NCSS) 2007
(Kaysville, Utah) was used for statistical analysis of the
study findings. Descriptive statistical methods (mean, stan-
dard deviation, median, frequency, and rate) were used to
evaluate the study’s data. Independent samples t-test (av-
erage t-test of independent samples) was used in intergroup
comparison of parameters within normal distribution, while
the Mann–Whitney U test was used in the intergroup com-
parison of parameters without normal distribution. Wilcox-
on singed-rank test (Bonferroni corrected) was used for
ingroup comparison of variables with normal distribution.
Yates’ continuity correction test was used for comparison of
quantitative variables. Levels of P < 0.01 and P < 0.05 were
considered statistically significant. Data from the right eye
were used for statistical analysis in all patients
Results
A total of 30 subjects were included in the study. Both
topical and oral treatment groups comprised 15 patients. The
mean age and gender distribution of the groups are sum-
marized in Table 3.
All evaluated posterior blepharitis signs (eyelid hyper-
emia, eyelid debris, and meibomian gland secretion) and
symptoms (itching and foreign body sensation) significantly
improved in both groups after treatment. All variables were
Table 3. Demographic Characteristics
of the Patients
Topical Oral
treatment treatment P
Age
Mean – SD 57.73 – 13.19 59.33 – 6.78 0.679a
Minimum–maximum 24–77 (62) 47–68 (60)
(median)
Gender
Female, n (%) 6 (40.0) 7 (46.7) 0.999b
Male, n (%) 9 (60.0) 8 (53.3)
a
Student’s t-test.
b
Yates continuity correction test.
SD, standard deviation.
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Table 4. Changes in the Clinical Signs and Symptoms of Meibomian Gland Dysfunction After Oral and Topical Treatments
1 Week 5 Weeks Baseline: 1 week Baseline: 5 weeks 1 Week after the
after the end after the end after the end after the end end of treatment–5 weeks
Baseline of treatment of treatment Pa of treatment, Pb of treatment, Pb after the end of treatment, Pb
Eyelid hyperemia
Topical treatment
Minimum–maximum (median) 1–3 (2) 0–2 (1) 0–1 (0) <0.001** 0.008** 0.002** 0.307
Mean – SD 1.80 – 0.56 0.73 – 0.59 0.47 – 0.52
Oral treatment
Minimum–maximum (median) 2–3 (2) 0–2 (1) 0–1 (0.5) <0.001** 0.001** 0.001** 0.176
Mean – SD 2.27 – 0.46 0.80 – 0.56 0.50 – 0.52
c
P 0.220 0.732 0.860
Eyelid debris
Topical treatment
Minimum–maximum (median) 1–3 (2) 0–2 (0) 0–2 (1) <0.001** 0.002** 0.006** 0.999
Mean – SD 2.20 – 0.56 0.40 – 0.63 0.61 – 0.65
Oral treatment
Minimum–maximum (median) 1–3 (2) 0–2 (1) 0–2 (0.5) <0.001** 0.007** 0.013* 0.307
Mean – SD 2.00 – 0.65 1.00 – 0.65 0.71 – 0.82
Pc 0.383 0.014* 0.853
Meibomian gland secretion
Topical treatment
Minimum–maximum (median) 1–3 (2) 0–1 (1) 0–1 (1) <0.001** 0.003** 0.004** 0.307

4
Mean – SD 2.13 – 0.64 0.80 – 0.41 0.54 – 0.52
Oral treatment
Minimum–maximum (median) 1–3 (2) 0–2 (1) 0–1 (0.5) <0.001** 0.001** 0.003** 0.999
Mean – SD 2.07 – 0.46 0.67 – 0.72 0.50 – 0.52
Pc 0.699 0.388 0.845
Itching
Topical treatment
Minimum–maximum (median) 2–3 (2) 0–1 (0) 0–2 (1) <0.001** 0.001** 0.004** 0.472
Mean – SD 2.33 – 0.49 0.33 – 0.49 0.62 – 0.65
Oral treatment
Minimum–maximum (median) 1–3 (2) 0–1 (1) 0–2 (1) <0.001** 0.002** 0.003** 0.999
Mean – SD 2.07 – 0.46 0.53 – 0.52 0.64 – 0.63
Pc 0.139 0.277 0.892
Foreign body sensation
Topical treatment
Minimum–maximum (median) 1–3 (2) 0–1 (0) 0–2 (0) <0.001** 0.002** 0.003** 0.952
Mean – SD 1.80 – 0.56 0.27 – 0.46 0.46 – 0.66
Oral treatment
Minimum–maximum (median) 1–3 (2) 0–1 (0) 0–1 (0.5) <0.001** 0.001** 0.003** 0.952
Mean – SD 2.07 – 0.46 0.33 – 0.49 0.50 – 0.52
Pc 0.156 0.695 0.672
a
Friedman test.
b
Wilcoxon signed-rank test (Bonferroni corrected).
c
Mann–Whitney U test.
*P < 0.05; **P < 0.01.
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Table 5. Changes in the Clinical Test Results After Oral and Topical Treatments
Baseline: 1 week Baseline: 5 weeks 1 Week after the end
1 Week after the 5 Weeks after the after the end after the end of treatment–5 weeks
a
Baseline end of treatment end of treatment P of treatment, Pb of treatment, Pb after the end of treatment, Pb
OSDI
Topical treatment
Minimum–maximum (median) 10–69 (35) 10–28.1 (17.5) — — 0.001** — —
Mean – SD 36.15 – 14.68 17.48 – 4.48 —
Oral treatment
Minimum–maximum (median) 22.5–58.3 (33.3) 12.5–25 (18.75) — — 0.001** — —
Mean – SD 36.14 – 11.61 18.62 – 3.48 —
Pc 0.967 0.370
Fluorescein staining
Topical treatment
Minimum–maximum (median) 1–2 (2) 1–2 (1) 0–2 (1) 0.013* 0.999 0.034* 0.102
Mean – SD 1.60 – 0.51 1.47 – 0.52 1.00 – 0.58
Oral treatment
Minimum–maximum (median) 1–3 (2) 1–2 (2) 1–2 (1) 0.155 0.395 0.160 0.999
Mean – SD 1.93 – 0.80 1.60 – 0.51 1.43 – 0.51
c
P 0.244 0.472 0.060
Lissamine green staining
Topical treatment
Minimum–maximum (median) 1–2 (2) 1–2 (1) 1–1 (1) 0.004** 0.102 0.014* 0.250
Mean – SD 1.60 – 0.51 1.20 – 0.41 1.00 – 0.00

5
Oral treatment
Minimum–maximum (median) 1–3 (2) 1–2 (1) 1–2 (1) 0.001** 0.005** 0.015* 0.999
Mean – SD 2.00 – 0.53 1.33 – 0.49 1.21 – 0.43
Pc 0.051 0.417 0.082
Schirmer
Topical treatment
Minimum–maximum (median) 10–23 (19) 12–25 (21) 17–25 (20) 0.007** 0.235 0.006** 0.999
Mean – SD 17.73 – 3.56 19.93 – 4.30 20.46 – 1.98
Oral treatment
Minimum–maximum (median) 8–25 (17) 15–28 (22) 15–23 (20) 0.006** 0.014* 0.202 0.372
Mean – SD 16.27 – 4.50 21.47 – 3.72 19.43 – 2.65
Pc 0.234 0.380 0.495
TBUT
Topical treatment
Minimum–maximum (median) 4–10 (8) 6–10 (7) 7–10 (8) 0.159 0.999 0.999 0.143
Mean – SD 7.87 – 1.51 7.53 – 1.60 8.39 – 1.26
Oral treatment
Minimum–maximum (median) 4–10 (7) 6–10 (8) 6–9 (7) 0.640 0.869 0.999 0.711
Mean – SD 7.00 – 2.10 7.73 – 1.49 7.21 – 0.98
Pc 0.215 0.623 0.025*
a
Friedman test.
b
Wilcoxon signed-rank test (Bonferroni corrected).
c
Mann–Whitney U test.
*P < 0.05; **P < 0.0.
OSDI, Ocular Surface Disease Index; TBUT, tear film break-up time.
 6 YILDIZ ET AL.

after the end of treatment, Pb

significantly better at 1 and 5 weeks after discontinuation of
the oral and topical treatments compared to the baseline
of treatment–5 weeks
1 Week after the end measurements (Table 4). Between-group analysis showed
that the mean eyelid debris score at 1 week after the end of

0.045*

0.034*
0.732

0.999
treatment was significantly better in the topical treatment
group compared with the oral treatment group (P = 0.014;
P < 0.05) (Table 4).
The mean OSDI scores, lissamine green staining scores, and
Schirmer test results showed improvements after both topical
Changes in the Brush Cytology Scores and the Nelson Grading After Oral and Topical Treatment

and oral treatments (Table 5). Improvement in the fluorescein

staining score was significant only in the topical treatment
Baseline: 5 weeks after the

group (P = 0.013). Between-group analyses showed that the

end of treatment, Pb

mean TBUT at 5 weeks after discontinuation of treatment was

significantly better in the topical treatment group compared
with the oral treatment group (P = 0.025).
0.110

0.840

0.104

0.472
Compared to the baseline values, changes in the mean
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brush cytology scores were significant in the topical treat-

ment group (P = 0.012) and the mean Nelson grading score
significantly improved only in the topical treatment group
(P = 0.023) (Table 6).
Baseline: 1 week after the
end of treatment, Pb

Discussion
0.999

0.124

0.999

0.287

Our results showed that both topical azithromycin and oral

azithromycin were effective in the treatment of MGD, how-
ever, topical treatment was more effective than oral treatment
in improving eyelid margin changes. Topical treatment was
also shown to be associated with longer cytological im-
provements that persist at least 5 weeks and with better sta-
bilization of the tear film, which is well documented by
0.012*

0.023*
0.058

0.156
Pa

showing longer TFBUT in the topical treatment group.

Although the exact cause of MGD is unclear, both in-
flammation and heavy colonization of ocular flora, including
5 Weeks after the
end of treatment

Staphylococcus epidermidis, Propionibacterium acnes, and S.

4.80 – 0.86

5.13 – 1.51

1.13 – 0.52

1.27 – 0.59
3–6 (5)

3–9 (5)

0–2 (1)

0–2 (1)

aureus, play an important role in the pathogenesis of the

0.745

0.483

disease. Microorganisms colonized more than normal release

lipolytic exoenzymes that produce highly irritating fatty acids
and cholesterol, which cause tear film instability, inflamma-
tion, and increased evaporation of the tears.23 Pharmacoki-
1 Week after the

netic features and tolerance of azithromycin add to its

end of treatment

5.67 – 0.72

4.67 – 0.72

1.67 – 0.49

1.20 – 0.41

potential value in treating MGD; a single dose of 1 g azi-

4–7 (6)

4–6 (5)

1–2 (2)

1–2 (1)
0.080

0.010

thromycin has been shown to provide prolonged high-level

tissue concentration. With a good intraocular penetration and
a long half-life time, azithromycin shows antimicrobial as
Wilcoxon signed-rank tests (Bonferroni corrected).

well as anti-inflammatory effects by suppressing the pro-

duction of proinflammatory mediators, including cytokines
5.67 – 0.98

5.67 – 1.45

1.60 – 0.51

1.53 – 0.52
Baseline

4–7 (6)

3–9 (6)

1–2 (2)

1–2 (2)

(TNFa and IL-1b), metalloproteinases (MMP-1, MMP-3, and

0.914

0.717

MMP-9), and chemokines.24–26 Oral 5-day azithromycin

treatment, as used in the current report, was shown to be
effective in the treatment of MGD. Moreover, it has been
(median)

(median)

(median)

(median)

shown that compared to the 1-month doxycycline regimen, 5-

Table 6.

day azithromycin treatment is associated with better overall

clinical response with a shorter duration of treatment.27
Supporting these findings, the oral treatment group in our
Minimum–maximum

Minimum–maximum

Minimum–maximum

Minimum–maximum

Mann–Whitney U test.

study showed significant improvement in the ocular symp-

Brush cytology score
Topical treatment

Topical treatment

toms and eyelid margin sings with well tolerance and com-
Friedman test.

pliance of oral azithromycin.

Oral treatment

Oral treatment
Mean – SD

Mean – SD

Mean – SD

Mean – SD
Nelson grading

In accordance with the previous reports, we found that topical

*P < 0.05.

azithromycin relieved sign and symptoms of MGD.16,17,28,29 In

the current report, we used the 1-month topical treatment pro-
tocol (1 drop twice daily for 3 days and then once daily for 4
Pc

Pc

b
a

weeks) as reported in the previous studies.16,17 In an earlier

 TOPICAL VS. SYSTEMIC AZITHROMYCIN FOR POSTERIOR BLEPHARITIS
report, the 1-month topical azithromycin treatment was shown to
be associated with a more pronounced and long-lasting im-
provement compared with the 3-day shorter course of treat-
ment.30 Like oral administration, prolonged high-level tissue
concentration of azithromycin has been shown in humans.
Conjunctival concentration of azithromycin more than 300 mg/
mL was reported after 7 days of therapy, with levels persisting
above 50 mg/mL for 5 days after stopping the drug.31 The effi-
cacy of topical azithromycin therapy for 1 month and oral
doxycycline therapy for 2 months has been compared. In that
study, changes in the signs and symptoms of MGD were eval-
uated and the meibomian gland excreta were collected and fur-
ther examined. Topical azithromycin was shown to be slightly
more effective in improving foreign body sensation and the sign
of plugging and secretion. Oral doxycycline needed longer use to
achieve the effect. Spectroscopic analysis of meibomian gland
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secretion showed that the 2 drugs changed the composition and
characteristics of meibum differently, suggesting they have
different mechanisms of action.17
The main feature that emphasized our work is the com-
parison of the 2 different methods of azithromycin adminis-
tration that were proven to be effective in the treatment of
MGD by different studies.14–16,18–20 In our study, although
both treatment methods are found to be effective, the results of
topical treatment group showed some superiority over those of
systemic treatment group, specifically better eyelid margin
changes, more stable tear film, and longer lasting conjunctival
cytological changes. These results may suggest that topical
administration of azithromycin may be associated with higher
targeted ocular tissue drug concentration, and therefore, better
anti-inflammatory and antimicrobial effectiveness compared
with the oral administration of azithromycin.
Author Disclosure Statement
No competing financial interests exist.
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 8 YILDIZ ET AL.

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