Azithromycin and Dry Eye

Azithromycin eye drops for dry eye appear to help symptoms, but studies have been conflicting. Some studies show it works well but others show it does not really help patients long term (see bold in Reference 2).

Most of the studies I could find that say it does help are usually sponsored by the company. Also the use of Azasite is off label for dry eye and its adverse effects list “Dry Eye” as a side effect (see below).

Still I have a few patients who love this drop, despite it’s cost. It does not do any harm to the eye that we can see.

There is some data showing Azithromycin may help meibomian glands produce more oil (see Reference 3). I am still waiting for good trials to show it does provide good symptomatic relief beyond a few months as well.



Because clinical trials are conducted under widely varying conditions, adverse reaction
rates observed in one clinical trial of a drug cannot be directly compared with the rates
in the clinical trials of the same or another drug and may not reflect the rates observed
in practice.
The data described below reflect exposure to AzaSite in 698 patients. The population was
between 1 and 87 years old with clinical signs and symptoms of bacterial conjunctivitis.
The most frequently reported ocular adverse reaction reported in patients receiving AzaSite
was eye irritation. This reaction occurred in approximately 1-2% of patients. Other adverse
reactions associated with the use of AzaSite were reported in less than 1% of patients and
included ocular reactions (blurred vision, burning, stinging and irritation upon instillation,
contact dermatitis, corneal erosion, dry eye, eye pain, itching, ocular discharge, punctate
keratitis, visual acuity reduction) and non-ocular reactions (dysgeusia, facial swelling,
hives, nasal congestion, periocular swelling, rash, sinusitis, urticaria).

2. Assessment of efficacy of topical azithromycin 1.5 per cent ophthalmic
solution for the treatment of meibomian gland dysfunction
Clin Exp Optom 2018; 101: 18–22 DOI:10.1111/cxo.12557
Ozlem Balci MD
Gokhan Gulkilik MD
Department of Ophthalmology, Istanbul Medipol
University School of Medicine, Istanbul, Turkey
Submitted: 21 November 2016
Revised: 3 March 2017
Accepted for publication: 16 March 2017
Background: The aim was to evaluate the clinical efficacy of topical azithromycin 1.5 per
cent ophthalmic solution in treatment of the clinical signs and symptoms associated with
meibomian gland dysfunction (MGD).
Methods: In this retrospective study, 35 patients with MGD were treated with topical azithromycin
1.5 per cent ophthalmic solution for 30 days. Topical azithromycin 1.5 per cent
ophthalmic solution was prescribed twice daily for two days and then once daily for a total
of 30 days. Daily lid hygiene with dilute baby shampoo was instructed for all patients.
Patient total symptom score, meibomian gland grading score, Schirmer score with anaesthetic,
tear film break-up time (TFBUT) and corneal fluorescein staining score were evaluated
at baseline and after one and three months.
Results: Patient total symptom score, meibomian gland grading score, Schirmer score
with anaesthetic, TFBUT and corneal staining score reduced significantly from the baseline
to the first month (p < 0.05, for each); however, at the third month, there was no significant
difference from baseline in the meibomian gland grading score, Schirmer score
with anaesthetic, TFBUT and corneal fluorescein staining score (p > 0.05, for each).
Conclusion: These results demonstrate that topical azithromycin 1.5 per cent ophthalmic
solution appears effective in the short-term treatment of the clinical signs and symptoms
associated with MGD.

In our study, significant improvements
were achieved one month after topical azithromycin
1.5 per cent ophthalmic solution
in all clinical signs and symptoms associated
with MGD; however, the improvements
in clinical signs did not persist
during the three-month follow-up.

3.  2018 Jun;43(6):683-688. doi: 10.1080/02713683.2017.1418894. Epub 2017 Dec 28.

The Effect of Solithromycin, a Cationic Amphiphilic Drug, on the Proliferation and Differentiation of Human Meibomian Gland Epithelial Cells.



We previously discovered that azithromycin (AZM) acts directly on immortalized human meibomian gland epithelial cells (IHMGECs) to stimulate their lipid and lysosome accumulation and overall differentiation. We hypothesize that this phospholipidosis-like effect is due to AZM’s cationic amphiphilic drug (CAD) nature. If our hypothesis is correct, then other CADs (e.g., solithromycin [SOL]) should be able to duplicate AZM’s action on IHMGECs. Our purpose was to test this hypothesis.


IHMGECs were cultured in the presence of vehicle or SOL (2, 10, or 20 µg/ml) for up to 7 days under proliferating or differentiating conditions. Positive (epidermal growth factor and bovine pituitary extract for proliferation; AZM for differentiation) and negative (vehicle) controls were included with the experiments. IHMGECs were evaluated for cell number, neutral lipid content, and lysosome accumulation.


Our results demonstrate that SOL induces a rapid and dose-dependent increase in the accumulation of neutral lipids and lysosomes in HMGECs. The lysosomal effects were most prominent with the 10 and 20 µg/ml doses, and occurred earlier (i.e., 1 day) with SOL than with the AZM (10 µg/ml) control. The effects of SOL and AZM on IHMGEC differentiation were essentially the same after 3 days of culture. SOL did not influence the proliferation of HMGECs during a 7-day time period.


Our results support our hypothesis that SOL, a CAD, is able to reproduce AZM’s impact on lysosome and lipid accumulation, as well as the differentiation, of HMGECs. The effect of SOL on lysosome appearance was faster than that of AZM.

No financial disclosures available on the below paper:
 2018 May;34(4):365-372. doi: 10.1089/jop.2017.0095. Epub 2018 Mar 1.

Comparison of the Clinical Efficacy of Topical and Systemic Azithromycin Treatment for Posterior Blepharitis.



To compare the clinical efficacy of topical and oral azithromycin treatments for posterior blepharitis.


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.


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.


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.
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