Is Azithromycin by Mouth Better than Doxycycline by Mouth for Dry Eyes?

Many patients fly in to see me every year in a quest to find relief for debilitating neuropathy and dry eye symptoms. Many of these patients have become world’s experts in dry eye treatments due to this quest as neuropathy and dry eye can wreak havoc on one’s life and loved ones.

Recently a wonderful patient shared her research with me on her experience with Pulsed Dose of Azithromycin. This really helped the pressure she had behind her eyes. While she is not sure the pressure is Not due to sinusitis, her meibomian gland dysfunction could explain her symptoms.
She found a pulse dose of Azithromycin (Zpack) worked very well after she had to stop oral doxycycline 20mg per day.

She noted a study below from 2015 (Ref2).

Likely the reason why most eye doctors do not prescribe oral azithromycin is because of the following:
1. The below study has not been reproduced to my knowledge.
2. Concern for GI gut flora: Azithromycin at this does is an antibiotic and will alter gut flora and long term issues with this are still being debated and investigated. Doxycycline 20mg per day works as an anti-inflammatory and does not affect gut flora according to multiple papers (Ref1)
3. The cost of 1-month treatment with doxycycline is almost 50% more than 5-day treatment with oral azithromycin, though long term it might equal out.
4. We could increase antibiotic resistance by giving oral Azithromycin pulses. Thus when we really need Azithromycin, it may not work. This is a concern.

Still some patients may want to try an oral pulse of Azithromycin if they cannot tolerate Doxycycline. 


1.  2005 Nov;32(11):1163-9.

Long-term treatment with sub-antimicrobial dose doxycycline has no antibacterial effect on intestinal flora.



The purpose of this study was to determine if a 9-month regimen of sub-antimicrobial doxycycline (20 mg, bid) had an effect on either the intestinal or the vaginal microflora.


A total of 69 periodontally diseased subjects were randomized to receive drug or placebo control for a 9-month period. Stool specimens and vaginal swabs were collected at baseline and after 3 and 9 months of therapy. Samples were examined for total anaerobic counts, opportunistic pathogens, and doxycycline-resistant (>or=4 microg/ml) bacteria. All isolates that survived sub-culture were identified and their susceptibilities determined to six antibiotics. Analyses were performed to determine if treatment differences were present.


The only statistically significant differences (p<0.05) between the two treatment groups occurred in the doxycycline-resistant counts at the baseline sample period for the faecal samples. This imbalance was before treatment initiation and the administration of the study drug. No between-treatment differences were detected at either the 3- or 9-month sample period either in the predominant bacterial taxa present or in their antibiotic susceptibilities.


There was no evidence that sub-antimicrobial doxycycline treatment exerted an effect on the composition or doxycycline resistance level of either the faecal or the vaginal microflora.

Oral azithromycin versus doxycycline in meibomian gland dysfunction: a randomised double-masked open-label clinical trial

  1. Mohsen Bahmani Kashkouli1
  2. Ali Jalili Fazel1
  3. Victoria Kiavash1
  4. Marzieh Nojomi2
  5. Leila Ghiasian3

  1. Epidemiology and Community Medicine DepartmentIran University of Medical SciencesTehran, Iran

  2. Eye Research Center, Rassoul Akram Hospital, Iran University of Medical SciencesTehran, Iran
  1. Correspondence toDr Mohsen Bahmani Kashkouli, Eye Research Center, Rassoul Akram Hospital, Sattarkhan-Niayesh St, Tehran 14455-364, Iran;


Background/aims To assess the efficacy and safety of oral azithromycin compared with oral doxycycline in patients with meibomian gland dysfunction (MGD) who had failed to respond to prior conservative management.
Methods 110 patients (>12 years old) with MGD were randomly assigned to receive either oral 5-day azithromycin (500 mg on day 1 and then 250 mg/day) or 1-month doxycycline (200 mg/day). They also continued eyelid warming/cleaning and artificial tears. A score comprising five symptoms and seven signs (primary outcome) was recorded prior to treatment and at 1 week, and 1 and 2 months after treatment. Total score was the sum of both scores at each follow-up. Side effects were recorded and overall clinical improvement was categorised as excellent, good, fair or poor based on the percentage of change in the total score.
Results Symptoms and signs improved significantly in both groups (p=0.001). While improvement of symptoms was not different between the groups, bulbar conjunctival redness (p=0.004) and ocular surface staining (p=0.01) were significantly better in the azithromycin group. The azithromycin group showed a significantly better overall clinical response (p=0.01). Mild gastrointestinal side effects were not significantly different between the groups except for the second visit, when the doxycycline group had significantly more side effects (p=0.002).
Conclusions Although both oral azithromycin and doxycycline improved the symptoms of MGD, 5-day oral azithromycin is recommended for its better effect on improving the signs, better overall clinical response and shorter duration of treatment.

PMCID: PMC4138220
PMID: 22668581

Topical Azithromycin and Oral Doxycycline Therapy of Meibomian Gland Dysfunction: A Comparative Clinical and Spectroscopic Pilot Study

Corresponding author: Douglas Borchman, Ph.D., 301 E Muhammad Ali Blvd, Louisville, KY 40202, 502-852-7435 (phone) 502-852-7450 (fax), ude.ellivsiuol@namhcrob
Shopping Cart