Azithromycin for Meibomian Gland Disease

NCT03953118 | Terminated Phase 4 Results DMC FDA Drug

• 1 other identifier: 17-23877
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to elucidate the effectiveness of oral azithromycin in treating symptomatic dry eye syndrome secondary to Meibomian gland dysfunction.

Conditions

Dry Eye; Neuropathic Eye Pain; Ocular Microbiome; Depression, Anxiety

Outcome Measures

Primary Outcomes (2)

• Ocular Surface Disease Index (OSDI) Questionnaire

  Ocular surface disease index - used to evaluate the degree of dry eye symptoms. Scores will range from 0 to 48, where 48 indicates severe dry eye.

  Baseline to 1 month

• Ocular Surface Disease Index (OSDI) Questionnaire

  Ocular surface disease index - used to evaluate the degree of dry eye symptoms. Scores will range from 0 to 48, where 48 indicates severe dry eye.

  Baseline to 3 months

Secondary Outcomes (8)

• Ocular Surface Microbiome Testing

  Baseline to 1 month

• Ocular Surface Microbiome Testing

  Baseline to 3 months

• Dry Eye Questionnaire 5 (DE-5)

  Baseline to 1 month

• Dry Eye Questionnaire 5 (DE-5)

  Baseline to 3 months

• Neuropathic Pain Inventory for the Eye (NPSI-E)

  Baseline to 1 month.

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Drug: Placebo Oral

Azithromycin

ACTIVE COMPARATOR

Drug: Azithromycin Oral Product

Interventions

Azithromycin Oral Product DRUG

Oral azithromycin dosed at 1 gram per week for 3 weeks

Also known as: Zithromax

Azithromycin

Placebo Oral DRUG

Oral placebo tablet

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Symptomatic Meibomian gland disease, defined as patient-reported ocular surface symptoms such as dryness, grittiness, foreign body sensation, or eye fatigue in combination with clinically identifiable Meibomian gland disease with Grade 2 or greater involvement on the Meibomian Gland Grading Scale (Section XV, item 2).
• OSDI Score greater than or equal to 20
• Ability to give informed consent

You may not qualify if:

• Age less than 18 years
• Allergy or intolerance to oral azithromycin or topical dexamethasone
• Allergy or intolerance to the preservatives used in topical ophthalmic 0.1% dexamethasone: sodium bisulfite, phenylethyl alcohol, benzalkonium chloride
• History of prolonged QT interval, history of torsades des pointes, congenital long QT syndrome, bradyarrhythmias, heart failure
• Patients currently taking medications that prolong the QT interval (Table 1)
• Aqueous deficiency dry eye defined as Schirmer's strip testing without anesthesia with £ 5mm of tears on two separate tests.
• Ocular surface inflammatory disease, including cicatrizing conjunctivitis, graft versus host disease, Stevens Johnson syndrome
• Atopic disease with ocular involvement
• Limbal stem cell deficiency
• Oral or topical ophthalmic antibiotic use within the last 90 days
• Oral prednisone use \>5mg per day
• Topical ophthalmic steroid use within the past 30 days
• Topical ophthalmic anti-inflammatory (including non-steroidal anti-inflammatory medications, lifitegrast, or cyclosporine) use within the past 30 days
• Patients who are currently pregnant, planning on becoming pregnant during the study period, or currently breastfeeding.

Sponsors & Collaborators

• University of California, San Francisco: lead

Study Sites (1)

University of California San Francisco

San Francisco, California, 94143, United States

Location

Related Publications (26)

• Pflugfelder SC. Prevalence, burden, and pharmacoeconomics of dry eye disease. Am J Manag Care. 2008 Apr;14(3 Suppl):S102-6.

  PMID: 18452369 BACKGROUND

• The epidemiology of dry eye disease: report of the Epidemiology Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf. 2007 Apr;5(2):93-107. doi: 10.1016/s1542-0124(12)70082-4.

  PMID: 17508117 BACKGROUND

• Schaumberg DA, Nichols JJ, Papas EB, Tong L, Uchino M, Nichols KK. The international workshop on meibomian gland dysfunction: report of the subcommittee on the epidemiology of, and associated risk factors for, MGD. Invest Ophthalmol Vis Sci. 2011 Mar 30;52(4):1994-2005. doi: 10.1167/iovs.10-6997e. Print 2011 Mar. No abstract available.

  PMID: 21450917 BACKGROUND

• Foulks GN, Bron AJ. Meibomian gland dysfunction: a clinical scheme for description, diagnosis, classification, and grading. Ocul Surf. 2003 Jul;1(3):107-26. doi: 10.1016/s1542-0124(12)70139-8.

  PMID: 17075643 BACKGROUND

• Knop E, Knop N, Millar T, Obata H, Sullivan DA. The international workshop on meibomian gland dysfunction: report of the subcommittee on anatomy, physiology, and pathophysiology of the meibomian gland. Invest Ophthalmol Vis Sci. 2011 Mar 30;52(4):1938-78. doi: 10.1167/iovs.10-6997c. Print 2011 Mar. No abstract available.

  PMID: 21450915 BACKGROUND

• King-Smith PE, Bailey MD, Braun RJ. Four characteristics and a model of an effective tear film lipid layer (TFLL). Ocul Surf. 2013 Oct;11(4):236-45. doi: 10.1016/j.jtos.2013.05.003. Epub 2013 Jul 12.

  PMID: 24112227 BACKGROUND

• Lane SS, DuBiner HB, Epstein RJ, Ernest PH, Greiner JV, Hardten DR, Holland EJ, Lemp MA, McDonald JE 2nd, Silbert DI, Blackie CA, Stevens CA, Bedi R. A new system, the LipiFlow, for the treatment of meibomian gland dysfunction. Cornea. 2012 Apr;31(4):396-404. doi: 10.1097/ICO.0b013e318239aaea.

  PMID: 22222996 BACKGROUND

• Lee H, Chung B, Kim KS, Seo KY, Choi BJ, Kim TI. Effects of topical loteprednol etabonate on tear cytokines and clinical outcomes in moderate and severe meibomian gland dysfunction: randomized clinical trial. Am J Ophthalmol. 2014 Dec;158(6):1172-1183.e1. doi: 10.1016/j.ajo.2014.08.015. Epub 2014 Aug 13.

  PMID: 25128594 BACKGROUND

• Prabhasawat P, Tesavibul N, Mahawong W. A randomized double-masked study of 0.05% cyclosporine ophthalmic emulsion in the treatment of meibomian gland dysfunction. Cornea. 2012 Dec;31(12):1386-93. doi: 10.1097/ICO.0b013e31823cc098.

  PMID: 23135530 BACKGROUND

• Macsai MS. The role of omega-3 dietary supplementation in blepharitis and meibomian gland dysfunction (an AOS thesis). Trans Am Ophthalmol Soc. 2008;106:336-56.

  PMID: 19277245 BACKGROUND

• Deinema LA, Vingrys AJ, Wong CY, Jackson DC, Chinnery HR, Downie LE. A Randomized, Double-Masked, Placebo-Controlled Clinical Trial of Two Forms of Omega-3 Supplements for Treating Dry Eye Disease. Ophthalmology. 2017 Jan;124(1):43-52. doi: 10.1016/j.ophtha.2016.09.023. Epub 2016 Nov 3.

  PMID: 27817918 BACKGROUND

• Hosseini K, Lindstrom RL, Foulks G, Nichols KK. A randomized, double-masked, parallel-group, comparative study to evaluate the clinical efficacy and safety of 1% azithromycin-0.1% dexamethasone combination compared to 1% azithromycin alone, 0.1% dexamethasone alone, and vehicle in the treatment of subjects with blepharitis. Clin Ophthalmol. 2016 Aug 10;10:1495-503. doi: 10.2147/OPTH.S110739. eCollection 2016.

  PMID: 27570444 BACKGROUND

• Greene JB, Jeng BH, Fintelmann RE, Margolis TP. Oral azithromycin for the treatment of meibomitis. JAMA Ophthalmol. 2014 Jan;132(1):121-2. doi: 10.1001/jamaophthalmol.2013.5295. No abstract available.

  PMID: 24201556 BACKGROUND

• Yoo SE, Lee DC, Chang MH. The effect of low-dose doxycycline therapy in chronic meibomian gland dysfunction. Korean J Ophthalmol. 2005 Dec;19(4):258-63. doi: 10.3341/kjo.2005.19.4.258.

  PMID: 16491814 BACKGROUND

• Ta CN, Shine WE, McCulley JP, Pandya A, Trattler W, Norbury JW. Effects of minocycline on the ocular flora of patients with acne rosacea or seborrheic blepharitis. Cornea. 2003 Aug;22(6):545-8. doi: 10.1097/00003226-200308000-00011.

  PMID: 12883348 BACKGROUND

• Wladis EJ, Bradley EA, Bilyk JR, Yen MT, Mawn LA. Oral Antibiotics for Meibomian Gland-Related Ocular Surface Disease: A Report by the American Academy of Ophthalmology. Ophthalmology. 2016 Mar;123(3):492-6. doi: 10.1016/j.ophtha.2015.10.062. Epub 2015 Dec 23.

  PMID: 26707417 BACKGROUND

• Watters GA, Turnbull PR, Swift S, Petty A, Craig JP. Ocular surface microbiome in meibomian gland dysfunction. Clin Exp Ophthalmol. 2017 Mar;45(2):105-111. doi: 10.1111/ceo.12810. Epub 2016 Sep 7.

  PMID: 27473509 BACKGROUND

• Giamarellos-Bourboulis EJ. Macrolides beyond the conventional antimicrobials: a class of potent immunomodulators. Int J Antimicrob Agents. 2008 Jan;31(1):12-20. doi: 10.1016/j.ijantimicag.2007.08.001. Epub 2007 Nov 1.

  PMID: 17935949 BACKGROUND

• Liu Y, Ding J. The combined effect of azithromycin and insulin-like growth factor-1 on cultured human meibomian gland epithelial cells. Invest Ophthalmol Vis Sci. 2014 Aug 14;55(9):5596-601. doi: 10.1167/iovs.14-14782.

  PMID: 25125598 BACKGROUND

• Liu Y, Kam WR, Ding J, Sullivan DA. Effect of azithromycin on lipid accumulation in immortalized human meibomian gland epithelial cells. JAMA Ophthalmol. 2014 Feb;132(2):226-8. doi: 10.1001/jamaophthalmol.2013.6030. No abstract available.

  PMID: 24357250 BACKGROUND

• Igami TZ, Holzchuh R, Osaki TH, Santo RM, Kara-Jose N, Hida RY. Oral azithromycin for treatment of posterior blepharitis. Cornea. 2011 Oct;30(10):1145-9. doi: 10.1097/ICO.0b013e318207fc42.

  PMID: 21849891 BACKGROUND

• Haque RM, Torkildsen GL, Brubaker K, Zink RC, Kowalski RP, Mah FS, Pflugfelder SC. Multicenter open-label study evaluating the efficacy of azithromycin ophthalmic solution 1% on the signs and symptoms of subjects with blepharitis. Cornea. 2010 Aug;29(8):871-7. doi: 10.1097/ICO.0b013e3181ca38a0.

  PMID: 20508503 BACKGROUND

• Luchs J. Azithromycin in DuraSite for the treatment of blepharitis. Clin Ophthalmol. 2010 Jul 30;4:681-8. doi: 10.2147/opth.s6370.

  PMID: 20689782 BACKGROUND

• Schiffman RM, Christianson MD, Jacobsen G, Hirsch JD, Reis BL. Reliability and validity of the Ocular Surface Disease Index. Arch Ophthalmol. 2000 May;118(5):615-21. doi: 10.1001/archopht.118.5.615.

  PMID: 10815152 BACKGROUND

• Korb DR, Blackie CA. Meibomian gland diagnostic expressibility: correlation with dry eye symptoms and gland location. Cornea. 2008 Dec;27(10):1142-7. doi: 10.1097/ICO.0b013e3181814cff.

  PMID: 19034129 BACKGROUND

• Meadows JF, Ramamoorthy P, Nichols JJ, Nichols KK. Development of the 4-3-2-1 meibum expressibility scale. Eye Contact Lens. 2012 Mar;38(2):86-92. doi: 10.1097/ICL.0b013e318242b494.

  PMID: 22249431 BACKGROUND

MeSH Terms

Conditions

Dry Eye Syndromes; Depression; Anxiety Disorders

Interventions

Azithromycin

Condition Hierarchy (Ancestors)

Lacrimal Apparatus Diseases; Eye Diseases; Behavioral Symptoms; Behavior; Mental Disorders

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals

Limitations and Caveats

Study terminated due to lack of funding prior to data collection for outcome measures and adverse events. There are no data to report.

Results Point of Contact

• Title: Julie Schallhorn, MD
• Organization: University of California San Francisco CA

julie.schallhorn@ucsf.edu

415-514-1922

Study Officials

• Julie Schallhorn, MD, MS

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

• Thuy Doan, MD, PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 27, 2018
• First Posted: May 16, 2019
• Study Start: September 1, 2019
• Primary Completion: July 1, 2021
• Study Completion: July 1, 2021
• Last Updated: August 6, 2025
• Results First Posted: August 6, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)