Ocular rosacea is an inflammatory disease of the eyelids and ocular surface. Like the facial disease, the ocular condition is chronic and recurrent. Sequelae of ocular rosacea vary from mild to severe. Ocular rosacea may cause chronic eye redness, blepharitis, recurrent chalazia, dry eye, corneal erosion, corneal vascularization, and corneal ulceration. Rosacea affecting the cornea can result in vision loss.

Prescription eye drops and ointments can be used topically to control mild ocular rosacea. However, severe disease, or rosacea that is not well controlled with local treatments is treated systemically. The most commonly used systemic treatment for rosacea is the bacteriostatic antibiotic doxycycline. Rosacea treatment doses of doxycycline vary widely. Treatment-dose doxycycline for systemic infections is 100mg twice a day. However, as rosacea is considered an inflammatory disease, doxycycline is often dosed at what is termed, sub-microbial dose doxycycline (SDD). Initially introduced in the oral medicine literature, SDD are doses 40mg and lower because systemic administration at this dose does not appear to alter the oral mucosa flora or increase resistance rates when given long-term for periodontal disease. Whereas 100mg doxycycline, even when given short term, may increase the percentage of culturable nasopharyngeal flora that is resistant to doxycycline. The FDA does not categorize SDD an antibiotic, stating this dosing is expected to exhibit only anti-inflammatory activity.

Even though SDD is widely used for the treatment of rosacea, very little confirmatory data exists, to indicate if this dose alters any other systemic mucosa flora or increases antibiotic resistance rates. The classification of 40mg as "sub-microbial" has never been evaluated in patients diagnosed with ocular rosacea. Additionally, confirmation of a "sub-microbial" dose has not been investigated with more sophisticated genomics and resistance tools such as metagenomic deep sequencing (MDS). The goal of this proposal is to use MDS to determine whether SDD given to patients with ocular rosacea can be truly considered sub-microbial, or if a 40mg dose of doxycycline can in fact alter the microbiome of the conjunctiva and gut and increase resistance rates when prescribed for 8 weeks. The investigators plan to evaluate the effect of SDD on resistance and microbiome alteration through a randomized controlled masked trial.

This is a randomized, controlled, masked trial comparing sub-microbial dose doxycycline, treatment dose Doxycycline, and placebo in the treatment of ocular rosacea.

Participants will be recruited from the F.I. Proctor Foundation and the Ophthalmology clinics at the UCSF Wayne and Gladys Valley Center for Vision and consented for participation in an IRB-approved study protocol. Participants with a diagnosis of ocular rosacea (n=50) will be prospectively enrolled and randomized to one of three arms in a 2:2:1 fashion:

Arm A will receive submicrobial dose doxycycline (40mg) administered as 20mg twice day for 8 weeks Arm B will receive 200mg of oral doxycycline administered as 100mg twice a day for 8 weeks Arm C will receive a placebo twice a day for 8 weeks

Inclusion Criteria:

• Have symptomatic ocular disease attributed to ocular rosacea as the primary diagnosis
• Ability to give informed consent
• Be aged 18 years old or older

Exclusion Criteria:

• Have an active ocular or systemic infection
• Have a known allergy or intolerance to tetracycline antibiotics
• Have had prior use of oral antibiotics within the last three months
• Pregnancy or the possibility of becoming pregnant within the 8-week study medication timeline.

All patients will be masked to their SDD allocation and informed that they will be taking a pill by mouth twice a day. Participants taking 40mg doxycycline will be taking one 20mg doxycycline pill twice a day. Participants taking 200mg doxycycline will be taking 100mg twice a day. Participants allocated to placebo will be taking a placebo pill twice daily All examining physicians responsible for TBUT determination and ocular photography will be masked to patient allocation assignment. The study analyst only will have access to the randomization key.