For Mild Thyroid Eye Disease, Oral Doxycycline May Improve Symptoms

Doxycycline may be a treatment option for patients with mild thyroid-associated ophthalmopathy.

Doxycycline may be an effective treatment option for mild cases of thyroid-associated ophthalmopathy (TAO), according to a study published in JAMA Ophthalmology. Patients in a trial experienced superior symptom improvement when managed with oral doxycycline than with a placebo. 

In the multicenter randomized double-masked placebo-controlled parallel-group study ( Identifier: NCT02203682), researchers investigated the efficacy of doxycycline 50 mg daily vs placebo in patients with mild TAO between July 2013 and December 2019. The study included 2 phases: a screening period (2 to 6 weeks) and a treatment/follow-up period (12 weeks). Participants were assessed for thyroid and ophthalmic function throughout the study. The primary outcome was the rate of improvement in the composite indicator of mild TAO signs and symptoms at week 12: eyelid aperture, proptosis, ocular motility, and Graves ophthalmopathy-specific quality-of-life (GO-QOL). 

A total of 100 patients enrolled with 50 participants assigned to the doxycycline group (mean [SD] age, 38.1 years [9.5 years]; 82% women) and 50 to the placebo group (mean [SD] age, 35.6 years [8.8 years]; 68% women. At week 12 for the intention-to-treat (ITT) population, the doxycycline group had a higher number of patients demonstrating improvement, as determined by the composite indicators compared with the placebo group (38% vs 16%; difference, 22% [95% CI, 5.0-39.0); P =.01). Sensitivity analysis of the per protocol (n=98), had similar results with a higher improvement rate for the doxycycline group compared with primary analysis (39.6% vs 16%; difference 23.6% [95% CI, 25.7-53.4]; P =.009). There was 1 doxycycline-related adverse event compared with none in the placebo group. 

Doxycycline is relatively affordable and is a promising therapy to tackle the public health burden associated with TAO.

Treatment with doxycycline for 12 weeks showed a higher improvement rate of mild TAO signs and symptoms compared with placebo. However, the short study duration of follow-up and small sample size suggests longer-term studies with larger cohorts to confirm the results for patients similar to those enrolled in this trial. 

“Doxycycline is relatively affordable and is a promising therapy to tackle the public health burden associated with TAO,” the researchers explain.

The study’s limitations were that the 12-week treatment period did not allow for long-term outcomes to be assessed and the efficacy and safety of higher doses of doxycycline in patients with TAO could be explored in a future study.


Pan Y, Chen YX, Zhang J, et al. Doxycycline vs placebo at 12 weeks in patients with mild thyroid-associated ophthalmopathy. JAMA Ophthalmol. Published online September 29, 2022. doi:10.1001/jamaophthalmol.2022.3779