Doxycycline demonstrates short-term effectiveness for treating mild thyroid-associated ophthalmopathy


A team of researchers reported that oral doxycycline was effective, at least in the short term, for treating patients diagnosed with mild thyroid-associated ophthalmopathy.

A team of Chinese researchers, led by Yuan Pan, MD, PhD, reported that oral doxycycline was effective, at least in the short term, for treating patients diagnosed with mild thyroid-associated ophthalmopathy (TAO).1

Pan is from the Department of Ocular Immunology, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, China.

Even mild TAO negatively can impact patients’ quality of life, but there are no current clinical guidelines for its treatment.

Because doxycycline has been shown to be beneficial for treating mild TAO, Pan and colleagues conducted a placebo-controlled, multicenter, randomized, double-masked trial to determine the effectiveness of doxycycline after 12 weeks of therapy for mild TAO.

One hundred patients with mild TAO, in which the orbital soft tissue was affected mildly, were included and enrolled from July 2013 to December 2019 at 5 centers in China.

The patients were randomized to either 50 mg of doxycycline (50 patients) or placebo (50 patients) once daily for 12 weeks. The main outcome measure was the rate of TAO improvement at the end of the study compared with baseline. The factors assessed by a composite indicator of eyelid aperture (reduction ≥ 2 mm), proptosis (reduction ≥ 2 mm), ocular motility (increase ≥ 8 degrees), and Graves ophthalmopathy-specific quality-of-life (GO-QOL) scale score (increase ≥ 6 points), Pan described.

12-week results of doxycycline

The mean patient age was 36.7 years; 75 were women and all were Asian.

At week 12, a 38% improvement rate was seen (19 of 50 patients) in the doxycycline group compared with 16% (8 of 50 patients) in the placebo group, a difference of 22% that reached significance (95% confidence interval [CI], 5.0-39.0; p = 0 .01) in the intention-to-treat population, the investigators noted.

The per-protocol sensitivity analysis showed similar results (39.6% in 19 of 48 patients vs 16.0% in 8 of 50 patients, a difference of 23.6%; 95% CI, 6.4-40.8; p = 0.009).

No adverse events except for 1 case of mild gastric acid regurgitation occurred in either group.

The results showed a significant improvement in the mild symptoms of TAO in patients actively treated with doxycycline.

“These findings support the consideration of doxycycline for mild TAO but should be tempered by recognizing the relatively short follow-up and the size of the cohort,” the investigators concluded.


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

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