Clinicians have several options in their treatment toolbox for chronic but a new study suggests oral antibiotics may not be a particularly effective choice and can cause side effects at both high and low doses.

The investigation reviewed two randomized controlled trials that compared oral antibiotics with placebo in 220 adult participants with chronic blepharitis, including staphylococcal, seborrhoeic or MGD.

One United States-based study, which was funded by a pharmaceutical company, enrolled 70 subjects with blepharitis and facial rosacea. Over a three-month period, individuals took either oral doxycycline (40mg once a day) or a placebo.

The other investigation was a three-arm randomized control trial based in South Korea that evaluated the effect of high-dose (200mg twice a day) and low-dose (20mg twice a day) doxycycline vs. placebo taken for a month. A total of fifty participants with chronic MGD were placed in each study arm.

The two studies didn’t evaluate the same outcome measures, so the current investigation couldn’t conduct a meta-analysis, directly comparing the findings. Additionally, neither study considered the number of bacteria in the study eyes before or after treatment, quality of life measures or the costs and benefits of the treatments.

One of the studies suggested oral doxycycline had little to no effect on subjective symptoms based on OSDI scores and bulbar conjunctival hyperemia.

The three-arm paper showed that oral doxycycline may have slightly improved the number of symptoms in those who took the high and low dose antibiotic regimens, in addition to increasing the proportion of participants with symptom improvement, but the investigators cautioned the evidence was inconclusive.

The South Korean study evaluated aqueous tear production by Schirmer’s test and tear film stability by measuring TBUT at one month.

“We found very low certainty evidence that oral doxycycline may improve these clinical signs,” researchers wrote in their paper.

The estimated MD in Schirmer’s test scores after one month of treatment was 4.09mm in the high-dose doxycycline group vs. the placebo group, and 3.76mm in the low-dose doxycycline group vs. the controls. The estimated MD in TBUT after one month was 1.58 seconds when comparing the high-dose doxycycline subjects with those who took the placebo and 1.70 seconds in the low low-dose doxycycline group vs. the controls. Although there was a noted improvement in these scores, their clinical importance remains uncertain, researchers said.

Of note: the South Korean study suggested that oral doxycycline could increase the incidence of serious side effects and found the number of unwanted effects was more acute in the high‐dose group.

Specifically, 18 (39%) participants in the high‐dose doxycycline group, eight (17%) in the low-dose group and three (6%) out of 47 participants in the placebo group experienced serious side effects.

One of the investigations reported a case of migraine and five cases of headache in the oral doxycycline group, and one case of non-Hodgkin's lymphoma in the placebo group. Still, the investigators suggested the certainty of evidence for adverse events was very low.

“There was insufficient evidence to draw any meaningful conclusions on the use of oral antibiotics for chronic blepharitis. Very low certainty evidence suggests that oral antibiotics may improve clinical signs but may cause more adverse events,” researchers wrote in their paper.

Further trials are needed to provide high quality evidence on the use of oral antibiotics in the treatment of chronic blepharitis, they added.