Findings from a study published in Cornea evaluated the efficacy of topical 1% 5-fluorouracil (5-FU) in treating Demodex-associated blepharitis.
Give me some background first.
Ocular demodicosis is an overpopulation of Demodex folliculorum and brevis in the eyelash follicles and sebaceous glands, respectively, that can cause symptoms of blepharitis.
Until recently, the mainstay treatment for ocular demodicosis was eyelid hygiene with tea tree oil (TTO)-containing products—which often resulted in variable outcomes.
However, the FDA approval and launch of XDEMVY (lotilaner ophthalmic solution) 0.25% have changed the treatment landscape for ocular demodicosis—paving the way for more targeted treatments.
Bring in 5-FU.
5-FU is a chemotherapeutic agent with antimetabolite activity that blocks DNA and RNA synthesis and is often used topically to treat ocular surface squamous neoplasia (OSSN).
While treating conjunctival neoplastic lesions with topical 1% 5-FU, the research team observed that eyes with concurrent ocular demodicosis showed clinical improvement after two treatment cycles—sparking their interest in exploring its potential clinical utility further.
Now, talk about the study.
In this observational retrospective study, investigators reviewed the charts from 13 eyes of 13 individuals with conjunctival neoplastic lesions and concomitant Demodex lash infestation who received topical 1% 5-FU drops.
All patients were evaluated for ocular demodicosis after 2, 4, 6, and 8 cycles of 1% 5-FU.
Of note, one treatment cycle comprised of 1 week of eye drop application, 4 times per day in the affected eye followed by a 3-week treatment break.
Tell me more.
The mean age of the cohort was 68±14 years (range 30-84 years), and 92% of patients were male.
Participants underwent slit-lamp examination at every follow-up visit, and clinical photographs of the lash line were taken after treatment initiation.
A subset of patients also had lashes that were epilated bilaterally and microscopically analyzed for the presence of Demodex mites prior to and following treatment initiation.
Findings?
In all 13 patients, a notable reduction in cylindrical dandruff (CD) was observed via slit-lamp examination in the treated eye after two cycles of 5-FU.
Further, there was complete resolution of CD in 10 of 13 treated eyes compared with 0 resolution of cylindrical dandruff in the fellow untreated eyes (P=0.0001).
In the six patients who received epilation, the lashes from the treated eye showed no Demodex mites, while lashes from the fellow untreated eye demonstrated persistent presence of Demodex mites.
How does 5-FU target ocular demodicosis?
There are two potential explanations for the clinical effect of 5-FU on ocular demodicosis:
- 5-FU may have a direct toxic effect on Demodex mites by inhibiting thymidylate synthase, an essential enzyme in DNA replication, which hinders Demodex proliferation.
- 5-FU may have an indirect effect on Demodex mites by changing the local microbiome—making the environment unsuitable for survival.
Expert opinion?
“It is thus encouraging that in our study, 5-FU improved clinical signs in all patients, with a sustained response up to 55 months post-therapy,” noted the study authors.
Limitations?
Due to the observational and retrospective study design, symptom improvement was not investigated or quantified.
Additionally, because the findings were incidental during the treatment course for a conjunctival neoplastic lesion, the baseline clinical photographs were focused on the ocular surface instead of the eyelashes.
Consequently, baseline pretreatment photographs of the lash line of the treated eyes were unavailable in some patients.
Take home.
These findings provide evidence that topical 1% 5-FU is efficacious in reducing cylindrical dandruff—the chief clinical sign of Demodex-associated blepharitis.
Next steps?
Per the research team, “We would suspect that the next steps would be to formulate a product which contains 5-FU and that perhaps would be placed on the lids only and obviate the direct topical ocular surface contact.”
They also recommended further studies to confirm these findings, assess the potential use of 5-FU as a treatment ingredient, and determine the ideal concentration, vehicle, and method of use.