Clinical Characteristics and Treatment of Dupilumab-Related Ocular Complications in Atopic Dermatitis Patients

Atopic dermatitis is diagnosed based on physical exam findings of circumscribed eczematous skin lesions that commonly involve the face and extremities and flexural regions. It is a heterogeneous disease that can be persistent or relapsing, with different morphological eruptions and regional manifestations in the body in different demographic groups.

For opthal purposes, it is important to note that conjunctivitis and eyelid dermatitis are a common manifestation and part of the 23 clinical signs and symptoms of the disease. It can lead to chronic periocular inflammation with resultant damage that can include eyelid malpositioning, keratitis, cicatricial conjunctivitis, as well as cataracts and glaucoma from long-term use of steroids.

In randomized clinical trials (RCT), dupilumab use was associated with a greater incidence of conjunctivitis compared to placebo in patients with AD. It has also been found to have higher relative risk of developing conjunctivitis in AD patients compared to other immunomodulatory treatments for AD, such as methotrexate, cyclosporine, and mycophenolate mofetil. Other ocular adverse effects reported in association with this medication include blepharitis, herpes simplex keratitis and herpes zoster ophthalmicus, and dry eye disease.

Tauqeer et al reported the largest case series to date of patients presenting initially to an academic ophthalmology practice with ocular or visual complaints and underlying AD actively being treated with dupilumab. They delineated the ophthalmologic exam findings in these patients, reported any underlying history of ophthalmologic conditions, detail the treatment approaches, and describes their follow-up and response to treatment. This will enable ophthalmologists to better understand the presentation of undifferentiated dupilumab-associated ocular disease and guide management.

Retrospective study of 19 dupilumab-treated AD patients seen for a new ocular complaint. Primary outcomes were specific ocular exam findings (conjunctival injection, corneal fluorescein staining, blepharitis, meibomian gland dysfunction (MGD)), treatments, and follow-up.

Nineteen dupilumab-treated AD patients were included. Median age was 47 years (range 18–73). Over half were women (11/ 19) and majority were Caucasian (13/19).

Symptom onset occurred at a mean of 99 days (range 23–520 days) from first dupilumab dose.

The most common symptoms were redness (63%), tearing (47%), and pruritus (37%). Most common ocular findings were conjunctival injection (75%) and corneal staining (60%).

Blepharitis was seen in about a third (30%), and 25% had MGD. Initially, 10% were observed without treatment, while 15% were treated with artificial tears alone.

Other treatments included antihistamine drops (20%) and steroid drops alone (15%).

In 40% of patients, a combination of steroids and various other topical eye drops were prescribed. Eighty-four percent (16/19) of patients were seen for follow-up. Steroid drops were required at follow-up in 3 out of 4 patients initially treated with antihistamines alone and in two-thirds of patients initially treated with artificial tears only. Mean followup period was 88 days (range 5–369). Dupilumab was discontinued in 31.5% (6/19) of patients; of those who discontinued, 3 restarted it later.

In this study of AD patients on dupilumab presenting with visual changes or ocular discomfort to an ophthalmology practice, there were high incidences of conjunctival injection with a papillary or follicular reaction, corneal punctate epithelial erosions, and MGD/blepharitis. Patients typically presented with symptoms of redness, pruritus, tearing; severe cases also had blurred vision and light sensitivity

As compared to most other similar case series, initial treatment in the study was typically conservative with observation, artificial tears, and antihistamine drops. This enables to show that in the majority of cases, conservative treatment failed to control symptoms, and topical steroid with or without anti-inflammatory treatments was invariably needed to control the ocular side effects. In this case series, authors found that a higher number of patients failed over-the-counter treatments and required subsequent topical prescription, highlighting the need for closer ophthalmologic evaluation of AD patients on dupilumab.

"In our experience, patients with dupilumab-associated ocular issues may have underlying MGD, which could potentially worsen. This suggests that patients with severe atopic dermatitis or a history of conjunctivitis should be evaluated by an ophthalmologist before dupilumab initiation to treat underlying predisposing conditions for ocular surface inflammation. Interestingly, the severity of conjunctivitis in patients with atopic dermatitis has been found to be correlated with the severity of their dermatitis, suggesting that these patients may be at highest risk. The continued use of dupilumab must be evaluated jointly by the ophthalmologist and dermatologist or allergist based on the ocular risk versus systemic benefit. Our finding that often topical anti-inflammatory therapies are required would demand closer monitoring by an ophthalmologist."

All physicians should be aware of the possibility of significant ocular surface adverse effects associated with dupilumab treatment, which can become debilitating. Given the findings seen in this case series, authors hypothesize that dupilumab may initiate or exacerbate ocular surface inflammation, due to underlying predisposition to ocular surface inflammation or due to atopy exacerbated by a drug-induced reaction. Supporting this hypothesis are findings from clinical trials of patients with underlying AD, where dupilumab use was significantly associated with higher incidence of conjunctivitis compared to placebo

In summary, the ocular manifestations of dupilumab-associated conjunctivitis can be severe and will often require immunosuppressive topical therapies. Identification of patients at higher risk is crucial and ophthalmologists should be aware of this important medication-induced condition and how to manage ocular complications in these patients.

Source: Tauqeer et al; Clinical Ophthalmology 2022:16 947–958