Allergic contact dermatitis (ACD) of the eyelid and/or periocular area is one of the most common causes of eczematous eruptions in this region,1,2 followed by atopic dermatitis, seborrheic dermatitis, and psoriasis. There appears to be a predilection for the female sex.1 Undoubtedly, ACD can be a diagnostic challenge if a targeted and comprehensive medical history is not conducted, including the patient's personal and family history of interest, the current or past presence of clinical signs of another dermatosis, and the possible chronological relationship between the application of ophthalmic products (both prescription and over-the-counter drugs). Although we do not have specific epidemiological data of ACD after the use ophthalmic products, recent reports have confirmed an increase in the number of cases reported in recent years, both due to known allergens, such as benzalkonium chloride, and new molecules as well.

There are differences in the prescription of active ingredients according to the country, suggesting different sensitization rates for marketed molecules, which is why we through it was more interesting for our field to review the ophthalmic products prescribed nationwide.

Undoubtedly, the biggest challenge in studying these patients is to put together a complete battery of allergens that allows for proper patch testing. Although the trend is to use unmodified marketed products (without separating their different components - active ingredient(s), excipients), the truth is is that the interpretation of reactions must be done with caution since this methodology does not conclude which allergen is responsible for sensitization. Hence the importance of having complete series of allergens fully available, or collaboration from the manufacturer.

The objective of this article is to review the most relevant literature on ophthalmic product-induced eyelid ACD, providing the main allergens and vehicles based on the type of pharmacological class to study them through patch testing. Therefore, a bibliographic search was conducted including articles considered most relevant (case series or more comprehensive or updated literature reviews, and reports of interest on commonly used drugs not included in the reviews) published in the past 10 years in the PubMed database as of May 2023. The keyterms used in the search section were (eyelid contact dermatitis) / (palpebral dermatitis) / (periocular dermatitis) / (periorbital dermatitis) AND (ophthalmic medications) / (ophthalmic products) / (eye products) / (eyedrops). Information on the composition of marketed ophthalmic products and their use was obtained by entering the trade names of the corresponding drugs into the Spanish Agency of Medicines and Medical Devices (CIMA) official website. The sections of this article are categorized based on the therapeutic classes by 3 independent reviewers, who manually selected and reviewed the articles, drafted the text, and eventually conducted a final joint review.

Lesions are mainly located on the eyelid and/or periocular area, usually unilateral (except when treatment is applied to both eyes), and primarily in the form of dermatitis (in its different phases: acute, subacute, and chronic). Itching is usually the main symptom. Some patients also describe a burning or foreign body sensation.2 Conjunctivitis can be a clinical form of ophthalmic ACD, although suspicious sensitization component will likely be evaluated by an ophthalmologist, and it will be considered essential when considering referral to dermatology for patch testing.

The clinical presentation of dermatitis can be identified through different patterns already described in the literature,3 where the drip pattern seems to be the most characteristic of all. Erythematous-scaly plaques are usually much more frequent than the presence of vesiculation. In case of vesiculation, a possible herpes simplex virus infection should be ruled out. Differential diagnoses can include diseases such as rosacea, dermatomyositis, or preseptal cellulitis.3 The self-transported (hand-face), airborne,4 and connubial forms5 of dermatitis should be considered in these patients, whose contact source of the causative allergen is usually not of ophthalmological origin. The absence of lesion improvement despite proper treatment with anti-inflammatories (topical corticosteroids and/or calcineurin inhibitors) should raise suspicion of corticosteroid sensitization,6 or excipients sensitization such as propylene glycol.7

In addition to the Spanish standard series, the Spanish Working Group of Research in Contact Dermatitis and Cutaneous Allergy (GEIDAC)8 recommends adding the allergens included in the problematic product(s) (eye drops, solutions, etc.). Most active ingredients are not marketed, therefore, in general, the “unmodified” product per se is often used.

Classic preservatives such as benzalkonium chloride, propylene glycol, EDTA, or thimerosal, among others, are available in marketed preparations, although they are not all are present in different ophthalmic preparations.

Late readings past 96hours (preferably at 7 and 14 days) are recommended since corticosteroids or aminoglycosides can show positive reactions at a later point in time.9 The Repeat Open Application Test (ROAT) with eye drops on the antecubital flexure twice a day for 2 to 3 weeks may be very useful, if neccesary. ROAT10 can be performed before patch testing to confirm suspicion of ACD to it, or after patch testing, when, although they still test negative for the product, suspicion of sensitization remains high. The use test (applying the ophthalmic product as instructed) may be useful when both the ROAT and patch testing test negative,11 even in cases of conjunctivitis.12 The prick test can be interesting to study latex hypersensitivity as the causative agent for eyelid ACD.13 The scratch test may be useful in selected cases.14 Collaboration from the manufacturer when requesting the product composition on an individual basis is usually scarce, which complicates patient study even more. The ophthalmic series commercialized by MartiTor includes a total of 20 allergens (Table 1),15 and may be useful in some cases, although some active ingredients and/or excipients are still missing, meaning that a complete ophthalmology series cannot be created.

Since the list of marketed ophthalmic products is extensive, information has focused on eye drops and ophthalmic ointments alone. Table 2 lists the different trade names with their active ingredients and excipients.

We can add the following list of allergens to ophthalmic products: makeup, facial moisturizers, facial cleansers (preservatives, surfactants), shampoo (perfumes, preservatives, surfactants), hair conditioner, false eyelashes (acrylates, colophony), hair dye (paraphenylenediamine), sunscreens, eyelash curlers (nickel, rubber), makeup sponges (rubber), jewelry (metals), acrylic nails (self-applied or ectopic dermatitis), non-acrylic nails (toluene formaldehyde resin), plants (airborne), and connuvial dermatitis (usually due to cosmetic ingredients). Anamnesis remains the key point for an adequate approach to patch testing. Table 3 shows the list of allergens most frequently patched in ACD due to ophthalmic products.

ACD due to ophthalmic products can be a significant diagnostic challenge that requires familiarity with commercially available allergens. Proper preparation of allergens and knowing the most important excipients will be key for proper study through patch testing. Collaboration with the ophthalmologist is important to assist in decision-making regarding treatment changes, avoiding possible drug-related cross-reactions, and eventually leading the dermatologist to provide individualized information of special interest for each particular case.

None declared.