Blurred Lines: The Interaction and Overlap of Ocular Allergy and Dry Eye

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Topical cetirizine empowers physicians and patients alike to take control of itchy eyes associated with allergic conjunctivitis with minimal risk of causing unwanted dryness.

By Joseph Terrence Kavanagh, MD

Allergic conjunctivitis and dry eye disease (DED) are the most common ocular surface disorders, with each—or both—being associated with anywhere from a mild to a severe impact on patients’ daily life. Although these two clinical entities are different, a growing body of research indicates that there are shared pathogenic pathways that may blur the lines between the two conditions. Ocular allergy causes alterations of the tear film, the epithelial barrier, and corneal innervation, which can pave the way to DED. On the other hand, DED may worsen allergic reactions in some predisposed patients. Ocular allergy and DED should therefore be considered as reciprocal predisposing conditions, with ocular surface inflammation as their common thread.1

Differentiating the two conditions can be problematic. One study showed that, in almost 700 patients presenting with symptoms of dryness or itch, 57.7% of the 194 with itch had clinically significant dryness and of the 247 who were dry, 45.3% had clinically significant itching.2 Redness was not a differentiator as 62% of the itch patients and 49% of the dry patients also had redness clinically.

For my DED patients who present with ocular allergy, I want to ensure that the treatment I prescribe does not make their underlying ocular surface dryness worse. Some antihistamines are associated with the signs and symptoms of dry eye due to their antimuscarinic action and may serve to compound preexisting dry eye.3 Zerviate (cetirizine ophthalmic solution 0.24%; Eyevance Pharmaceuticals), is a highly specific H1 receptor antagonist with no anti-muscarinic receptor activity. It is the first new molecule to be Food and Drug Administration approved for the treatment of ocular itch associated with allergic conjunctivitis in 10 years, is comprised of the same active ingredient found in Zyrtec (Johnson & Johnson). The fact that Zyrtec is the number one oral antihistamine recommended by allergists provides eye care practitioners and patients with confidence.4

The second reason cetirizine drops are effective for patients with DED is that the vehicle contains a combination of glycerin and hydroxypropyl methylcellulose (Hydrella), the same soothing components contained in artificial tears. In phase 3 clinical trials, cetirizine was associated with a mean comfort score of <1 at all time points (scale of 1 to 10 with 1 being very comfortable), and only one subject out of 511 (0.2%) reported dry eyes.5,6 The medication has a neutral pH of 7, designed to reduce burning or stinging upon instillation.

A third advantage of cetirizine drops is how effective they’ve proven to quickly relieve ocular itching. The drug was shown to have a rapid onset of action at 3 minutes following allergen exposure and was effective in patients with moderate and severe allergic conjunctivitis.7 In two phase 3 efficacy studies, subjects assigned to treatment with cetirizine ophthalmic solution experienced significant reduction of ocular itch compared with vehicle.8

Write it Out
Patients with allergic conjunctivitis will often experience some relief by self-treating with artificial tears, which will wash away some of the allergens on the surface of the eye. Most will need additional relief, however, and may try over-the-counter (OTC) non-steroidal anti-inflammatory drops or antihistamines like ketotifen or olopatadine—which also come in varying strengths. These drops may not provide the needed relief or may exacerbate dry eye, as the latter products are not as selective H1 receptor antagonists as prescription cetirizine ophthalmic solution.

Patients may lack the knowledge to select the appropriate OTC drops and, if patients are shopping for medications, we as physicians lose control over what product the patent is using. The allergy aisle is crowded and confusing: vasoconstrictors may be labeled as anti-allergy drops and some products have preservatives that can exacerbate the symptoms of dry eye and not address the ocular itchiness of allergic conjunctivitis. By writing a prescription, we eliminate the guesswork and ensure patients are being treated with the most appropriate therapy for their condition. Patients also feel more empowered with a prescription because they know that they are getting the exact medication that their physician has chosen for their specific condition.

Year ‘Round Allergy Season
Prescription Zerviate represents a powerful new tool for our management of patients with allergic conjunctivitis. Texas, where I practice, ranks among the top 10 states for allergy prevalence in all months—there is no “allergy season.” I estimate that as many as 25% to 40% of my dry eye patients have some degree of allergic conjunctivitis. I will often instill the drop in the exam lane so that patients with allergic conjunctivitis can experience rapid relief from their ocular itch and added confidence that what I am prescribing will work for them.

Dr Kavanagh is a board-certified ophthalmologist and a fellowship-trained glaucoma specialist in practice at Eye Associates of South Texas. He is a clinical assistant professor of ophthalmology at the UTHSC San Antonio. Dr. Kavanagh may be reached at [email protected].

Dr Kavanagh discloses that he is a speaker.


  1. Leonardi A, Modugno RL, Salami E. Allergy and Dry Eye Disease. Ocul Immunol Inflamm. 2021;5:1-9. doi: 10.1080/09273948.2020.1841804.
  2. Hom MM, Nguyen AL, Bielory L. Allergic conjunctivitis and dry eye syndrome. Ann Allergy Asthma Immunol. 2012;108(3):163-6. doi: 10.1016/j.anai.2012.01.006.
  3. Liu H, Farley JM. Effects of first and second generation antihistamines on muscarinic induced mucus gland cell ion transport. BMC Pharmacol. 2005; 5: 8. doi: 10.1186/1471-2210-5-8.
  4. Johnson & Johnson Consumer Companies, I. Zyrtec The #1 Allergist Recommended Brand*, Available from: http://www.multivu.com/ assets/52078/documents/Zyrtec-fact-sheet-99-original.pdf. 2011.
  5. Malhotra RP, Meier E, Torkildsen G, et al. Safety of cetirizine ophthalmic solution 0.24% for the treatment of allergic conjunctivitis in adult and pediatric subjects. Clin Ophthalmol. 2019;13:403-413.
  6. Data on file. Fort Worth, TX: Eyevance Pharmaceuticals LLC.
  7. Zerviate [package insert]. Fort Worth, TX: Eyevance Pharmaceuticals LLC; 2020.
  8. Meier EJ, Torkildsen GL, Gomes PJ, Jasek MC. Phase III trials examining the efficacy of cetirizine ophthalmic solution 0.24% compared to vehicle for the treatment of allergic conjunctivitis in the Conjunctival Allergen Challenge model. Clin Ophthalmol. 2018;12:2617-2628. DOI: 10.2147/OPTH.S185835