What is the safety and efficacy of ocular Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) compared to ocular antihistamines or a combination of both?

From the Guidelines

For the treatment of allergic conjunctivitis, ocular antihistamines are generally recommended as the first-line treatment, with ocular NSAIDs or combination therapy considered for more severe or persistent symptoms. Both ocular NSAIDs and antihistamines are effective for treating allergic conjunctivitis, but they work through different mechanisms and may be used alone or in combination depending on symptom severity 1. For mild to moderate allergic eye symptoms, an ocular antihistamine like olopatadine (0.1% or 0.2%), ketotifen (0.025%), or alcaftadine (0.25%) is typically the first-line treatment, used 1-2 times daily. These medications block histamine receptors, providing quick relief from itching and redness.

Key Considerations

• For more severe or persistent symptoms, especially when inflammation is prominent, an ocular NSAID such as ketorolac 0.5% (4 times daily) or nepafenac 0.1% (3 times daily) may be added to reduce inflammation by inhibiting prostaglandin synthesis.
• Combination therapy with both an antihistamine and NSAID can provide more comprehensive symptom relief in moderate to severe cases by addressing both the allergic and inflammatory components simultaneously.
• However, NSAIDs may cause stinging upon application and rarely corneal melting with prolonged use, so they should be used for shorter durations (typically 1-2 weeks) and with caution in patients with compromised corneas.
• Antihistamines generally have better safety profiles for long-term use but may cause mild dryness or irritation in some patients.

Recent Evidence

A more recent study from 2017 1 supports the use of combination therapy for improved symptom relief, although it notes that the addition of an intranasal antihistamine to an intranasal corticosteroid provides additional benefit in patients with moderate-to-severe seasonal allergic rhinitis. This suggests that combination therapy can be effective, but the specific agents and their routes of administration should be carefully considered based on the patient's symptoms and condition.

Safety and Efficacy

The safety and efficacy of ocular NSAIDs versus ocular antihistamines or combination of both should be evaluated based on the individual patient's needs and the severity of their symptoms. Ocular antihistamines are generally well-tolerated and effective for mild to moderate symptoms, while ocular NSAIDs or combination therapy may be necessary for more severe cases. It is essential to weigh the potential benefits and risks of each treatment option and to consider the most recent and highest-quality evidence when making treatment decisions 1.

From the Research

Safety and Effectiveness of Ocular NSAIDs versus Ocular Antihistamines or Combination of Both

• The provided studies do not directly compare the safety and effectiveness of ocular NSAIDs versus ocular antihistamines or a combination of both 2, 3, 4, 5, 6.
• However, the studies discuss the effectiveness of topical antihistamines and mast cell stabilizers in treating allergic conjunctivitis (AC) 2, 4, 5, 6.
• Topical dual-action antihistamines/MCS, such as olopatadine, azelastine, ketotifen, and epinastine, are commonly used to treat mild subtypes of AC 2.
• High-concentration olopatadine (0.77%) has been shown to have a longer duration of action and better efficacy on ocular itch compared to low-concentration olopatadine (0.2%) 2.
• Ketotifen fumarate and olopatadine HCl have dual action, offering a combination of antihistamine and mast-cell stabilizer mechanisms, and have been shown to be effective in treating seasonal allergic conjunctivitis (SAC) 5, 6.
• The expression rates of cell adhesion molecules and inflammatory markers in conjunctival surface cells were significantly reduced with ketotifen and olopatadine compared to artificial tear substitute (ATS) 5.
• Both ketotifen and olopatadine were well-tolerated and had comparable comfort ratings 5, 6.
• The most common adverse events reported were burning/stinging and headache 6.

Comparison of Ketotifen and Olopatadine

• A 30-day, randomized, double-masked, artificial tear substitute-controlled trial compared the clinical efficacy of topical ketotifen and olopatadine eye drops in patients with SAC 5.
• The results showed that both ketotifen and olopatadine were effective in reducing clinical scores, but ketotifen had a more pronounced effect on tearing and itching scores 5.
• A 3-week prospective, randomized, double-masked, parallel-group study compared ketotifen fumarate 0.025% ophthalmic solution and olopatadine hydrochloride 0.1% ophthalmic solution in patients with seasonal allergic conjunctivitis 6.
• The results showed that ketotifen had a higher responder rate and better global efficacy ratings compared to olopatadine 6.

Management of Ocular Allergy

• Ocular allergy is a frequent accompaniment of systemic allergy, and in some situations, ocular signs and symptoms are the most prominent features of allergic disease 3.
• The management of ocular allergy involves recognizing and differentiating it from other ocular conditions, and using medications such as antihistamines, mast cell stabilizers, and topical corticosteroids 3, 4.
• A proactive approach to managing ocular allergies, anticipating regional spring and fall allergen spikes, is needed for optimal management 4.
• A multifaceted treatment regimen comprising patient education, lifestyle modification, and topical medications may be required to manage ocular allergies effectively 4.