What are the alternative therapies to VEVYE (cyclosporine 0.1% preservative‑free ophthalmic solution) for treating dry eye disease?

Alternatives to VEVYE (Cyclosporine 0.1%) for Dry Eye Disease

For moderate to severe dry eye disease, the primary alternatives to VEVYE include cyclosporine 0.05% (Restasis), lifitegrast 5% (Xiidra), and short-term topical corticosteroids, with the choice depending on disease severity and patient response to initial therapy. 1

First-Line Alternatives for Moderate Dry Eye

Cyclosporine 0.05% (Restasis)

• Cyclosporine 0.05% represents the most established alternative, demonstrating success rates of 74% in mild, 72% in moderate, and 67% in severe dry eye disease. 1
• This formulation works by preventing T-cell activation and inflammatory cytokine production while inhibiting mitochondrial pathways of apoptosis 1
• Standard dosing is one drop in each eye twice daily, with the option to decrease to once daily after 1 full year of therapy in select patients 1
• Ocular burning occurs in approximately 17% of patients but is generally well tolerated, with prolonged improvement lasting a median of 20 months after discontinuation following 23 months of treatment 1
• FDA approval was based on trials showing a statistically significant 10-mm increase in Schirmer test results at 6 months in 15% of cyclosporine-treated patients versus 5% of vehicle-treated patients 1, 2

Lifitegrast 5% (Xiidra)

• Lifitegrast blocks the interaction between LFA-1 and ICAM-1, preventing T-cell activation, and improves both signs and symptoms of dry eye disease. 1, 3
• FDA-approved in 2016, lifitegrast demonstrates benefit in both objective signs (corneal and conjunctival staining) and subjective symptoms (eye dryness score and ocular discomfort) over 3 months 3, 4
• This agent can be used as an alternative to cyclosporine for patients refractory to artificial tears 1, 3
• The most common side effects include eye irritation, discomfort, blurred vision upon application, and unusual taste sensation (dysgeusia) 4
• While safe over 12 months of use, long-term effects beyond this period remain unknown 3

Short-Term Topical Corticosteroids

• Topical corticosteroids decrease ocular irritation symptoms and corneal fluorescein staining but must be limited to 2-4 weeks of use to avoid complications including infections and increased intraocular pressure. 1
• These agents are particularly useful for refractory or severe cases when rapid anti-inflammatory effect is needed 1

Advanced Treatment Alternatives for Severe Disease

Punctal Occlusion

• Punctal occlusion using temporary silicone plugs or permanent thermal/laser cautery can be considered for tear retention after optimizing topical therapy 1
• Plug-containing regimens increase tear wetness initially and may be superior when combined with cyclosporine therapy 5
• Combination therapy with punctal plugs and cyclosporine produces the greatest overall improvements compared to either treatment alone 5

Autologous Serum Eye Drops

• Autologous serum eye drops are beneficial for severe dry eye, particularly in Sjögren's syndrome, improving ocular irritation symptoms and corneal/conjunctival staining 1
• Autologous plasma rich in growth factors can also be beneficial in severe cases 1

Oral Secretagogues

• Oral pilocarpine (5mg four times daily) and oral cevimeline stimulate tear production in patients with Sjögren's syndrome 1
• These medications improve visual function and reduce symptoms but may cause side effects like excessive sweating 1

Varenicline Nasal Spray (Tyrvaya)

• Varenicline is a highly selective nicotinic acetylcholine receptor agonist administered as a nasal spray that works as a neuroactivator of tear film production. 1
• It activates nicotinic acetylcholine receptors on the trigeminal nerve within the nasal mucosa, stimulating the lacrimal functional unit to produce natural tears 1
• This agent can be considered for moderate to severe dry eye in patients with inadequate response to or intolerance of traditional eye drops 1

Perfluorohexyloctane (Miebo)

• Perfluorohexyloctane can be considered for direct evaporation control in patients with evaporative dry eye 1
• Clinical trials show consistent improvements in both signs and symptoms as early as 2 weeks, with sustained efficacy over 12 months 1

Essential Adjunctive Therapies

Environmental and Behavioral Modifications

• Eliminating exposure to cigarette smoke, which adversely affects the lipid layer of the tear film 1
• Humidifying ambient air and avoiding air drafts by using side shields on spectacles 1
• Lowering computer screens below eye level and scheduling regular breaks every 20 minutes 1

Treatment of Underlying Conditions

• Treating concurrent blepharitis or meibomian gland dysfunction is essential, as these conditions coexist in the majority of dry eye patients. 1
• Daily lid hygiene with warm compresses for 5-10 minutes and gentle massage to express meibomian gland secretions 1
• In-office physical heating and expression of meibomian glands using device-assisted therapies such as LipiFlow or TearCare system 1

Preservative-Free Artificial Tears

• Preservative-free artificial tears containing methylcellulose or hyaluronate remain first-line therapy and should be used at least twice daily 1
• These should be used more than four times daily when needed, as preserved tears cause ocular surface toxicity with frequent use 1

Critical Pitfalls to Avoid

• Failing to recognize when to advance therapy from artificial tears to anti-inflammatory agents in moderate to severe disease leads to inadequate treatment. 1
• Overuse of preserved artificial tears (more than 4 times daily) causes ocular surface toxicity 1
• Extended use of topical corticosteroids beyond 2-4 weeks can lead to complications including infections and increased intraocular pressure 1
• Neglecting underlying blepharitis or meibomian gland dysfunction exacerbates dry eye and must be treated concurrently 1
• Purchasing over-the-counter eye drops independently is not recommended, as many contain preservatives or vasoconstricting agents that worsen dry eye 1