Written and Medically Reviewed by Dr Leigh Plowman, Optometrist (updated Sept 2022)
Do you have dry eyes? Dry eyes often occurs when the normal tear film that covers your eyes is out of balance.
This may be because the right ingredients are out of balance. Or because your eyes lack enough moisture.
Dry eye disease causes a vicious cycle of inflammation. You may notice symptoms like redness, grittiness, soreness, blurred vision, filmy vision or tired eyes.
Xiidra (lifitegrast, Restasis, Cequa and Ikervis (all cyclosporin) are anti-inflammatory eye drops.
Unlike cortisone or steroid eye drops, these prescription drops do not alter the intraocular pressure of your eyes. They are safe to use in the long term.
2022 Update:
Until mid-2022, there were no comprehensive comparisons between Xiidra, Restasis, Cequa and Ikervis.
There are currently no direct studies comparing each of the four dry eye medications.
Then a comprehensive review study was published in Ophthalmology and Therapy in mid-2022.
The study authors reviewed all of the published evidence about Xiidra, Restasis, Cequa and Ikervis
The study conclusions were as follows:
- Each medication was shown to be effective and safe in reducing dry eye symptoms and signs
- Variability was seen between starting treatment and when improvement was starting to be noticeable
- Symptom improvements and the extent of improvement varied depending on individual person’s dry eye causes
In summary, your doctor may recommend trying one medication for a length of time. You may switch to another medication and find that it is more effective for you.
What are the differences between Xiidra vs Restasis?
Xiidra (lifitegrast) was approved by the FDA in 2016. It is a lymphocyte function-associated antigen 1 (LFA-1) antagonist.
In particular, it targets part of the immune system that affects inflammation. These cells, called T-helper cells, become activated in dry eye disease.
They respond by releasing signals to nearby cells that increase inflammation. This signalling produces a wave of more inflammation as more cells are recruited.
Lifitegrast blocks a protein called LFA-1 from attaching onto ICAM-1 on the T-helper cells. This reduces activation and inflammation in dry eye disease.
Xiidra is taken twice daily for dry eye disease (approximately twelve hours apart). You may start to notice a difference after two weeks. However, most people find that it takes around six to twelve weeks to notice a difference.
Restasis (cyclosporin) was one of the first anti-inflammatory drops to be FDA approved for dry eye disease. It was approved in 1983.
Cyclosporin works to reduce inflammation in dry eyes. It does this through Calcineurin Inhibitor immunosuppression. Cyclosporin increases tear production and goblet cell density.
According to this article, Cyclosporin may also reduce T-cell activation and chemical signalling factors.
Cyclosporin is taken twice daily for dry eye disease. Some people notice a difference with Restasis within two months. Other people say that it takes up to six months to notice a difference.
Newer formulations of cyclosporin
Cequa and Ikervis are newer formulations of cyclosporin.
Cyclosporin itself is lipophilic (lipid loving, water hating). Cequa and Ikervis drops use coatings of nano-particles to help them travel through the tear film and reach the surface of the eye.
The theory is that these coatings make Cequa or Ikervis more effective than compounded cyclosporin or Restasis.
Conditions treated
The Tear Film & Ocular Surface Society (TFOS) Dry Eye Workshop II (DEWS II) recommended anti-inflammatory treatments for dry eyes.
When artificial tears or environmental changes don’t bring relief, anti-inflammatories can help. The American Academy of Ophthalmology suggests anti-inflammatory drops in their Preferred Practice Pattern.
Here is a table summarising some of the anti-inflammatory medical therapies for dry eyes:
| Brand Name | Generic Name | Manufacturer | Preparation | Additional Information |
| Lotemax SM | Loteprednol etabonate 0.38% | Bausch & Lomb | Gel drops | 0.38% approved for three times daily dosage 0.5% approved for four times daily dosage |
| Lotemax Gel | Loteprednol etabonate 0.5% | Bausch & Lomb | Gel drops | 0.38% approved for three times daily dosage 0.5% approved for four times daily dosage |
| Lotemax Ointment | Loteprednol etabonate 0.5% | Bausch & Lomb | Ointment | 0.38% approved for three times daily dosage 0.5% approved for four times daily dosage |
| Inveltys | Loteprednol etabonate 1.0% | Kala | Suspension | Twice daily |
| Alrex | Loteprednol etabonate 0.2% | Bausch & Lomb | Suspension | Twice to four times daily |
| Pred Forte | Prednisolone acetate 1% Phenylephrine | Allergan/Abbvie | Suspension | Twice to four times daily |
| FML | Fluorometholone alcohol 0.1% | Allergan/Abbvie | Suspension | Twice to four times daily |
| Restasis | Cyclosporine 0.05% | Allergan/Abbvie | Emulsion | Twice daily |
| Cequa | Cyclosporine 0.09% | Sun Pharma | Emulsion | Twice daily |
| Xiidra | Lifitegrast 5% | Novartis | Solution | Twice daily |
| Ikervis | Cyclosporine 0.1% | Santen | Emulsion | One drop at night |
| Eyesuvis | Loteprednol etabonate 0.25% | Kala | Solution | Four times per day for two weeks |
| Doxycycline Minocycline | Tablets | Generic | Oral | 50mg per day for at least two months |
| Azithromycin | Tablets | Generic | Oral | 500mg on day one 250mg on day two to fourteen 250mg every other day for day fifteen to twenty-eight |
| Azasite | Azithromycin 1% | Akorn | Solution | Twice daily |
Why causes inflammation in dry eyes?
Inflammation normally helps the eyes to protect and defend themselves from infection or debris.
However, irritation to the eyes (either from the environment or the eyes themselves) or microbes on the surface of the eye can trigger inflammation.
Dry eye disease of various causes enter the same cycle of inflammation, according to Review of Optometry.
Initially Cytokines, MMPs and Chemokines are released. Then T Cells migrate in response.
They release inflammation, which drives more Cytokines, MMP and Chemokines. This causes a vicious cycle of inflammation.
In Dry Eye Disease, inflammation can cause damage and can self-perpetuate if left untreated.
How is Cyclosporin different to Lifitegrast?
The exact mechanisms of cyclosporin and lifitegrast are unknown. However, we know so far that:
Cyclosporin works by
- Reduces T-Cell activation (blocking CD11a which is a subunit of LFA-1)
- Decreasead IL2 & IL6
- Decreased epithelial and goblet cell apoptosis
Xiidra works by
- LFA-1 antagonist (reduces binding of LFA-1 to ICAM-1)
- Reduces inflammation in a bi-pathway manner (afferent and efferent)
- Inhibited cytokines (IFNs)
- Less corneal barrier disruption
- Greater conjunctival goblet cell density
| Xiidra | Restasis | Cequa | Ikervis | |
| Dosing | One drop twice per day (about twelve hours apart) | One drop twice per day (about twelve hours apart) | One drop twice per day (about twelve hours apart) | One drop at night |
| FDA Approval Year | 2016 | 2002 | 2018 | n/a |
| Common Side Effects | Blurred vision Headache Eye irritation Itchy eyes Metallic taste in mouth (dysgeusia) Redness | Burning sensation Redness Tearing Discomfort Itchiness Stinging Blurred vision | Mild eye pain Redness Irritation Watery eyes Blurred vision Feeling like something is in your eye. | Discomfort Irritation Watery eyes Redness Blurred vision |
| When do you start to notice a difference? | May be as soon as two weeks Usually around six to twelve weeks | May be as soon as two months Usually around six months | May be as soon as one month Usually around four to six months | May be as soon as one month Usually around four to six months |
| Cost | List $554 per box | List $586 per box | Lis t $507 per box | n/a |
Commonly asked questions:
Which is better: Xiidra, Restasis, Cequa or Ikervis?
Currently, there have been no direct comparison studies between these prescription drops.
Xiidra was recently reviewed in a scientific journal. They looked at twelve-week studies of Xiidra. They found that it was effective for people with moderate-to-severe dry eyes and who had corneal fluorescein staining.
Restasis (cyclosporin A) has shown to be effective in a review article.
How long does it take for Xiidra to work?
You may notice that Xiidra starts to have an effect in as little as two weeks. However, most people take around six-to-twelve weeks to notice a difference.
What’s the difference between Restasis and Xiidra eye drops?
Restasis and Xiidra are both anti-inflammatory drops. Both come in individual preservative-free vials.
They work differently to reduce inflammation in the eye due to dry eyes. However, the exact way they work requires more research. Some people try Restasis first for around 6-12 months. Then switch to Xiidra.
What is the cost of Xiidra, Restasis, Cequa and Ikervis?
A variety of factors, such as what kind of health insurance you have, will determine how much you will pay for prescription eye drops.
The list price is approximately
Xiidra– $554 per box
Restasis– $586 per box
Cequa– $507 per box
Ikervis– (Available in Europe, Asia and Australia. USA currently not available.)
Can you switch from Restasis to Xiidra?
Yes, it is possible to switch. Some people may take four weeks to start to notice a difference, and around twelve weeks for full-effect.
Can Xiidra cure dry eyes?
Xiidra can make a significant difference for people with dry eyes. Some people find that they rarely need to use artificial tears. Other people use Xiidra as part of a holistic approach to treating dry eyes.
Xiidra does not cure other causes of dry eyes. For example, Blepharitis, Meibomian Gland Dysfunction or other medical causes of dry eyes.
It is important to work with a dry eye doctor to identify other dry eye causes. Find a dry eye specialist here
Can I use Xiidra or Restasis with other treatments?
Inflammation is one of the key factors in dry eyes. If there is a small amount of inflammation, Xiidra and Restasis can work well.
Sometimes, stronger inflammation control is required. Xiidra and Restasis can be important parts of a bigger plan to treat inflammation.
For example, this may include a short course of cortisone drops followed by Xiidra or Restasis.
Intense Pulsed Light can also reduce inflammation in the eyes. IPL can also help to treat Allergic Conjunctivitis and Meibomian Gland Dysfunction.
Biological treatments can include Regener-Eyes, Autologous Serum or Amniotic Membranes placed over the cornea.
Dr David Kading, O.D. explains how anti-inflammatory drops help, and what to do if you need more anti-inflammatory effect:
Will I need to use Xiidra, Restasis, Cequa or Ikervis for life?
Inflammation is a key factor in dry eye disease. Left untreated, inflammation drives increased dry eyes and damage to your eyes.
Anti-inflammatory prescription medication such as Xiidra, Restasis, Cequa or Ikervis is designed for long term usage.
Talk with your doctor about the right prescription medication for you.
Need a dry eye specialist near you? Search our database of specialists.