Prescription dry eye drops: ciclosporin, lifitegrast, steroids

There are three families of prescription drop used in dry eye, and they do different jobs. Ciclosporin is a long-game immunomodulator, taken for months, aimed at the chronic inflammation behind the disease. Lifitegrast is a different anti-inflammatory mechanism, studied over twelve weeks, with symptom improvement seen as early as two weeks. Corticosteroid drops are the fast, short-course option, used to break an inflammatory flare and then stopped.

All three sit on top of a base layer of lubricating drops rather than replacing it. None of them is chosen from an article. They are prescribed after an examination, by an ophthalmologist or an optometrist with prescribing rights, and each needs some form of monitoring while you are on it. What follows is what the published trials actually found, so that the conversation with your prescriber starts from the right place.

The base layer: lubricating drops

Before anything is prescribed, the unglamorous part has to be right. Lubricants do not treat the disease, but they buy comfort while slower treatments work, and getting the formulation wrong undermines everything above it.

The usual mistake is frequent use of a preserved drop. The DEWS II iatrogenic report records that topical medications can cause dry eye through allergic, toxic and immuno-inflammatory effects on the ocular surface, and that preservatives such as benzalkonium chloride may further aggravate it (Gomes 2017). If you are instilling drops more than about four times a day, preservative-free is the sensible default, and it is a change you can make yourself. The rest of the daily groundwork is set out in the daily dry eye routine.

Ciclosporin

What it does. Ciclosporin is an immunomodulator applied topically to damp down the T-cell-driven inflammation that keeps dry eye disease going, rather than to lubricate or to replace tears.

What the evidence shows. The pivotal work is two identical multicentre, randomised, double-masked, vehicle-controlled trials running six months, combined for analysis, in 877 patients with moderate to severe dry eye disease. Patients were treated twice daily with cyclosporin A ophthalmic emulsion at 0.05 per cent or 0.1 per cent, or with vehicle. Both concentrations gave significantly greater improvement than vehicle in two objective signs, corneal staining and categorised Schirmer values. The 0.05 per cent treatment also gave significantly greater improvement in three subjective measures: blurred vision, the need for concomitant artificial tears, and the physician's evaluation of global response to treatment. There was no dose-response effect, meaning the higher concentration was not better. The authors reported no significant topical or systemic adverse safety findings (Sall 2000).

Both trials were the manufacturer's own registration studies, as were the lifitegrast trials below. That does not make the results wrong, and regulators saw the full datasets, but the wording in the abstracts is the sponsor's.

Time to effect. The trials that support it ran for six months, which is a fair guide to the patience required. This is not a drop that tells you within a week whether it is working, and stopping at four weeks because nothing has happened is the most common way people waste a course of it.

Side effects. The published trial found no significant topical or systemic safety findings. Beyond that, burning or stinging on instillation is the complaint prescribers hear most often. The abstract does not break down which adverse events were most frequent, so ask your prescriber what to expect, and report it rather than quietly stopping, because there are ways to manage it.

Lifitegrast

What it does. Lifitegrast is an antagonist of lymphocyte function-associated antigen-1, developed to reduce inflammation in dry eye disease. Same broad target as ciclosporin, different mechanism.

What the evidence shows. The OPUS-3 trial was a twelve-week, phase III, randomised, double-masked, multicentre, placebo-controlled study. After a fourteen-day placebo run-in, 711 participants were randomised to lifitegrast ophthalmic solution 5.0 per cent or placebo twice daily for 84 days. The primary endpoint was change in eye dryness score, a 0 to 100 visual analogue scale. At day 84 the lifitegrast group improved significantly more than placebo, with a treatment effect of 7.16 points (95 per cent confidence interval 3.04 to 11.28). The same direction was seen at day 42 (9.32 points) and day 14 (7.85 points). Most treatment-emergent adverse events were mild to moderate in severity and no serious ocular adverse events were reported (Holland 2017).

The honest caveat. In the same trial, no statistically significant difference was found between the groups in the ocular discomfort score at day 84, day 42 or day 14. Eye dryness improved; that particular discomfort measure did not separate. A trial can move one symptom scale and not another, and it is worth knowing that before you form an expectation.

Time to effect. OPUS-3 reported improvement in the dryness score as early as day 14 (Holland 2017). The ciclosporin trials ran for six months and did not report an earliest effect, so the two cannot be ranked against each other.

Side effects. The abstract reports that most treatment-emergent adverse events were mild to moderate and that no serious ocular adverse events occurred, without breaking down which were most frequent. Ask your prescriber what to expect in the first week; the taste and instillation-site complaints people mention are best discussed in the consulting room, where they can be weighed against your own history.

Short-course corticosteroid drops

What they do. Corticosteroids suppress inflammation quickly and broadly. In dry eye they are used to settle a flare, or to make a surface comfortable enough that a slower treatment can be started, not as ongoing therapy.

What the evidence shows. A randomised, double-masked, placebo-controlled multicentre trial gave 64 patients with keratoconjunctivitis sicca and delayed tear clearance either loteprednol etabonate 0.5 per cent or vehicle, four times daily for four weeks, with review at two and four weeks and again two weeks after stopping. In subsets of patients with at least moderate clinical inflammation there was a significant difference between the treated and vehicle groups after two weeks of therapy. The difference did not reach statistical significance at four weeks, although the treated patients retained their improvement compared with vehicle. Both treatments were well tolerated, with similar frequency and type of adverse event. The authors concluded that use four times a day may be beneficial in patients who have keratoconjunctivitis sicca with at least a moderate inflammatory component (Pflugfelder 2004).

Why the course is short. Two well-known risks of prolonged topical corticosteroid use are a rise in intraocular pressure and, over longer periods, cataract formation. That is why courses are typically measured in weeks, why a pressure check is part of the deal, and why repeat prescriptions are not handed out casually. It is telling that in the trial above, safety was assessed by funduscopy, lens examination, biomicroscopy, visual acuity and Goldmann tonometry (Pflugfelder 2004). Those are precisely the things clinicians watch.

If you have an eye infection, have had eye surgery recently, have glaucoma or a family history of it, or notice any change in your vision, say so before any of these is prescribed, and speak to your optometrist or ophthalmologist promptly if it develops while you are on treatment.

How a prescriber chooses

The choice follows the assessment, not the other way round. DEWS II sets out a staged management algorithm applied step-wise according to severity, and found that distinguishing aqueous-deficient from evaporative disease is critical in selecting the strategy. The same review noted that many dry eye treatments lack the Level 1 evidence needed to support a firm recommendation (Jones 2017). Which is to say the prescriber is weighing imperfect evidence against your particular eyes, and that is a job for someone who has examined them. Where the shortage is of tears rather than oil, punctal plugs may come into the conversation too. If you have not had that examination, start with the tests that are actually used.

Availability, licensing and funding for all three differ substantially between countries, and the concentrations and formulations approved in one place are not always the same as in another. Ask locally rather than assuming what you have read online applies where you live.

The framing that matters: these are not products you select and then request. They are prescribed after an examination that establishes what type of dry eye you have and how severe it is, by an ophthalmologist or an optometrist with prescribing rights, and they are reviewed while you are on them. Go in with good questions rather than a preferred answer.

Frequently asked questions

How long does ciclosporin take to work for dry eye?

Longer than most people expect. The two pivotal randomised trials, in 877 patients with moderate to severe dry eye, ran for six months, and that is a reasonable guide to how patient you need to be. Judging it at four weeks is the most common reason a course gets abandoned early. Your prescriber will set a review point, so keep it.

How quickly do prescription dry eye drops start to work?

It depends on the drop and on what is measured, and none has been compared head to head. In its phase III trial, lifitegrast improved an eye dryness score by day 14. In a randomised trial of a corticosteroid, a difference appeared after two weeks in patients with at least moderate inflammation. The ciclosporin trials ran for six months and did not report an earliest effect. Your prescriber will set a review point; keep it rather than judging early.

Why can I not stay on steroid eye drops long term?

Two risks limit them: prolonged topical corticosteroid use can raise pressure inside the eye and, over longer periods, contribute to cataract formation. That is why courses run for weeks rather than months, why pressure checks and a lens examination form part of the follow-up, and why repeat prescriptions are not issued casually. Any course should be supervised by the prescriber who started it.

Do prescription drops replace artificial tears?

No. They sit on top of a base layer of lubrication rather than replacing it, and one trial measure of ciclosporin's benefit was a reduced need for concomitant artificial tears rather than none at all. If you instil drops more than about four times a day, preservative-free formulations are the sensible default, since preservatives such as benzalkonium chloride may aggravate the ocular surface.

Educational information only, not medical advice. References: Sall K, et al. Ophthalmology. 2000;107:631–639; Holland EJ, et al. Ophthalmology. 2017;124:53–60; Pflugfelder SC, et al. Am J Ophthalmol. 2004;138:444–457; Gomes JAP, et al. Ocul Surf. 2017;15:511–538; Jones L, et al. Ocul Surf. 2017;15:575–628.