Cyclosporine for dry eye disease appears to be efficacious at all levels and the choice of which formulation to use usually depends on tolerability and affordability. Tolerability hinges primarily on the vehicle, which varies among different products.
My clinic is busier than ever managing dry eye, as our already-strong demand for services has swelled in response to patients’ COVID-19-era increased screen time, work-from-home arrangements and elevated stress. People need help. During this past year, I have implanted more punctal plugs, prescribed more dry eye medications and scheduled more in-office dry eye procedures than ever before.
Cyclosporine is a well-established stalwart of long-term management for dry eye disease (DED). Ophthalmologists have trusted it for years as an effective immunomodulator that alleviates dry eye symptoms without major negative side effects.
We have several options for cyclosporine: Cequa (0.09%, Sun Ophthalmics), Restasis (0.05%, Allergan) and the compounded Klarity-C Drops (0.1%, Imprimis). Several more are in the pipeline, including generic Restasis, CyclASol (0.1%, Novaliq), Ikervis (0.1%, Santen Pharmaceutical) and OTX-CSI ophthalmic insert (0.36 mg, Ocular Therapeutix).
How do we choose which one to use? Although the concentrations range from 0.05% to 0.1%, I have found cyclosporine to be efficacious at all levels, with some subtle differences. The choice usually comes down to tolerability of the formulation and affordability with patients’ insurance.
Vehicles and tolerability
As a topical ophthalmic agent, cyclosporine poses several challenges. Firstly, it is a hydrophobic, lipophilic molecule, which makes it difficult to penetrate the aqueous layer and reach the eye. Secondly, cyclosporine can cause burning or stinging on instillation.
As a result, manufacturers need to formulate a vehicle that achieves the penetration required for efficacy, produces minimal side effects and feels comfortable for chronic use – a notoriously difficult set of challenges. The tolerability of different cyclosporine formulations hinges primarily on the vehicle, which varies among different products.
Although I tend to favour products with an established track record of comfort, some patients might tolerate one better than another. Therefore, I offer samples to let them find what works best.
Because I have used Restasis—which has an anionic castor oil-in-water emulsion vehicle1—for many years, I know to expect patients to be comfortable with its long-term use. As it has been around a long time, Restasis is also covered by most insurance plans, making it easier for patients to obtain and resulting in fewer call backs to the office.
My patients also have tolerated Cequa well, which has a nanomicelle-based solution. Commercial patients can obtain Cequa at its lowest price through a specialty pharmacy, so we check with patients in advance to see if that is a convenient arrangement.
The third current option, Klarity-C Drops, has a chondroitin sulfate, glycerin and dextran-based solution.2 This compounded option can be the most cost-effective choice for some patients. However, in my limited experience, it also seems to be more difficult for patients to tolerate, with greater burning and stinging upon instillation than the other options available.
Looking at the pipeline, I do not yet know which vehicle generic cyclosporine will use. But my general concern with generics is always how true they are to the original formulation.
Prescriptions for long-term management
I use both cyclosporine and lifitegrast (Xiidra, Novartis) as part of long-term management plans for dry eye. With cyclosporine, my best candidates have chronic dry eye symptoms and possibly wear contact lenses, so they need long-term relief from inflammation.
It can take up to 3 months for cyclosporine to build up the concentration required for full efficacy, so I tend to choose it for patients who can patiently await some improvement. For more severe cases, I also utilise a steroid during the cyclosporine induction period, such as loteprednol etabonate ophthalmic suspension 0.25% (Eysuvis, Kala Pharmaceuticals) which can be used on-label for short term treatment of dry eye signs and symptoms.
In addition, my patients who have dry eye secondary to autoimmune conditions such as Sjogren’s syndrome or rheumatoid arthritis tend to respond very well to cyclosporine. From a clinical standpoint, it has been great to see an emphasis on DED result in options for long-term treatment.
Whether we get the long-lasting effects of a dry eye procedure, prescribe an immunomodulator or, optimally, offer some combination of both therapies, the options allow ophthalmologists to tailor effective, economical and comfortable care to every patient.
Lisa M. Nijm, MD, JD
Dr Nijm is a corneal surgeon and medical director of Warrenville Eye Care and LASIK, Warrenville, Illinois, United States, founder of MDNegotiation.com and an assistant clinical professor of ophthalmology at the University of Illinois Eye and Ear Infirmary, Chicago, Illinois. She is a consultant for Allergan, Kala Pharmaceuticals, Novartis, Ocular Therapeutix and Sun Pharmaceuticals.