Water-free VEVYE® eye drops improve dry eye symptoms and adherence
The contents of this article are informational only and are not intended to be a substitute for professional medical advice, diagnosis, or treatment recommendations. This editorial presents the views and experiences of the author and does not reflect the opinions or recommendations of the publisher of Ophthalmology 360.
By Lauren Zimski, MD
Today’s ubiquitous use of computers, smartphones, and digital devices goes hand in hand with the escalating prevalence of dry eye disease (DED). In Denver, where I practice, the arid climate and high altitude further drive the need for an effective dry-eye solution. My practice is heavily populated by patients who have severe chronic dry-eye symptoms. By the time they show up in my clinic, many are at the end of their rope, having already tried numerous treatments without achieving satisfactory improvement, while others are just at the start of their journey in search of relief. Word-of-mouth referrals from satisfied dry eye patients have reconfigured my practice, which once included ophthalmic surgery and general ophthalmology, but now is exclusively focused on DED.
Helping these patients is extremely gratifying. DED is often linked to ongoing inflammation and, if left untreated, can cause symptoms like stinging, burning, or blurry vision. People with DED are significantly more likely to struggle with daily activities such as driving, reading, using a computer, or even watching television. These symptoms greatly impact quality of life, as well as productivity. Beyond the dreadful effects of chronic discomfort associated with DED is the fact that in many cases it can impact the quality of vision and lead to fluctuating vision, which can be particularly problematic after cataract and refractive surgery.
Effective Treatment
Given the pervasiveness of DED and the severe impact of its symptoms, my goal is to offer treatments that provide patients with the most relief in the shortest amount of time. The newest—and most effective—tool in my dry eye armamentarium is VEVYE® (cyclosporine ophthalmic solution, Harrow) 0.1%, which was approved for treatment of signs and symptoms of DED by the US Food and Drug Administration a little over a year ago.
Topical cyclosporine has an established decades-long efficacy and safety profile, and VEVYE improves on that because it is the first and only water-free cyclosporine eye drop. Over half of patients show benefit at day 15 compared to other cyclosporine formulations such as RESTASIS® (cyclosporine ophthalmic emulsion, AbvVie), which can take 6 months to see a benefit. With VEVYE, cyclosporine is dissolved in perfluorobutylpentane, a semifluorinated alkane, which provides a lower surface tension allowing rapid, even spreading over the corneal surface and better penetration of cyclosporine. Since it is not a water-based formula, there is no pH or osmolarity so there is no burning or stinging with use. Increased tolerability, in addition to its quick onset of action, improves patient compliance. A caveat is that because VEVYE doesn’t burn or sting, some of my patients don’t know if they got the drop in their eye initially; however, they get used to it quickly once they know what to expect.
Clinical Trial Evidence
Pooled data from 3 randomized (ESSENCE) studies involving almost 1,400 participants demonstrated that the majority of patients treated with VEVYE achieved clinically and statistically significant improvement in corneal staining or healing by day 15.1-3 Notably, 99.8% of patients reported no or only mild stinging or burning upon application.1,2 Results of an open-label extension (OLE) study revealed that VEVYE sustains improvement over 12 months and that participants saw an average 98% increase in tear production.3 Also, patients randomized to receive VEVYE in the ESSENCE-2 study who continued into the OLE saw on average their natural tear production nearly double after 56 weeks of treatment from baseline and experienced a statistically significant improvement in all measured symptoms at all measured time points compared to baseline.3
In my practice, these clinical trial findings are reflected in the way my patients respond to VEVYE. When they return for evaluation after 1 month of treatment, patients say the burning, irritation, and dryness that had affected their quality of life either significantly diminished or was completely resolved.
Improved Comfort and Adherence
Historically, adherence has been one of the problems associated with topical cyclosporine formulations. For instance, with RESTASIS, my patients complain of a burning or stinging sensation when the drop is used and often don’t continue using it long enough to see if they will derive benefit.
Compliance has not been a problem with VEVYE because there is no discomfort when the drop is applied, and my patients say they get quick and steady symptom relief. Personally, I have not had patients discontinue because of side effects, which is an anomaly when treating DED, where patients often stop medications before they are able to see symptom improvement. In the ESSENCE OLE study, 1 patient stopped using VEVYE because of an ocular adverse event—mild burning and stinging.
InflammaDry Testing
With DED, the symptoms don’t always match the signs. My most challenging patients are those who are highly symptomatic but have no signs of DED on the ocular surface. I use InflammaDry to help with this.
InflammaDry is a diagnostic tool that tests the patient’s tears for the molecule MMP-9, which causes inflammation in the eye. InflammaDry testing provides objective evidence of inflammation and often shows that improvement in inflammation correlates with decreased burning, stinging, and discomfort. I’ve had patients with strongly positive MMP-9 testing who I then treated with RESTASIS and XIIDRA® (lifitegrast ophthalmic solution, Bausch + Lomb) as well as an additional steroid in cases where symptoms were extremely severe. When I administered a follow-up InflammaDry test, the patients still tested positive for inflammation. When I switch these patients to VEVYE, their InflammadDry often becomes negative, and it correlates with improvements in burning and stinging.
It is important to note, that there is no clinical trial data proving that VEVYE controls inflammation better, but after more than a year of prescribing it, I do have substantial anecdotal evidence suggesting that when patients follow a consistent VEVYE regimen, their symptoms improve or resolve, and they test negative for inflammation.
Cost, Coverage, and Accessibility
Patients tend to be impressed with the tolerability and effectiveness of VEVYE, and this along with clinical trial findings has not gone unnoticed by third-party payers. As clinical and anecdotal evidence of the efficacy of VEVYE grows, payers are acknowledging its potential, and a growing number are adding it to their formularies. Even when not covered by insurance, patients can access the treatment at a reasonable cost. There is a dedicated access program facilitated by manufacturer Harrow that ensures the cost is capped at $79 per month per patient. Because my patients are experiencing significant benefits from VEVYE, they say the out-of-pocket fee is worth the expense.
Biomarkers and Real-Life Relief
As ophthalmologists, we understand that cyclosporine is effective because it targets multiple biomarkers involved in DED. It inhibits the NF-KB pathway, which triggers T-cell activation and inflammation. It lowers MMP-9 levels, which are often elevated in DED patients; it reduces ICAM-1, linked to T-cell migration and lower tear production. It addresses CD147, which attracts immune cells and ramps up inflammation, and it helps control MPTP, which can lead to cell death on the eye’s surface when inflammation is present. VEVYE does all of those things but more quickly and with enhanced tolerability compared to other topical cyclosporine DED treatments.
When patients present in my clinic desperate for relief from excruciating DED symptoms, they’re not interested in molecular explanations regarding why they have DED or scientific minutiae detailing what is needed to quell their symptoms. They are interested in knowing that they can count on me to recognize their symptoms, validate their problem, and help them feel better. VEVYE enables me to do this more efficiently and effectively than many other treatments. Because the formula starts to work quickly and is consistently well tolerated, my patients tend to adhere to the recommended course of treatment, which is critical to ongoing success.
Lauren Zimski MD, specializes in treating ocular surface disease in Denver, Colorado. She can be reached at 303-863-1231 or office@denvereyemd.
References
- Sheppard JD, Wirta DL, McLaurin E, et al. A water-free 0.1% cyclosporine A solution for treatment of dry eye disease: results of the randomized phase 2B/3 ESSENCE study. Cornea. 2021;40(10):1290-1297. doi:10.1097/ICO.0000000000002633
- Akpek E, Wirta DL, Downing JE, et al. Efficacy and safety of a water-free topical cyclosporine, 0.1%, solution for the treatment of moderate to severe dry eye disease: the ESSENCE-2 randomized clinical trial. JAMA Ophthalmol. 2023;141(5):459-466. doi:10.1001/jamaophthalmol.2023.0709
- Wirta D, et al. Long-term safety and efficacy of a water-free topical cyclosporine 0.1% ophthalmic solution for the treatment of dry-eye disease: ESSENCE-2 OLE. Cornea. 2024. doi:10.1097/ICO.0000000000003567
