Published in Ocular Surface

Why the Vehicle Matters: Branded vs. Unbranded Treatment for OSD

This is editorially independent content supported by advertising from Sun Ophthalmics
10 min read

Sit down with Damon Dierker, OD, FAAO, and Selina McGee, OD, FAAO, to review the importance of vehicles in topical medications for ocular surface disease (OSD).

In this episode of Dry Eye Fireside Chat, Damon Dierker, OD, FAAO, and Selina R. McGee, OD, FAAO, discuss their approaches to the decision of a branded prescription medication for their dry eye patients—the when, the who, and the what.

Choosing the frequency of prescription solutions for OSD

At BeSpoke Vision, Dr. McGee characterizes her approach as “interventional dry eye”—a new concept for patients and payers alike. The interventional approach is familiar in the context of glaucoma management, where the development of effective, low-risk procedures has prompted an updated protocol and surgical interventions.
For example, laser therapies can be offered as first-line treatments, while microinvasive glaucoma surgery (MIGS) may be introduced earlier in the treatment algorithm. In the context of an interventional approach to dry eye disease (DED) management, in-office procedures could take center stage as a first-line treatment consideration.
However, the most important benefit of an interventional mindset for dry eye treatment is that it can allow for a treatment plan to be tailored to the individual patient. Subsequently, in-office procedures often may go hand-in-hand with prescription therapies in Dr. McGee’s office.

Developments in topical medications for DED

2023 was an exciting year for dry eye treatment. The US Food and Drug Administration (FDA) approved three medications to treat ocular surface disease (OSD)—VEVYE (cyclosporine ophthalmic solution 0.1%, Harrow) and MIEBO (100% perfluorohexyloctane ophthalmic solution, Bausch + Lomb) for the treatment of the signs and symptoms of dry eye disease, and XDEMVY (lotilaner ophthalmic solution 0.25%, Tarsus Pharmaceuticals) for the treatment of Demodex blepharitis.
These medications join established therapies such as CEQUA (cyclosporine ophthalmic solution 0.09%, Sun Ophthalmics), RESTASIS (cyclosporine ophthalmic solution 0.05%, AbbVie), and XIIDRA (lifitegrast ophthalmic solution 5%, Bausch + Lomb), EYSUVIS (loteprednol etabonate ophthalmic suspension 0.25%, Alcon) as well as Viatris’s TYRVAYA (varenicline solution) nasal spray 0.03mg.
With all of these options commercially available by prescription to eyecare practitioners (ECPs) to treat patients with dry eye, there is an opportunity to explore customized treatment regimens for patients. In Dr. McGee’s office, she notes, almost every one of her patients who are undergoing interventional treatment are also prescribed a drop or a spray.

The importance of the vehicle in a DED topical solution

When considering the various medications available for DED treatment, one of the differentiators within these formulations would be the vehicle—an aspect of the medication that Dr. McGee argues is important for both doctors and patients to understand.
To put it in simple terms, a formulation is made up of two components: the medication itself and the vehicle, an inactive component that may change the chemical and physical properties of the medication with which it is mixed in order to deliver the medication on application to the target tissues.
In the case of an eyedrop, the vehicle is leveraged to aid in the delivery of a topical medication to the ocular tissue that is often resistant to penetration. The cornea and the tear film are structurally protective to maintain ocular surface homeostasis along with acting as a barrier to pathogens.
For a formulation of cyclosporine, which is highly lipophilic, the vehicle must be able to penetrate the lipophobic surface of the eye in order to potentially reduce inflammation in corneal and conjunctival tissue via immunomodulation.1
It would be beneficial for optometrists to appreciate the nature and the role of the vehicles used for each medication they’re prescribing, Dr. McGee argues, since that understanding is a necessary first step in patient education. Patients may recognize preservative-free formulations but tend to be less educated about the importance of the vehicle.

When the vehicle matters for DED topical medications

Topical cyclosporine is among the most commonly prescribed topical medications for the treatment of dry eye and has been part of the standard of care for over two decades since Restasis was first approved by the FDA in 2003.
Now, there are several formulations of cyclosporine available to ECPs, and they are all unique and different.


Restasis uses the vehicle of Refresh Endura, which Dr. McGee suggests was one of the best artificial tears that used to be on the market. This vehicle allowed cyclosporine to remain encapsulated within the emulsion, allowing the molecule, when dropped onto the ocular surface, to maintain stability prior to penetration.
At the time of Restasis’s approval, this was game-changing.


Fast-forward to 2019 and the approval of Cequa, a cyclosporine formulation utilizing nanomicellar technology with a hydrophobic core and a hydrophilic outer layer to deliver cyclosporine to the ocular surface.2-5
This drug delivery platform allowed up to three times (3X) the concentration of 0.05% cyclosporine across ocular tissues, as noted in studies, forging Cequa’s FDA-approved concentration of 0.09%.2


The latest formulation of cyclosporine to come to market is Vevye, which uses the novel, water-free, semifluorinated alkane (SFA) molecule perfluorobutylpentane. SFAs have a variety of unique properties that have resulted in their recent emergence as useful components of multiple drug formulations.
Among these properties are high gas solubility, low surface tensions, and an ability to dissolve lipophilic drugs (like cyclosporine).6


The unique properties of SFAs lend themselves to a variety of applications. While perfluorobutylpentane is key to the ability of Vevye to deliver cyclosporine into the ocular surface, Miebo utilizes its own SFA molecule in a very different manner.
Perfluorohexyloctane is an amphiphilic molecule that can “sit” on the ocular surface and does not evaporate but rather creates a new monolayer, potentially preventing evaporation and lowering surface tension.
The vehicle and formulation absolutely matters, Dr. McGee points out, because, in the case of SFAs, perfluorohexyloctane could not be used to deliver cyclosporine—it would just sit on top of the eye rather than penetrate into the tissue.
Understanding these different molecules and how they organize themselves on the ocular surface is key to selecting the proper medication for your patient. Of note, ECPs may elect to prescribe certain DED medications in tandem to facilitate synergistic action to possibly accelerate the reduction in signs and symptoms.

Picking the best solution for your dry eye patient

Ultimately, Dr. McGee states that one of the biggest considerations for which medication you prescribe to your patient is access. There are many channels that ECPs and patients can use to fill prescriptions, but Dr. McGee notes that she has moved away from the typical box stores and solely utilizes specialized pharmacies with her patients.
Part of this paradigm shift is not just due to availability at the pharmacy, but to advocate for patient education to help them understand what distinguishes these branded medications from a standard artificial tear or an unbranded drop. Setting them up for success means adjusting their expectations—including how the drop may feel upon administration.
While a water-based drop is between 30 and 50 microliters, in contrast, a SFA drop is about 10 to 11 microliters. Consequently, a patient may not feel the drop hit the ocular surface upon instillation, especially when these drops have a silky or oily feel that is a significant departure from a water-based drop. These differences are important to discuss with patients so that they can appreciate the features and benefits of the respective medications.

Final pearls

Recent phase 4 data suggests that patients can experience an improved benefit when switched between medications within a class when switched from cyclosporine ophthalmic solution 0.05% to 0.09%.7
If a patient isn’t experiencing success with the first drop you prescribe, Dr. McGee suggests switching within the class—whether from an unbranded to a branded product or between concentrations—before adding another medication or changing the medication entirely.
Once patients understand this concept, Dr. Dierker notes, even if ECPs are not used to operating in this manner, at the end of the day, it’s about ensuring the best outcome for the patient while using the latest advancements in technology.
One significant challenge that ECPs may face is understanding how the prescription access programs work. While coming up against friction in the system (aka prescription denials or switches) is inevitable, it may require you to be your patients’ advocate and stand your ground.
By doing so, you can provide them with an opportunity to receive your first choice of prescription treatment to potentially improve patient outcomes.
Dr. McGee said it best in a succinct manner—treat the patient and know your molecules.

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  1. Periman LM, Mah FS, Karpecki PM. A Review of the Mechanism of Action of Cyclosporine A: The Role of Cyclosporine A in Dry Eye Disease and Recent Formulation Developments. Clin Ophthalmol. 2020;14:4187-4200.. doi:10.2147/OPTH.S279051
  2. CEQUA Prescribing Information. Cranbury, NJ: Sun Pharmaceutical Industries, Inc.; 2022.
  3. Cholkar K, Gilger BC, Mitra AK. Topical, aqueous, clear cyclosporine formulation design for anterior and posterior ocular delivery. Transl Vis Sci Technol. 2015;4(3):1-16.
  4. Mandal A, Bisht R, Rupenthal ID, et al. Polymeric micelles for ocular drug delivery: from structural frameworks to recent preclinical studies. J Control Release. 2017;248:96-116.
  5. Cholkar K, Patel A, Vadlapudi AD, et al. Novel nanomicellar formulation approaches for anterior and posterior segment ocular drug delivery. Recent Pat Nanomed. 2012;2(2):82-95.
  6. Tsagogiorgas C, Otto M. Semifluorinated Alkanes as New Drug Carriers-An Overview of Potential Medical and Clinical Applications. Pharmaceutics. 2023;15(4):1211. doi:10.3390/pharmaceutics15041211
  7. Johnston, J. Effect of OTX-101 0.09% on corneal staining and SANDE scores in patients with dry eye disease uncontrolled on cyclosporine ophthalmic emulsion 0.05%. Abstract presented at American Academy of Optometry 2023; October 12, 2023; New Orleans, LA.
Selina McGee, OD, FAAO
About Selina McGee, OD, FAAO

Dr. McGee is the visionary founder of Precision Vision of Edmond, a boutique-style eyecare practice that specializes in dry eye disease, specialty contact lenses, and aesthetics. She is also the co-founder of Precision Vision of Midwest City, an MD-OD practice specializing in premium IOL and cataract surgery. She earned her OD degree from Northeastern State University College of Optometry, graduating Summa Cum Laude. She is a member of the Oklahoma Association of Optometric Physicians and the American Optometric Association. Currently she serves as the Immediate Past-President the OAOP. She is also an adjunct faculty member of Northeastern State University College of Optometry. She was named Young Optometrist of the year in 2012 by the OAOP.

Selina McGee, OD, FAAO
Damon Dierker, OD, FAAO
About Damon Dierker, OD, FAAO

Dr. Dierker is Director of Optometric Services at Eye Surgeons of Indiana, an adjunct faculty member at the Indiana University School of Optometry, and Immediate Past President of the Indiana Optometric Association. Dr. Dierker is the Co-Founder and Program Chair of Eyes On Dry Eye, the largest event for eyecare professionals in the industry. He has made significant contributions to raising awareness of dry eye and ocular surface disease in the eyecare community, including the development of Dry Eye Boot Camp and other content resources across dozens of publications.

Damon Dierker, OD, FAAO
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