In the fifth episode of Dry Eye Fireside Chat, Damon Dierker, OD, FAAO, sits around the campfire with John Sheppard, MD, to discuss the importance of restoring tear film instability as a treatment goal for dry eye disease (DED) patients.
The changing understanding of the pathogenesis of DED
To start, Dr. Sheppard outlined how cyclosporine emulsion revolutionized the treatment of DED because it could more directly target the chronic inflammation that is a signature feature of dry eye.
In the ensuing decade, researchers began to gain insight and greater appreciation for evaporative tear loss as a key component of dry eye as well.
As a result, tear film breakup time (TBUT), assessing meibomian glands (i.e., meibography) and eyelid health, coupled with other parameters were added to dry eye exams to account for the nearly 86% of dry eye patients with evaporative tear loss.
Shifting to DED treatments that target inflammation
He added that this discovery spurred the development of treatments, such as thermal pulsation, intense pulsed light (IPL) therapy, lid scrubs, and warm compresses, to be more widely prescribed and performed in-office.
Due to the fact that these treatment approaches complement medical interventions that target inflammation with improved efficacy, DED patients began to see better results.
Now, we have a number of medications on the market in the United States that include a wide variety of anti-inflammatories, with several more to come into Food and Drug Administration (FDA) approval channels very soon, plus a true secretagogue, varenicline solution (Tyrvaya).
This nasal spray allows upregulation of the trigeminal nerve pathway that stimulates the lacrimal functional unit (LFU) to produce aqueous, mucus, and liquid tears. Broadening the approach, Dr. Sheppard argues, has allowed clinicians to broaden their diagnostic perspective.
The current state of dry eye diagnostic technologies
As dry eye treatments became broader, so did point-of-care (POC) instrumentation to measure osmolarity and matrix metalloproteinase-9 (MMP-9) levels, along with assessing meibomian gland structure with meibography to create a comprehensive snapshot of a dry eye patient, similar to a cholesterol profile for a patient with hyperlipidemia.
Dr. Sheppard emphasized that because dry eye is such a heterogeneous disease, eyecare practitioners (ECPs) continue to find challenges with correlating diagnostics, signs and symptoms, and treatments. Consequently, the best treatment results stem from having a broad understanding of the different etiologies of dry eye in order to get consistent, predictable symptom alleviation.
Dr. Dierker noted the key to this is to match diagnostics with specific and effective treatment algorithms that account for unique, individual patient profiles. While it is currently possible to create such an algorithm for ECPs (especially those who specialize in dry eye), it needs to become even easier and more accessible due to the prevalence of DED.
Getting started with identifying and prescribing effective DED treatments
Dr. Sheppard highlighted the first step to ensuring a successful treatment plan, which is to start simple and pick the obvious, number one choice where the ECP can provide the biggest impact with a single action. Why?
Because many patients have complex medical histories and have seen other providers, making it more beneficial to address the most salient problem initially and then follow up to iron out the details of the broader plan to manage their ocular surface and eyelid health.
For example, if a patient is taking over-the-counter (OTC) antihistamines and doesn’t have allergies, that would be an obvious target; similarly, if they ride a motorcycle without goggles on, explaining the deleterious effects of this is another effective and simple piece of advice to offer.
Dr. Sheppard observed that picking the obvious choice in a patient with a complex condition, such as DED, will make a difference, as a single intervention each visit, spaced 6 to 16 weeks apart (depending on the severity of the disease), will allow the ECP to make the most impactful decisions.
However, this timeline changes when treating a surgical patient, whether it is laser in situ keratomileusis (LASIK), refractive cataract surgery, or even an aggressive glaucoma drainage shunt procedure. Surgical patients will need to be evaluated and treated quickly, so in this situation, ECPs need to shift the focus from selecting one treatment to treating the ocular surface disease (OSD) as aggressively as possible to optimize their ocular surface prior to surgery day.
Targeting tear film instability in DED treatments
When performing an eye exam and recording the patient’s medical history, Dr. Sheppard noted that it is important to listen for patients reporting variable vision or visual fluctuations, as this is a hallmark of DED and a signal for tear film instability.
With this in mind, ECPs can assess the stability of the tear film by checking the tear meniscus, TBUT, and osmolarity, as well as understand that hyperosmolarity can result from many different pathways, such as aqueous and lipid deficiencies, environmental stimuli, inflammatory disease, and autoimmune disease.
Recent developments in DED medical therapies: Enter MIEBO
As patients with DED are more likely than not to have an evaporative component, it is a key target to manage and treat as proactively as possible. Luckily, in May 2023, the Food and Drug Administration (FDA) approved MIEBO (perfluorohexyloctane ophthalmic solution, Bausch + Lomb), a new drug composed of a semifluorinated alkane, and indicated for the treatment of the signs and symptoms of DED.
MIEBO is a proprietary non-steroidal, single-component, water- and preservative-free eyedrop formulated with 100% perfluorohexyloctane to treat DED. Additionally, MIEBO is a novel treatment because it produces a physicochemical stability on the ocular surface without any active pharmaceutical ingredients; instead, the entire drug can be considered a tear film stabilizer.
Further, MIEBO is formulated with an aerophilic and lipophilic molecule that forms a monolayer at the air-liquid interface of the tear film for up to 6 hours, thereby stabilizing the tear film, inhibiting evaporative tear loss, and promoting healing on the ocular surface.
Interestingly, the semifluorinated alkanes present in MIEBO are also used in retinal surgery and blood byproducts to increase oxygenation in circulation.
Restoring tear film instability with MIEBO
This is the first medication approved for patients with dry eye targeting the evaporative component. However, it is also beneficial to all forms of DED where tear preservation is necessary.
Subsequently, Dr. Sheppard mentioned a possible off-label combination option where MIEBO is prescribed alongside punctal plug insertion. The latter can prevent existing tears from draining into the nasolacrimal system, while the drop conserves existing tears and prevents them from evaporating into the environment.
As the osmolarity improves, the destruction of ocular surface cells is reduced, overall improving tear film instability and reducing inflammation as well. This type of intervention offers ECPs yet another choice in their armamentarium to select treatments that target specific forms of DED and tailor treatment plans to specific patient needs.
What’s on the horizon for DED treatments?
Dr. Sheppard expressed that he is most excited to see how the growing toolbox of genomic diagnostics and gene therapies might shape the future of DED treatments, as clarifying the etiology of dry eye might help ECPs get closer to finding a treatment that could possibly cure DED.
Currently, the genetic basis for DED is unknown, though it is understood that there is a strong association with hormones and inflammatory diseases, such as Sjögren’s syndrome and rheumatoid arthritis, and tends to occur earlier in women, he added.
Hopefully, in the future, Dr Sheppard ruminated it could be possible to change the phenotype of the secretory apparatus in patients instead of having to restimulate it over and over again with medical interventions.
Many pharmaceutical companies are invested in genomic analyses and interventions for DED, possibly with bacteriophages that allow for the transfection of a restored, previously genetically deficient cell in the lacrimal or meibomian glands to figuratively revive that cell and allow it to create anti-inflammatory cytokines, beneficial proteins, and other critical substances to protect the ocular surface.
Conclusion
With the rollout of new DED treatments, such as MIEBO, ECPs continue to get closer to uncovering a long-term treatment for patients who have suffered for decades with DED.
Advances are occurring rapidly in the realm of dry eye, so discovering a potentially curative treatment that might be able to reverse the course of this chronic disease based on its etiology may be closer to fruition than clinicians expect.
