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Subspecialties Cornea / Ocular Surface, Business and Innovation, Practice Management, Health Economics and Policy

What’s Under the Ocular Surface Disease Umbrella?

How should we view ocular surface disease (OSD)? In my opinion, OSD should be considered a broad umbrella that encompasses dry eye disease (which is an imbalance of the tear film), allergic conjunctivitis, Meibomian gland disease (MGD), and blepharitis. The signs and symptoms of all those disorders can be so similar, such as redness and itching. That is why it’s so important to take a closer look and find the differentiator for one of the above disorders.

Recently, the ATLAS study, conducted on patients diagnosed with Demodex blepharitis, showed that 80 percent of patients saw the disease and its symptoms as negatively affecting their daily life (1). These numbers are huge! Some blepharitis patients report that they might see a doctor up to six times before getting a clear diagnosis (2). The study really highlights the need to detect and diagnose the condition sooner, with an effective therapy following.

Why do doctors so often fall short of diagnosing blepharitis? One of the reasons has been the lack of an effective therapeutic that would elevate the space. If you can’t effectively manage or treat a disease, there is much less incentive to detect and diagnose it. This was the situation for dry eye disease a decade ago – and with the advent of effective medications, precise diagnosing has become much more common in the dry eye disease (DED) sphere.

Many experts have been underdiagnosing the condition due to the lack of knowledge of how simple and quick this diagnosis can be.

The therapeutic

The results of the Phase 2b/3 Saturn-1 pivotal trial, conducted by 15 different eyecare centers, show that we will most likely have the therapeutic, TP-03 (lotilaner ophthalmic solution, 0.25%), available to us very soon (see box The Saturn-1 study findings). What we need now is greater awareness of blepharitis. At the recent American Society of Cataract and Refractive Surgery (ASCRS) 2021 Annual Meeting in Las Vegas, Nevada, USA (July 23-27, 2021), I saw a real buzz around the topic of blepharitis. There was a lot of blepharitis information projected from the podium and discussed among clinicians, but there is still a great need for education about the clinical diagnosis.

Many experts have been underdiagnosing the condition due to the lack of knowledge of how simple and quick this diagnosis can be. It has a pathognomonic sign, collarettes (cylindrical dandruff cuffing the base of the lash), that are a result of Demodex mite infestation.  When I bring my patients to the slit lamp, the first thing I ask them to do is to look down. This enables me to clearly check the upper lid margin with particular attention to the lash line along the anterior surface of the upper lid margins where collarettes are most easily seen. Then I ask them to look up, which allows me to look across the lower lid margin, including the posterior lid margin for MGD. This should be the first step in any examination – having a good macroscopic look at low magnification.

When I consider TP-03, what grabs my attention is that it reduces or gets rid of redness in a statistically significant number (over 60 percent) of patients, even though it doesn’t contain any anti-inflammatory agents (it gets rid of redness completely in one in five patients) (3). This shows me that the therapeutic addresses of the source of the redness, on top of removing collarettes.

The ATLAS study findings (1, 2)

The study used questionnaires to survey 311 patients pre-screened at eight sites taking part in the phase 2b/3 Saturn-1 trial, showing three objective signs of Demodex blepharitis, including the presence of Demodex mites, collarettes, and lid margin erythema.

Over 50 percent of patients reported having symptoms of blepharitis for at least four years, and 58 percent reported that they were never diagnosed despite making between two and six appointments with an eyecare professional.

The emotional impact of the symptoms included patients being conscious of their eyes all day (47 percent), constantly worrying about their eyes (23 percent) and considering the disease to be giving their eyes or eyelids a negative appearance (23 percent).

The majority of patients – 52 percent – reported experiencing itchy and/or dry eyes frequently or constantly in the month before taking the questionnaire.

Forty-seven percent of patients reported difficulty driving at night, and nearly a third reported the disease added time to their daily hygiene routine.

A vast majority – 82 percent – of these blepharitis patients sought treatment, but many then discontinued it due to side effects or perceived ineffectiveness.  

The near future

According to DEWS II, management of Demodex blepharitis, if present, should be treated early on in the treatment of OSD, but it is commonly avoided or treated after multiple visits and other modalities have been attempted, mostly because there are no clearly effective solutions. This condition, while very common, is without a prescription therapeutic option. There are various homeopathic, minimally effective therapies available, some of which require chronic management, raise safety concerns, such as the potential toxicity of terpinen-4-ol to the meibomian gland epithelial cells, and are accompanied by uncomfortable side effects.

In my opinion, I believe that currently only a fraction – maybe eight to 10 percent – of patients under the umbrella of ocular surface disease are being adequately managed to the patient’s satisfaction. Many current treatment options for OSD require indefinite, chronic use with maybe marginal efficacy. It will be great to have a therapeutic that can mitigate a major underlying or exacerbating disease of the ocular surface with a six-week treatment cycle and six to nine months before mite repopulation. Now that we are so close to having an effective therapeutic, there needs to be greater awareness and understanding of how to diagnose and manage the condition.

It is incumbent upon us to make the clinical diagnoses which are affecting the ocular surface. Fortunately, the diagnosis of Demodex blepharitis is refreshingly obvious by biomicroscopic observation alone. This requires a slight adjustment at the start of the slit lamp exam by simply observing the upper lash line with the patient looking down. Making this a routine part of the clinical exam will further strengthen our ability to assess the variety of ocular surface conditions that exist, thus improving detection and diagnosis of OSD accurately, so that when a treatment is available – we are ready to use it to improve patient care.

The Saturn-1 study findings (3)

The randomized, double-masked Phase 2b/3 pivotal trial evaluated a novel therapeutic, TP-03 (lotilaner ophthalmic solution, 0.25%), for patients with confirmed Demodex blepharitis, in 421 adults who had more than 10 collarettes on their upper eyelid, at least mild erythema of the upper eyelid margin, and at least 1.5 mites per lash on the upper and lower eyelids.

The trial found that the medication cleared the signs of Demodex blepharitis and met all primary and secondary endpoints with high statistical significance.  Treatment with TP-03 resulted in a clinically meaningful collarette cure by day 43 in 81 percent of patients, with 44 percent of patients achieving complete collarette cure. Sixty-eight percent of patients using the therapeutic achieved Demodex mite eradication by day 43, with no mites present on eyelashes.

The trial also showed good tolerability of TP-03, with 93 percent of patients reporting neutral to high levels of comfort. No serious adverse effects were recorded, with mild effects such as pain, burning and stinging noted in under 12 percent of participants.

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  1. E Yeu et al., “Psychosocial impact of Demodex blepharitis,” Invest Ophthalmol Vis Sci, 62, 1261 (2021).
  2. S Schachter et al., “Clinical manifestations of Demodex blepharitis,” Invest Ophthalmol Vis Sci, 62, 1268 (2021).
  3. E Yeu et al., “Safety and efficacy of topical Lotilaner 0.25% for the treatment of Demodex blepharitis: Results of the Saturn-1 Ph 2b/3 FDA-pivotal trial.” Presented at: ASCRS 2021; Las Vegas, USA. Abstract #75012.
About the Author
Elizabeth Yeu

Elizabeth Yeu is Assistant Professor at Eastern Virginia Medical School and Cornea, Cataract and Refractive Surgeon with Virginia Eye Consultants, VA, USA

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