Exploring Demodex Blepharitis From a Clinical Perspective

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AJMC®: Does the prevalence of Demodex blepharitis found by Trattler and colleagues¹ match what you see in clinical practice?

BRUJIC: The prevalence of Demodex blepharitis is interesting. Prior to around 2 years ago, I would have said that the prevalence was very low. Since that time, awareness of the condition among clinicians has increased greatly, and the results of the Trattler study showed that approximately 57% to 58% of patients visiting eye care clinics had Demodex blepharitis. This result changed our clinical perspectives as eye care providers, and we started more actively looking for Demodex blepharitis. We found that the prevalence is much higher than previously thought. Unfortunately, we were treating some of these individuals for conditions that have overlapping symptoms with Demodex blepharitis. We have taken these patients off some other treatments, put them on an appropriate treatment for Demodex blepharitis, and eliminated the need for most of the ocular medications they were utilizing. Again, prior to this study, I would not have predicted such a high prevalence, but based on my practical experience, it’s very close to what we’re seeing in clinical practice.

AJMC: How would you describe the clinical burden of Demodex blepharitis?

BRUJIC: Demodex blepharitis manifests with a wide range of signs and symptoms. With this condition, we see patients who are burdened with eye discomfort and eye itching. Some of these patients have very mild to moderate symptoms. Interestingly, we find that when we treat these individuals appropriately and eliminate excessive Demodex population on the lid margin, patients return for their 2-month follow-up relieved and stating that they never knew their symptoms were related to Demodex blepharitis. Patients may have had crusting or matter in the corners of their eyes, and this is eliminated. There is vague itchiness that they no longer experience. Patients sometimes experience discomfort in what we consider extreme environments. For example, if a person without Demodex blepharitis is sitting in a car with air conditioning, they do not usually experience irritation. However, a patient with Demodex blepharitis does experience irritation in this environment. Bright lights do not bother most individuals, but they can bother patients with Demodex blepharitis. Patients have experienced remarkable improvements in symptoms that we didn’t know were associated with this disease. The disease burden for our patients can be relatively high.

AJMC: What symptoms of Demodex blepharitis do you see most frequently in clinical practice?

BRUJIC: We are learning more about the symptoms associated with Demodex blepharitis as our understanding of the disease improves. The classic, stereotypical patient with Demodex describes itching along the lash margins and the eyelid margins and a diffuse discomfort in the eyes. This is very similar to the presentation of a patient with dry eye disease. A patient with Demodex blepharitis may experience itching, eye discomfort, fluctuating vision, and occasionally secondary meibomian gland dysfunction, which is presumed to be secondary to the overpopulation of Demodex. Additionally, these individuals are much more likely to develop internal or external hordeola, which are commonly referred to as styes. Both conditions can lead to chalazion formation, which occurs when a gland becomes clogged and infected and a residue of hardened oil forms in that gland, leaving the patient with a small bump on the eyelid. The impact of Demodex blepharitis and its sequelae on patients can be substantial.

AJMC: Why are secondary manifestations of Demodex blepharitis a concern?

BRUJIC: In a patient with Demodex blepharitis, overpopulation of Demodex mites or ectoparasites in the hair follicles on the lashes creates collarettes or a small scurf around the base of the lashes. Patients may experience eyelid discomfort, specifically along the lash line. However, there are significant secondary sequelae. If the oils along the lid margin are not being appropriately produced and if Demodex mites are overpopulating those regions and causing collarettes to form, the collarettes can cause thickening and even obstruct the meibomian glands. Demodex blepharitis can cause symptoms that are very similar to those of dry eye disease. Inferior corneal staining, which is a band of dryness that can be detected on the cornea, may also occur. Patients can experience reduced tear film breakup time, which is how long a tear film remains stable on the eye surface before dry spots are observed; a normal result is 10 seconds or more. Tear breakup time can be severely reduced in patients with Demodex blepharitis. These secondary manifestations are important to consider when treating patients.

AJMC: How important are investigations like the Atlas study² for understanding and raising awareness of this disease?

BRUJIC: Studies like the Atlas study are critical from a clinical perspective. When we examine patients, we have a routine approach to examining the eye, and we also look for certain symptoms. Sometimes, patients have become so accustomed to their symptoms that they do not feel the need to share them with us; because we are unaware of the symptoms, we do not seek out their cause. Many of these patients are chronically affected by Demodex blepharitis, but they use lid wipes 2 to 3 times a day. Lid wipes do not strongly sequester the collarettes or the Demodex population, but their use gives patients a sense of agency over disease management. However, the results of the Atlas study make clear that the symptom burden of Demodex blepharitis is great and that patients are regularly discontinuing traditional therapies like lid wipes because they cannot tolerate the treatments or the treatments are not effective. The study also provides guidance on how to identify affected patients in a more streamlined and straightforward manner during the clinical examination. Understanding how to better identify patients with Demodex blepharitis is important because we now know that the prevalence of this disease is over 50%. Clinical behaviors must be changed to identify these patients and ensure that they receive appropriate treatment.

AJMC: What are the long-term ocular health risks associated with untreated Demodex blepharitis?

BRUJIC: When I first graduated in 2002, we were taught that individuals of a certain age will probably have a certain level of blepharitis or collarettes along the lash margin. The understanding of this disease has increased over the past 22 years. We are now aware that collarettes are pathognomonic for Demodex overpopulation in the lash follicles. We also understand that this is not a normal situation and that Demodex mites release exotoxins. The lid margin is more likely to have collarettes and be thickened, and, thus, is more likely to be inflamed and to have telangiectatic blood vessels, which are a critical sign of inflammation. Affected individuals are also more likely to experience obstruction of the meibomian glands and thickening of the lid margins. The line of Marx is the border where the keratinized epithelium on the anterior surface of the lid margin meets the mucous membrane of the posterior lid margin. In individuals without collarettes, we tend to see the line of Marx more posteriorly and in a straighter or normal pattern. In individuals with long-term collarettes, the line of Marx tends to migrate forward, which is a sign of chronic inflammation. Long-term manifestations are observed in areas with overpopulation of Demodex. Diffuse hyperemia may occur at the lid margin as well as deeper at the bulbar conjunctiva. Additionally, corneal staining and conjunctival staining are sometimes observed in these patients. It is important to consider not only what is happening today on the eye surface but also the potential long-term ramifications of untreated Demodex blepharitis, how this disease can affect the health of the ocular surface over time, and how it potentially prevents the ocular surface from functioning normally.

AJMC: How prevalent are underdiagnosis and misdiagnosis of Demodex blepharitis?

BRUJIC: Misdiagnosis and underdiagnosis are difficult to quantify clinically because we sometimes do not know that we have missed a diagnosis unless the patient returns. I have had patients on treatments for other conditions with similar symptoms whom I subsequently diagnose with Demodex blepharitis when I view their lid margin. Misdiagnosis and underdiagnosis probably happen in other offices, as well. Investigations such as the Trattler study help us understand the prevalence of these conditions, which can help us clinically understand whether we are appropriately identifying these patients and whether we are underdiagnosing these conditions.

AJMC: How might underdiagnosis or misdiagnosis impact patient care and outcomes?

BRUJIC: Underdiagnosis or misdiagnosis of Demodex blepharitis can certainly affect patient outcomes. I will give you 2 examples. An individual who is wearing contact lenses successfully while having a Demodex mite overpopulation with visible collarettes may be comfortable today; however, if we do not diagnose and appropriately treat the condition, the individual may not be able to wear contact lenses in the future. Many people can wear glasses instead of contact lenses. However, in my practice, we work with a specialized patient population, and we see a lot of individuals with keratoconus, epithelial basement membrane dystrophy, and advanced dry eye disease. In these cases, the special types of contact lenses and scleral shells that we are placing on the eyes are a means of preserving the cornea. If the patient cannot wear contact lenses, they are not able to utilize this form of treatment. This is part of the reason we have taken Demodex so seriously. Let me share another example. What happens if we misdiagnose or if we do not appropriately treat Demodex blepharitis? An individual visits the office with complaints about vision issues. I perform a refraction and determine their prescription, and there is no significant change in the prescription. The patient updates their glasses but still cannot see as well as expected. This often results from an undiagnosed case of Demodex blepharitis. This patient returns to us for years and casually mentions their vision issues. Upon closer examination, we observe Demodex overpopulation and collarettes, which can reduce the integrity and quality of the tear film. The tear film is the first surface light hits before entering the eye. If the tear film is not viable or smooth, individuals feel like their vision is off and may not be able to describe exactly how or why, but they often describe it as occasional fuzziness. This is frequently a manifestation of a disrupted tear film that’s secondary to Demodex overpopulation.

AJMC: What diagnostic methods and tools are commonly used to identify Demodex mites in patients?

BRUJIC: A practical aspect about the diagnostic algorithm for Demodex blepharitis is that it requires nothing more than an observant clinician appropriately viewing the lid margin. Many conditions that we have a better understanding of and that we encounter in the industry and in our profession require new diagnostic tools. That is not the case here. The good news is that different diagnostic technologies are not required to identify Demodex. It just requires the clinician to understand that it is important to take a closer look at the lid margin and make sure that in addition to the low-magnification scan performed for the upper and lower lid margin, we are also increasing the magnification to closely examine the lid margin while having the patient look down. This is different from the way that we were traditionally taught. When looking at a patient’s eyes through a slit lamp, we were typically taught to look at that lid margin at low magnification; however, at low magnification, fine collarettes at the base of the lashes are often missed. At high magnification, which is 2 clicks on the slit lamp, you can see collarettes at the base of the lashes much better than when at low magnification. If there is any redundant skin that may be covering the collarettes at the base of the lashes, having the patient look down while we hold the upper eyelid skin exposes the base of the lashes where collarettes can be easily seen.

AJMC: With what other diseases do the symptoms of Demodex blepharitis overlap?

BRUJIC: The symptoms of Demodex blepharitis overlap with those of other conditions, including allergic diseases. Allergic conjunctivitis can present very similarly to Demodex blepharitis. Infectious conjunctivitis has symptomatic overlap, too—this is an acute infectious conjunctivitis as opposed to the more chronic form of blepharitis. Demodex blepharitis shares symptoms with dry eye disease and floppy eyelid syndrome, in which individuals have loose-lid apposition. Sometimes their lids will easily evert when they are sleeping, causing discomfort; this condition has a strong association with sleep apnea. Epithelial basement membrane dystrophy, recurrent corneal erosion, and episcleritis also have overlapping symptomology with Demodex blepharitis. these other conditions. The good news is that Demodex blepharitis is easily diagnosed based on the overpopulation of collarettes at the lash margin.

AJMC: What strategies can health care providers employ to improve the rate of accurate diagnosis?

BRUJIC: Clinicians should ask 2 questions to accurately diagnose Demodex blepharitis. The first is, with what symptoms are the patients presenting? The second is, what are we seeing? Based on our understanding of the data from the Atlas and Trattler studies, we are redefining the way we are examining the lid margin. Rather than using the traditional method of sweeping the outside of the lid margin and lashes at low magnification at a wide beam, we should increase the magnification along the lash margin to determine whether collarettes are present. The good news is that the collarettes are very easily seen. We expect to see either a flat lid margin with protruding lashes or a slight involution around the lash follicle. At the base of the lash, any visible collarettes or tenting of the skin represents a Demodex overpopulation. Tenting of the skin at the base of the lash is a precursor to a collarette exposing itself outside of the hair follicle; it occurs before we physically see the collarette. We need to consider what our patients are telling us and ensure that we are using higher magnification while viewing the lid margin. If there is an obstruction of the lash margin via the upper lid skin, having patients look down while holding the upper eyelid skin enables better visualization of the lash base.

AJMC: In early 2024, the American Academy of Ophthalmology released the Blepharitis Preferred Practice Pattern.³ What insights do these guidelines offer for clinical practice?

BRUJIC: The guidelines cite lotilaner ophthalmic solution, 0.25%, as the only FDA-approved treatment, but they do not discuss it—or any treatment for Demodex blepharitis—at great length. At the time the manuscript was written, eye care professionals had little clinical experience with lotilaner, which was approved by the FDA in July 2023.⁴ Clinicians started prescribing it in August or September, and they started to see results in November after the first rounds of lotilaner’s 6-week course of treatment. At the time of this interview, we have had lotilaner for about half a year, and we are just starting to see the results. There is also a wait time to get access to the medication, so the first patients who were prescribed lotilaner were seen for follow-up visits at the end of 2023. The next versions of guidelines will likely include recommendations for lotilaner because clinicians who are involved in the publications will likely have had more experience with it. However, a multifaceted approach is important. Lid hygiene is important. There are no negative aspects to lid hygiene, which can be used as a supplement to other treatments for Demodex blepharitis. To eliminate collarettes, it is necessary to kill the mites. The mites can only be killed if lotilaner enters the lash follicles.

AJMC: How, if at all, has your experience of treating Demodex blepharitis changed in recent months?

BRUJIC: As a clinician, it is frustrating to see a condition for which you have no treatment. Posterior vitreous detachments and floaters are frustrating conditions in that respect. Patients are unhappy with having vision issues. We do not enjoy explaining the condition to them and telling them that there is nothing we can do about it. Demodex blepharitis was very similar to that until relatively recently. The results reported by patients are remarkable. We postponed LASIK [laser-assisted in situ keratomileusis] surgery in a patient because he had substantial collarette formation along the upper lower lid margin. He came back, and some of his comments were interesting. He said that he couldn't believe how much more comfortable his eyes were and that his eyes didn’t itch anymore. The third thing he said was, ‘My eyelashes just seem so much straighter.’ They do, because when you have blepharitis, lashes become crossed when they start to entwine because of the stickiness of collarettes. Collarettes can change the trajectory of the lashes coming out of the lash follicles, resulting in misdirection of the lashes. When you remove the collarettes, lashes just follow the natural trajectory of the lash follicle, which typically shows a consistent course. The patient recognized that his eyelashes looked fuller and straighter.

AJMC: What final thoughts do you have about Demodex blepharitis for our managed care audience?

BRUJIC: Demodex blepharitis used to be one of the most concerning and most time-consuming conditions to treat: we put in a lot of effort clinically for a small reward for the patient and practitioner. We recommend treatments such as hypochlorous spray, lash hygiene, lid scrubs, warm compresses, and wipes containing tea tree oil. These treatments are very regimented for the patient and often do very little to alleviate symptoms at the lash margin and long-term symptoms experienced by the patient. Patients are exerting great effort for little reward. Clinically, the reason why these treatments are not rewarding is that a treatment should provide patients with a successful outcome. If I prescribe a pair of –2.5 diopter glasses, patients should put on the pair of glasses and say, ‘That looks perfect to me.’ When we’re prescribing a –2 diopter contact lens to a –2-diopter patient, I hope they say, ‘That’s perfect.’ When we were previously treating Demodex blepharitis, there was a lot of emphasis on education of the patient and clinician and few tangible results. Lotilaner ophthalmic solution, 0.25%, is now available, and we have a way to very effectively treat this condition via an eye drop administered twice a day for 6 weeks or 42 days. In my clinical practice, we have not had a patient who has not responded to therapy. I know how adherent to treatment the patient is based on what I see clinically. I schedule follow-up visits at 2 months. If the patient is adhering to the treatment regimen, the lid margin changes and normalizes. With lotilaner, other treatments that we previously used, such as the lid scrubs, are not required. The sophistication of the medication entering the lash follicle to reach the Demodex is probably just as important as the toxicity of lotilaner toward Demodex ectoparasites. Again, this treatment enters the lash follicle, where it acts. In summary, we need to make sure that we are thinking about and looking appropriately for Demodex blepharitis. We also need to make sure that we are treating the disease effectively, which not only benefits the patients in the chair but also provides patients with long-term relief.

REFERENCES

1. Trattler W, Karpecki P, Rapoport Y, et al. The prevalence of Demodex blepharitis in US eye care clinic patients as determined by collarettes: a pathognomonic sign. Clin Ophthalmol. 2022;16:1153-1164. doi:10.2147/opth.S354692

2. Barnett M, Simmons B, Vollmer P, et al. The impact of Demodex blepharitis on patient symptoms and daily life. Optom Vis Sci. 2024;101(3):151-156. doi:10.1097/OPX.0000000000002111

3. Lin A, Ahmad S, Amescua G, et al. Blepharitis Preferred Practice Pattern. Ophthalmology. 2024;131(4):P50-P86. doi:10.1016/j.ophtha.2023.12.036

4. NDA approval for Xdemvy. FDA. July 24, 2023. Accessed May 22, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2023/217603Orig1s000ltr.pdf