A Q&A with Paul M. Karpecki, OD, FAAO
AJMC®: Can you walk us through your published findings regarding the real-world prevalence of Demodex blepharitis?1 Why is this an important disease to study?
KARPECKI: Demodex blepharitis is one of the more common forms of blepharitis, and there’s no good treatment for it. Some 45% of people diagnosed with blepharitis reportedly experience infestation involving the Demodex genus; however, that percentage is probably low. When you start to look for the pathognomonic sign of Demodex blepharitis—collarettes at the base of the lashes—you see a considerable number of cases. Moreover, in a referral practice like mine, the prevalence is higher; more than 90% of blepharitis cases involve Demodex. This type of infestation is not easily treated, and patients who don’t respond to therapy are referred to our clinic. We have treatments for blepharitis associated with staphylococcal or bacterial infection and for dermatologic cases (eg, seborrheic dermatitis), but we really don’t have anything for Demodex infestation. There’s a real need to both appropriately diagnose the condition and find ways to manage it.
AJMC®: Demodex mites are commonly found on human skin—even in healthy humans—and symptoms of Demodex blepharitis (eg, swollen and irritated eyelids, ocular burning) are not specific to this disease. How do you study this disease and its prevalence?
KARPECKI: Demodex mites are the most common ectoparasites detected on the human body. They are a natural pathogen, so to speak. Certain people experience infestation of the skin, which has been associated with rosacea. Others may experience Demodex infestation on their eyelashes that occurs in different forms. D folliculorum tends to concentrate or localize on the lashes and the lash follicle; it also eats skin cells. D brevis tends to get into the sebaceous glands and the meibomian glands of the eyelid that produce the oils for tear film.
We do not know why infestation doesn’t occur on everybody. We are not sure whether it is related to genetics, race, or another cause, but we see Demodex mite infestation in almost all populations. It is also unclear how age affects disease prevalence. According to some publications, Demodex blepharitis is commonly detected in people of all ages; according to others, it becomes more common as we become older. In my experience, prevalence seems to increase with age. Regardless of why this normal pathogen gets out of control, infestation is related to complications like redness, erythema, matting, crusting, dryness, and grittiness of the eyes.
Those are all common symptoms for the various forms of blepharitis. Demodex blepharitis is unique, because the Demodex parasite gets into the follicles. The excrement, nits, and debris that is extruded by the mites shows up on the base of the lashes. This is partially because the mites live inside smaller hair follicles; as the lash grows out, that mixture is forced out of the follicles. This manifests as a clear or, sometimes, whitish sleeve at the base of the lashes. No other form of blepharitis is associated with the development of this sleeve, making it pathognomonic for Demodex-related disease. The formation of this sleeve also helps with accurate diagnosis. While the physician is at the slit lamp, the patient simply has to look down. They do not need to close the eyelids, but rather just look down, and then a physician can see evidence of Demodex infestation at the base. That really separates Demodex blepharitis from other forms of the disease.
The symptoms and progression of Demodex blepharitis can also differ from those of other blepharitis types. Itching tends to be a more common symptom of Demodex blepharitis than of other types of the disease. Loss and thinning of lashes occurs more often with Demodex blepharitis than with some of the other types. And because this type of blepharitis is not very treatable, these conditions can advance and cause more inflammation. We often see more severe disease with Demodex blepharitis because of our lack of adequate treatments.
AJMC®: What were the findings from your study regarding the prevalence of Demodex blepharitis in the United States?
KARPECKI: Demodex blepharitis was found to be more prevalent than we anticipated. We analyzed data from ophthalmologists and optometrists in specialty practices, general practices, contact lens practices, and even surgical practices; we had quite a mix among the various physicians. Also, all comers had to be noted in this study, meaning that a provider could not exclude any patient, even if they were pediatric or geriatric. We taught the doctors how to look for collarettes; most providers knew how to look for them, but for some it was new. It’s a nice 5-second test. Looking at lashes using a slit lamp is already standard practice, so the only added step was to have the patient look down while the providers scans the base of the lashes. Participating physicians were to examine each patient.
The results showed that Demodex blepharitis does not only appear in patients with dry eye or rosacea, in whom we might have expected to find infestation. Demodex blepharitis appeared in patients being treated for glaucoma, cataract surgery, contact lenses, and even those who visited their provider for routine eye examinations for glasses. Some 58% of all comers had collarettes, the pathognomonic sign of Demodex infestation. Some 58% of all comers presented with Demodex blepharitis! That’s a surprisingly large number. I would have anticipated 58% of patients with dry eye or of certain subtypes would have presented with Demodex infestation, but this was 58% of patients of all types. Also, the study was conducted in the offices of various professionals, including subspecialists and general primary eye care providers. Because Demodex infestation was found in patients visiting their provider for many reasons and in such a wide variety of offices, we expect that this condition is very prevalent. They were fascinating data.
AJMC®: Did you find any notable demographic differences among affected patient populations?
KARPECKI: My assumption going into this study was that we would see a significantly greater incidence of Demodex blepharitis with age. I always assumed that Demodex infestation may be detected in 70% of people aged at least 70 years, 50% of those aged at least 50 years, and approximately 30% of those aged at least 30 years. At some time, I’d been taught that, or at least I had that assumption. We decided that we needed to look into that.
What was surprising was that the prevalence of Demodex infestation was consistent across all age groups. There was not a significant difference from 1 age group to the other. Statistically, prevalence was about the same for 20- to 30-year-olds as it was for 60- to 70-year-olds. That prevalence didn’t correlate with age was an interesting finding.
The second part of the study was also interesting. For example, a slightly larger percentage of contact lens wearers harbored Demodex. Obviously, among patients with blepharitis, 69% showed collarettes. Mixed conditions—meaning that patients also could have staphylococcal blepharitis—may have been involved, but the patients also had Demodex infestation. Some 65% of patients with glaucoma had Demodex blepharitis; that may reflect the prostaglandin analogues that we prescribe for glaucoma patients. Those drops tend to be proinflammatory, and that may promote infestation. I would have expected a 90% correlation or more among patients with rosacea, but that ended up being 60%; however, we had an unexpectedly small sample of patients with rosacea.
The key stand-up point was that there was a lot of consistency. Some 59% of patients with dry eye disease exhibited collarettes, as did 56% of those with cataracts or who were about to have cataract surgery. That may speak a little bit to patient age, although the ages of affected patients were across the board. Finally, 51% of contact lens wearers had collarettes. So Demodex blepharitis is prevalent among patients with many conditions, but especially among those using glaucoma medications, in whom 68% had collarettes. It was interesting to see that the range for contact lens wearers with blepharitis was always between 50% and 70%. It was large in those subtypes that we identified and above 50% across the board. I guess there’s logic for that. The prostaglandin analogues for glaucoma are proinflammatory; these highly inflammatory agents may promote overgrowth of something like a Demodex parasite. Dry eye makes sense, because the parasites—especially the brevis form—probably enter the meibomian glands, which could damage those glands and lead to more dry eye. Patients with cataracts could represent a small percentage of the affected population, and comorbidities could be relatively common. But the incidences among other subgroups (eg, contact lens wearers, patients with rosacea) were still quite high.
AJMC®: Your study examined why patients given a diagnosis of Demodex blepharitis came to the clinic and the reasons for their visits. Can you share the results?
KARPECKI: In those patients with blepharitis, we primarily looked at what they were using for treatment. We already thought that tea tree oil was the better therapeutic option for patients with Demodex blepharitis. But we found that 75% of patients currently being treated with tea tree oil still had a significant prevalence of collarettes. What that first told us is that doctors were doing a good job of recognizing collarettes, which is why they treating patients with tea tree oil. You would not typically treat bacterial—and certainly not seborrheic or otherwise dermatologic—forms of blepharitis with tea tree oil. We found that 75% of people using tea tree oil still had significant collarettes present. They still had Demodex infestation. Perhaps, at mild or moderate levels or even across the board, tea tree oil could have some effect, but we didn’t break it down to that point.
Second, we looked at patients who used standard lid wipes. These are surfactant cleaners, are thought of as antibacterial products, and could have been why those patients who used them had fewer collarettes. However, 57% of patients using lid wipes still had collarettes. If the doctor can differentiate the form of blepharitis—which seemed to be happening—and put patients on tea tree oil, that means that there is a higher incidence of Demodex blepharitis. That’s why they’ve used the tea tree oil. They’ve identified the patient with the disease properly, but the tea tree oil is not clearing the problem.
We found a 51% prevalence of collarettes among patients who were coming in for contact lens examinations. That’s how we recognized the prevalence among patients with glaucoma—we noted that 68% were using prostaglandin analogue drops. Sixty percent of those on dry eye therapies (eg, lifitegrast, cyclosporine) had collarettes. Among those using topical steroids, 50% had collarettes. Their reasons for visits helped us to calculate percentages and form subgroups. We still noted whether patients had, for example, meibomian gland dysfunction but weren’t at a disease state. Among that group, 57% had collarettes.
In all cases, there was a very diverse group of examinations, but we still noted a very high prevalence of collarettes. There were 7 medical investigators at 6 different sites. Data were included for over 1000 patients. That’s how we could assess patients coming in for cataract evaluation or for cataract surgery. For those individuals, the examination was not to evaluate the possibility of having blepharitis.
AJMC®: Study results also indicated that many patients with collarettes were misdiagnosed. Could you describe these results and what they suggest about the misdiagnosis or underdiagnosis of this disease in the United States?
KARPECKI: I’ve always been fascinated how, until we have a therapeutic for a certain disease, we tend to underdiagnose it. It doesn’t make a lot of sense, because we still would give the diagnosis, even if we didn’t have treatments that were extremely effective, so we could identify and treat those patients in the future. For the most part, we are taught to look for a condition if we have a therapy available to treat it. We don’t have a therapy to prescribe for Demodex blepharitis at this point, and I don’t think doctors know to look for clues to make this diagnosis. They don’t know how to differentiate it from other conditions. They are relatively good at diagnosing blepharitis, but they don’t tend to differentiate the staphylococcal, dermatological, seborrheic, and Demodex infestation forms of the condition. That’s why Demodex blepharitis is underdiagnosed. Seasoned practitioners will use the slit lamp for its diagnosis, but this practice is not universal.
Further, our medical coding system (ie, International Classification of Diseases, 10th Revision) lacks a specific code for Demodex blepharitis that’s easily identified and recorded.2 Many patients are simply given a broad diagnosis, at best, and there’s nothing that allows differentiation. Providers who detect Demodex blepharitis should record it that way, but most providers do not.
AJMC®: What are the consequences of misdiagnosis or underdiagnosis of Demodex blepharitis?
KARPECKI: That’s very important. Many times, we may deal with a benign condition; not like glaucoma where someone can lose vision or go blind. I would include blepharitis with those types of benign conditions—providers are less concerned about treating it unless a patient is highly symptomatic. That’s an error, and there are common consequences of not treating affected patients. I have patients who may not have symptoms of blepharitis, but I note the presence of collarettes. I have to treat them and resolve the issue, and I tell the patient that, too. I say, “If I don’t treat this, it will progress and lead to long-term issues.” These include development of chronic immune-mediated dry eye disease; if those glands are significantly affected, patients will need anti-inflammatory agents, immunomodulators, and certain supplements, among other therapies, for the rest of their lives.
There is a point when dry eye disease becomes chronic and progressive and affects the oil glands, which are critical to maintaining tear film. Dry eye disease also can lead to hordeola—or styes—and chalazion. Those are somewhat disfiguring if you have enough of them. The early stages of hordeola are painful. Patients don’t like how they look, and multiple hordeola affect the eyelid contour or proper apposition. In turn, improper apposition could lead to more dry eye and more disease formation. Exposure keratitis, in which the eyes don’t close properly, can lead to more eye exposure and corneal damage. Further, lash loss or thinning of lashes may occur; both men and women complain about how thin their lashes become, and they eventually lose their lashes. Some patients have scalloped eyelid margins, which involves atrophy of the glands. Demodex blepharitis is one of the more common culprits for these problems.
Dry eye related to Demodex blepharitis may affect a patient’s ability to wear contact lenses. It also may cause chronic inflammation, associated comorbidities, and other forms of blepharitis. Pterygium is chronic inflammatory condition associated with a fibroblastic growth that eventually may cause significantly decreased vision. Patients don’t appreciate chronically red eyes and eyelids that make it look like they’ve been drinking, smoking, or crying. Those are just some of the consequences of not treating Demodex blepharitis.
AJMC®: What advice about screening for this disease do you have for clinicians?
KARPECKI: During a regular slit-lamp examination, simply have the patient look down. Look for these sleeves at the base of the lashes. You don’t need to do anything more complex than that. Clinicians have purchased microscopes to look at the lashes of patients having a red skin tone to determine the prevalence of Demodex infestation. Still, there is no need for anything more complex than a physician doing a slit-lamp examination of the lashes as a patient looks downward, and everyone has that equipment.
In addition, look for grittiness, irritation, and dryness of the eyes. When itching is mentioned, many practitioners commonly consider allergic conjunctivitis, since itching and allergies go together. However, good insight would include asking the patient the location of itching, since that manifestation of irritation is the most common symptom of Demodex blepharitis. If it’s in the canthi, it’s probably more allergic conjunctivitis in the corner. However, if the patient points to or shows the lash margin or the eyelid margin, then they typically are affected by Demodex infestation.
AJMC®: Studies of the incidence of Demodex blepharitis in the United States are limited. Additional estimates of the global prevalence exist but vary widely. Studies from individual countries report the detection of Demodex mites in 30% to 90% of patients with blepharitis. How can we learn more about this disease and its prevalence? What would you like to see from future studies?
KARPECKI: I’d love to see longitudinal studies that help us understand progression of the disease. A lot of clinical complications that have been described occur in our patients. That provides a clinical perspective of what we see in specific patient populations. Depending on the sort of studies that point to that progression, those studies would be clinically valuable. In addition, we have international studies on prevalence and subtypes related to age, but we need more of them. Doctors will start looking for Demodex blepharitis when treatments become available. Finally, the social and cosmetic impact—the psychosocial impact—on patients with this disease must be considered. Many times, the human component is overlooked by clinicians looking at the disease itself and ocular findings. Affected patients experience considerable effects that warrant a diagnosis and subsequent treatment.
AJMC®: Demodex blepharitis has been reported in a majority of patients with dry eye disease, and it may be a precursor to the disease. Do prevalence studies of Demodex blepharitis in dry eye disease provide a firm foundation to estimate the economic impact of this condition? If not, what factors might managed health care professionals consider as they estimate the economic burden of Demodex blepharitis?
KARPECKI: You can get an idea of it. There’s no doubt that tying prevalence to existing evidence is a central problem. There’s a lot of overlap that occurs between dry eye and Demodex blepharitis that gives us an estimate, but it goes beyond that. There are some patients with dry eye who avoid work and other people; they have that burden from that standpoint. That burden is greater among people with Demodex blepharitis. There is more of an impact on productivity, activity, and presenteeism or absenteeism. The disease probably would be underestimated by looking at patients with dry eye, because those with the worst symptoms more likely have Demodex blepharitis. We can get a little more specific to that group in terms of costs.
We have approved therapies for dry eye disease that work for some patients. We don’t have that for Demodex blepharitis. People may have to spend more money to try different things. More aggressive treatments, like intense pulsed light therapy, are very costly and not covered by insurance.
The burden from a financial standpoint is also greater in terms of the limited number of available treatments for these patients. We don’t have as many options as we would with dry eye disease. And treatments that work temporarily are quite costly and often are not covered by insurance. There are many other factors unrelated to the cost burden that include the time required to treat, the need to try different treatments, and the effectiveness of certain scrubs. Also, since we’re diagnosing slowly, we tend to have more severely affected patients who have a far greater burden than does a patient with dry eye disease who is getting a diagnosis early. More specific data on Demodex blepharitis and other types of the disease would be beneficial. Demodex blepharitis is far more debilitating to patients than are other forms in terms of the lash loss, visual effects, dry eye, and other symptoms. That alone involves a more significant financial burden.
AJMC®: Are there major takeaways from the study that you would like to highlight?
KARPECKI: We must look for Demodex blepharitis in all patient types. No patient subgroup studied had a significantly higher percentage of the condition than did the others. We want to consider all patients—from those seeking contact lenses to others investigating cataract surgery—instead of specifically focusing on individuals with ocular surface disease, dry eye disease, or symptoms that appear to be related to blepharitis.
The second key component is age. We may have falsely assumed that we’re going to see a dramatically greater incidence as patients get older. Actually, Demodex blepharitis presents among individuals in all age categories. Finally, the differential diagnosis is important; this disease must be differentiated from other conditions (eg, allergies), because itching is a common symptom. Further, we must scrutinize individual cases to differentiate Demodex blepharitis from other types of the condition; lid scrubs and surfactants are being used instead of something that targets the Demodex infestation. Because of the potential cosmetic, medical, and financial burden on patients with this chronic, progressive disease, we must make a diagnosis promptly and give patients hope for future treatments.
Dr Karpecki is associate professor at Kentucky College of Optometry.
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. World Health Organization. International Classification of Diseases, Tenth Revision, Fifth Edition. World Health Organization; 2016. Accessed August 17, 2022. https://icd.who.int/browse10/Content/statichtml/ICD10Volume2_en_2019.pdf
For other articles and videos in this AJMC® Perspectives publication, please visit “The Evolving Landscape of Demodex Blepharitis Management.”