Optometry & Vision Science:
doi: 10.1097/OPX.0b013e3182968c77


Hom, Milton M.*; Mastrota, Katherine M.; Schachter, Scott E.

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Private Practice, Azusa, California (MMH); Omni Eye Surgery, New York, New York (KMM); Southern California College of Optometry, Fullerton, California (SES); and Private Practice, Pismo Beach, California (SES).

Milton M. Hom, 1131 East Alosta Ave, Azusa, CA 91702; e-mail: eyemage@mminternet.com

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Purpose: Demodex folliculorum and Demodex brevis are ectoparasites with an astounding prevalence of 100% in patients aged 70 years and older. Every person in this age group is estimated to carry a colony of 1000 to 2000 mites. With such a high prevalence, little attention has been paid to the mite among eye care practitioners. We demonstrate a clinical sequence in a set of case reports to identify the mite. The clinical sequence includes a clinical history of blepharitis, dry eyes, and/or ocular allergy; slit lamp examination of cylindrical dandruff; and confirmation using light microscope evaluation of epilated lashes.

Case Reports: Patient 1 was a 68-year-old woman who demonstrates associations with dry eyes and diabetes. Patient 2 was a 44-year-old man with uncommonly seen D. brevis present. Patient 3 was a 40-year-old woman with dry eyes and allergy, showing mite tails protruding from base of lashes. Patient 4 was a 60-year-old woman who demonstrates the association with rosacea. Patient 5 was a 53-year-old woman intermittently taking topical steroid and antibiotic combination medications, with an actual mite photographed on the surface.

Conclusions: Following a clinical sequence helps identify Demodex, the underdiagnosed, undertreated, and underappreciated ocular surface disease.

Demodex folliculorum and Demodex brevis are ectoparasites with a prevalence of 100% in patients aged 70 years and older.1 Demodex is regarded as the most common ectoparasite in humans.2 Demodex folliculorum resides in the lash follicles and relies on sebum as its main source of food.3 Despite high prevalence, little attention has been paid to the mite among eye care practitioners. The purpose of this case series is to explore the diagnosis of demodicosis with a clinical sequence within multiple optometric practices.

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Demodex colonization in humans is high (20 to 80%) and reaches 100% in elderly people.4–7 Alejo et al.8 described D. folliculorum in the lids of 50% of randomly chosen Filipino patients at the Philippine General Hospital. Demodex is considered to be acquired soon after birth. It has been found to be present in young infants.9 Numbers vary from study to study, but studies agree that the prevalence of Demodex trend increases with age. The prevalence is only about 13 to 20% in patients younger than 20 years and approaches 95 to 100% by age 71 years.1,4,10 Not only does prevalence increase with age, but average numbers of Demodex per patient also increase.5 Gutierrez9 estimates that every person carries a colony of 1000 to 2000 mites and is part of the normal skin fauna where there are hair follicles.4,9 Thousands often exist on one person, and the mites show a high propensity to reproduce. Coston11 states “Consider the scrambling of this microscopic octopoded mob while the host sleeps: males seeking, finding, breeding females; gravid females seeking new follicles; inhabitants of follicles sweeping feces outside.”

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Clinical sequence was followed for all of the cases, modified from Liu et al.12:

1. Clinical history: a high index of suspicion when anterior blepharitis, meibomian gland dysfunction (MGD), dry eyes, and/or ocular allergy is present.

2. Slit lamp examination: typical cylindrical dandruff (CD) at the root of eyelashes.

3. Microscopic confirmation: detection and counting of Demodex eggs, larvae, and adult mites in epilated lashes.11,12

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Several studies have connected Demodex with blepharitis. Sumer et al.13 showed that 62.9% of chronic blepharitis patients had Demodex. Alejo et al.8 diagnosed 88% of the blepharitis patients with Demodex. De Venecia and Siong14 found that 95% of anterior blepharitis and 97% of anterior and posterior blepharitis had Demodex. Zhao et al.15 performed a meta-analysis of 11 articles and found Demodex and blepharitis to have a statistically significant association.

Dry eyes are a classic symptom of MGD and blepharitis.16,17 Demodex has been reported to increase Ocular Surface Disease Index scores.6 What is interesting is Demodex has been associated with dry eye but not necessarily with aqueous tear deficiency based on Schirmer scores. Some studies have shown normal Schirmer test scores with patients with mite infestation.6,18 In fact, aqueous deficient dry eye has been theorized to interfere with Demodex. The mite may thrive better with normal tear volume as opposed to a tear-deficient state.19 The other major category for dry eye is evaporative. There is support for evaporative dry eye and Demodex. With respect to MGD, De Venecia and Siong14 found 85% of MGD patients had Demodex. Kheirkhah et al.20 found that five of six patients with Demodex and corneal findings displayed MGD.

For ocular allergy, there are positive correlations between mite infestations and conjunctival papillary reactions. Groups with conjunctival papillary hypertrophy often have allergies that may be caused by Demodex.6 The debris and wastes from the mites may elicit an inflammatory response.12 The presence of papillary conjunctivitis and itching can lead a clinician to diagnose ocular allergy instead of Demodex.

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The main symptoms are ocular dryness, severe itching, burning, foreign body sensation, crusting, and redness of the lid margin and blurry vision.5,12,18 The most common eye symptoms were itchiness and foreign body sensation.20 Other reported signs and symptoms were subjective lash loss, heavy lids, and misdirected lashes.21

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One notable characteristic of the infestation is the past unresponsiveness to conventional treatments for blepharitis, dry eye, and allergy. Patients will have a history of trying out different treatment strategies with little to no success. The failed treatments are typically for ocular surface conditions mainly because the infestation has many of the same signs and symptoms. Ineffective treatments include artificial tears, cyclosporine, antihistamines, doxycycline, lid hygiene, baby shampoo, and steroids.

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Cylindrical or cuff dandruff is a fine, waxy, sometimes dry, debris seen with slit lamp at the base of lashes contiguous with the lids. A smooth transparent collar of mite feces, keratin, and lipids surrounds the bases of lashes for 1 to 2 mm. This collar has the appearance of sometimes clear plastic insulation about the lash.11,22,23

One hundred percent of the patients with CD have Demodex infestation. Gao et al.24 found that the average count of Demodex was 12.9 mites per patient with CD compared with 0.35 mites without. The significant difference was more than 30 times higher when CD is present. Clinical severity judged by CD correlates well with greater numbers of Demodex.24

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Demodex is extremely difficult to see with the naked eye and requires magnification. The size of a mite is about half the diameter of a grain of table salt.25 The bodies of both D. folliculorum and D. brevis are worm shaped. The gnathosoma is composed of the mouth and feeding parts. Gnathosoma has sharp stylet-like chelicerae used to cut and take food. Pedipalps are used to hold the food. The rest of the body consists of the head and neck area called prosoma or prodosoma. Adults have four pairs of legs in the prosoma. Opisthosoma forms the tail.26 The morphology has been described and measured by Desch and Nutting27 (Table 1; Fig. 1).

Table 1
Table 1
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Figure 1
Figure 1
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When viewing with the microscope, identification of Demodex is easier with knowledge of relative sizes for comparison. Adults are distinct, with well-developed head, neck, and legs. The other forms are more difficult to identify. In 1842, Simon identified D. folliculorum to be 0.3 to 0.4 mm long.3 The adult folliculorum average length for both males and females is about 0.286 mm, calculated using Desch measurements. Larva (length, 0.283 mm) is about the same length and width. Protonymph (length, 0.364 mm) is about 25% or one-fourth longer than the adult, with about the same width. Nymph or deutonymph (length, 0.392 mm) are much longer than adults, about 35 to 40% longer and 15 to 20% wider. The size range of 0.3 to 0.4 mm stated by other authors probably includes adults and the larger nymphs (based on Desch findings). Demodex brevis adult average length for males and females is 0.186 mm and about 50% shorter in length than D. folliculorum.

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Sampling the lashes with CD is more likely to yield better results than random epilation.23 Demodex usually resides in compact and opaque CD or deeper in the follicle. Because of this, Demodex can be very difficult to detect. Addition of fluorescein or alcohol has been used to enhance viewing with a microscope of the epilated lash.23,24 Fluorescein solution creates a yellowish contrast and induces instant dissolution and expansion of CD. Together, both properties helped significantly increase detection of mites compared with the time before the fluorescein was added. When the CD is immersed in fluorescein, it becomes semitransparent. This allows better viewing of mite structures within and behind the CD.23

Alcohol is effective in enhancing microscope confirmation of mites present. Gao et al.24,28 found that Demodex embedded in CD could not be counted unless 100% alcohol is added to stimulate them to migrate out. Drawbacks of alcohol were sometimes it could take up to 20 minutes for the mites to become visible. Alcohol can also kill the mite in 3.9 minutes.24,28

Coston11 described the original method of epilation and viewing. He advocated random epilation of four nonadjacent lashes per lid and adding a drop of oil before mounting the coverslip. Gao et al.24 improved the method to epilate lashes with CD, instead of random lashes, and to add alcohol. The method has been further modified by Kheirkhah et al.23 to add fluorescein at the edge of the coverslip11,24 (Table 2; Fig. 2).

Table 2
Table 2
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Figure 2
Figure 2
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The focus of these case reports is detection and diagnosis of the infestation. However, current treatment for this condition includes lid hygiene and tea tree oil lid scrubs and shampoo.5,6,11,12,21,25,29 As stated before, the following cases used the clinical sequence outlined previously.

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Patient 1

A 68-year-old woman has been diagnosed with diabetes since 2008 and has been taking oral medications for the condition. The patient complained of dryness all the time and no itchiness or redness. Meibomian gland expression appeared opaque and solid (toothpaste-like) in both eyes. Schirmer test results were OD 10 mm OS 11 mm. There was moderate to severe amount of lid debris (flakes and crusting) in both eyes. There was no debris in the tear film. Diffuse CD was present with less than 10 pieces per eye, as classified by Gao et al.24 (Fig. 3). There was moderate distention of the follicles in both eyes. Lashes were epilated and viewed under a liquid-crystal display microscope (Celestron 44340 LCD Digital LDM Biological Microscope). Demodex was present in both eyes.

Figure 3
Figure 3
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Patient 1 Discussion

This case demonstrates severe dryness symptoms but no itching or redness. Based on the observations of Koo et al.,5 less than one-half of Demodex patients have itching or redness. They identified that the most common symptom for Demodex was ocular dryness (74.7%), followed by itching sensation (42.7%), ocular irritation (39.1%), visual disturbance (32.0%), conjunctival injection (9.9%), and glare (3.6%). Schirmer test results were normal. Based on lid expression and the amount of lid debris, a diagnosis of evaporative dry eye or blepharitis could be made. Because the Schirmer test results were normal for this patient, aqueous deficient dry eye could be ruled out. However, a closer examination of the lids reveals a diffuse amount of CD, pathognomonic for Demodex, along with the lid debris. As mentioned previously, literature points to the link between MGD and blepharitis with Demodex.14,20

Three studies have associated diabetes with Demodex infestation.30–32 Yamashita et al.30 studied 42 patients in each group (control and Demodex). They found no statistically significant differences between the control and diabetes groups with regard to age and sex in both groups (p > 0.05). Demodex folliculorum was significantly more prevalent in diabetic patients (27.4%) than in control patients (19.0%).30 Clifford and Fulk32 analyzed the prevalence of Demodex on 256 subjects and also concluded that mites were more abundant in patients with diabetes. Akdeniz et al.31 found a significantly higher mean mite density and bigger mite mean size on cheek biopsy of diabetic patients compared with a control group. Both Yamashita et al.30 and Clifford and Fulk32 examined lash follicles, whereas Akdeniz et al.31 did not. The relationship between diabetes and Demodex has been theorized as a result of peripheral vascular insufficiency. Persons with diabetes may have a reduced ability of their immune systems to control mites because of vascular insufficiency.31–33

In contrast, Lee et al.6 found no relationships between Demodex in lashes and systemic diseases such as diabetes and hypertension. The number of subjects with diabetes was not stated. Lee et al.6 mention the study by Forton et al.,33 where 96% of their Demodex patients were healthy. Forton et al.33 only found three patients with diabetes in his Demodex sample of 115 patients. Forton et al.33 did not study lash follicles but found Demodex by skin biopsy.6,33

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Patient 2

A 44-year-old Hispanic man presents with moderate to severe dry eye. The patient reported the frequency of dryness and redness to be sometimes (mild). Meibomian gland expression appears clear to mildly opaque, few particles, low viscosity. The cornea was clear in both eyes. There was mild bulbar conjunctival injection and a diffuse amount of CD present in both eyes. The lids appeared to be mildly greasy, with a mild amount of distention at the base of the lashes. Epilation of two lashes from each upper lid reveals Demodex present. On one follicle, the microscope at 10× showed D. brevis (Fig. 4).

Figure 4
Figure 4
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Patient 2 Discussion

Of the two species in humans, D. brevis is not commonly seen in the general population. Demodex brevis normally resides singly in the sebaceous and meibomian glands.14 Because the mite is not usually found on the lash follicles, detection after epilation is rare.3 Gao et al.24 reported that five of 422 epilated specimens were D. brevis. According to Tseng, the prevalence of D. brevis is 9.1%.14 From an eye care practitioner’s point of view, D. brevis may be rarely seen and may require more lashes to be epilated.19 But, in the big picture outside the lids, D. brevis does inhabit a larger area of the human body compared with D. folliculorum.26

In 1963, Akbulatova first identified D. brevis.3,22 Demodex brevis is typically smaller than D. folliculorum and has a spindle shape and stubby legs.3 Demodex brevis presence is much higher in patients who developed corneal lesions, such as peripheral and nodular scarring, vascularization, and central opacities.3,14 Because D. brevis primarily resides in meibomian glands, the inflammation has greater proximity and might more easily reach the conjunctiva and the cornea.19 In this case, the patient did not have any corneal abnormalities.

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Patient 3

A 40-year-old white woman presented with a history of allergies and dry eyes. There was MGD present (opaque or many particles with medium viscosity) in both eyes and inferior nasal and temporal lissamine green staining in the right eye. The right eye also had grade 1 corneal infiltration in the peripheral cornea. Closer examination of the lids revealed CD (diffuse amount; greater than 10 pieces per eye) in both eyes and the appearance of D. folliculorum tails (Fig. 5).

Figure 5
Figure 5
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Patient 3 Discussion

Demodex avoids light, and it is unusual to see the mites under a biomicroscope.11 Demodex mites position themselves with their heads upside down in the deeper parts of the follicle. The elongated bodies protrude with their tails (opisthosoma) from the follicle in groups of three to five mites.34,35 Infrequently, the tails can be seen under the bright illumination of a biomicroscope. The tails have been described as cream-colored tails protruding from the lid margin like fine bristles.11,22 Because of their photosensitivity, most of the mating and movement of the mite are believed to occur at night. Mating plays an important role in perpetuating Demodex infestation because of the limited life span of 1 to 2 weeks for the adults.1,12 Females are territorial; they remain in their respective follicles and wait for the nomadic males that travel over the surface of the skin from one follicle to another in search of females. After copulation, the female burrows back into the follicle near the opening of the pilosebaceous gland and lays her eggs.35 Larva and protonymph develop in the sebaceous gland. They are brought to the opening of follicle and mature into deutonymph. Deutonymph crawls onto skin surface and reenters a hair follicle to become an adult.3 All of this movement likely happens in the dark.

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Patient 4

A 60-year-old white woman with a history of rosacea came in with complaints of eyelid swelling, redness, and loss of lashes. She is currently using oral antihistamines for a history of allergy. In the past 3 years, she was prescribed topical antihistamines and a combination of steroid and antibiotic for eyelid inflammation, with no success. Meibomian gland dysfunction was grade 2+ OU and conjunctival redness grade 1+ OU. Mites were present on epilated lashes under the microscope.

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Patient 4 Discussion

In 1930, Ayers called attention to D. folliculorum as a causative agent of Pityriasis folliculorum and one type of acne rosacea.11 Since that time, several studies show an association between Demodex and rosacea.33,34,36–41 For years, skin biopsy was the definitive dermatological test for Demodex. One study performed skin biopsy on rosacea patients and normal subjects. Rosacea patients had an average of 12.8 mites per square centimeter of skin; significantly greater than 0.7 mites per square centimeter in normal subjects.40 A meta-analysis has added further support to the association. Zhao and colleagues41 performed a meta-analysis of 48 separate studies done in 10 different countries on 28,527 subjects. Rosacea patients are seven to eight times more likely to have Demodex infestation.41

There are two bacterial links that may explain the connection between Demodex and rosacea. Bacillus oleronius has also been detected inside the digestive tract of the mites.12 Li et al.19 looked at 59 rosacea patients and found a significant correlation among serum immunoreactivity to bacillus antigens, Demodex infestation, and facial rosacea.19,26 Their study confirms the presence of bacillus in both the gut of the mite and rosacea patients. The second bacterium implicated is Staphylococcus epidermis, which was found in the pustules of the rosacea patients, but not in healthy (rosacea-free) skin. The theory is that Demodex serves as a carrier of Staphylococcus to areas where the bacteria can proliferate on the host.26 Once Demodex mite infestation establishes in the face, it is likely to spread and flourish in the eyelid.3

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Patient 5

A 53-year-old woman with moderate dry eye signs and symptoms has been taking topical steroid–antibiotic combination off and on for the past 2 years. She is also taking 4% cromolyn eyedrops four times a day. The patient has a history of allergies. Meibomian gland dysfunction grade 2 OU is present. Cylindrical dandruff, eyelid edema, greasy oily debris, and telangiectasia were present in both eyes. On epilation of lashes, a mite appeared on the lash (Figs. 6, 7).

Figure 6
Figure 6
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Figure 7
Figure 7
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Patient 5 Discussion

The appearance of an actual mite on the surface in Figs. 5 and 6 is a rare occurrence. As stated previously, Demodex is highly photophobic and avoids light. Coston11 writes that he has seen hundreds of mites appear in severely infested lids but has never seen a mite emerge completely.

Two modern techniques allow imaging of Demodex in vivo. Sattler et al.34 used confocal laser scanning microscopy to view lesional skin in 25 patients with rosacea. If imaged partially sideways, the mites were detected as lengthy cone-shaped structures similar to their appearance under the light microscope.34 The high-definition optical coherence tomography imaging is another new technique for detecting mites. The detection rate of Demodex mites by high-definition optical coherence tomography in infested patients was significantly higher than in healthy controls.36 Maier et al.36 imaged 20 rosacea patients and found 192 mites versus 13 mites seen in the control group. Both techniques are noninvasive compared with traditional methods such as epilation or skin biopsy.

Demodicosis can manifest itself in many patients in different ways and needs to be diagnosed properly.42 To paraphrase Forton et al.,33 although Demodex are greatly underdiagnosed, they nevertheless concern the daily practice of the eye care professional.

Milton M. Hom

1131 East Alosta Ave

Azusa, CA 91702

e-mail: eyemage@mminternet.com

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We acknowledge Jerry Paugh, Alan Sasai, and Leonard Bielory for their encouragement and enthusiastic support.

Received February 4, 2013; accepted March 6, 2013.

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Demodex; meibomian gland dysfunction; dry eye; blepharitis; evaporative dry eye; Demodex folliculorum; Demodex brevis; demodicosis; diabetes; parasite

© 2013 American Academy of Optometry


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