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DEMODEX , ON by DIAGNOSIS AND Steven Duck (1736) Dear Madam, did you never gaze, MANAGEMENT Thro' Optic-glass, on rotten Cheese? There, Madam, did you ne'er perceive A Crowd of dwarfish Creatures live? The vain, Lords of their plelittle Things, elate with Pride, Strut to and from, from Side to Side: In tiny Pomp, and pertly asing Orb, they reign; And, fill'd with harden'd Curds and Cream, Think the whole Dairy made for them. So Men, conceited Lords of all, Walk proudly o'er this pendent Ball, Fond of their little Spot below, Nor greater Beings care to know; But think, those Worlds, which deck the Skies, Scott E. Schachter, O.D. Were only form'd to please their Eyes. Vision Source-Pismo Beach, CA

WHERE IS THE For thirty years, under NEAREST ? slit-lamp magnification, I Most likely on the end of the studied patients with nose or in the lid symptoms, follicles of the reader. unaware that mites were literally”at the -T.O. Coston, M.D., 1967 root"of the trouble.

-T.O. Coston, M.D., 1967

BLEPHARITIS Swelling or inflammation of the , usually where the eyelash hair follicles are located. The most common lid margin READ THIS! disease.

Coston, Tullos O. " folliculorum Common Causes of Blepharitis: blepharitis." Transactions of the • Demodex Infestation American Ophthalmological Society 65 • Excessive oil, MGD • Excessive bacteria (1967): 361-392 • Allergies •

Increasing severity, A-H

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HUMAN An Often Overlooked Link to DEMODEX Blepharitis Demodex Infestation TYPES Brevis • shorter .2-.3mm • live in oil glands • harder to find • posterior blepharitis, chalazia, rosacea • solitary Folliculorum • longer .3-4mm • live in follicle • anterior blepharitis, rosacea • live in clusters

ANATOMY AND LIFE CYCLE CYLINDRICAL DANDRUFF

30 minutes time lapsed

Male folliculorum sex organs

A rare sighting

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Laying an egg FOLLICULORUM Adults and Nymphs

Demodex Mites Linked to Lid Margin Demodex Mites Linked to Many Lid Margin & Diseases through Various Mechanisms Ocular Surface Diseases

Demodex Mites1: 1. Mechanically block hair follicles • 2. Secrete digestive enzymes Blepharitis • 3. Destroy the epithelial barrier and penetrate into surrounding tissue Meibomian Gland 4. Trigger reactions of the immune system as a foreign body and as Dysfunction their waste is exposed upon death and decay • Rosacea 5. Transport bacteria around the ocular and surface • Chalazia • Pterygia

Results in irritation, inflammation, and unhealthy dermis and epidermis

1Jarmuda, Stanislaw et al. Potential Role of Demodex mites and bacteria in the induction of rosacea. Journal of Medical Microbiology. 2012; 61;1504-1510.

High Age-Dependent Prevalence of Ubiquity and Diversity of Ocular Demodex Infestation -Associated Demodex Mites

Eyelashes from 435 people with ages from 2 to 96 years were examined under a light microscope. Demodex infestation was classified on the 100% of people over 18 years of age appear to host basis of presence of mature and larval forms or after observing chitinous at least one Demodex species exuviae (cylindrical dandruff) affixed to the subjects eyelashes1

95% in 71 to 96 year-old • N = 29 87% in 51 to 70 year-old 69% in 31 to 50 year-old • Mites found in 70% of 18 yo 34% in 19 to 25 year-old 13% in 3 to 15 year-old • Verified by DNA scrapings

Thoemmes MS, Fergus DJ, Urban J, Trautwein M, Dunn RR (2014) Ubiquity and Diversity of Human- 1Czepita, D. et al . Investigations on the occurrence as well as the role of and Associated Demodex Mites. PLoS ONE9(8): e106265. https://doi.org/10.1371/journal.pone.0106265 in the pathogenesis of blepharitis. Klin Oczna 2005;107(1-3):80-2

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If Demodex is so common, why isn’t Diagnosing Demodex everyone symptomatic?

Symptoms and conditions occur when a Demodex population overgrowth or infestation occurs () Cylindrical dandruff (CD) is diagnostic for Demodex mites1,2 What causes an infestation?

• Because the eye is surrounded by the projecting bones of the eyebrow and nose, hygiene in this area can be limited1 • Research suggests that altered fatty acid profiles produce sebum that Diffuse CD Sporadic CD Greasy Scales Clean is favorable for mite development2 • Demodex Infestations are more prone in patients whose immune status is compromised by topical or systemic administration of steroids or other immunosuppressive agents3

1Liu, Jingbo et al. Pathogenic role of Demodex mites in blepharitis. Current Opinion in Allergy and Clinical Immunology. 2012; 10: 505-510. 2Ni Raghallaigh, S., et al. The fatty acid profile of the skin surface lipid layer in papulopustular rosacea. Br Journal of Dermatology. 2012; 166; 279-287 1Coston, Tullos. Demodex Folliculorum Blepharitis. Tr. Am. Ophthalmology Soc. 1967; 65:361-392. 3Kulac, M. et al. Clinical importance of Demodex folliculorum in patients receiving phototherapy. Int J Dermatology. 2008; 47:72-77 2Gao, Ying-Ying et al. High Prevalence of Demodex in with Cylindrical Dandruff. IOVS. 2005; 46:3089-3094.

Diagnosing Demodex Demodex Blepharitis is Frequently Associated

with Conjunctival Inflammation1 Lash Epilation or Rotation & Microscope Examination Tips Consider Demodex as a possibility when you see • Lash selection is important: crusty, lots of debris and mucus blepharitis with conjunctival inflammation • Rotate or twirl the lash to better express debris and mites • Use fluorescein on the slide for better mite visibility1 • Sample two from each lid • Examine under 100x magnification

Supplies • Epilation forceps • Glass slides and cover slides • LCD Digital Microscope Celestron LCD #44345 (40x – 1600x total Eyelash manifestation magnification) • Trichiasis, malalignment, madarosis

1Scott G Hauswirth, Scott E Schachter, and Milton M Hom 1Kheirkhah, Ahmad et al. Fluorescein Dye Improves Microscopic Evaluation and Counting of Demodex in Symptoms Associated with the Presence of Demodex folliculorum Blepharitis With Cylindrical Dandruff. Cornea. 2007; 26: 697-700 Invest. Ophthalmol. Vis. Sci. 55: E-Abstract 1996.

Skin Manifestation Meibomian Gland Manifestation Demodex mites live in and feed on the oil in the sebaceous Demodex has been linked to rosacea, pityriasis folliculorum, glands. Demodex Brevis in particular is most commonly perioral dermatitis, pustular , and basal cell carcinoma1 found in the meibomian glands.1

1Liu, Jingbo et al. Pathogenic role of Demodex mites in blepharitis. Current Opinion in Allergy and Clinical 1Coston, 1967, English, 1971, English & Nutting, 1981, Heacock,1986, Fulk & Clifford, 1990, Fulk et Immunology: 2012; 10: 505-510. al, 1996, Kamoun et al. 1999, Morfin, 2003

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Statistically Significant Correlation between Demodex Infestation and Serum Immunoreactivity Study Reports Demodicosis is Significantly More

to Bacillus Oleronius in Rosacea Patients1 Prevalent in Chalazia than Control1 all P<0.001 • A prospective, masked study of 59 age-matched patients • The Demodex count was statistically significantly higher in patients with facial rosacea (6.6 ± 9.0 vs. 1.9 ± 2.2, P=0.014). • A statistically significant correlation between serum immunoreactivity and facial rosacea (P=0.009), lid margin inflammation (P=0.040), and ocular Demodex infestation (P=0.048), but not inferior bulbar conjunctival inflammation (P=0.573). • A statistically significant correlation of facial rosacea with lid margin inflammation (P=0.016), but not with inferior bulbar conjunctival inflammation (P=0.728).

1Li, Jianjing et al, Correlation between Ocular Demodex Infestation and Serum Immunoreactivity to Bacillus Proteins in Patients with Facial Rosacea. Ophthalmology, 2010; 117:870-877. 1Liang et al, Am. J. Ophthalmol., in press, 2013

Infestation of Particular D. Brevis Is Significantly Study Reports that Ocular Demodicosis is a Risk

More Prevalent In Chalazia Than Control1 Factor for Pterygium Recurrence1 With Without Brevis and Folliculorum Infestation BREVIS Total P in Chalazia and Control Demodicosis Demodicosis Eyes 68 34 34 M:F 43:25 27:7 16:18 0.006 Age 51.9±14.3 53.2±14.4 50.6±14.2 0.448 Range 26-80 27-77 26-80 FOLLICULORUM follow-up Follow-up (M) 15.7±8.7 17.3±13.9 0.568 (M) Range 6-72 6-40 6-72 Entire Pediatric Adult Brevis Folliculorum Brevis Folliculorum Brevis Folliculorum Recurrence 16 (23.5%) 14 (41.2%) 2 (5.9%) 0.001 all P<0.001 ATD Dry Eye 25(36.8%) 16 (47.1%) 9 (26.5%) 0.078

1Huang, Yukan et al, Ocular Demodicosis as a Risk Factor of Pterygium Recurrence. Ophthalmology, 2013; 1Liang et al, Am. J. Ophthalmol., in press, 2013 120:1341-7.

Clinical Evidence on the Role of Eye Hygiene in THE OLDE WAY Managing Lid Margin Diseases (The Janitor)

NONE of these kill mites

Approach Targets Warm compress Oil glands

Baby shampoo Lid margin, lashes

Lid scrub Lid margin, lashes

Topical antibiotics Microbes AFTER 1 MONTH OF AT-HOME TREATMENT, 22 YO MALE Omega-3 fatty acids Inflammation

Oral Tetracycline/Doxycycline Microbes

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Study Shows that Conventional Treatment Methods Are Not Effective in Killing DEMODEX Tea Tree Oil is MITES1 the Cannot be killed by 10% Providone iodine (surgical scrub) EXTERMINATOR Cannot be killed by 75% alcohol

Cannot be killed by Macrolides such as erythromycin (antibiotic)

Cannot be killed by Metronidazole (for Rosacea treatment)

Demodex mites killed dose-dependently by Tea Tree Oil (TTO) 1Gao, Ying-Ying et al. In vitro and in vivo killing of ocular Demodex by tea tree oil. Br J Ophthalmol, 2005;89;1468- 1473.

Treatment with TTO Before After 8 weeks Before

Example 1: Blepharitis

After

Before After 6 weeks Example 2: Conjunctival inflammation

1Kheirkhah, Ahmad et al, Corneal Manifestations of Ocular Demodex Infestation. AJO, 2007; 143:743-749.

INNOVATION

OKRA-based Zocukit

-Well-tolerated, no anesthetic required -Commercially available -Low cost of goods -Takes about 8 minutes-

RS, 70 yo F • OD, June 2014 and September 2014. • Did Cliradex bid, OU x 1 month. Now twice per week.

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INNOVATION PRACTICE MANAGEMENT Intense Pulsed Light How to talk to patients: “You have a very common condition, affecting about 25% of my -Likely kills demodex patients. It’s caused by a small mite. Most people have SOME of these -Effective against rosacea mites, you have TOO MANY, and we need to reduce the population”. -Low/no cost of goods -Takes about 5 minutes- If you think compliance will be an issue, show anterior segment -Treats chalazion photos, or epilate and show them the mites.

Take baseline photographs to monitor effectiveness of treatment, and to educate patients.

If mild, treat at home, TTO bid and recheck in one month. Taper.

If moderate to severe, treat in-office 3 times, one week apart. Support with bid use of TTO at home.

Demonstrate the use of TTO so patients knows what to expect.

PRACTICE MANAGEMENT DEMODEX MYTHS 1.Ocular Demodex infestation is treated the same way as eyelash infestation by Fan the face after applying to cool off. Pediculus humanus capitis (head lice).

TTO is better tolerated the longer it is used. 2. 100% eradication of demodex infestation is the goal.

Use it as a facial wipe, eyelashes, forehead, cheeks, base of nose, and ears. 3. Tea tree oil is safe and non toxic.

4. The clinician must epilate to detect demodex in a lash/follicle Wash all linens on high heat. 5. Demodex is only found in the . Discard makeup. 6. One can get demodex infestation from a . Evaluate family members. 7. There is a procedure code to treat demodex in the office. Use an ABN for in-office treatment. 8. Demodex blepharitis is an isolated condition.

Look for improvement, not eradication. 9. Demodex excretion/droplets produce collarettes and greasy eyelashes.

Sometimes, you just can’t win. 10. Demodex is only seen in elderly patients.

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