Traditional and Novel Treatment of Demodex Blepharitis

 Save as PDF

doi:10.62055/58832535Fx

ABSTRACT

BACKGROUND

Demodex blepharitis is a common condition that can easily be misdiagnosed by eye care providers. The use of traditional and novel treatment options may be necessary for effective treatment. The purpose of this study is to present a case of Demodex blepharitis where thorough anterior segment evaluation was critical to properly identifying the etiology of blepharitis. Traditional treatment was temporarily efficacious while implementation of novel treatment provided lasting relief of symptoms.

CASE REPORT

A 77-year-old male presented for a dry eye evaluation with symptoms of irritation that started in the right eye and then the left eye for at least four days. After a thorough anterior segment examination, the top differential diagnosis was Demodex blepharitis. Traditional tea tree oil treatment was performed in-office. Although this remedy was successful, his symptoms returned after two weeks. The FDA-approved medication, lotilaner ophthalmic solution 0.25%, was prescribed, with improvement in signs and symptoms after six weeks of treatment.

CONCLUSION

A careful anterior segment examination is necessary for diagnosis of Demodex blepharitis and use of novel treatment options may be necessary. This case report discusses the signs and symptoms, diagnosis, and traditional versus novel treatment options of this condition.

Keywords: blepharitis, demodex, dry eye, tea tree oil

INTRODUCTION

Demodex blepharitis is a common chronic inflammatory condition of the eyelashes and eyelids. Patients with this condition experience symptoms of redness, irritation, dry eye, and foreign body sensation.¹ Patients experience a symptomatic burden, as well as issues with treatment tolerability.² Currently, there are treatment options that can be performed in the office and at home. A new treatment option has been FDA-approved for patients suffering from this disease. Patients with multiple ocular surface conditions should receive additional treatment options to help manage their symptoms. Eye care providers should routinely perform a thorough anterior segment exam and utilize the most up-to-date information to provide the best patient care.

CASE REPORT

Figure 1. Clinical timeline: 77-year-old male diagnosed and treated for Demodex blepharitis.

Initial Visit

A 77-year-old male presented with a chief complaint of severe dryness and irritation of the right eye, followed by irritation of the left eye for at least four days. He reported that he started using artificial tears three to four times per day with mild relief of symptoms. He denied eye pain, light sensitivity, itching, mucous discharge, or recent upper respiratory illness. He denied any other changes to his vision or his ocular or medical history since his last visit one month prior.

The patient’s ocular history included severe bilateral primary open angle glaucoma (diagnosed more than ten years prior), bilateral selective laser trabeculoplasty eight years prior, and tube shunts placed in both eyes three years prior. The patient had a history of bilateral cataract extraction ten years prior. Current ocular medications included dorzolamide hcl/timolol maleate ophthalmic solution (22.3 mg/6.8 mg/mL) twice a day in each eye, brimonidine ophthalmic solution 0.2% twice a day in each eye and artificial tears three to four times a day in both eyes. The patient reported allergies to pollen and no known drug allergies. He denied ocular trauma, flashes, floaters, headaches and diplopia.

The patient’s uncorrected distance visual acuity was 20/200 in the right eye and 20/30 in the left eye with no improvement through pinhole. He used no habitual spectacle correction. Pupillary testing in the right eye revealed a minimal reaction to light and a 1+ afferent pupillary defect. The left eye was responsive to light. The extraocular muscle testing was not restricted.

Slit-lamp examination revealed dermatochalasis, severe collarettes and lid debris, capped meibomian glands and scalloped lid margins in both eyes (Figure 2A). There was moderate conjunctival injection 360 degrees, moderate superficial punctate keratitis inferiorly and instant tear break up time in each eye. Bilateral tube shunts were present and the posterior chamber intraocular lenses were in good position in both eyes. The intraocular pressures were 11 mmHg in the right and left eye.

A diagnosis of Demodex blepharitis was made. In addition, the preservatives in the patient’s glaucoma medications may have irritated the ocular surface and contributed to dry eye disease. Preservative-free glaucoma medications were prescribed in the past, however the patient was unable to obtain the medications due to financial burden. The patient was educated on the findings and correspondence to his symptoms of severe dryness and irritation. He was offered an in-office tea tree oil treatment for Demodex and the patient consented. A single drop of proparacaine 0.5% was instilled in both eyes. The patient was educated to keep his eyes closed throughout the procedure. The eyelashes and eyelids were cleaned with lid scrubs. The 50% concentration tea tree oil was applied to the patient’s eyelashes using the included applicator. The tea tree oil was left on the eyelashes for five minutes. Lid scrubs were used to wipe off the tea tree oil from the patient’s eyelashes and saline was used to irrigate the patient’s eyes. After, the residual collarettes were removed in the slit lamp with a brush which resulted in grade zero collarettes (Figure 2B).

Figure 2. Comparison of anterior segment photographs before and after an in-office procedure for Demodex blepharitis. (A) Severe lid debris and collarettes noted on eyelashes with slit lamp examination. (B) Post in-office tea tree oil treatment of eyelashes with removal of collarettes.

The patient was instructed to use lid scrubs twice daily for eyelid cleansing and hygiene, preservative-free artificial tears three to four times a day, perform warm compresses for ten minutes daily and continue his current glaucoma medications in both eyes. The patient was advised to separate the drop instillation between drops at least five minutes apart. He was educated on a new FDA-approved medication, lotilaner ophthalmic solution 0.25%, which could help with his condition if his symptoms persisted at the next visit. The patient was instructed to report his symptoms at his follow-up appointment in one month.

Follow-up, one month later

The patient returned in one month for his follow-up visit and reported that he initially felt a great improvement in his symptoms, however the symptoms of irritation returned after two to three weeks from the initial visit. He reported the use of preservative-free artificial tears three to four times a day but admitted to poor compliance with lid scrubs.

Examination of the anterior segment revealed improved but persistent moderate scurf and collarettes with capped glands in both eyes. There was mild diffuse conjunctival injection, moderate superficial punctate keratitis inferiorly, and instant tear break-up time in each eye. The intraocular pressures were 10 mmHg in the right eye and 9 mmHg in the left eye.

The patient was prescribed lotilaner ophthalmic solution 0.25% twice a day in each eye for six weeks in addition to using preservative free artificial tears three to four times a day. The patient was advised to separate the drop instillation at least five minutes apart between drops. The patient was instructed to return in six weeks for follow up.

Follow-up, 1.5 months later

The patient returned in six weeks reporting significant improvement in his symptoms with the use of preservative-free artificial tears three to four times daily in each eye and the new lotilaner ophthalmic solution 0.25% twice daily in each eye which he used for about five weeks with great compliance. The patient reported a delay of seven days to receive the medication. He denied using hot compresses or lid scrubs.

Examination of the anterior segment revealed marked improvement with persistent mild collarettes and capped glands in each eye (Figure 3). There was mild diffuse conjunctival injection, mild superficial punctate keratitis inferiorly, and an instant tear break-up time in each eye. The intraocular pressures were 13 mmHg in the right eye and 11 mmHg in the left eye.

Figure 3. Slit lamp photograph demonstrating trace collarettes post six weeks of lotilaner ophthalmic solution 0.25% (Tarsus, Irvine, CA) twice a day treatment with marked improvement since initial visit.

The patient was educated on the improvement of his ocular surface signs. He was instructed to continue using preservative-free artificial tears three to four times a day, start warm compresses for ten minutes daily and continue with his glaucoma medication as instructed in both eyes. The patient was instructed to return to the anterior segment clinic in two months. There has been recent controversy with the use of tea tree oil on meibomian glands, however, our in-office use of tea tree oil is typically only 3-5 minutes in comparison to the prolonged use in the study and we have not found direct correlation with loss of meibomian glands.20 Modern treatments such as lotilaner ophthalmic solution 0.25% (Tarsus, Irvine, CA) would improve the quality of life of patients and provide another effective treatment option for individuals suffering from Demodex blepharitis.

DISCUSSION

Demodex is the name of a genus of small parasites that live on mammals; the two species found on humans are Demodex folliculorum and Demodex brevis. The first, Demodex folliculorum, inhabit hair follicles and are distributed more commonly on the face, while the latter, Demodex brevis, inhabit the sebaceous glands near hair follicles and are distributed along a wider area across the body.³ The prevalence of infestation of these mites is incredibly high and increases with age.⁴ The prevalence of infestation is equal in males and females, and similar prevalence regardless of ethnicity.^3,5 In terms of comorbidities, there is a strong correlation between Demodex infestation and rosacea. Demodex infestation is also more likely to occur in immunosuppressed individuals.⁷

Demodex infestation is mainly asymptomatic as the mites live on the eyelids in symbiosis with humans of all ages.⁸ The mites mate in the hair follicle and lay their eggs inside.³ Transmission occurs from direct contact between human hosts through their hair or sebaceous glands. In addition, indirect contact with shared cosmetics has been shown to be another source of transmission of these mites.⁹ Demodicosis occurs when the mites have increased in population size, cause direct damage to the eyelids with their sharp claws and produce the common signs and symptoms of blepharitis that bring patients into the eye care clinic.

The signs and symptoms of Demodex blepharitis can be vague and similar to various types of dry eye and conjunctivitis. Symptoms include itching, burning, irritation, foreign body sensation, tearing, redness and crusting around the eyes.¹ Upon clinical examination, crusty, red, thickened eyelid margins with prominent blood vessels are noted. However, the diagnosis of Demodex blepharitis may be made with the findings of collarettes and cylindrical sleeves around eyelash bases, which are thought to be excretory remains from the Demodex mite. In addition, an eyelash may be epilated and examined under a microscope to locate the mite body and further confirm the diagnosis; however, this is not common practice in a clinical setting. In the current study, the patient exhibited symptoms of eye irritation and redness with signs of collarettes. Epilation was not performed on this patient as the diagnosis was made based on clinical signs and symptoms. Unfortunately, misdiagnosis can prevent the proper treatment of Demodex blepharitis, resulting in the continuation of symptoms.²

Current treatment for Demodex blepharitis includes multiple options for relief of symptoms. Palliative therapy for symptom management may include wetting agents such as artificial tears and eyelid scrubs to clean the lid debris. However, to target the Demodex and treat the disease, multiple in-office and at-home therapies can be applied. Tea tree oil in a gel, ointment or lid scrub composition is an effective treatment option and, if available, can be performed with the oil in higher concentrations in-office in conjunction with mechanical blepharoexfoliation. Tea tree oil can reduce signs and symptoms of Demodex blepharitis as well as reduce mite survival. Although the mechanism of action is thought to be due to the action of the derivative terpinen-4-ol on the mite, the specifics are unknown.¹⁰ Other treatment options include manuka honey and metronidazole gel therapy which have been shown to eradicate the mites due to their anti-parasitic and anti-microbial properties.¹¹ Intense pulsed light therapy may reduce mite density through heat transfer.¹² There is also a strong association of Demodex blepharitis with ocular and facial rosacea in which co-management with a dermatologist is necessary. Okra (Abelmoschus esculentus) is a tropical vegetable with anti‑oxidative, anti‑inflammatory, and anti‑demodectic effects.¹³ Lastly, hypochlorous acid solution has been thought to be an effective treatment for Demodex infestation, however, it has poor clinical evidence of mite eradication. It can be a useful and comfortable treatment for blepharitis with anti-bacterial properties.¹⁴ Currently, with the various options available for Demodex blepharitis treatment, tea tree oil is the most effective.¹ Therefore, the patient in the current study was treated with a 50% concentration tea tree oil in-office. This treatment may require repeat treatment within several months and throughout the year. As the patient reported temporary and mild improvement in his symptoms with persistent clinical signs, an alternative and longer lasting therapy was necessary.

A novel treatment for Demodex blepharitis is lotilaner ophthalmic solution 0.25%, the only FDA-approved treatment for this disease. Lotilaner is an anti-parasitic agent which eradicates mites and reduces collarettes by its action as a mite-specific GABA chloride channel inhibitor, attacking the neurological system of the Demodex mite.¹⁵ In Saturn-2, a randomized, double-masked, vehicle-controlled, phase three clinical trial, a one-drop dose in each eye, two times a day, twelve hours apart, for six weeks yielded improvement in signs of Demodex blepharitis and was safe and comfortable for the subjects.¹⁶ The Demodex mite life cycle is approximately three weeks; the treatment course of six weeks allows the novel medication to attack two life cycles of the mite.¹⁷ Grading scales for the collarettes and lid erythema were used in the evaluation of treatment effectivity.^16,18 By day 43, subjects in the treatment group compared to the control group exhibited a statistically significant increase in collarette cure, collarette reduction, mite eradication, erythema cure and composite cure. In addition, the treatment group exhibited excellent compliance with the medication and found it “neutral” to “very comfortable” when asked to grade on a comfort scale. The most common adverse event exhibited by the use of lotilaner 0.25% ophthalmic solution was pain upon instillation.¹⁶ In the case presented, the results were similar to the literature with significant improvement in collarette reduction. The patient reported the medication was comfortable and easy to tolerate with no side effects noted.

A study comparing the efficacy of tea tree oil to lotilaner 0.25% ophthalmic solution would be useful. Tea tree oil has been known to be associated with allergic reactions, dermatitis and irritation so the use of a novel treatment may be indicated to avoid these complications.19 There has been recent controversy with the use of tea tree oil on meibomian glands, however, our in-office use of tea tree oil is typically only 3-5 minutes in comparison to the prolonged use in the study and we have not found direct correlation with loss of meibomian glands.20 Modern treatments such as lotilaner ophthalmic solution 0.25% (Tarsus, Irvine, CA) would improve the quality of life of patients and provide another effective treatment option for individuals suffering from Demodex blepharitis.

Conclusion

Demodex blepharitis is a common condition that causes symptoms of ocular irritation. Eye care providers can easily diagnose this condition based on clinical signs and symptoms and  manage this condition with appropriate treatment. Modern treatments such as lotilaner ophthalmic solution 0.25% can improve patients’ quality of life and provide another effective treatment option for individuals suffering from Demodex blepharitis.

References

1. Rhee MK, Yeu E, Barnett M, Rapuano CJ, Dhaliwal DK, Nichols K, et al. Demodex Blepharitis: A Comprehensive Review of the Disease, Current Management, and Emerging Therapies. Eye Contact Lens. 2023;49(8):311-318.
2. Barnett M, Simmons B, Vollmer P, Patel A, Whitson WE, Berdy GJ, et al. The impact of Demodex blepharitis on patient symptoms and daily life. Optom Vis Sci. 2024;101(3):151-156.
3. Paichitrojjana A. Demodex: The worst enemies are the ones that used to be friends. Dermatology Reports. 2022;14(3).
4. Rather PA, Hassan I. Human Demodex Mite: The Versatile Mite of Dermatological Importance. Indian J Dermatol. 2014;59(1):60.
5. Trattler W, Karpecki P, Rapoport Y, Sadri E, Schachter S, Whitley WO, 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.
6. Li J, O’Reilly N, Sheha H, Katz R, Raju VK, Kavanagh K, et al. Correlation between Ocular Demodex Infestation and Serum Immunoreactivity to Bacillus Proteins in Patients with Facial Rosacea. Ophthalmology. 2010;117(5):870.
7. Ivy SP, Mackall CL, Gore L, Gress RE, Hartley AH. Demodicidosis in childhood acute lymphoblastic leukemia; an opportunistic infection occurring with immunosuppression. J Pediatr. 1995;127(5):751-754.
8. Biernat MM, Rusiecka-Ziółkowska J, Piątkowska E, Helemejko I, Biernat P, Gościniak G. Occurrence of Demodex species in patients with blepharitis and in healthy individuals: a 10-year observational study. Jpn J Ophthalmol. 2018;62(6):628-633.
9. Sędzikowska A, Bartosik K, Przydatek-Tyrajska R, Dybicz M. Shared Makeup Cosmetics as a Route of Demodex folliculorum Infections. Acta Parasitol. 2021;66(2):631.
10. Cheung I, Xue A, Kim A, Ammundsen K, Wang M, Craig J. In vitro anti-demodectic effects and terpinen-4-ol content of commercial eyelid cleansers. Contact Lens Anterior Eye. 2018;41(6):513-517.
11. Ávila MY, Martínez-Pulgarín DF, Rizo Madrid C. Topical ivermectin-metronidazole gel therapy in the treatment of blepharitis caused by Demodex spp.: A randomized clinical trial. Cont Lens Anterior Eye. 2021;44(3).
12. Cheng S, Jiang F, Chen H, Gao H, Huang Y. Intense Pulsed Light Therapy for Patients with Meibomian Gland Dysfunction and Ocular Demodex Infestation. Curr Med Sci. 2019;39(5):800-809.
13. Liu W, Gong L. Anti-demodectic effects of okra eyelid patch in Demodex blepharitis compared with tea tree oil. Exp Ther Med. 2021;21(4).
14. Fromstein SR, Harthan JS, Patel J, Opitz DL. Demodex blepharitis: clinical perspectives. Clin Optom. 2018;10:57.
15. Syed YY. Lotilaner Ophthalmic Solution 0.25%: First Approval. 2023;83:1537-1541.
16. Gaddie IB, Donnenfeld ED, Karpecki P, Vollmer P, Berdy GJ, Peterson JD, et al. Lotilaner Ophthalmic Solution 0.25% for Demodex Blepharitis: Randomized, Vehicle-Controlled, Multicenter, Phase 3 Trial (Saturn-2). Ophthalmology. 2023;130(10):1015-1023.
17. Spickett SG. Studies on Demodex folliculorum Simon (1842). I. Life history. Parasitology. 1961;51(1-2):181-192.
18. Yeu E, Wirta DL, Karpecki P, Baba SN, Holdbrook M. Lotilaner Ophthalmic Solution, 0.25%, for the Treatment of Demodex Blepharitis: Results of a Prospective, Randomized, Vehicle-Controlled, Double-Masked, Pivotal Trial (Saturn-1). Cornea. 2023;42(4):435.
19. Koo H, Kim TH, Kim KW, Wee SW, Chun YS, Kim JC. Ocular Surface Discomfort and Demodex: Effect of Tea Tree Oil Eyelid Scrub in Demodex Blepharitis. J Korean Med Sci. 2012;27(12):1574.
20. Chen D, Wang J, Sullivan DA, Kam WR, Liu Y. Effects of Terpinen-4-ol on meibomian gland epithelial cells in vitro HHS Public Access. Cornea. 2020;39(12):1541-1546.

Gulnoza Azieva Gomez, OD, FAAO

SUNY Optometry / University Eye Center | New York, NY

Dr. Azieva graduated with her Doctor of Optometry degree from SUNY College of Optometry, where she also completed a Master of Vision Science degree. She also completed her residency in Primary Eye Care with an emphasis in Ocular Disease. She currently supervises interns in Primary Care and Contact Lens clinics. In addition, she works with 2nd year students in both Clinical Optometry and Optics laboratories as well as with 3rd year students in Contact Lens lab.

Harriette Canellos, OD, FAAO, Dipl ABO

SUNY College of Optometry | New York, NY

Dr. Canellos is a full-time faculty member of SUNY State College of Optometry. She is an Associate Clinical Professor, Instructor of Record of the Fourth Year Program and the Director of the University Eye Center’s Referral Service. She supervises interns and residents in the Anterior Segment/Cataract clinics of the Advanced Care Service.

Kamila Mikos, OD, FAAO

SUNY College of Optometry | New York, NY

Dr. Kamila Mikos, OD, is an Assistant Clinical Professor at SUNY College of Optometry, where she serves as the attending doctor in various clinical settings including retina, anterior segment, dry eye, cataract and primary care. She earned her Doctor of Optometry degree from SUNY College of Optometry and completed her residency in Ocular Disease at SUNY College of Optometry and Woodhull Hospital. In addition to teaching and supervising clinical interns and residents, Dr. Mikos actively participates in scholarly activities with a focus on ocular disease and has presented at national conferences. She is a member of the American Academy of Optometry.