Lotilaner ophthalmic solution 0.25% in the treatment of Demodex blepharitis: A case report

Abstract

Demodex blepharitis is a chronic inflammatory ocular condition caused by Demodex mite infestation of the eyelid that can negatively impact quality of life. Currently, lotilaner ophthalmic solution 0.25% is the only FDA-approved treatment for Demodex blepharitis. The Demodex Expert Panel on Treatment and Eyelid Health has established consensus that lotilaner ophthalmic solution 0.25% should be considered the preferred first-line treatment for Demodex blepharitis. We report a patient who presented with collarettes, the pathognomonic sign of Demodex blepharitis, meibomian gland dysfunction, and poor visual acuity. The patient also had a history of neovascular age-related macular degeneration. Consistent with the Demodex Expert Panel on Treatment and Eyelid Health consensus recommendations, the patient was treated with lotilaner ophthalmic solution 0.25%, lid scrubs, and warm compresses. At the 2-month follow-up, collarettes had resolved, and signs of meibomian gland dysfunction had improved. This case supports the Demodex Expert Panel on Treatment and Eyelid Health recommendation that lotilaner ophthalmic solution 0.25% should be considered the preferred first-line treatment for Demodex blepharitis.

Introduction

Blepharitis is a chronic inflammatory eyelid margin disease that can lead to functional tear deficiency, conjunctival erythema, and keratitis. ¹ Overgrowth of Demodex mites in the eyelid causes Demodex blepharitis (DB). Approximately 25 million U.S. eye care patients live with DB, but its prevalence is likely higher because of underdiagnosis, which is partially due to overlapping clinical findings with other conditions, such as meibomian gland dysfunction (MGD).^1–3 DB negatively impacts daily life activities such as nighttime driving and hygiene routines. ²

In 2021, a panel of ophthalmologists and optometrists formed the Demodex Expert Panel on Treatment and Eyelid Health (DEPTH) to raise awareness and establish consensus regarding diagnosis and management strategies.^1,3 In the first DEPTH study, experts agreed that collarettes, cylindrical dandruff at the eyelash base, are pathognomonic for DB, and that itching in the eyelid margin is the most common symptom. ¹ In the second DEPTH study, advisors agreed that patients who present with collarettes on >10 lashes/eyelid (greater than or equal to grade 2) and additional signs should be treated. ³

Until 2023, treatment options for DB were primarily focused on symptom management and did not address the underlying cause of the disease, contributing to a subset of patients remaining refractory to available therapies. ⁴ In 2023, lotilaner ophthalmic solution 0.25% (XDEMVY^®; Tarsus Pharmaceuticals, Inc., Irvine, CA, USA; hereafter referred to as lotilaner 0.25%) became the first FDA-approved drug for the treatment of DB.^5,6 Lotilaner is a gamma-aminobutyric acid–gated chloride channel inhibitor that paralyzes mites, leading to their eradication. ⁵ The efficacy of lotilaner 0.25% in reducing collarettes and mite infestation and its favorable tolerability and safety profile have been established in several clinical trials.^5,7–12

FDA approval of lotilaner 0.25% prompted DEPTH experts to reconvene in 2023 to discuss the preferred first-line treatment for the disease. ¹³ Experts agreed that lotilaner 0.25% should be the first-line treatment for DB. Importantly, DEPTH experts agreed that no additional clinical findings are required to prompt treatment with lotilaner 0.25% in patients with grade 2 collarettes or worse (>10 lashes/eyelid).

To date, real-world evidence of the treatment of DB with lotilaner 0.25% is limited. This case helps fill that gap. With its successful outcome, this case emphasizes the importance of implementing DEPTH consensus findings regarding the diagnosis and treatment of DB in real-world practice.

Case

The 75-year-old female patient presented to her primary eye care provider (ECP) with eye crusting, redness, and burning, as well as a foreign body sensation that occurred most prominently in the morning. The patient also exhibited mattering along the eyelid margin. The patient was diagnosed with dry eye disease and neovascular age-related macular degeneration (nAMD) and was prescribed artificial tears containing carboxymethylcellulose for dry eye. A slit-lamp examination was not performed at this visit, and collarettes were not assessed. As such, an alternative diagnosis of dry eye disease due to DB could not be ruled out. The patient was then referred to a retinal specialist who confirmed the nAMD diagnosis and prescribed bilateral intravitreal aflibercept injections, a vascular endothelial growth factor (VEGF) inhibitor. The retinal specialist also recognized clinical findings consistent with blepharitis and referred the patient to an ocular surface disease specialty center.

Ocular examination revealed reduced visual acuity (VA) in the right eye (OD) and more severe impairment in the left eye (OS), measured as 20/150 + 2 with pinhole no improvement (PHNI) in the OD and counting fingers at 3 feet PHNI in the OS. A slit lamp examination at 10×–16× magnification showed grade 3+ collarettes (⩾1/3–<2/3 of lashes/eyelid), indicating DB (Figure 1(a) and (b)). Additional findings included MGD with a Meibomian Glands Yielding Liquid Secretion (MGYLS) score of 1/15 glands expressing, moderate conjunctival inflammation, redness, trace corneal staining, and moderate to normal tear meniscus height (Figure 2(a) and (b)), Meibography via LipiScan provided further evidence of MGD. The patient was diagnosed with DB based on the presence of collarettes and prescribed lotilaner 0.25% BID for 6 weeks, along with lid scrubs BID and warm compresses. Treatment adherence was emphasized.

Figure 1.

Slit lamp images of patients’ upper eyelashes before and after treatment with lotilaner ophthalmic solution 0.25%. (a, b) The patient presented with grade 3+ collarettes (⩾1/3–<2/3 of lashes/eyelid with collarettes). (c, d) After treatment with lotilaner ophthalmic solution 0.25% twice per day OU for 6 weeks, along with lid scrubs twice per day OU with warm compresses, the patient presented with no collarettes at the 2-month follow-up visit.

Figure 2.

Images of the patient’s palpebral and bulbar conjunctiva at initial visit with ocular surface disease specialist. (a, b) The patient presented with moderate conjunctival inflammation and redness.

At the 2-month follow-up visit, the patient reported proper adherence to the treatment regimen. Upon examination, collarettes had resolved (Figure 1(c) and (d)), and the MGYLS score had improved to 6/16 glands. In addition, VA improved to 20/40 OD, while VA OS decreased to counting fingers at 1 foot PHNI, which is likely due to the administration of an additional anti-VEGF injection in response to nAMD progression. The patient reported that her eyes were “feeling better,” although some foreign body sensation remained. Mild conjunctival redness and trace corneal staining persisted. Interestingly, blurred vision in the OS was now reported. The patient was instructed to continue lid scrubs and warm compresses and was prescribed artificial tears.

Discussion

This patient case highlights DEPTH consensus findings regarding diagnosis and treatment of DB. According to DEPTH, collarettes should be evaluated using a slit lamp, and treatment is indicated when the collarette grade is greater than or equal to grade 2 (>10–<1/3 lashes/eyelid). Elimination of collarettes is considered the main clinical goal of treatment.^4,13 In this case, a slit lamp examination at 10×–16× magnification revealed grade 3+ collarettes (⩾1/3 lashes/eyelid), which was sufficient to diagnose this patient with DB and initiate treatment with lotilaner 0.25% following the recommended dose of one drop BID for 6 weeks in the affected eye(s). Lotilaner 0.25% is the only FDA-approved treatment available to eradicate Demodex mites, ¹³ acting via a mechanism that induces mite-selective paralysis, starvation, and death without affecting mammalian cells. ⁵ Treatment with lotilaner 0.25% resulted in elimination of the mite infestation, as evidenced by the absence of collarettes at follow-up.

Following treatment with lotilaner 0.25%, the patient’s MGYLS score improved from 1/15 to 6/15 glands. This finding suggests that DB contributed to the patient’s MGD, consistent with studies reporting a higher incidence of DB in patients with MGD. ¹⁴ While lotilaner 0.25% eradicated the mites, MGD persisted. This may be attributed to the chronic nature of MGD, the presence of other contributing factors, or the longer time required to resolve MGD. Persistent MGD may also be associated with residual mite debris, which can physically obstruct the meibomian glands. ¹⁴ In this case, continued application of lid hygiene products could continue clearing debris from the meibomian glands and lead to further resolution of MGD (Supplemental Material).

At the follow-up visit, the patient presented with improved VA OD, but worsened VA OS. Though it is possible that lotilaner 0.25% contributed to improved VA OD, as DB is associated with fluctuating and blurred vision, ¹⁴ these results are confounded by the patient’s history with nAMD and ongoing anti-VEGF injections.

Conclusion

This case exemplifies several key points in the diagnosis and treatment of DB. First, the best method to test for DB is to have the patient look down during a slit lamp examination to check for collarettes at the base of the eyelashes. This assessment should be conducted for all patients undergoing an eye examination. ³ Second, prompt, first-line treatment with lotilaner 0.25% eradicated collarettes and Demodex mites, which is the goal of treatment. ³ Third, this case highlights a concurrence of DB with MGD, which were completely and partially resolved, respectively, by treatment with lotilaner 0.25%. This also emphasizes the advantage of resolving DB in patients also diagnosed with MGD, as this enables ECPs to focus treatment on the latter once DB has been resolved.

Although this case report is limited to a single patient, it provides much-needed real-world evidence of the effectiveness of lotilaner 0.25% to treat DB, with resulting improvement in signs of MGD.

Supplemental Material

sj-pdf-1-sco-10.1177_2050313X261443128 – Supplemental material for Lotilaner ophthalmic solution 0.25% in the treatment of Demodex blepharitis: A case report

Supplemental material, sj-pdf-1-sco-10.1177_2050313X261443128 for Lotilaner ophthalmic solution 0.25% in the treatment of Demodex blepharitis: A case report by Paul Karpecki, Brandon Ayres, Eric Donnenfeld, Marjan Farid, Ian Benjamin Gaddie, Preeya K. Gupta, Cecelia Koetting, Richard Lindstrom, Selina McGee, Kelly K. Nichols, Laura M. Periman, Stephen Pflugfelder, Christopher Starr, Nandini Venkateswaran and Elizabeth Yeu in SAGE Open Medical Case Reports