Demodex blepharitis is a common disease of the eyelid, affecting approximately 25 million Americans. This article reviews what is known about the mechanisms and impact of Demodex blepharitis, risk factors, signs and symptoms, diagnostic techniques, current management options, and emerging treatments. Demodex mites contribute to blepharitis in several ways: direct mechanical damage, as a vector for bacteria, and by inducing hypersensitivity and inflammation. Risk factors for Demodex blepharitis include increasing age, rosacea, and diabetes. The costs, symptom burden, and psychosocial effects of Demodex blepharitis are considerable. The presence of collarettes is pathognomonic for Demodex blepharitis. Redness, dryness, discomfort, foreign body sensation, lash anomalies, and itching are also hallmarks of the disease. Although a number of oral, topical, eyelid hygiene and device-based options have been used clinically and evaluated in studies for the management of Demodex blepharitis, none have been FDA approved to treat the disease. Recent randomized controlled clinical trials suggest that lotilaner ophthalmic solution, 0.25%, is a topical treatment with the potential to eradicate Demodex mites and eliminate collarettes and eyelid redness for an extended period.

To evaluate the safety and efficacy of lotilaner ophthalmic solution, 0.25% compared to the vehicle for the treatment of Demodex blepharitis. Prospective, randomized, double-masked, vehicle-controlled, multicenter, phase 3 clinical trial. Participants, and/or Controls: Four hundred and twelve (412) Demodex blepharitis patients were randomly assigned in a 1:1 ratio to receive either lotilaner ophthalmic solution, 0.25% (study group) or vehicle without lotilaner (control group). In this study, conducted at 21 U.S. clinical sites, Demodex blepharitis patients assigned to the study group (N=203) received lotilaner ophthalmic solution, 0.25% and those in the control group (N=209) received vehicle without lotilaner bilaterally, twice daily for six weeks. Patients were evaluated on Days 8, 15, 22, and 43. Collarettes and erythema were graded for each eyelid at screening and at all post-baseline visits. At screening, and on Days 15, 22, and 43, 4 or more eyelashes were epilated from each eye, and the number of Demodex mites present on the lashes was counted with a microscope. Mite density was calculated as the number of mites per lash. Outcome measures included collarette cure (collarette grade 0), clinically meaningful collarette reduction to ≤10 collarettes (grade 0 or 1), mite eradication (0 mites/lash), erythema cure (grade 0), composite cure (grade 0 for collarettes as well as erythema), compliance with the drop regimen, drop comfort, and adverse events. At Day 43, the study group achieved a statistically significant (p<0.0001) higher proportion of patients with collarette cure (56.0% vs 12.5%), clinically meaningful collarette reduction to ≤10 collarettes (89.1% vs 33.0%), mite eradication (51.8% vs 14.6%), erythema cure (31.1% vs 9.0%), and composite cure (19.2% vs 4.0%) than the control group. High compliance with the drop regimen (mean ± standard deviation: 98.7 ± 5.3%) in the study group was observed, and 90.7% of patients found the drops to be neutral to very comfortable. Twice-daily treatment with lotilaner ophthalmic solution, 0.25% for 6 weeks was generally safe and well tolerated and met the primary endpoint and all secondary endpoints for the treatment of Demodex blepharitis compared to the vehicle control.

There are close to two billion individuals globally living with presbyopia. In spite of its ubiquitous and progressive nature, there is no widely accepted, formal guideline or consensus statement on the classification of presbyopia by degree of severity. A panel of leading eye care professionals representing both optometrists and ophthalmologists convened virtually to discuss and document their combined assessments from the body of literature and clinical practice expertise in this commentary. In light of emerging therapies, classifying presbyopia by mild, moderate, or advanced severity may help provide consistency of diagnosis among eye care providers and may aid in managing patient expectations with different treatment options.

Demodex blepharitis, a chronic lid margin disease, is caused by an infestation of Demodex mites, the most common ectoparasites in human skin and eyelids. Lotilaner ophthalmic solution, 0.25% (Xdemvy, Tarsus Pharmaceuticals), is the first therapy approved to treat Demodex blepharitis. This narrative review characterizes lotilaner ophthalmic solution, 0.25%, and describes its efficacy, safety, and tolerability. The safety and efficacy of lotilaner ophthalmic solution, 0.25%, for treating Demodex blepharitis was evaluated in four phase 2 and two phase 3 trials. The data of 980 patients included in these phase 2 and 3 clinical trials revealed that the proportion of eyes with a clinically meaningful reduction to 10 or fewer collarettes (the cylindrical, waxy debris found at the base of the eyelashes) ranged from 81 to 93%. The mite eradication rate confirmed by a microscopy of epilated lashes ranged from 52 to 78%. No serious treatment-related adverse events were reported in any of these clinical studies. As high as 92% of the patients receiving lotilaner eyedrops in the phase 3 trials found it to be neutral to very comfortable. Given the positive safety and efficacy outcomes, the drug is likely to become the standard of care in the treatment of Demodex blepharitis.

Purpose: To evaluate the efficacy of 0.2% and 0.4% pilocarpine HCl (CSF-1) for the treatment of presbyopia and to determine the contributions of pilocarpine HCl and diclofenac sodium on the efficacy of fixed-dose combination (FDC) formulations. Patients and Methods: This was a Phase 2b, multicenter, randomized, double-masked, parallel-group clinical trial. Adults (45– 64 years) with presbyopia were randomized 1:1:1 to 3 arms (Pilo arm: pilocarpine HCl; Pilo-Diclo FDC arm: pilocarpine HCl with 0.006% diclofenac sodium; Control arm: 0.006% diclofenac sodium). Participants in Pilo and Pilo-Diclo FDC arms received 0.2% pilocarpine HCl (0.2% Pilo or 0.2% Pilo FDC, respectively) from days 1– 8, and 0.4% pilocarpine HCl (CSF-1 or CSF-1-FDC, respectively) from days 8– 15. Primary efficacy endpoint was achievement of ≥ 3-line (15-letter) gain in mesopic, monocular distance-corrected near visual acuity (DCNVA) at 40 cm, 1 hour post-treatment of the study eye on days 8 and 15 in the per protocol (PP) population. Safety endpoints were assessed. Results: One hundred and sixty-six participants were randomized (intent-to-treat, N = 166; PP, n = 160). There were no statistical differences between 0.2% Pilo or 0.2% Pilo FDC versus Control at 1 hour post-treatment on day 8. On day 15, 43.1% and 46.9% of participants receiving CSF-1-FDC (0.4% Pilo FDC) or CSF-1 (0.4% Pilo), respectively, achieved ≥ 3-line gain at 1 hour post-treatment in mesopic DCNVA compared with 16.1% of Control group in the PP population, meeting the primary endpoint (P = 0.0015 and P = 0.0002, respectively). All formulations were well tolerated. Conclusion: CSF-1 demonstrated significant improvements in mesopic DCNVA and favorable safety. Pilocarpine HCl as a single active ingredient, at the concentration of 0.4% (CSF-1), provided a transient, therapeutic effect for presbyopia.

Purpose: To reach consensus on Demodex blepharitis (DB) treatment approaches using a modified Delphi process involving 15 ocular surface disease experts. Methods: The Demodex Expert Panel on Treatment and Eyelid Health (DEPTH) consisted of 15 well-published ocular surface disease experts. Panelists completed two online surveys, a live consensus meeting, and a follow-up survey. The surveys consisted of scaled and multiple-choice questions related to the clinical and patient-reported outcomes of DB and its treatment. For the scaled questions using a 1 to 9 Likert scale, consensus was defined as weighted mean scores of 1– 3 and 7– 9, whereas for multiple-choice questions, consensus was achieved when a minimum of 10 of 15 panelists agreed. Results: The DEPTH panel reached consensus that lotilaner ophthalmic solution, 0.25% should be the first-line treatment for DB. Experts agreed no additional clinical findings are needed to prompt treatment with lotilaner ophthalmic solution, 0.25% for patients with > 10 collarettes (12/15), while one additional clinical finding is needed for patients with 0– 2 (11/15) or 3– 10 collarettes (10/15). In the absence of allergies, panelists would consider first-line treatment for DB in a patient with eyelid itching but without collarettes (weighted mean: 7.47; range: 2– 9). Panelists agreed that blepharoexfoliation (weighted mean: 8.27; range: 3– 9) or intense pulsed light (IPL) therapy (weighted mean: 8.4; range: 6– 9) could supplement first-line treatment with lotilaner ophthalmic solution, 0.25%. The DEPTH panelists agreed that topical (10/15) and systemic ivermectin (14/15) are not their preferred treatment for DB. Experts did not reach consensus about the use of tea tree oil to treat DB. Conclusion: Experts achieved consensus on the use of lotilaner ophthalmic solution, 0.25% as the first-line treatment for patients with DB. Panelists also agreed that blepharoexfoliation or IPL therapy could serve supplementally to lotilaner ophthalmic solution, 0.25%, if needed.