Efficacy and safety of lotilaner ophthalmic solution in the treatment of Demodex Blepharitis: a meta-analysis of randomized controlled trials

doi:10.5246/jcps.2024.12.081

Abstract

Abstract:

In this meta-analysis, our aim was to systematically evaluate the efficacy and safety of lotilaner ophthalmic solution in treating Demodex Blepharitis (DB), with the goal of providing evidence for clinical practice. PubMed, Embase, Web of Science, The Cochrane Library, CNKI, Wanfang, and CBM were searched from inception to November 28, 2023. Randomized controlled trials (RCTs) comparing lotilaner ophthalmic solution (experimental group) with placebo (control group) for the treatment of DB were included. Two researchers independently screened the literature, extracted the data, and assessed the quality of the included studies. Meta-analysis was conducted using RevMan 5.4 software. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach was used to evaluate the evidence quality of outcomes. Publication bias was assessed using a funnel plot. Four RCTs involving 947 patients were included. Meta-analysis revealed that compared to placebo, lotilaner ophthalmic solution significantly increased the rate of mite eradication (RR = 3.61, 95% CI (2.90, 4.49), P < 0.00001). Additionally, lotilaner treatment resulted in higher rates of collarette cure, erythema cure, composite erythema/collarette cure, and clinically meaningful collarette cure; the differences were statistically significant, with effect sizes (RR = 5.74, 95% CI (4.27, 7.72), P < 0.00001), (RR = 3.16, 95% CI (2.18, 4.58), P < 0.00001), (RR = 6.75, 95% CI (3.75, 12.16), P < 0.00001), and (RR = 3.09, 95% CI (2.65, 3.60), P < 0.00001), respectively. Mite density (MD = –1.42, 95% CI (–2.09, –0.74), P < 0.0001) and collarette grade (MD = –1.51, 95% CI (–1.77, –1.25), P < 0.00001) were significantly reduced. Indeed, no discernible discrepancies in the comfort levels experienced with eye drops emerged between the two groups. Although the experimental group did exhibit a slightly higher occurrence of treatment-related adverse events, ranging from instillation site discomfort to eye discharge and eyelid swelling, these variances did not attain statistical significance. Notably, upon GRADE evaluation, the study’s evidence quality was deemed moderate, while scrutiny for publication bias revealed minimal indications thereof. In the realm of treatment, lotilaner ophthalmic solution shined as a beacon of efficacy, effectively combating mite infections and bolstering cure rates among patients with DB. Moreover, its administration was met with commendable compliance and upheld safety standards.

Key words: Lotilaner ophthalmic solution, Demodex Blepharitis, Meta-analysis, Randomized controlled trial

Supporting:

Qiwen Zhang, Jing Yang, Yongjie Yang, Jingli Lu, Xiaojing Lu, Kefeng Liu, Qi Zhou, Jian Kang. Efficacy and safety of lotilaner ophthalmic solution in the treatment of Demodex Blepharitis: a meta-analysis of randomized controlled trials[J]. Journal of Chinese Pharmaceutical Sciences, 2024, 33(12): 1118-1128.

Figures/Tables 10

Table 1. Search strategy in PubMed.

Table 2. Basic characteristics of included studies.

Table 3. Meta-analysis results of adverse events.

Table 4. Results of GRADE.

References 20

[1]	Luo, X.H.; Li, J.; Chen, C.; Tseng, S.; Liang, L.Y. Ocular demodicosis as a potential cause of ocular surface inflammation. Cornea. 2017, 36, S9–S14.
[2]	Zhang, A.C.; Muntz, A.; Wang, M.T.M.; Craig, J.P.; Downie, L.E. Ocular Demodex: a systematic review of the clinical literature. Ophthalmic Physiol. Opt. 2020, 40, 389–432.
[3]	Karakurt, Y.; Zeytun, E. Evaluation of the efficacy of tea tree oil on the density of demodex mites (acari: Demodicidae) and ocular symptoms in patients with demodectic blepharitis. J. Parasitol. 2018, 104, 473–478.
[4]	Bhandari, V.; Reddy, J. Blepharitis: always remember demodex. Middle East Afr. J. Ophthalmol. 2014, 21, 317.
[5]	Zhao, Y.E.; Wu, L.P.; Hu, L.; Xu, J.R. Association of blepharitis with demodex: a meta-analysis. Ophthalmic Epidemiol. 2012, 19, 95–102.
[6]	Hou, X.Y.; Qin, Y.; Nong, L.; Jin, M. Research progress on the pathogenesis of Demodex blepharitis. China J. Chin. Ophthalmol. 2022, 32, 744–747.
[7]	Syed, Y.Y. Lotilaner ophthalmic solution 0.25%: first approval. Drugs. 2023, 83, 1537–1541.
[8]	Yeu, E.; Wirta, D.L.; Karpecki, P.; Baba, S.N.; Holdbrook, M.; Study Group, S.I. 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, 435–443.
[9]	Gaddie, I.B.; Donnenfeld, E.D.; Karpecki, P.; Vollmer, P.; Berdy, G.J.; Peterson, J.D.; Simmons, B.; Edell, A.R.P.; Whitson, W.E.; Ciolino, J.B.; Baba, S.N.; Holdbrook, M.; Trevejo, J.; Meyer, J.; Yeu, E.; Group, S.2 S. Lotilaner ophthalmic solution 0.25% for demodex blepharitis: randomized, vehicle-controlled, multicenter, phase 3 trial (saturn-2). Ophthalmology. 2023, 130, 1015–1023.
[10]	Gonzalez-Salinas, R.; Karpecki, P.; Yeu, E.; Holdbrook, M.; Baba, S.N.; Ceballos, J.C.; Massaro-Corredor, M.; Corredor-Ortega, C.; Ramos-Betancourt, N.; Quiroz-Mercado, H. Safety and efficacy of lotilaner ophthalmic solution, 0.25% for the treatment of blepharitis due to demodex infestation: a randomized, controlled, double-masked clinical trial. Cont. Lens Anterior Eye. 2022, 45, 101492.
[11]	Yeu, E.; Holdbrook, M.; Baba, S.N.; Ceballos, J.C.; Massaro-Corredor, M.; Corredor-Ortega, C.; Ramos-Betancourt, N.; Quiroz-Mercado, H.; Gonzalez-Salinas, R. Treatment of Demodex blepharitis: a prospective, randomized, controlled, double-masked clinical trial comparing topical lotilaner ophthalmic solution, 0.25% eyedrops to vehicle. Ocul. Immunol. Inflamm. 2023, 31, 1653–1661.
[12]	Higgins, J.; Green, S. Cochrane handbook for systematic reviews of interventions, version 5.1.0. the cochrane collaboration [EB/OL]. (2011-03-20) [2023-12-10] https://handbook-5-1.cochrane.org/.
[13]	Guyatt, G.H.; Oxman, A.D.; Vist, G.E.; Kunz, R.; Falck-Ytter, Y.; Alonso-Coello, P.; Schünemann, H.J.; Working Group, G.R.A.D.E. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ. 2008, 336, 924–926.
[14]	Liu, Z.; Liang, L. Emphasizing the diagnosis and treatment of Demodex blepharitis. Chin. J. Exp. Ophthalmol. 2018, 36, 81–85.
[15]	Rodriguez, A. E.; Ferrer, C.; Alio, J.L. Chronic blepharitis and Demodex. Archivos de la Sociedad Española de Oftalmología. 2005, 80, 635–642.
[16]	Liang, L.Y.; Safran, S.; Gao, Y.Y.; Sheha, H.; Raju, V.K.; Tseng, S.C.G. Ocular demodicosis as a potential cause of pediatric blepharoconjunctivitis. Cornea. 2010, 29, 1386–1391.
[17]	Kemal, M.; Sümer, Z.; Toker, M.I.; Erdoğan, H.; Topalkara, A.; Akbulut, M. The Prevalence of Demodex folliculorum in blepharitis patients and the normal population. Ophthalmic Epidemiol. 2005, 12, 287–290.
[18]	Fromstein, S.R.; Harthan, J.S.; Patel, J.; Opitz, D.L. Demodex blepharitis: clinical perspectives. Clin. Optom. 2018, 10, 57–63.
[19]	Nicholls, S.G.; Oakley, C.L.; Tan, A.; Vote, B.J. Demodex species in human ocular disease: new clinicopathological aspects. Int. Ophthalmol. 2017, 37, 303–312.
[20]	Lyu, X.F. Optimal pulse technology combined with tea tree essential oil paste in the treatment of Demodex blepharitis. Inter. Eye Sci. 2021, 21, 178–181.