Efficacy and Safety of VisuEvo® and Cationorm® for the Treatment of Evaporative and Non-Evaporative Dry Eye Disease: A Multicenter, Double-Blind, Cross-Over, Randomized Clinical Trial

Paolo Fogagnolo, Chiara Quisisana, Anna Caretti, Daniele Marchina, Michele Dei Cas, Ettore Melardi, Luca Rossetti, Paolo Fogagnolo, Chiara Quisisana, Anna Caretti, Daniele Marchina, Michele Dei Cas, Ettore Melardi, Luca Rossetti

Abstract

Purpose: To compare the efficacy of the new lubricating product VisuEvo® (VSE) vs Cationorm® (CTN) in patients with dry eye disease (DED).

Methods: Seventy-two patients with evaporative (n=54) and non-evaporative DED (n=18) were included in a multicenter, double-blind, 12-week cross-over study to receive VSE (6 weeks) and CTN (6 weeks) in randomized sequence. After baseline, two visits were performed during each period (intermediate and final visit, respectively at 2 and 6 weeks from the beginning of each period). Primary (tear break-up time, TBUT) and secondary endpoints (Schirmer I, Ferning, blink rate, osmometry, cytokine and lipid expression, ocular surface staining, patient satisfaction, and OSDI score) were compared.

Results: Sixty-three patients were evaluated for efficacy and 68 patients for safety. The intergroup differences for mean TBUT values were not significant at any study visit (baseline 3.2 ±1.5 sec; intermediate visits 4.5 ± 1.9 and 4.5 ± 1.8 sec in VSE and CTN groups, respectively, p = 0.10; final visits 5.4 ± 2.4 and 6.0 ± 3.1, respectively, p=0.63). Also, the assessment of secondary endpoints showed no significant difference between the two groups. The two study treatments were equally effective in evaporative and non-evaporative DED. The safety profile was excellent for both ocular treatments; transient blurred vision was observed in 11 patients only during CTN, 10 patients only during VSE, and 16 during both treatments.

Conclusion: VSE was non-inferior to CTN in restoring tear film composition, increasing its stability and reducing ocular surface damage in evaporative and non-evaporative DED patients.

Study identifier: NCT03833882.

Keywords: Ocular Surface Disease Index questionnaire; evaporative dry eye disease; glaucoma; meibomian gland disturbance; ocular surface; tear break-up time.

Conflict of interest statement

Paolo Fogagnolo and Luca Rossetti received honoraria for medical meetings and advisory board from Visufarma S.p.A, Rome, Italy. The authors report no other conflicts of interest in this work.

© 2020 Fogagnolo et al.

Figures

Figure 1
Figure 1
Flow of the study design. After verifying eligibility at V1, patients received washout from lubricating treatments until V2. They then entered two 6-week periods. The first product was randomly assigned at V2, the second at V4. V3 and V5 were the intermediate visits of the first and second 6-week period, respectively. No washout occurred between V4 and V5.
Figure 2
Figure 2
Blandt–Altmann plot for comparison of baseline and final TBUT values between study treatments.
Figure 3
Figure 3
Blandt–Altmann plot for comparison of baseline and final OSDI scores between study treatments.
Figure 4
Figure 4
Changes of proportion (%) of patients with staining grade with fluorescein during the study visits with both ophthalmic solutions (VisuEvo® and Cationorm®).
Figure 5
Figure 5
Distribution of proportion (%) of patients during study visits, according to Ferning test grading scale, between the two treatment groups.

References

    1. Craig JP, Nichols KK, Akpek E, et al. TFOS DEWS II definition and classification report. Ocul Surf. 2017;15(3):276e83.
    1. Stapleton F, Alves M, Bunya VY, et al. TFOS DEWS II epidemiology report. Ocul Surf. 2017;15(3):334–365. doi:10.1016/j.jtos.2017.05.003.
    1. No authors listed. The epidemiology of dry eye disease: report of the epidemiology subcommittee of the international dry eye workShop. Ocul Surf. 2007;5(2):93–107. doi:10.1016/S1542-0124(12)70082-4.
    1. Sullivan DA, Rocha EM, Aragona P, et al. TFOS DEWS II sex, gender, and hormones report. Ocul Surf. 2017;15(3):284–333. doi:10.1016/j.jtos.2017.04.001.
    1. Bron AJ, de Paiva CS, Chauhan SK, et al. TFOS DEWS II pathophysiology report. Ocul Surf. 2017;5(3):438–510. doi:10.1016/j.jtos.2017.05.011.
    1. Pflugfelder SC, da Paiva CS. The pathophysiology of dry eye disease: what we know and future directions for research. Ophthalmology. 2017;124(11S):S4–S13. doi:10.1016/j.ophtha.2017.07.010.
    1. Semba CP, Gadek TR. Development of lifitegrast: a novel T-cell inhibitor for the treatment of dry eye disease. Clin Ophthalmol. 2016; 10:1083–1094. doi:10.2147/OPTH.S110557.
    1. Kahook MY, Noecker R. Quantitative analysis of conjunctival goblet cells after chronic application of topical drops. Adv Ther. 2008;25(8):743–751. doi:10.1007/s12325-008-0078-y.
    1. Jones L, Downie LE, Korb D, et al. TFOS DEWS II management and therapy report. Ocul Surf. 2017;15(3):575–628. doi:10.1016/j.jtos.2017.05.006.
    1. Amrane M, Creuzot-Garcher C, Robert PY, et al. Ocular tolerability and efficacy of a cationic emulsion in patients with mild to moderate dry eye disease - a randomised comparative study. J Fr Ophtalmol. 2014;37(8):589–598. doi:10.1016/j.jfo.2014.05.001.
    1. Filion MC, Phillips NC. Anti-inflammatory activity of cationic lipids. Br J Pharmacol. 1997;122(3):551–557. doi:10.1038/sj.bjp.0701396.
    1. Serhan CN, Chiang N. Endogenous pro-resolving and anti-inflammatory lipid mediators: a new pharmacologic genus. Br J Pharmacol. 2008;153(Suppl 1):S200–S215. doi:10.1038/sj.bjp.0707489.
    1. Zhang J, Dai Y, Wu D, Xu J. Calcitriol, the active metabolite of vitamin D3, inhibits dry eye related corneal inflammation in vivo and in vitro. Ocul Immunol Inflamm. 2019;27(2):257–265. doi:10.1080/09273948.2017.1372486
    1. Hatchell DL, Sommer A. Detection of ocular surface abnormalities in experimental vitamin A deficiency. Arch Ophthalmol. 1984;102(9):1389–1393. doi:10.1001/archopht.1984.01040031131040.
    1. Rolando M. Tear mucus ferning test in normal and keratoconjunctivitis sicca eyes. Chibret Int J Ophthalmol. 1984;2:32–41.
    1. Schiffman RM, Christianson MD, Jacobsen G, Hirsch JD, Reis BL. Reliability and validity of the ocular surface disease index. Arch Ophthalmol. 2000;118(5):615–621. doi:10.1001/archopht.118.5.615.
    1. Wolffsohn JS, Arita R, Chalmers R, et al. TFOS DEWS II diagnostic methodology report. Ocul Surf. 2017;15(3):539–574. doi:10.1016/j.jtos.2017.05.001.
    1. Nolfi J, Caffery B. Randomized comparison of in vivo performance of two point-of-care tear film osmometers. Clin Ophthalmol. 2017;11:945–950. doi:10.2147/OPTH.S135068.
    1. Masmali AM, Purslow C, Murphy PJ. The tear ferning test: a simple clinical technique to evaluate the ocular tear film. Clin Exp Optom. 2014;97(5):399–406. doi:10.1111/cxo.12160.
    1. Fong PY, Shih KC, Lam PY, Chan TCY, Jhanji V, Tong L. Role of tear film biomarkers in the diagnosis and management of dry eye disease. Taiwan J Ophthalmol. 2019;9(3):150–159. doi:10.4103/tjo.tjo_56_19.
    1. Lam SM, Tong L, Yong SS, et al. Meibum lipid composition in Asians with dry eye disease. PLoS One. 2011;6(10):e24339. doi:10.1371/journal.pone.0024339.
    1. Kasetsuwan N, Satitpitakul V, Changul T, Jariyakosol S, Wedrich A. Incidence and pattern of dry eye after cataract surgery. PLoS One. 2013;8(11):e78657. doi:10.1371/journal.pone.0078657.
    1. Goto E, Shimazaki J, Monden Y, et al. Low-concentration homogenized castor oil eye drops for noninflamed obstructive meibomian gland dysfunction. Ophthalmology. 2002;109(11):2030Y5. doi:10.1016/S0161-6420(02)01262-9.
    1. McCann LC, Tomlinson A, Pearce EI, Papa V. Effectiveness of artificial tears in the management of evaporative dry eye. Cornea. 2012;31(1):1–5. doi:10.1097/ICO.0b013e31821b71e6.
    1. Robert PY, Cochener B, Amrane M, et al. Efficacy and safety of a cationic emulsion in the treatment of moderate to severe dry eye disease: a randomized controlled study. Eur J Ophthalmol. 2016;26(6):546–555. doi:10.5301/ejo.5000830.
    1. Khanal S, Tomlinson A, Pearce EI, Simmons PA. Effect of an oil- in-water emulsion on the tear physiology of patients with mild to moderate dry eye. Cornea. 2007;26(2):175Y81. doi:10.1097/ICO.0b013e31802b492d.
    1. Wang TJ, Wang IJ, Ho JD, Chou HC, Lin SY, Huang MC. Comparison of the clinical effects of carbomer-based lipid- containing gel and hydroxypropyl-guar gel artificial tear formulations in patients with dry eye syndrome: a 4-week, prospective, open-label, randomized, parallel-group, noninferiority study. Clin Ther. 2010;32(1):44Y52. doi:10.1016/j.clinthera.2010.01.024.

Source: PubMed

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