Efficacy of eyedrops containing cross-linked hyaluronic acid and coenzyme Q10 in treating patients with mild to moderate dry eye

Abstract

Purpose:

Dry eye disease (DED) is a common condition causing substantial burden. A randomized, controlled, single-masked study was performed in 40 patients with mild to moderate DED to evaluate the efficacy and safety of a collyrium based on crosslinked hyaluronic acid (XLHA) with coenzyme Q10 (CoQ10).

Methods:

Enrolled subjects were divided into 2 groups: group A, treated with XLHA + CoQ10; and group B, treated with hyaluronic acid (HA). Eyedrops were administered 4 times daily for 3 months. The Ocular Surface Disease Index (OSDI) questionnaire, tear break-up time (TBUT), corneal and conjunctival staining, and meibomian gland assessment (MGD) were evaluated; furthermore, corneal aesthesiometry, in vivo corneal confocal microscopy, visual acuity, intraocular pressure (IOP), and fundus examination were performed.

Results:

At the end of treatment, OSDI score significantly decreased in groups A and B (p<0.01 and p<0.05, respectively); the decrease was significantly higher in group A. Corneal staining decreased in both groups, with lower scores in group A. The MGD was significantly ameliorated in group A patients. No differences were found for corneal aesthesiometry or TBUT. Epithelial cell reflectivity was significantly reduced only in group A. For keratocytes and stromal matrix parameters, there was a significant improvement in group A. No changes were found for visual acuity, IOP, or fundus examination.

Conclusions:

The XLHA + CoQ10 treatment showed greater effectiveness in DED compared to HA alone, probably due to the longer permanency on ocular surface and the antioxidant activity of CoQ10. Therefore, XLHA + CoQ10 eyedrops could represent a new possibility in dry eye treatment.

Keywords

Coenzyme Q10 Conjunctiva Cornea Crosslinked hyaluronic acid Dry eye Linear hyaluronic acid

Get full access to this article

View all access options for this article.

References

Benítez-Del-Castillo

Labetoulle

Baudouin

et al . Visual acuity and quality of life in dry eye disease: Proceedings of the OCEAN group meeting. Ocul Surf. 2007;15(2):169-178.

Miljanović

Dana

Sullivan

Schaumberg

. Impact of dry eye syndrome on vision-related quality of life. Am J Ophthalmol. 2007;143(3):409-415.

Pflugfelder

. Prevalence, burden, and pharmacoeconomics of dry eye disease. Am J Manag Care. 2008;14(3)(Suppl):S102-S106.

Uchino

Dogru

et al . Dry eye disease and work productivity loss in visual display users: the Osaka study. Am J Ophthalmol. 2014;157(2):294-300.

Clegg

Guest

Lehman

Smith

. The annual cost of dry eye syndrome in France, Germany, Italy, Spain, Sweden and the United Kingdom among patients managed by ophthalmologists. Ophthalmic Epidemiol. 2006;13(4):263-274.

The epidemiology of dry eye disease: report of the Epidemiology Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf. 2007;5(2):93-107.

Gayton

. Etiology, prevalence, and treatment of dry eye disease. Clin Ophthalmol. 2009;3(1):405-412.

Schaumberg

Sullivan

Buring

Dana

. Prevalence of dry eye syndrome among US women. Am J Ophthalmol. 2003;136(2):318-326.

Yazdani

McLaughlin

Smeeding

Walt

. Prevalence of treated dry eye disease in a managed care population. Clin Ther. 2001;23(10):1672-1682.

10.

Musumeci

Aragona

Bellin

et al . Acidic mammalian chitinase in dry eye conditions. Cornea. 2009;28(6):667-672.

11.

Aragona

Aguennouz

Rania

et al . Matrix metalloproteinase 9 and transglutaminase 2 expression at the ocular surface in patients with different forms of dry eye disease. Ophthalmology. 2015;122(1):62-71.

12.

Al-Saedi

Zimmerman

Bachu

et al . Dry Eye Disease: Present Challenges in the Management and Future Trends. Curr Pharm Des. 2016;22(28):4470-4490.

13.

DEWS. Report of the International Dry Eye WorkShop 2007. Ocul Surf. 2007;5:1-204.

14.

Hori

Maeda

Sakamoto

Koh

Inoue

Tano

. Bacteriologic profile of the conjunctiva in the patients with dry eye. Am J Ophthalmol. 2008;146(5):729-734.

15.

Stern

Gao

Siemasko

Beuerman

Pflugfelder

. The role of the lacrimal functional unit in the pathophysiology of dry eye. Exp Eye Res. 2004;78(3):409-416.

16.

Baudouin

Aragona

Messmer

et al . Role of hyperosmolarity in the pathogenesis and management of dry eye disease: proceedings of the OCEAN group meeting. Ocul Surf. 2013;11(4):246-258.

17.

Gong

Sun

Chapin

. Anxiety and depression in patients with dry eye syndrome. Curr Eye Res. 2011;36(1):1-7.

18.

DEWS. The definition and classification of dry eye disease: report of the Definition and Classification Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf. 2007;5(2):75-92.

19.

Stevenson

Chauhan

Dana

. Dry eye disease: an immune-mediated ocular surface disorder. Arch Ophthalmol. 2012;130(1):90-100.

20.

Sullivan

Hammitt

Schaumberg

et al . Report of the TFOS/ARVO Symposium on global treatments for dry eye disease: an unmet need. Ocul Surf. 2012;10(2):108-116.

21.

Savini

Prabhawasat

Kojima

Grueterich

Espana

Goto

. The challenge of dry eye diagnosis. Clin Ophthalmol. 2008;2(1):31-55.

22.

Baudouin

Aragona

Van Setten

et al . ODISSEY European Consensus Group members. Diagnosing the severity of dry eye: a clear and practical algorithm. Br J Ophthalmol. 2014;98(9):1168-1176.

23.

Hessen

Akpek

. Dry eye: an inflammatory ocular disease. J Ophthalmic Vis Res. 2014;9(2):240-250.

24.

OBrien

Liu

et al . Expert opinion in the management of aqueous Deficient Dry Eye Disease (DED). BMC Ophthalmol. 2015;15:133.

25.

Papa

Aragona

Russo

Di Bella

Russo

Milazzo

. Comparison of hypotonic and isotonic solutions containing sodium hyaluronate on the symptomatic treatment of dry eye patients. Ophthalmologica. 2001;215(2):124-127.

26.

She

Xiao

et al . Evaluation of a Novel Artificial Tear in the Prevention and Treatment of Dry Eye in an Animal Model. J Ocul Pharmacol Ther. 2015;31(9):525-530.

27.

Aragona

Papa

Micali

Santocono

Milazzo

. Long term treatment with sodium hyaluronate-containing artificial tears reduces ocular surface damage in patients with dry eye. Br J Ophthalmol. 2002;86(2):181-184.

28.

Gomes

Amankwah

Powell-Richards

Dua

. Sodium hyaluronate (hyaluronic acid) promotes migration of human corneal epithelial cells in vitro. Br J Ophthalmol. 2004;88(6):821-825.

29.

Baeyens

Bron

Baudouin

; Vismed/Hylovis Study Group. Efficacy of 0.18% hypotonic sodium hyaluronate ophthalmic solution in the treatment of signs and symptoms of dry eye disease. J Fr Ophtalmol. 2012;35(6):412-419.

30.

Baudouin

Cochener

Pisella

et al . Randomized, phase III study comparing osmoprotective carboxymethylcellulose with sodium hyaluronate in dry eye disease. Eur J Ophthalmol. 2012;22(5):751-761.

31.

Lanzini

Curcio

Colabelli-Gisoldi

et al . In Vivo and Impression Cytology Study on the Effect of Compatible Solutes Eye Drops on the Ocular Surface Epithelial Cell Quality in Dry Eye Patients. Mediators Inflamm. 2015;2015:351424.

32.

Kiss

Németh

. Isotonic Glycerol and Sodium Hyaluronate Containing Artificial Tear Decreases Conjunctivochalasis after One and Three Months: A Self-Controlled, Unmasked Study. PLoS One. 2015;10(7):e0132656.

33.

Barabino

Rolando

Nardi

Bonini

Aragona

Traverso

. The effect of an artificial tear combining hyaluronic acid and tamarind seeds polysaccharide in patients with moderate dry eye syndrome: a new treatment for dry eye. Eur J Ophthalmol. 2014;24(2):173-178.

34.

Frei

Kim

Ames

. Ubiquinol-10 is an effective lipid-soluble antioxidant at physiological concentrations. Proc Natl Acad Sci U S A. 1990;87(12):4879-4883.

35.

Stocker

Bowry

Frei

. Ubiquinol-10 protects human low density lipoprotein more efficiently against lipid peroxidation than does alpha-tocopherol. Proc Natl Acad Sci U S A. 1991;88(5):1646-1650.

36.

Kalén

Appelkvist

Dallner

. Age-related changes in the lipid compositions of rat and human tissues. Lipids. 1989;24(7):579-584.

37.

Fernandez

Afshari

. Nutrition and the prevention of cataracts. Curr Opin Ophthalmol. 2008;19(1):66-70.

38.

Kaufman

Washington

. Coenzyme Q10 in the human retina. Invest Ophthalmol Vis Sci. 2009;50(4):1814-1818.

39.

Schiffman

Christianson

Jacobsen

Hirsch

Reis

. Reliability and validity of the Ocular Surface Disease Index. Arch Ophthalmol. 2000;118(5):615-621.

40.

Sullivan

Whitmer

Nichols

et al . An objective approach to dry eye disease severity. Invest Ophthalmol Vis Sci. 2010;51(12):6125-6130.

41.

Mandell

. Slit lamp classification system. J Am Optom Assoc. 1987;58(3):198-201.

42.

Faulkner

Varley

. Corneal diagnostic techniques. In: Krachmer

Mannis

Holland

, eds. Cornea. 2nd ed. Vol. 1 Philadelphia, PA: Elsevier/Mosby 2005;229-235.

43.

Fenga

Aragona

Di Nola

Spinella

. Comparison of ocular surface disease index and tear osmolarity as markers of ocular surface dysfunction in video terminal display workers. Am J Ophthalmol. 2014;158(1):41-48.e2.

44.

Aragona

Allegra

Postorino

et al . Corneal Structural Changes in Nonneoplastic and Neoplastic Monoclonal Gammopathies. Invest Ophthalmol Vis Sci. 2016;57(6):2657-2665.

45.

Chiou

Kaufman

Beuerman

. Clinical corneal confocal microscopy. Surv Ophthalmol. 2006;51(5):482-500.

46.

Fabiani

Barabino

Rashid

Dana

. Corneal epithelial proliferation and thickness in a mouse model of dry eye. Exp Eye Res. 2009;89(2):166-171.

47.

Kim

Ryu

Park

et al . Comparison of Topical Application of TSG-6, Cyclosporine, and Prednisolone for Treating Dry Eye. Cornea. 2016;35(4):536-542.

48.

Lemp

. Management of dry eye disease. Am J Manag Care. 2008;14(3)(Suppl):S88-S101.

49.

Aragona

Di Pietro

Spinella

Mobrici

. Conjunctival epithelium improvement after systemic pilocarpine in patients with Sjogrens syndrome. Br J Ophthalmol. 2006;90(2):166-170.

50.

Aragona

Di Stefano

Ferreri

Spinella

Stilo

. Sodium hyaluronate eye drops of different osmolarity for the treatment of dry eye in Sjögrens syndrome patients. Br J Ophthalmol. 2002;86(8):879-884.