Therapeutic Effects of Sodium Hyaluronate on Ocular Surface Damage Induced by Benzalkonium Chloride Preserved Anti-glaucoma Medications

Abstract

Background:Long-term use of benzalkonium chloride (BAC)-preserved drugs is often associated with ocular surface toxicity. Ocular surface symptoms had a substantial impact on the glaucoma patients’ quality of life and compliance. This study aimed to investigate the effects of sodium hyaluronate (SH) on ocular surface toxicity induced by BAC-preserved anti-glaucoma medications treatment.Methods:Fifty-eight patients (101 eyes), who received topical BAC-preserved anti-glaucoma medications treatment and met the severe dry eye criteria, were included in the analysis. All patients were maintained the original topical anti-glaucoma treatment. In the SH-treated group (56 eyes), unpreserved 0.3% SH eye drops were administered with 3 times daily for 90 days. In the control group (55 eyes), phosphate-buffered saline were administered with 3 times daily for 90 days. Ocular Surface Disease Index (OSDI) questionnaire, break-up time (BUT) test, corneal fluorescein staining, corneal and conjunctival rose Bengal staining, Schirmer test, and conjunctiva impression cytology were performed sequentially on days 0 and 91.Results:Compared with the control group, SH-treated group showed decrease in OSDI scores (Kruskal-Wallis test: H = 38.668, P < 0.001), fluorescein and rose Bengal scores (Wilcoxon signed-ranks test: z = −3.843, P < 0.001, and z = −3.508, P < 0.001, respectively), increase in tear film BUT (t-test: t = −10.994, P < 0.001) and aqueous tear production (t-test: t = −10.328, P < 0.001) on day 91. The goblet cell density was increased (t-test: t = −9.981, P < 0.001), and the morphology of the conjunctival epithelium were also improved after SH treatment.Conclusions:SH significantly improved both symptoms and signs of ocular surface damage in patients with BAC-preserved anti-glaucoma medications treatment. SH could be proposed as a new attempt to reduce ocular surface toxicity, and alleviate symptoms of ocular surface damage in BAC-preserved anti-glaucoma medications treatment.

Ocular Surface Disease and Glaucoma Medications: A Clinical Approach

“…In a trial comparing safety and efficacy of hydroxypropyl-methycellulose/dextran with 0.18% sodium hyaluronate, glaucoma patients with ocular surface disease who used 0.18% sodium hyaluronate showed significantly more improvement in mean OSDI score, lid margin inflammation, and conjunctival injection 81 . For patients who are tolerant to BAK preserved anti-glaucoma medications, adding sodium hyaluronate containing artificial tears as an adjunct appears to decrease OSDI scores, increase goblet cell density, and increase TBUT 82–84 . Furthermore, visual field test parameters were improved in patients using artificial tears, highlighting the impact of a stable tear film and healthy corneal surface 1 .…”

Why Chain Length of Hyaluronan in Eye Drops Matters

“…This is a novel option to transport active pharmaceutical ingredients (API) with HMW HA molecules as vehicle through the cell membrane of epithelial cells without damaging the cell membrane. In combination with the ability of HA to ameliorate the negative effects of corneotoxic substances [93,[255][256][257], it is anticipated that particularly patients requiring long-term topical treatment of diseases like glaucoma, who currently suffer from negative side effects of their treatment, will benefit from the new technology.…”

“…The use of hyaluronan in ophthalmic drug vehicles has been suggested in numerous publications [242,[248][249][250][251][252][253][254]. Hyaluronan has a proven effect of counteracting the irritating effect of substances to the ocular epithelium [93,[255][256][257].…”

Biomarkers of Ocular Surface Disease Using Impression Cytology

“…For example, in 1986 Wittpenn et al [19] first demonstrated reduced goblet cell numbers and increased epithelial cell size of the conjunctiva in vitamin A deficiency-induced xerophthalmia in children, and suggested a role for IC in early detection of this condition. Since then, various groups have used IC to assess the effects of DED therapies on the ocular surface, including the effects of preservatives in ophthalmic medications and autologous serum [20][21][22]. A summary of potential OSD-related biomarkers using IC can be found in Table 1.…”