Sodium Hyaluronate Decreases Ocular Surface Toxicity Induced by Benzalkonium Chloride–Preserved Latanoprost: An In Vivo Study

Abstract

METHODS. Twenty-one white rabbits (42 eyes) were randomly divided into three groups. The control group was untreated. The two experimental groups were treated with 0.02% BACcontaining latanoprost once a day combined with unpreserved 0.3% SH or PBS three times daily for 60 days. Schirmer test, fluorescein and rose bengal staining, and conjunctiva impression cytology were performed on days 0, 31, and 61. Apoptosis of conjunctival epithelium was detected by TUNEL assay on day 61. Conjunctival inflammation was evaluated with light microscopy. Cornea and conjunctiva ultrastructure were observed by electron microscopy. RESULTS.Compared with the control group, the PBS-treated latanoprost group showed increases in fluorescein and rose bengal scores, decreases in Schirmer scores, and goblet cell density (GCD) on days 31 and 61. Increases in inflammatory and apoptotic cells in conjunctiva, and ultrastructural disorders of the cornea and conjunctiva were also observed on day 61. Compared with the PBS-treated latanoprost group, the SH-treated latanoprost group showed decreases in fluorescein and rose bengal scores, and increases in Schirmer scores and GCD on days 31 and 61. Decreases in inflammatory and apoptotic cells in conjunctiva and amelioration of ultrastructural disorders were also observed.CONCLUSIONS. Topical application of SH significantly decreased the ocular surface toxicity induced by BAC-preserved latanoprost. As a vehicle or neutralizing material, SH could be proposed to reduce ocular toxicity and protect the ocular surface in long-term BAK-preserved antiglaucoma medication treatment.

Corneal Alterations Induced by Topical Application of Commercial Latanoprost, Travoprost and Bimatoprost in Rabbit

“…In this study, we found that after commercial PG analogs treatment dry eye symptoms occurred only in the eyes treated with latanoprost, which contains the highest concentration of BAK. This finding is agreement with a recent study reporting significant decreases in Schirmer score and goblet cell density and increase in fluorescein score in rabbits after 30 days treatment of commercial latanoprost [26]. Our group has proven that the reduced aqueous tear production in eyes treated with BAK is a consequence of corneal nerve damage [27].…”

The Impact of Glaucoma Medications on Corneal Wound Healing

“…17,18 Besides its preservative properties, there were indications that BAC would have the advantage of enhancing the efficacy of antiglaucomatous drugs. This was disproved by showing that newer BAC-free drugs such as timolol are as effective as their preserved preparations.…”

A systematic assessment of goblet cell sampling of the bulbar conjunctiva by impression cytology

“…Across the various reports on rabbit conjunctiva, the average numbers of goblet cells/'HPF' have been reported to be from 55 to 170 (Oh et al, 2007;Xiong et al, 2008;Kim et al, 2011;Li et al, 2012Li et al, , 2013Yu et al, 2013), yet very similar numbers have also been reported when 'MPF' have been used (Qiu et al, 2010;Hwang and Kim, 2014) and just 12/field when an intermediate magnification was used (Shellans et al, 1989) (although in the latter study, the rabbits had been treated with an artificial tear for 1 day prior to CIC). Even allowing for the ambiguities in what constitutes an HPF or MPF (in terms of the actual area over which goblet cells were assessed), and allowing for the specific GCD reports (in cells/mm 2 ) (Marino et al, 2005;Altinors et al, 2007;Toshida et al, 2007;Cai et al, 2011), the various reports on rabbit conjunctiva could yield GCD estimates of anywhere between 60 and approximately 4500 goblet cells/mm 2 .…”

“…Assessments of the conjunctiva and its goblet cells by CIC have been widely used in clinical studies (Doughty, 2012a;Calonge et al, 2004;Lopin et al, 2009), but the method has also been undertaken on rabbits, usually as part of toxicology or disease-related studies that constitute an important element of understanding the clinical applications of CIC (Hatchell and Sommer, 1984;Shellans et al, 1989;Driot and Bonne, 1992;Hareuveni and Maurice, 1994;Nakamura et al, 1998;Martinez et al, 1995;Murakami et al, 2003;Marino et al, 2005;Oh et al, 2007;Altinors et al, 2007;Toshida et al, 2007;Xiong et al, 2008;Qiu et al, 2010;Kim et al, 2011;Liang et al, 2011;Cai et al, 2011;Li et al, 2012;Pauly et al, 2012;Yu et al, 2013;Li et al, 2013;Hwang and Kim, 2014). The use of CIC in such animal studies provides an opportunity, not routinely available for human studies, to further investigate the structural organization of the bulbar conjunctiva in relation to the CIC sampling.…”

“…In one such approach, five different HPF were selected for the counting, but only from the central region of the filter surface where multilayering of cells was evident (Driot and Bonne, 1992). Other investigators appear to have usually used three microscope fields for counting, although not necessarily at high power (Shellans et al, 1989;Nakamura et al, 1998;Murakami et al, 2003;Xiong et al, 2008;Kim et al, 2011;Li et al, 2012;Yu et al, 2013;Hwang and Kim, 2014), or 10 fields (Oh et al, 2007;Toshida et al, 2007;Qiu et al, 2010;Li et al, 2013). In none of these studies, however, has any indication been provided of the basis of the visual selection of the microscope fields for counting, nor on the actual variability in the counts across different fields.…”