Efficacy and Safety of Sodium Hyaluronate/chondroitin Sulfate Preservative-free Ophthalmic Solution in the Treatment of Dry Eye: A Clinical Trial

Abstract

Purpose: To evaluate the efficacy of a preservative free sodium hyaluronate/chondroitin sulfate ophthalmic solution (SH/CS-PF) in patients with dry eye disease (DED). Methods: This was a randomized phase IV, multicentric, prospective, double-blind clinical trial. Intent-totreat (ITT) and per-protocol (PP) analyses were performed. Patients were assigned to receive either SH/CS-PF, Systane® Ultra (PEG/PG) or Systane® Ultra PF (PEG/PG-PF) for 90 days. A total of 326 patients were included in the ITT, and 217 in the PP analysis. Efficacy endpoints were goblet cell density, Nelson's grades (conjunctival impression cytology), tear break-up time (TBUT), Ocular Surface Disease Index (OSDI), and Schirmer's test. Other parameters included were tolerability, measured by the ocular symptomatology; and safety, measured through corneal staining, intraocular pressure, visual acuity and adverse events. Results: In the ITT, there was a significant increase in mean goblet cell density in all treatments compared with their baseline (28.4% vs 21.4% and 30.8%), without difference between arms (p = .159). Eyes exposed to SH/CS-PF, PEG/PG and PEG/PG-PF showed Grade 0-I squamous metaplasia (85.5%, 87.9% and 93.2%, respectively). Similar improvements were observed for TBUT (1.24 ± 2.3s vs 1.27 ± 2.4s and 1.39 ± 2.3s) and OSDI scores at day 90 (−8.81 ± 8.6 vs −7.95 ± 9.2 and −8.78 ± 9.8), although no significant intergroup difference was found. Schirmer's test also presented improvement compared to baseline (1.38 ± 4.9 vs 1.50 ± 4.7 and 2.63 ± 5.9), with a significantly higher variation for PEG/PG-PF. There were no significant differences between treatments for any tolerability and safety parameter, nor between ITT and PP analyses for any outcome. Conclusions:The topical application of SH/CS-PF is as effective, safe and well tolerated as that of PEG/PG or PEG/PG-PF. The results suggest that SH/CS-PF may lead to normalization of clinical parameters and symptom alleviation in patients treated for DED.

Heterologous production of chondroitin

“…Depending on their application, different systems have been implemented for the administration of chondroitin and its derivatives, including oral administration as food additives, in pharmaceutical preparations, nutraceuticals or veterinary supplements [ 74 , 75 , 76 , 77 ]; incorporation in intra-articular or intravenous injectables [78] ; integration in skin dermatology/cosmeceutical and ophthalmic products [ 79 , 80 , 81 ]; as part of medical devices [ 82 , 83 , 84 , 85 ]; or as biomaterials for regenerative medicine [ 9 , 86 ].…”

“…In these studies, CS has shown to be safe and, generally, exhibited slight to moderate efficacy over placebo in pain relief and function improvement in osteoarthritis patients. Also, CS is included in eye drop solutions for dry eyes [ 79 , 80 ]. Preservative-free ophthalmic solutions combining xanthan gum and CS or combining sodium HA and CS showed similar efficacy compared to polyethylene glycol and propylene glycol solutions in the treatment of dry eye disease.…”

Imaging of Escherichia coli K5 and glycosaminoglycan precursors via targeted metabolic labeling of capsular polysaccharides in bacteria

“…Hyaluronan (HA), heparin (HP), heparan sulfate (HS), and various chondroitin sulfates (CSs) are members of the GAG family that vary in the type of saccharide unit and the geometry of the glycosidic linkage they contain. These glycans are involved in various biological processes through interaction with extracellular signaling molecules (1,2) and have become commonly used drugs (3)(4)(5). Development of chemical tools for imaging, activity-based glycan (or protein) profiling, and pharmacological perturbation of GAGs is urgently needed (6,7).…”

Oxidized chondroitin sulfate eye drops ameliorate the prognosis of fungal keratitis with anti-inflammatory and antifungal effects

“…13 Previous investigations have revealed that CS exerts multiple biological effects and pharmacological activities, such as promoting cell regeneration, 14 anti-inflammation, 15 and antioxidation 16 and has been clinically used for osteoarthritis 17–19 and dry eye treatment. 20,21 The anti-inflammatory property is one of the most important biological activities of CS. 22,23 Our previous study showed that CS ameliorated the prognosis of FK by inhibiting the recruitment of neutrophils and alleviating the inflammatory response by downregulating the TLR-4/nuclear factor-k-gene binding (NF-κB) pathway.…”